Important Note: The following information is provided for your education. It should not be relied upon for personal diagnosis or treatment. If you believe that a particular therapy applies to you or someone you care about, be sure to consult a doctor before trying it.
   

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Previous Angina Research: 2002-2006   
The Angina File also contains summaries of past research that has shown promise and may still be standard practice among many physicians. To download earlier research findings on Angina, click HERE.
  

Latest Research on Angina
   
Am Heart J. 2008 Aug;156(2):241-7.
Verapamil-sustained release-based treatment strategy is equivalent to atenolol-based treatment strategy at reducing cardiovascular events in patients with prior myocardial infarction: an INternational VErapamil SR-Trandolapril (INVEST) substudy.
Bangalore S, Messerli FH, Cohen JD, Bacher PH, Sleight P, Mancia G, Kowey P, Zhou Q, Champion A, Pepine CJ; INVEST Investigators.
Division of Cardiovascular Medicine, St. Luke's-Roosevelt Hospital Center, New York, NY 10025, USA.

BACKGROUND: In patients with prior myocardial infarction (MI), beta-blockers reduce mortality by 23% to 40%. However, despite this favorable effect, adverse effects limit compliance to this medication. The purpose of the study was to compare a beta-blocker-based strategy with a heart rate-lowering calcium antagonists-based strategy in patients with prior MI. METHODS: We evaluated 7,218 patients with prior MI enrolled in the INternational VErapamil SR-Trandolapril (INVEST) substudy randomized to verapamil-sustained release (SR)- or atenolol-based strategies. Primary outcome was time to first occurrence of death (all-cause), nonfatal MI, or nonfatal stroke. Secondary outcomes included death, total MI (fatal and nonfatal), and total stroke (fatal and nonfatal) considered separately. RESULTS: During the 2.8 +/- 1.0 years of follow-up, patients assigned to the verapamil-SR-based and atenolol-based strategies had comparable blood pressure control, and the incidence of the primary outcome was equivalent. There was no difference between the 2 strategies for the outcomes of either death or total MI. However, more patients reported excellent/good well-being (82.3% vs 78.0%, P = .02) at 24 months with a trend toward less incidence of angina pectoris (12.0% vs 14.3%, adjusted P = .07), nonfatal stroke (1.4% vs 2.0%; P = .06), and total stroke (2.0% vs 2.5%, P = .18) in the verapamil-SR-based strategy group. CONCLUSIONS: In hypertensive patients with prior MI, a verapamil-SR-based strategy was equivalent to a beta-blocker-based strategy for blood pressure control and prevention of cardiovascular events, with greater subjective feeling of well-being and a trend toward lower incidence of angina pectoris and stroke in the verapamil-SR-based group.

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Arch Intern Med. 2008 Jul 14;168(13):1423-8.
Inducible ischemia and the risk of recurrent cardiovascular events in outpatients with stable coronary heart disease: the heart and soul study.
Gehi AK, Ali S, Na B, Schiller NB, Whooley MA.
Division of Cardiology, Emory University Hospital, 1364 Clifton Rd NE, Ste 424, Atlanta, GA 30322, USA. anilgehi@gmail.com

BACKGROUND: Current guidelines do not recommend routine cardiac stress testing in patients with stable coronary heart disease (CHD) unless they report symptoms of angina. Our objective was to compare the prognosis of self-reported angina symptoms, inducible ischemia, or both in patients with stable CHD. METHODS: We measured self-reported angina by questionnaire and inducible ischemia using treadmill stress echocardiography in 937 outpatients with stable CHD. We used Cox proportional hazard models, adjusted for traditional cardiovascular risk factors, to evaluate the independent association of angina and inducible ischemia with CHD events (myocardial infarction or CHD death) during a mean of 3.9 years of follow-up. RESULTS: Of the study participants, 129 (14%) had angina alone, 188 (20%) had inducible ischemia alone, and 40 (4%) had both angina and ischemia. Recurrent CHD events occurred in 7% of participants without angina or inducible ischemia, 10% of those with angina alone, 21% of those with inducible ischemia alone, and 23% of those with both angina and inducible ischemia (P < .001). The presence of angina alone was not associated with recurrent CHD events (adjusted hazard ratio, 1.4; 95% confidence interval, 0.7-2.9) (P = .31). However, the presence of inducible ischemia without self-reported angina strongly predicted recurrent CHD events (adjusted hazard ratio, 2.2; 95% CI, 1.4-3.5) (P = .005). CONCLUSIONS: We found that 24% of patients with stable CHD had inducible ischemia, and more than 80% of these patients did not report angina. The presence of inducible ischemia without self-reported angina is associated with a greater than 2-fold increased rate of recurrent CHD events.

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JAMA. 2008 Jul 2;300(1):71-80.
Early invasive vs conservative treatment strategies in women and men with unstable angina and non-ST-segment elevation myocardial infarction: a meta-analysis.
O'Donoghue M, Boden WE, Braunwald E, Cannon CP, Clayton TC, de Winter RJ, Fox KA, Lagerqvist B, McCullough PA, Murphy SA, Spacek R, Swahn E, Wallentin L, Windhausen F, Sabatine MS.
TIMI Study Group, Brigham and Women's Hospital, 350 Longwood Ave, First Floor, Boston, MA 02115, USA. modonoghue@partners.org

CONTEXT: Although an invasive strategy is frequently used in patients with non-ST-segment elevation acute coronary syndromes (NSTE ACS), data from some trials suggest that this strategy may not benefit women. OBJECTIVE: To conduct a meta-analysis of randomized trials to compare the effects of an invasive vs conservative strategy in women and men with NSTE ACS. DATA SOURCES: Trials were identified through a computerized literature search of the MEDLINE and Cochrane databases (1970-April 2008) using the search terms invasive strategy, conservative strategy, selective invasive strategy, acute coronary syndromes, non-ST-elevation myocardial infarction, and unstable angina. STUDY SELECTION: Randomized clinical trials comparing an invasive vs conservative treatment strategy in patients with NSTE ACS. DATA EXTRACTION: The principal investigators for each trial provided the sex-specific incidences of death, myocardial infarction (MI), and rehospitalization with ACS through 12 months of follow-up. DATA SYNTHESIS: Data were combined across 8 trials (3075 women and 7075 men). The odds ratio (OR) for the composite of death, MI, or ACS for invasive vs conservative strategy in women was 0.81 (95% confidence interval [CI], 0.65-1.01; 21.1% vs 25.0%) and in men was 0.73 (95% CI, 0.55-0.98; 21.2% vs 26.3%) without significant heterogeneity between sexes (P for interaction = .26). Among biomarker-positive women, an invasive strategy was associated with a 33% lower odds of death, MI, or ACS (OR, 0.67; 95% CI, 0.50-0.88) and a nonsignificant 23% lower odds of death or MI (OR, 0.77; 95% CI, 0.47-1.25). In contrast, an invasive strategy was not associated with a significant reduction in the triple composite end point in biomarker-negative women (OR, 0.94; 95% CI, 0.61-1.44; P for interaction = .36) and was associated with a nonsignificant 35% higher odds of death or MI (OR, 1.35; 95% CI, 0.78-2.35; P for interaction = .08). Among men, the OR for death, MI, or ACS was 0.56 (95% CI, 0.46-0.67) if biomarker-positive and 0.72 (95% CI, 0.51-1.01) if biomarker-negative (P for interaction = .09). CONCLUSIONS: In NSTE ACS, an invasive strategy has a comparable benefit in men and high-risk women for reducing the composite end point of death, MI, or rehospitalization with ACS. In contrast, our data provide evidence supporting the new guideline recommendation for a conservative strategy in low-risk women.

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Am J Health Syst Pharm. 2008 Jul 1;65(13 Suppl 5):S1-5; quiz S16-8.
Overview of advances in cardiovascular disease treatment and prevention: the evolving role of antiplatelet therapy.
Talbert RL.
College of Pharmacy, University of Texas-Austin, USA. talbert@uthscsa.edu

PURPOSE: The role of antiplatelet therapy in preventing and treating cardiovascular disease is reviewed. SUMMARY: Cardiovascular disease, especially coronary heart disease, contributes to substantial morbidity and mortality in the United States and raises healthcare costs. Current guidelines from the American College of Cardiology and the American Heart Association, in conjunction with the Society for Cardiovascular Angiography and Interventions, recommend percutaneous coronary intervention (PCI) and stent placement to improve cardiovascular outcomes in patients with acute coronary syndrome, which encompasses unstable angina and myocardial infarction. Following stent placement, dual antiplatelet therapy with aspirin and a thienopyridine (clopidogrel or ticlopidine) significantly reduces the incidence of early major adverse cardiac events and mortality compared with aspirin alone or in combination with warfarin, and is the current standard of care for patients undergoing PCI. Maintenance therapy should be continued for at least one month after placement of a bare-metal stent, and at least three months or six months after placement of a sirolimus- or paclitaxel-eluting stent; ideally, therapy should be continued for one year following PCI. Even utilizing this standard, however, adverse clinical events do occur. In addition, treatment is often discontinued within the first year after stent placement by either the healthcare provider or the patient. CONCLUSION: Premature discontinuation of antiplatelet therapy is associated with an increased risk of adverse outcomes and can be avoided through better understanding of these risks by healthcare professionals and improved patient education.

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Mayo Clin Proc. 2008 Jul;83(7):799-805.
Placing COURAGE in context: review of the recent literature on managing stable coronary artery disease.
Coylewright M, Blumenthal RS, Post W.
Department of Medicine, Johns Hopkins University, Baltimore, MD, USA.

Coronary artery disease (CAD) is the leading cause of death in the United States, but prevention and intervention efforts are lowering mortality. This progress is being undercut by rising rates of obesity and diabetes, and adherence to evidence-based prevention efforts is less than ideal. Many patients with CAD who are asymptomatic or have minimal symptoms undergo percutaneous coronary intervention (PCI) each year, even though PCI has not been demonstrated to improve survival for this group. Motivated by the recent controversy surrounding the Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation (COURAGE) trial, we reviewed randomized clinical trials with follow-up published in the past decade comparing medical management with revascularization for stable CAD to provide a context for the COURAGE trial. We searched for relevant studies published from January 1, 1997, until the date of electronic publication of the COURAGE study results, March 26, 2007; references cited in the COURAGE publication were also reviewed. Evidence shows that PCI does not decrease mortality or risk of myocardial infarction over optimal medical or lifestyle therapy in patients with chronic stable CAD. In published studies, early benefits in angina control afforded by revascularization wane over time; this could change with modern interventional therapies. The final word is not that medical therapy is superior for all patients, but that optimizing medical and lifestyle therapy is appropriate as an initial management strategy for most patients who do not have unstable or disabling symptoms. It is essential that systems are set in place to make the medical management of patients with CAD second nature; this focus could be one of the most powerful results of the COURAGE trial.

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Arch Intern Med. 2008 Jun 23;168(12):1310-6.
Angina at 1 year after myocardial infarction: prevalence and associated findings.
Maddox TM, Reid KJ, Spertus JA, Mittleman M, Krumholz HM, Parashar S, Ho PM, Rumsfeld JS.
Cardiology Section (111B), Denver Veterans Affairs MedicalCenter, 1055 Clermont St, Denver, CO 80209, USA. thomas.maddox@va.gov

BACKGROUND: Eradication of angina is a primary goal of care after myocardial infarction (MI). However, the prevalence of angina 1 year after MI and factors associated with it are unknown. METHODS: From January 1, 2003, through June 28, 2004, 2498 patients with acute MI were recruited from 19 hospitals in the United States. Among this multicenter cohort of patients, angina was measured by the Seattle Angina Questionnaire 1 year after hospitalization for MI. Multivariate regression modeling identified the sociodemographic factors, clinical history, MI presentation, inpatient treatments, and outpatient treatments associated with 1-year angina, adjusted for site. RESULTS: Of 1957 patients in the cohort, 389 (19.9%) reported angina 1 year after MI. After multivariate analysis, patients with 1-year angina were more likely to be younger (relative risk [RR] per 10-year decrease, 1.19; 95% confidence interval [CI], 1.09-1.30), to be nonwhite males (RR, 1.50; 95% CI, 1.16-1.96), to have had prior angina (RR, 1.78; 95% CI, 1.54-2.06), to have undergone prior coronary artery bypass graft surgery (RR, 1.92; 95% CI, 1.51-2.44), and to experience recurrent rest angina during their hospitalization (RR, 1.54; 95% CI, 1.22-1.93). Among the outpatient variables, patients with 1-year angina were more likely to continue smoking (RR, 1.23; 95% CI, 1.02-1.48), to undergo revascularization after index hospitalization (percutaneous coronary intervention or coronary artery bypass graft) (RR, 1.37; 95% CI, 1.09-1.73), and to have significant new (RR, 1.96; 95% CI, 1.34-2.87), persistent (RR, 1.88; 95% CI, 1.29-2.75), or transient (RR, 1.77; 95% CI, 1.49-2.11) depressive symptoms. CONCLUSIONS: Angina occurs in nearly 1 of 5 patients 1 year after MI. It is associated with several modifiable factors, including persistent smoking and depressive symptoms.

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Am J Cardiol. 2008 Jun 15;101(12):1700-3. Epub 2008 Apr 18.
Relation of low response to clopidogrel assessed with point-of-care assay to periprocedural myonecrosis in patients undergoing elective coronary stenting for stable angina pectoris.
Cuisset T, Hamilos M, Sarma J, Sarno G, Wyffels E, Vanderheyden M, Barbato E, Bartunek J, De Bruyne B, Wijns W.
Cardiovascular Center, OLV Hospital, Aalst, Belgium. thomascuisset@voila.fr

Impaired responses to antiplatelet therapy assessed by laboratory tests are associated with an increased risk of recurrent ischemic events after percutaneous coronary intervention (PCI). This study was designed to determine the relation between responses to aspirin and clopidogrel as assessed by a point-of-care assay (Verify Now, Accumetrics, San Diego, California) and periprocedural myocardial infarction (PMI) in patients undergoing elective PCI for stable angina. One hundred twenty-two consecutive patients undergoing elective coronary stenting prospectively received aspirin 500 mg and clopidogrel 600 mg >or=12 hours before PCI. Clopidogrel response was measured with P2Y12 reaction units (PRUs) and percent inhibition P2Y12 from baseline (percent inhibition P2Y12) and aspirin response with aspirin reaction units (ARUs). Troponin T level was considered positive if it was >0.03 ng/ml. Responses to aspirin and clopidogrel were correlated (r=0.42, p <0.0001). PMI occurred in 27 patients (22%) who showed significantly lower percent inhibition P2Y12 (25.3+/-26 vs 38.3+/-25, p=0.01) and a trend toward higher PRU values (221+/-87 vs 193+/-94, p=0.21). We did not find any difference for aspirin response as assessed by ARUs in patients with or without PMI (460+/-82 vs 454+/-73, p = 0.82). Stratification of percent inhibition P2Y12 isolated a quartile of clopidogrel nonresponders (inhibition P2Y12 <15%) with significantly higher incidence of PMI (44% vs 15%, odds ratio 4.6, 95% confidence interval 1.9 to 11.5, p=0.001). In conclusion, point-of-care assessment of clopidogrel response reliably predicted PMI after low- to medium-risk elective PCI for stable angina.

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J Manipulative Physiol Ther. 2008 Jun;31(5):344-7.
Muscular tenderness in the anterior chest wall in patients with stable angina pectoris is associated with normal myocardial perfusion.
Kumarathurai P, Farooq MK, Christensen HW, Vach W, Høilund-Carlsen PF.
Registrar, University of Southern Denmark, Denmark.

OBJECTIVE: This study examines the relationship between the existence of chest wall tenderness evoked by palpation and the absence of ischemic heart disease defined by myocardial perfusion imaging in patients with known or suspected stable angina pectoris. METHODS: Two hundred seventy-five patients were recruited. Myocardial perfusion imaging was performed on 273 of the subjects. Chest pain was classified according to type by criteria given by the Danish Society of Cardiology and severity by the Canadian Cardiovascular Society. Pectoralis major and pectoralis minor were palpated for tenderness using a standardized procedure. RESULTS: The association between tenderness and myocardial perfusion imaging (normal vs abnormal) produced an odds ratio (OR) of 2.24 (confidence interval, 1.26-3.99; P = .009). The OR was the same magnitude and significance when stratified by sex, age, type of pain, or class. When adjusting simultaneously for sex, age, type of pain, and class, the association between tenderness and myocardial perfusion imaging (normal vs abnormal) was still present (OR = 2.57; confidence interval, 1.342-4.902; P = .004). CONCLUSION: Presence of tenderness in the anterior chest wall is associated with a higher prevalence of normal myocardial perfusion imaging in patients with known or suspected angina pectoris, and this association cannot be explained by a common association to age, sex, or pain.

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Cleve Clin J Med. 2008 Mar;75 Suppl 2:S94-6.
Heart-brain interactions in cardiac arrhythmias: role of the autonomic nervous system.
Zipes DP.
Division of Cardiology, Krannert Institute of Cardiology, Indiana University School of Medicine, Indianapolis, IN 46202, USA. dzipes@iupui.edu

The autonomic nervous system plays an important role in the genesis of ventricular arrhythmias and sudden cardiac death. Evidence is substantial for a neural component in sudden cardiac death. Sympathetic nerve sprouting and regional myocardial hyperinnervation following myocardial injury promote cardiac arrhythmia and sudden cardiac death through several potential mechanisms. Modulating autonomic tone is a potential method to reduce the risk of ventricular arrhythmias. Thoracic spinal cord stimulation is showing promise as a treatment for refractory angina. In addition, spinal cord stimulation has protected against ventricular tachycardia/ventricular fibrillation in animal models of postinfarction heart failure.

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Drugs Today (Barc). 2008 Mar;44(3):171-81.
Ivabradine: I(f) inhibition in the management of stable angina pectoris and other cardiovascular diseases.
Tardif JC.
Montreal Heart Institute, University of Montreal, Montreal, QC, Canada. jean-claude.tardif@icm-mhi.org

Elevated heart rate plays a major role in coronary artery disease, not only as a trigger of most ischemic episodes but also as a significant predictor of cardiovascular morbidity and mortality. Heart rate is an important target in the management of stable angina pectoris. Against this background, a new class of antianginal drugs has recently become available: the selective and specific I(f) inhibitors. The mode of action of this novel class involves selective and specific inhibition of the major pacemaker current in the sinoatrial node, the mixed sodium/potassium current (I(f)), which results in pure heart rate reduction. The first member of this class available for clinical use is ivabradine (available under the brandnames of Procoralan, Coralan, Corlentor, Coraxan, Servier, France). Building on solid preclinical studies, ivabradine was shown to have anti-ischemic and antianginal efficacy in patients with stable angina pectoris in clinical trials versus placebo, beta-blockers and calcium channel blockers. Ongoing studies will determine the potential of pure heart rate reduction with ivabradine to improve morbidity and mortality.

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Ann Cardiol Angeiol (Paris). 2008 Feb;57 Suppl 1:16-23.
[Statins in coronary patients: a solved issue?]
[Article in French]
Ferrières J.
Service de Cardiologie B, CHU Rangueil, TSA 50032, 31059 Toulouse cedex 9, France. jean.ferrieres@cict.fr

Statin prescription in patients with coronary artery disease is justified by numerous randomized controlled trials. These trials were conducted in various clinical conditions such as acute coronary syndrome and stable angina. Statin therapy was nearly always associated with better clinical outcomes. These benefits were highly significant in stable coronary patients with hypercholesterolemia and less striking in the first days of acute coronary syndrome. However, in patients with or without acute coronary syndrome, long-term prognosis was favorably influenced in patients on statin therapy. In patients with coronary artery disease, physicians must prescribe a well-tolerated statin as soon as possible, and verify long-term compliance in every patient.

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Ann Thorac Surg. 2008 Feb;85(2):488-93.
Long-term results of coronary artery bypass grafting in patients with left ventricular dysfunction.
Soliman Hamad MA, Tan ME, van Straten AH, van Zundert AA, Schönberger JP.
Department of Cardiothoracic Surgery, Catharina Hospital, Eindhoven, The Netherlands. aasmsn@cze.nl

BACKGROUND: In this prospective study, we investigated the determinants of long-term outcome, symptoms, and left ventricular function after coronary artery bypass grafting in patients with a moderate to severely decreased left ventricular ejection fraction. METHODS: Between 1997 and 1998, 75 consecutive patients with moderate to severe left ventricular dysfunction underwent coronary artery bypass grafting procedures. The operative mortality rate was 4.0%, and the 72 survivors were monitored for 8 years. The end points were mortality, symptomatic status (New York Heart Association [NYHA] functional class), and left ventricular function. RESULTS: The total survival rate after 8 years was 89.3%. During follow-up, 8 patients died. Death was attributed to a cardiac cause in 5 patients and to a noncardiac cause in 3. There was no statistically significant difference between preoperative and late postoperative NYHA functional class, despite a statistically significant improvement that persisted for up to 4 years after CABG. The results of echocardiography showed a statistically significant improvement in the left ventricular ejection fraction (from 0.322 +/- 0.06 preoperatively to 0.463 +/- 0.02 at follow-up, p < 0.001). Multivariate analysis revealed that the left ventricular end-systolic volume index, the presence of angina pectoris, and absence of symptoms of congestive heart failure were preoperative indicators of freedom from heart failure after coronary operations (p < 0.05). CONCLUSIONS: Coronary artery bypass grafting for patients with moderate-to-severe left ventricular dysfunction is associated with acceptable long-term results. The left ventricular end-systolic volume index is a simple noninvasive method to aid in the preoperative decision making in such patients.

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JAMA. 2008 Jan 30;299(4):409-16.
Comparison of paclitaxel- and sirolimus-eluting stents in everyday clinical practice: the SORT OUT II randomized trial.
Galløe AM, Thuesen L, Kelbaek H, Thayssen P, Rasmussen K, Hansen PR, Bligaard N, Saunamäki K, Junker A, Aarøe J, Abildgaard U, Ravkilde J, Engstrøm T, Jensen JS, Andersen HR, Bøtker HE, Galatius S, Kristensen SD, Madsen JK, Krusell LR, Abildstrøm SZ, Stephansen GB, Lassen JF; SORT OUT II Investigators.
Department of Cardiology, Gentofte University Hospital, Hellerup, Copenhagen, Denmark. anders@galloe.dk

CONTEXT: Approval of drug-eluting coronary stents was based on results of relatively small trials of selected patients; however, in routine practice, stents are used in a broader spectrum of patients. OBJECTIVE: To compare the first 2 commercially available drug-eluting stents-sirolimus-eluting and paclitaxel-eluting-for prevention of symptom-driven clinical end points, using a study design reflecting everyday clinical practice. DESIGN, SETTING, AND PATIENTS: Randomized, blinded trial conducted August 2004 to January 2006 at 5 university hospitals in Denmark. Patients were 2098 men and women (mean [SD] age, 63.6 [10.8] years) treated with percutaneous coronary intervention (PCI) and randomized to receive either sirolimus-eluting (n = 1065) or paclitaxel-eluting (n = 1033) stents. Indications for PCI included ST-segment elevation myocardial infarction (STEMI), non-STEMI or unstable angina pectoris, and stable angina. MAIN OUTCOME MEASURES: The primary end point was a composite
clinical end point of major adverse cardiac events, defined as either cardiac death, acute myocardial infarction, target lesion revascularization, or target vessel revascularization. Secondary end points included individual components of the composite end point, all-cause mortality, and stent thrombosis. RESULTS: The sirolimus- and the paclitaxel-eluting stent groups did not differ significantly in major adverse cardiac events (98 [9.3%] vs 114 [11.2%]; hazard ratio, 0.83 [95% confidence interval, 0.63-1.08]; P = .16) or in any of the secondary end points. The stent thrombosis rates were 27 (2.5%) and 30 (2.9%) (hazard ratio, 0.87 [95% confidence interval, 0.52-1.46]; P = .60), respectively. CONCLUSION: In this practical randomized trial, there were no significant differences in clinical outcomes between patients receiving sirolimus- and paclitaxel-eluting stents. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00388934.

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Clin Pharmacol Ther. 2008 Jan;83(1):37-51. Epub 2007 Nov 28.
Coronary heart disease in women: update 2008.
Wenger NK, Shaw LJ, Vaccarino V.
Division of Cardiology, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia, USA. nwenger@emory.edu

Coronary heart disease (CHD) remains the leading cause of mortality for US women, responsible for almost 250,000 deaths annually. Preventive heart-health behavioral changes by women and aggressive coronary risk reduction can decrease the number of women disabled and killed by CHD. Angina is the predominant initial and subsequent presentation of CHD in women; categorization of chest pain and risk stratification of women assume pivotal roles. A robust evidence-based algorithm can guide cardiovascular imaging techniques to evaluate women with suspected myocardial ischemia to detect those with worsened survival. Restricted functional capacity (<5 METs) is a consistent marker of worsened prognosis. Younger women have substantially higher mortality rates than men following myocardial infarction and coronary bypass surgery. Although these women have more comorbidity and risk factors, other issues including biological differences, treatment differences, and psychosocial factors require management strategies tailored to the unique needs of women.

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Geriatrics. 2007 Dec;62(12):23-32.
Recognition and management of aortic stenosis in the elderly.
Aronow WS.
Department of Medicine, Division of Cardiology, Westchester Medical Center/New York Medical College, Valhalla, NY, USA.

Angina pectoris, syncope or near-syncope, and congestive heart failure (CHF) are the 3 cardinal manifestations of aortic stenosis (AS) in the elderly. Prolonged duration and late peaking of the aortic systolic ejection murmur best differentiate severe from mild AS. The agreement in quantitation of AS severity between Doppler echocardiography and cardiac catheterization is approximately 95%. The average survival is 3 years after the onset of angina pectoris or syncope and 1.5 to 2 years after the onset of CHF in patients with severe AS who does not undergo surgery. Indications for aortic valve replacement (AVR), for use of warfarin after AVR in patients with mechanical prostheses, and for use of aspirin or warfarin after AVR in patients with bioprostheses are listed in the article.

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Am J Med. 2007 Dec;120(12):1047-53.
Hospital discharge against advice after myocardial infarction: deaths and readmissions.
Fiscella K, Meldrum S, Barnett S.
Department of Family Medicine, University of Rochester School of Medicine, Rochester, NY 14620, USA. kevin_fiscella@urmc.rochester.edu

BACKGROUND: Approximately 1% of patients leave hospitals against medical advice, but the clinical significance of premature hospital discharge is unknown, particularly after admission for acute myocardial infarction (AMI). METHODS: We used California hospital discharge data (1998-2000) to compare readmissions and mortality among patients admitted for AMI who were discharged against medical advice with those who weren't. Effects were adjusted for age, race, income, comorbidity, insurance, and hospital characteristics. We also examined whether the effects of premature hospital discharge were partly explained by lower rates of coronary revascularization. RESULTS: There were 1079 patients (1.1% of the sample) with AMI on admission who left against medical advice. Compared with those who didn't leave against medical advice, these patients were younger, more often male, low income, black, insured through Medicaid or uninsured, and had less physical comorbidity, but greater mental health comorbidity. Their mean length of stay was shorter (4 vs 8 days) than those who stayed. They were transferred less often. They received fewer cardiac procedures, including coronary revascularization. In multivariate analyses, they had 60% higher risk for death or re-admission for AMI or unstable angina up to 2 years postdischarge than patients with standard discharge (hazard ratio 1.59; 95% confidence interval, 1.43-1.77). Adjustment for revascularization attenuated, but did not eliminate, this risk (hazard ratio 1.39; 95% confidence interval, 1.25-1.55). CONCLUSIONS: Discharge against medical advice after AMI is associated with appreciable morbidity and mortality. These results should be used to manage AMI patients contemplating such discharge.

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Compr Ther. 2007 Winter;33(4):174-83.
Aortic stenosis.
Aronow WS.
Depatment of Medicine, Divisions of Cardiology, Geriatrics, and Pulmonary/Critical Care, New York Medical College, Macy Pavilion, Room 138, Valhalla, NY, 10595, USA.

Patients with aortic stenosis (AS) have an increased prevalence of coronary risk factors, coronary artery disease, and other atherosclerotic vascular disease and an increased incidence of coronary events and death. Statins may reduce the progression of AS. Angina pectoris, syncope or near syncope, and heart failure are the three classic manifestations of severe AS. Prolonged duration and late peaking of an aortic systolic ejection murmur best differentiate severe AS from mild AS on physical examination. Doppler echocardiography is used to diagnose the presence and severity of AS. Once symptoms develop, aortic valve replacement (AVR) should be performed in patients with severe or moderate AS. Warfarin should be administered indefinitely after AVR in patients with a mechanical aortic valve and in patients with a bioprosthetic aortic valve who have either atrial fibrillation, prior thromboembolism, left ventricular systolic dysfunction, or a hypercoagulable condition. Patients with a bioprosthetic aortic valve without any of these four risk factors should be treated with aspirin 75-100 mg daily.

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Chin Med J (Engl). 2007 Nov 20;120(22):1986-91.
Early local intracoronary platelet activation after drug-eluting stent placement.
Mahemuti A, Meneveau N, Seronde MF, Schiele F, Mercier M, Racadot E, Bassand JP.
Department of Cardiology and UPRES EA3920-IFR133, University of Franche-Comte Medical School, Jean-Minjoz University Hospital, Bensancon, France. xahzad@hotmail.com

BACKGROUND: Early local platelet activation after coronary intervention identifies patients at increased risk of acute stent thrombosis (AST). However, early changes in platelet activation in coronary circulation following drug-eluting stent (DES) implantation have never been reported. METHODS: In a prospective study of 26 consecutive elective stable angina patients, platelet activation was analyzed by measuring soluble glycoprotein V (sGPV) and P-selectin (CD62P) before and after implantation of either DES or bare metal stent (BMS). All patients were pretreated with clopidogrel (300 mg loading dose) and aspirin (75 mg orally) the day before the procedure. Blood samples were drawn from the coronary ostium and 10 - 20 mm distal to the lesion site. RESULTS: Consistent with the lower baseline clinical risk, the levels of CD62P and sGPV were within normal reference range, both in the coronary ostium and distal to the lesion before percutaneous coronary intervention (PCI) procedure. The levels of CD62P and sGPV did not change significantly (CD62P: (31.1 +/- 9.86) ng/ml vs (29.5 +/- 9.02) ng/ml, P = 0.319 and sGPV: (52.4 +/- 13.5) ng/ml vs (51.8 +/- 11.7) ng/ml, P = 0.674, respectively) after stent implantation when compared with baseline. Changes in these platelet activation markers did not differ between stent types. CONCLUSIONS: Intracoronary local platelet activation does not occur in stable angina patients before and immediately following DES implantation when dual anti-platelet is administered.

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J Am Coll Cardiol. 2007 Nov 27;50(22):2111-6. Epub 2007 Nov 13.
Gender-specific outcomes after sirolimus-eluting stent implantation.
Solinas E, Nikolsky E, Lansky AJ, Kirtane AJ, Morice MC, Popma JJ, Schofer J, Schampaert E, Pucelikova T, Aoki J, Fahy M, Dangas GD, Moses JW, Cutlip DE, Leon MB, Mehran R.
Columbia University Medical Center and the Cardiovascular Research Foundation, New York, New York, USA.

OBJECTIVES: We examined the impact of gender on outcomes of patients undergoing percutaneous coronary intervention using sirolimus-eluting stents (SES). BACKGROUND: Although gender-specific differences in outcome after implantation of bare-metal stents (BMS) have been described, there are no data assessing outcomes of women treated with SES. METHODS: We performed a patient-level pooled analysis from 4 randomized SES versus BMS trials (RAVEL [Randomized Comparison of a Sirolimus-Eluting Stent with a Standard Stent for Coronary Revascularization], SIRIUS [SIRolImUS-coated Bx Velocity balloon expandable stent in the treatment of patients with de novo coronary artery lesions], E-SIRIUS [Sirolimus-eluting stents for treatment of patients with long atherosclerotic lesions in small coronary arteries], and C-SIRIUS [Canadian study of the sirolimus-eluting stent in the treatment of patients with long de novo lesions in small native coronary arteries]) and analyzed outcomes as a function of gender. RESULTS: Of 1,748 patients, 1,251 were men and 497 were women. A total of 878 patients were randomized to SES (629 men and 249 women), and 870 patients were randomized to BMS (622 men and 248 women). Compared with men, women were older and more frequently had diabetes mellitus, hypertension, and congestive heart failure. Although overall clinical outcomes were similar in both genders, treatment with SES was associated with significant (p < 0.0001) reductions in rates of in-segment binary restenosis both in women (6.3% vs. 43.8%) and in men (6.4% vs. 35.6%), resulting in a significant reduction in 1-year major adverse cardiac events, driven by a lower incidence of target lesion revascularization/target vessel revascularization in both genders. By multivariable analysis, female gender was not an independent predictor of in-segment binary restenosis or clinical outcomes regardless of stent type. CONCLUSIONS: In this analysis, despite less favorable baseline clinical and angiographic features in women compared with men, the angiographic and clinical benefits of SES were independent of gender.

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Am J Pharm Educ. 2007 Oct 15;71(5):95.
Antianginal actions of Beta-adrenoceptor antagonists.
O'Rourke ST.
College of Pharmacy, North Dakota State University.

Angina pectoris is usually the first clinical sign of underlying myocardial ischemia, which results from an imbalance between oxygen supply and oxygen demand in the heart. This report describes the pharmacology of beta-adrenoceptor antagonists as it relates to the treatment of angina. The beta-adrenoceptor antagonists are widely used in long-term maintenance therapy to prevent acute ischemic episodes in patients with chronic stable angina. Beta-adrenoceptor antagonists competitively inhibit the binding of endogenous catecholamines to beta(1)-adrenoceptors in the heart. Their anti-ischemic effects are due primarily to a reduction in myocardial oxygen demand. By decreasing heart rate, myocardial contractility and afterload, beta-adrenoceptor antagonists reduce myocardial workload and oxygen consumption at rest as well as during periods of exertion or stress. Predictable adverse effects include bradycardia and cardiac depression, both of which are a direct result of the blockade of cardiac beta(1)-adrenoceptors, but adverse effects related to the central nervous system (eg, lethargy, sleep disturbances, and depression) may also be bothersome to some patients. Beta-adrenoceptor antagonists must be used cautiously in patients with diabetes mellitus, peripheral vascular disease, heart failure, and asthma or other obstructive airway diseases. Beta-adrenoceptor antagonists may be used in combination with nitrates or calcium channel blockers, which takes advantage of the diverse mechanisms of action of drugs from each pharmacologic category. Moreover, concurrent use of beta-adrenoceptor antagonists may alleviate the reflex tachycardia that sometimes occurs with other antianginal agents.

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Rev Cardiovasc Med. 2007;8 Suppl 3:S9-17.
Anticoagulation for acute coronary syndromes: from heparin to direct thrombin inhibitors.
Lepor NE.
David Geffen School of Medicine at the University of California at Los Angeles, Cedars-Sinai Medical Center, Los Angeles, California, USA.

The anticoagulant properties of heparin were discovered in 1916, and by the 1930s researchers were evaluating its therapeutic use in clinical trials. Treatment of unstable angina with unfractionated heparin (UFH), in addition to aspirin, was introduced into clinical practice in the early 1980s. UFH was combined with aspirin to suppress thrombin propagation and fibrin formation in patients presenting with acute coronary syndromes (ACS) or patients undergoing percutaneous coronary intervention (PCI). However, UFH stimulates platelets, leading to both activation and aggregation, which may further promote clot formation. Clinical trials have demonstrated that newer agents, such as the low-molecular-weight heparins (LMWHs), are superior to UFH for medical management of unstable angina or non-ST-segment elevation myocardial infarction. Increasingly, the LMWHs have been used as the anticoagulant of choice for patients presenting with ACS. For patients undergoing PCI, LMWH provides no sub-stantial benefit over UFH for anticoagulation; however, direct thrombin inhibitors (DTIs) have demonstrated safety and efficacy in this setting. UFH is likely to be replaced by more effective and safer antithrombin agents, such as DTIs. DTIs have antiplatelet effects, anticoagulant action, and most do not bind to plasma proteins, thereby providing a more consistent dose-response effect than UFH. The FDA has approved 4 parenteral DTIs for various indications: lepirudin, argatroban, bivalirudin, and desirudin. The antiplatelet, anticoagulant, and pharmacokinetic properties of bivalirudin support its use as the anticoagulant of choice for both lower- and higher-risk patients, including those undergoing PCI.

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J Am Coll Cardiol. 2007 Oct 16;50(16):1598-603. Epub 2007 Sep 17.
The truth and consequences of the COURAGE trial.
Kereiakes DJ, Teirstein PS, Sarembock IJ, Holmes DR Jr, Krucoff MW, O'Neill WW, Waksman R, Williams DO, Popma JJ, Buchbinder M, Mehran R, Meredith IT, Moses JW, Stone GW.
Christ Hospital Heart and Vascular Center/The Lindner Research Center, Cincinnati, Ohio 45219, USA. lindner@fuse.net

Percutaneous coronary intervention (PCI) has played an integral role in the therapeutic management strategies for patients who present with either acute coronary syndromes or stable angina pectoris. The COURAGE (Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation) trial enrolled patients with chronic stable angina and at least 1 significant (> or =70%) angiographic coronary stenosis who were randomly assigned to an initial treatment of either PCI in conjunction with optimal medical therapy or optimal medical therapy alone. Although the initial management strategy of PCI did not reduce the risk of death, myocardial infarction, or other major cardiovascular events, improvement in angina-free status and a reduction in the requirement for subsequent revascularization was observed. An in-depth analysis of the COURAGE trial design and execution is provided.

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Am J Cardiol. 2007 Oct 1;100(7):1047-51. Epub 2007 Jul 18.
Effect of intensive lipid-lowering therapy on mortality after acute coronary syndrome (a patient-level analysis of the Aggrastat to Zocor and Pravastatin or Atorvastatin Evaluation and Infection Therapy-Thrombolysis in Myocardial Infarction 22 trials).
Murphy SA, Cannon CP, Wiviott SD, de Lemos JA, Blazing MA, McCabe CH, Califf RM, Braunwald E.
TIMI Study Group, Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA. smurphy@perfuse.org

Compared with moderate lipid lowering with standard-dose statin therapy, intensive lipid lowering with high-dose statin therapy after acute coronary syndromes (ACS) significantly reduces cardiovascular events. However, the 2 trials of high-dose versus standard-dose statin therapy in patients with ACS, Aggrastat to Zocor (A to Z) and Pravastatin or Atorvastatin Evaluation and Infection Therapy-Thrombolysis In Myocardial Infarction 22 (PROVE-IT-TIMI 22), were not individually powered to evaluate the impact on mortality alone. In this study, a pooled, patient-level analysis of these trials of 8,658 post-ACS patients was performed to provide a more robust estimate of the impact of intensive statin therapy on mortality. By 8 months, achieved low-density lipoprotein levels were lower in the group with intensive statin therapy (median 64 mg/dl, interquartile range 51 to 81) than in the group with moderate statin therapy (median 87 mg/dl, interquartile range 71 to 107) (p <0.001). All-cause mortality was significantly reduced in the group with intensive statin therapy compared with the group with moderate statin therapy (3.6% vs 4.9%, hazard ratio 0.77, 95% confidence interval 0.63 to 0.95, p = 0.015), without significant interaction by trial (interaction p = 0.63). The reduction in all-cause mortality with intensive statin therapy was consistent across key subgroups. In conclusion, in this analysis of >8,600 patients, intensive lipid lowering with high-dose statin therapy after ACS was associated with reduced mortality compared with moderate lipid lowering with standard-dose statin therapy. On the basis of these findings, 1 death was prevented for every 95 patients treated with high-dose statin therapy for 2 years. The results of this pooled analysis provide further evidence for early intensive statin therapy after ACS.

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J Cardiovasc Pharmacol Ther. 2007 Sep;12(3):192-204.
Tissue ACE inhibitors for secondary prevention of cardiovascular disease in patients with preserved left ventricular function: a pooled meta-analysis of randomized placebo-controlled trials.
Saha SA, Molnar J, Arora RR.
Department of Medicine, Chicago Medical School, North Chicago, Illinois 60064, USA.

OBJECTIVE: A pooled meta-analysis of published, randomized placebo-controlled clinical trials to evaluate the role of tissue angiotensin-converting enzyme (ACE) inhibitors in secondary prevention of cardiovascular disease in patients with preserved left ventricular function. SOURCES: Peer-reviewed journals listed in Index Medicus/MEDLINE, the Cochrane Central Register of Controlled Clinical Trials, and the Cochrane Database of Systematic Reviews. STUDY SELECTION: Randomized placebo-controlled clinical trials of at least 12 months' duration, in patients with a prior cardiovascular event or at high risk for cardiovascular events, were analyzed. DATA SYNTHESIS AND ANALYSIS: A total of 31,555 patients (136,882 patient-years) from 4 trials were selected for the meta-analysis. Relative risk estimations were made using data pooled from these trials, and statistical significance was determined using the chi2 test. The number of patients needed to treat was also calculated for each outcome. RESULTS: Tissue ACE inhibitors significantly reduced the risk of all-cause mortality, cardiovascular mortality, acute myocardial infarction, and stroke (P < .001 for each). The need for invasive coronary revascularization was reduced (P = .03), as was the risk of hospitalization for congestive heart failure (P = .001). The occurrence of new-onset diabetes was also significantly reduced (P < .001), but the risk of hospitalization for angina was not significantly affected (P = .677). Treating about 100 patients for about 4.5 years would prevent 1 death, 1 non-fatal myocardial infarction, 1 cardiovascular death, or 1 invasive coronary revascularization. CONCLUSIONS: Tissue ACE inhibitors have demonstrated benefit when used for secondary prevention of cardiovascular disease in patients with preserved left ventricular function in randomized placebo-controlled clinical trials.

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Ann Intern Med. 2007 Sep 4;147(5):304-10.
Influence of renal function on the efficacy and safety of fondaparinux relative to enoxaparin in non ST-segment elevation acute coronary syndromes.
Fox KA, Bassand JP, Mehta SR, Wallentin L, Theroux P, Piegas LS, Valentin V, Moccetti T, Chrolavicius S, Afzal R, Yusuf S; OASIS 5 Investigators.
Cardiovascular Research, University of Edinburgh, Edinburgh, United Kingdom. k.a.a.fox@ed.ac.uk

BACKGROUND: A recent randomized, controlled trial, the Fifth Organization to Assess Strategies in Acute Ischemic Syndromes (OASIS 5) trial, reported that major bleeding was 2-fold less frequent with fondaparinux than with enoxaparin in acute coronary syndromes (ACS). Renal dysfunction increases the risk for major bleeding. OBJECTIVE: To compare the efficacy and safety of fondaparinux and enoxaparin over the spectrum of renal dysfunction observed in the OASIS 5 trial. DESIGN: Subgroup analysis of a randomized, controlled trial. SETTING: Patients presenting to the hospital with non-ST-segment elevation ACS. PATIENTS: 19,979 of the 20,078 patients in the OASIS 5 trial in whom creatinine was measured at baseline. MEASUREMENTS: Death, myocardial infarction, refractory ischemia, and major bleeding were evaluated separately and as a composite end point at 9, 30, and 180 days. Glomerular filtration rate (GFR) was calculated by using the Modification of Diet in Renal Disease formula. RESULTS: The absolute differences in favor of fondaparinux (efficacy and safety) were most marked in patients with a GFR less than 58 mL/min per 1.73 m2; the largest differences occurred in major bleeding events. At 9 days, death, myocardial infarction, or refractory ischemia occurred in 6.7% of patients receiving fondaparinux and 7.4% of those receiving enoxaparin (hazard ratio, 0.90 [95% CI, 0.73 to 1.11]); major bleeding occurred in 2.8% and 6.4%, respectively (hazard ratio, 0.42 [CI, 0.32 to 0.56]). Statistically significant differences in major bleeding persisted at 30 and 180 days. The rates of the composite end point were lower with fondaparinux than with enoxaparin in all quartiles of GFR, but the differences were statistically significant only among patients with a GFR less than 58 mL/min per 1.73 m2. Limitations: Subgroup analyses warrant caution; the study was powered to detect noninferiority at 9 days. Fondaparinux is not approved for use in patients with ACS in the United States. CONCLUSIONS: The benefits of fondaparinux over enoxaparin when administered for non-ST-segment elevation ACS are most marked among patients with renal dysfunction and are largely explained by lower rates of major bleeding with fondaparinux.

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Expert Opin Pharmacother. 2007 Sep;8(13):2149-57.
Ranolazine in patients with coronary artery disease.
Scirica BM.
TIMI Study Group, Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA. bscirica@partners.org

Traditional anti-anginal agents such as beta-blockers and nitrates improve symptoms of cardiac ischemia by affecting either blood pressure or heart rates. Despite aggressive therapy, many patients suffer persistent angina, and optimal therapy is limited by intolerance to traditional agents. Ranolazine, a novel anti-anginal agent that is approved for use in the US, is felt to improve ischemic symptoms by reducing myocardial cellular sodium and calcium overload via inhibition of the late sodium current (I(Na)) of the cardiac action potential. Several Phase-III trials in patients with chronic angina have demonstrated that ranolazine improves exercise tolerance and reduces ischemic symptoms as compared with placebo. In the largest evaluation of ranolazine, the MERLIN-TIMI 36 trial (Metabolic Efficiency with Ranolazine for Less Ischemia in non ST elevation acute coronary syndrome), ranolazine did not reduce the risk of death or recurrent myocardial infarction in patients with non-ST-elevation acute coronary syndromes, but it did improve ischemic symptoms over the subsequent year of therapy. Thus, ranolazine offers clinicians a new therapy in the long-term treatment of patients with chronic angina.

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Can J Cardiol. 2007 Aug;23(10):779-81.
The role of enhanced external counterpulsation in the treatment of angina and heart failure.
Arora RR, Shah AG.
Department of Medicine, Chicago Medical School, Chicago, IL 60064, USA. rohit.arora@med.va.gov

As the incidence of angina and heart failure continue to rise, new therapeutic options will be needed to treat patients who remain symptomatic or who are intolerant to current treatment. Enhanced external counterpulsation (EECP) is a noninvasive modality being investigated in both angina and congestive heart failure patients. It has been proven to provide symptomatic benefit in angina patients, but has not been proven to show an increase in life expectancy or decrease in cardiovascular events. EECP in heart failure has been proven to be safe, but its efficacy is still uncertain. The present paper summarizes the current literature on the clinical use of EECP in angina and heart failure.

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Int J Cardiol. 2007 Aug 7; [Epub ahead of print]
Methylated arginines in stable and acute patients with coronary artery disease before and after percutaneous revascularization.
Frøbert O, Hjortshøj SP, Simonsen U, Ravkilde J.
Department of Cardiology, Center for Cardiovascular Research, Aalborg Hospital, Aarhus University Hospital, Denmark; Department of Pharmacology, University of Aarhus, Denmark.

BACKGROUND: Impairment of the nitric oxide synthase (NOS) pathway independently predicts cardiovascular events. We investigated whether plasma levels of the NOS inhibitor asymmetric dimethylarginine (ADMA), of symmetric dimethylarginine (SDMA) and of the nitrogen oxide substrate l-arginine can serve as additional staging biomarkers in stable coronary artery disease, non-ST-segment myocardial infarction (NSTEMI) and ST-segment myocardial infarction (STEMI). MATERIALS AND METHODS: Consecutive patients referred for percutaneous coronary intervention (PCI) were studied. Peripheral blood samples were drawn immediately before, immediately after and 24 h following PCI and analyzed by means of high-performance liquid chromatography. RESULTS: Seventy-four patients were studied: 27 patients with stable angina pectoris (7 women, 61.4+/-1.9 years), 23 NSTEMI patients (9 women, 61.8+/-2.3 years) and 24 STEMI patients (7 women, 61.3+/-2.8 years). Plasma concentrations of ADMA and SDMA were elevated following PCI compared to before PCI but there were no differences in concentrations between STEMI, NSTEMI and stable angina patients. Plasma concentrations of l-arginine rose after PCI but remained lower in patients with STEMI than in those with NSTEMI or in stable angina patients. Medication might influence l-arginine concentrations and the use of HMG CoA reductase inhibitors and beta-adrenoceptor antagonists at study inclusion was significantly less common in STEMI patients compared to NSTEMI and stable angina patients. CONCLUSION: l-arginine levels were lower in patients with STEMI and we found changes in ADMA levels over shorter time periods than previously considered possible. We speculate that these variations may be related to the natural history of myocardial infarction or to peri-procedural stress related to PCI.

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Heart. 2007 Jun;93(6):703-7. Epub 2007 May 8. Comment in: Heart. 2007 Jun;93(6):656-7.
Protective effect of an acute oral loading dose of trimetazidine on myocardial injury following percutaneous coronary intervention.
Bonello L, Sbragia P, Amabile N, Com O, Pierre SV, Levy S, Paganelli F.
Division of Cardiology, Hospital Nord, University of Marseille, School of Medicine, Marseille, France.

OBJECTIVE: To evaluate the effect of pre-procedural acute oral administration of trimetazidine (TMZ) on percutaneous coronary intervention (PCI)-induced myocardial injury. DESIGN: Single-centre, prospective, randomised evaluation study. SETTING: Patients with stable angina pectoris and single-vessel disease undergoing PCI. PATIENTS: 582 patients were prospectively randomised. Patients who underwent more than one inflation during PCI were excluded, resulting in 266 patients randomly assigned to 2 groups. INTERVENTIONS: Patients were randomly assigned to receive or not an acute loading dose of 60 mg of TMZ prior to intervention. Main outcome: The frequency and the increase in the level of cardiac troponin Ic (cTnI) after successful PCI. cTnI levels were measured before and 6, 12, 18 and 24 h after PCI. RESULTS: 136 patients were assigned to the TMZ group and 130 to the control group. Although no statistically significant difference was observed in the frequency of cTnI increase between the two groups, post-procedural cTnI levels were significantly reduced in the TMZ group at all time points (6 h: mean (SD) 4.2 (0.8) vs 1.7 (0.2), p<0.001; 12 h: 5.5 (1.5) vs 2.3 (0.4), p<0.001; 18 h: 9 (2.3) vs 3 (0.5), p<0.001; and 24 h: 3.2 (1.2) vs 1 (0.5), p<0.001). Moreover, the total amount of cTnI released after PCI, as assessed by the area under the curve of serial measurement, was significantly reduced in the TMZ group (p<0.05). CONCLUSION: Pre-procedural acute oral TMZ administration significantly reduces PCI-induced myocardial infarction.

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Crit Care Med. 2007 May 22; [Epub ahead of print]
Safety of intravenous nitroglycerin after administration of sildenafil citrate to men with coronary artery disease: A double-blind, placebo-controlled, randomized, crossover trial*
Parker JD, Bart BA, Webb DJ, Koren MJ, Siegel RL, Wang H, Malhotra B, Jen F, Glue P.
>From the Department of Medicine, University Health Network and Mount Sinai Hospitals, University of Toronto, Ontario, Canada (JDP); Hennepin County Medical Center, Minneapolis, MN (BAB); Centre for Cardiovascular Science, Queen’s Medical Research Institute, University of Edinburgh, Edinburgh, UK (DJW); Jacksonville Center for Clinical Research, Jacksonville, FL (MJK); and Pfizer, New York, NY (RLS, HW, BM, FJ, PG).

OBJECTIVE:: Although contraindicated, there are situations when a patient who has recently taken a phosphodiesterase 5 inhibitor (e.g., sildenafil) might need intravenous nitroglycerin (NTG) treatment. This study determined if, and at what dose, intravenous NTG could be administered safely to men with coronary artery disease who had recently ingested sildenafil. DESIGN:: Double-blind, placebo-controlled, randomized, crossover trial. SETTING:: Four clinical practice sites in Canada, Scotland, and the United States. PATIENTS:: A total of 34 men (>/=35 yrs) with a history of angina pectoris and coronary artery disease (>50% stenosis of at least one coronary artery), most of whom were taking antihypertensives. INTERVENTIONS:: Sildenafil (100 mg) or placebo (single dose; crossover after 3-7 days) followed 45 mins later by escalating doses of intravenous NTG (160 mug/min maximum). MEASUREMENTS AND MAIN RESULTS:: After sildenafil, there were slightly greater maximum (supine) blood pressure decreases and heart rate increases (e.g., 4 to 6 mm Hg [systolic] and </=1 beat/min, at NTG doses of </=80 mug/min) than after placebo. The median maximum tolerated NTG dose (range) was 80 (0-160) mug/min for sildenafil vs. 160 (20-160) mug/min for placebo (adjusted mean +/- se, 77 +/- 7 vs. 127 +/- 7; p < .0001; analysis of variance), and NTG 160 mug/min was tolerated by eight (25%) and 19 (59%) men, respectively (p = .0008). Treatment-related adverse events were mostly mild/moderate hypotension, headache, and dizziness, which are often associated with NTG alone. Sildenafil and metabolite plasma concentrations were lower than previously reported in healthy men. CONCLUSIONS:: With close monitoring of blood pressure and heart rate, men with stable coronary artery disease who have taken sildenafil may tolerate intravenous NTG (</=160 mug/min) with low starting dosage and gradual upward titration. The hemodynamic response might be different in subgroups not specifically examined in the study (e.g., men presenting with acute coronary symptoms). The explanation for the lower than expected plasma concentrations remains uncertain.

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Expert Rev Cardiovasc Ther. 2007 May;5(3):387-99.
Enoxaparin in acute coronary syndromes.
Lee S, Gibson CM.
Beth Israel Deaconess Medical Center, Division of Cardiology, Boston, MA 02215, USA. sjlee@bidmc.harvard.edu

Enoxaparin is a low-molecular-weight heparin (LMWH) derivative that exerts its anticoagulant activity through antithrombin III, an endogenous inhibitor of factor Xa and thrombin IIa. Unlike its unfractionated heparin (UFH) counterparts, enoxaparin has a greater bioavailability, lower incidence of heparin-induced thrombocytopenia and more stable and predictable anticoagulation, allowing fixed dosing without the need for monitoring. These advantages make it an attractive anticoagulant to be used in acute coronary syndrome management. Indeed, several clinical trials and meta-analyses have consistently demonstrated the efficacy of enoxaparin in reducing cardiovascular events and mortality in this population. Although initial clinical trials with enoxaparin during the early conservative approach suggested superior efficacy without differences in safety compared with UFH, emerging data in the current era of early revascularization approach indicate that superior effects of enoxaparin over heparin in reducing clinical events should be balanced against an increase in major hemorrhagic complications. Enoxaparin is a rational alternative to UFH in patients presenting with either unstable angina/non-ST-elevation myocardial infarction or ST-elevation myocardial infarction, with a clinically modest increase in bleeding complications.

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Expert Rev Cardiovasc Ther. 2007 May;5(3):401-12.
Present and evolving role of eptifibatide in the treatment of acute coronary syndromes.
Tricoci P, Newby LK, Kandzari DE, Harrington RA.
Duke Clinical Research Institute, Durham, NC 27705, USA. trico001@dcri.duke.edu

Platelet-dependent thrombosis plays a central role in the pathophysiology of myonecrosis in both percutaneous coronary interventions (PCIs) and acute coronary syndromes (ACS). Extensive data from randomized clinical trials support the use of acute therapies that interfere with platelet aggregation to provide clinical benefit to patients presenting with ACS and undergoing PCI. Glycoprotein (GP) IIb/IIIa receptor antagonists represent a major advance in the therapy of patients undergoing PCI and those with non-ST segment elevation (NSTE) ACS. Eptifibatide, a small molecule GP IIb/IIIa receptor antagonist, is one such agent. A more consistent platelet-inhibitory effect over time and the short half-life of eptifibatide represent potential pharmacologic advantages compared with other drugs within this class. Large, randomized clinical trials have demonstrated the benefits of eptifibatide for treating patients with NSTE ACS and patients undergoing PCI, establishing its central role in modern management of these conditions. However, recent new advances in the pharmacotherapy of ACS and PCI are requiring us to reconsider the role of GP IIb/IIIa inhibitors; therefore, ongoing and future randomized clinical trials will re-examine GP IIb/IIIa inhibition and establish the role of GP IIb/IIIa inhibitors for the next decade.

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J Am Coll Cardiol. 2007 May 1;49(17):1783-9.
Coronary sinus reducer stent for the treatment of chronic refractory angina pectoris: a prospective, open-label, multicenter, safety feasibility first-in-man study.
Banai S, Ben Muvhar S, Parikh KH, Medina A, Sievert H, Seth A, Tsehori J, Paz Y, Sheinfeld A, Keren G.
Cardiology Department, Tel Aviv Medical Center, Tel Aviv, Israel. banais@netvision.net.il

OBJECTIVES: This study sought to evaluate the safety of the Coronary Sinus Reducer (Neovasc Medical, Inc., Or Yehuda, Israel) as a potential alternate therapy for patients with refractory angina who are not candidates for conventional revascularization procedures. BACKGROUND: Increased coronary sinus (CS) pressure can reduce myocardial ischemia by redistribution of blood from nonischemic to ischemic territories. The Coronary Sinus Reducer is a percutaneous implantable device designed to establish CS narrowing and to elevate CS pressure. In preclinical experiments, implantation of the Reducer was safe and was associated with improved ischemic parameters. In the present study, the safety and feasibility of the Coronary Sinus Reducer was evaluated in patients with refractory angina who were not candidates for revascularization. METHODS: Fifteen coronary artery disease patients with severe angina and reversible ischemia were electively treated with the Reducer. Clinical evaluation, dobutamine echocardiography, thallium single-photon emission computed tomography, and administration of an angina questionnaire were performed before and 6 months after implantation. Cardiac computed tomography was performed 2 days and 6 months after implantation. RESULTS: All procedures were completed successfully. No procedure-related adverse events occurred during the periprocedural and the follow-up periods. Angina score improved in 12 of 14 patients. Average Canadian Cardiovascular Society score was 3.07 at baseline and 1.64 at follow-up (n = 14, p < 0.0001). Stress-induced ST-segment depression was reduced in 6 of 9 patients and was eliminated in 2 of these 6 (p = 0.047). The extent and severity of myocardial ischemia by dobutamine echocardiography and by thallium single-photon emission computed tomography was reduced (p = 0.004 [n = 13] and p = 0.042 [n = 10], respectively). CONCLUSIONS: Implantation of the Coronary Sinus Reducer is feasible and safe. These findings, along with the clinical improvement observed, support further evaluation of the Reducer as an alternative treatment for patients with chronic refractory angina who are not candidates for coronary revascularization.

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Am J Cardiol. 2007 Apr 15;99(8):1044-50. Epub 2007 Feb 26.
Safety of sirolimus-eluting stenting and its effect on restenosis in patients with unstable angina pectoris (a SIRIUS substudy).
Weisz G, Moses JW, Teirstein PS, Holmes DR, Raizner AE, Satler LF, Mishkel G, Wilensky RL, Wang P, Kuntz RE, Popma JJ, Leon MB.
Columbia University Medical Center, and Cardiovascular Research Foundation, New York, New York., USA. gweisz@crf.org

The SIRIUS study was a double-blinded, randomized trial of the sirolimus-eluting stent (SES) to evaluate its effect on the rate of restenosis. The present report is a retrospective analysis of short- and long-term outcomes of SESs compared with bare metal stents (BMSs) in a subgroup of patients with unstable angina enrolled in the trial. Of 1,058 patients randomized in SIRIUS, 533 (50.4%) had unstable angina pectoris and 490 had stable angina. In the unstable angina group, patients treated with SESs and BMSs had similar clinical and angiographic characteristics. The stenting procedure was highly successful in the 2 groups (95.9% and 97.4%, respectively) with similar immediate angiographic results and short-term (in-hospital) clinical event rates. At 1-year follow-up, compared with BMSs, patients with unstable angina treated with SESs had significantly lower rates of target lesion revascularization (5.5% vs 22.3%, p <0.0001), target vessel failure (10.9% vs 26.3%, p <0.0001), and major adverse cardiac events (8.4% vs 24.8%, p <0.0001). Stent thrombosis was a rare event, with only 1 patient (0.4%) in each group during the first 30 days. Late thrombosis occurred in 2 patients (0.7%) in the BMS group but in none of the SES group. In conclusion, in the higher risk subgroup of patients with unstable angina, SESs are as safe as BMSs in decreasing restenosis and the need for repeat revascularization. This is reflected by a significant decrease in major adverse cardiac events and target vessel failure. Patients with unstable angina undergoing percutaneous coronary intervention who meet the entry criteria of the SIRIUS study should be preferentially treated with SESs.

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J Am Coll Cardiol. 2007 Apr 17;49(15):1607-10. Epub 2007 Apr 2.
Pretreatment with intracoronary enalaprilat protects human myocardium during percutaneous coronary angioplasty.
Leesar MA, Jneid H, Tang XL, Bolli R.
Division of Cardiology, University of Louisville, Louisville, Kentucky 40292, USA.

OBJECTIVES: We tested the hypothesis that enalaprilat induces preconditioning (PC)-mimetic actions in patients with stable coronary artery disease. BACKGROUND: Angiotensin-converting enzyme (ACE) inhibitors increase the bioavailability of bradykinin, which induces cardiac PC. METHODS: Twenty-two patients undergoing coronary angioplasty were randomized to an intracoronary infusion of enalaprilat or placebo, followed 10 min later by a PC protocol. RESULTS: In control patients, the ST-segment shift was greater during the first inflation than during the second and third inflations, both on the intracoronary electrocardiogram (ECG) (21.0 +/- 2.8 mm vs. 13.0 +/- 2.0 mm and 13.0 +/- 2.0 mm, p < 0.05) and the surface ECG (16.0 +/- 4.0 mm vs. 10.0 +/- 2.0 mm and 9.0 +/- 2.0 mm, p < 0.05). In contrast, enalaprilat-pretreated patients showed no change in ST-segment shift during inflations on either the intracoronary or the surface ECG. During the first inflation, the ST-segment shift was significantly smaller in treated versus control patients. The chest pain score during the first inflation was also significantly smaller in treated patients versus control patients (33.0 +/- 6.0 mm vs. 64.0 +/- 6.0 mm) and did not change in treated patients during the second and third inflations, whereas it decreased significantly in control patients. In a subset of 6 patients, enalaprilat increased coronary blood flow during infusion, but this effect dissipated before the beginning of angioplasty. CONCLUSIONS: Pretreatment with enalaprilat attenuates the manifestations of myocardial ischemia during angioplasty. This is the first in vivo evidence showing that an ACE inhibitor protects human myocardium, possibly via PC-mimetics actions, a novel property that might explain the cardioprotective actions of these drugs.

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J Cardiovasc Pharmacol Ther. 2007 Mar;12(1):44-53.
Transmyocardial revascularization: peril and potential.
Tasse J, Arora R.
Department of Cardiology, Chicago Medical School, 3001 Green Bay Road, Chicago, IL 60064, USA.

Transmyocardial laser revascularization is a technique for the treatment of patients with chronic angina pectoris that is refractory to medical therapy and who are not eligible for surgical intervention. Percutaneous myocardial revascularization is a less-invasive catheter-based procedure that has been adapted from transmyocardial laser revascularization. Six prospective randomized clinical trials have been performed with transmyocardial laser revascularization and 5 have been performed using percutaneous myocardial revascularization. All of the transmyocardial laser revascularization and 4 of the percutaneous myocardial revascularization studies showed a significant improvement in angina class; however, results for improved survival, increased exercise tolerance, improved ejection fraction, and improved myocardial perfusion were less definitive. Transmyocardial laser revascularization has significant potential for morbidity and mortality. This article summarizes the results of the randomized trials, explains the current theories for the mechanism of transmyocardial laser revascularization, and discusses its current role in treatment for patients, considering the evidence that currently exists.

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Am J Cardiol. 2007 Jan 1;99(1):11-8. Epub 2006 Nov 2.
Gender comparison of efficacy and safety of ranolazine for chronic angina pectoris in four randomized clinical trials.
Wenger NK, Chaitman B, Vetrovec GW.
Department of Medicine, Emory University School of Medicine, Grady Memorial Hospital, Atlanta, GA, USA. nwenger@emory.edu

More women than men with myocardial infarction have previous stable angina pectoris. Women also have an increased incidence of angina after percutaneous coronary intervention and coronary artery bypass grafting. Data from 1,737 patients with stable angina pectoris in 4 international trials (Monotherapy Assessment of Ranolazine In Stable Angina [MARISA], Combination Assessment of Ranolazine In Stable Angina [CARISA], Ranolazine Versus Atenolol Comparison in Chronic Angina [RAN080], and Efficacy of Ranolazine in Chronic Angina [ERICA]) were used to compare efficacy and safety of ranolazine therapy for angina in women and men. MARISA, CARISA, and RAN080 included exercise testing; CARISA, RAN080, and ERICA assessed angina frequency and nitroglycerin consumption; and ERICA included quality-of-life assessment using the Seattle Angina Questionnaire. MARISA, CARISA, and ERICA used the extended-release formulation of ranolazine; RAN080 used ranolazine immediate release. All 4 studies showed overall efficacy and safety of ranolazine. In subgroup analyses, women showed less improvement than men in exercise testing. However, similar improvements for women and men were noted in angina frequency and nitroglycerin consumption, and in ERICA, in the angina frequency dimension of the Seattle Angina Questionnaire. In conclusion, explanations for the gender treatment differences for exercise parameters but comparable effects on decrease in angina frequency and nitroglycerin use are uncertain, but may include differences in patient demographics, reasons for stopping exercise, and type of exercise protocol used.

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Herz. 2006 Dec;31(9):820-826.
[Acute Coronary Syndrome with and without ST Elevation.][Article in German]
Mollmann H, Elsasser A, Nef HM, Weber M, Hamm CW.
Kerckhoff-Klinik Bad Nauheim, Benekestrasse 2-8, 61231, Bad Nauheim, Deutschland, h.moellmann@kerckhoff.mpg.de.

Coronary artery disease accounts for most deaths in western communities. The acute coronary syndrome subsidizes ST elevation myocardial infarction, non-ST elevation myocardial infarction, and unstable angina pectoris. They are characterized by an acute onset of chest pain.The high number of acute coronary syndromes of more than 400,000 per year in Germany demonstrates the necessity of guidelines. Such guidelines are available from different cardiac societies. The implementation of the guidelines of the German Cardiac Society and the European Society of Cardiology in the daily clinical practice are demonstrated in this review by means of two case presentations. Special attention has been given to diagnostic measures, risk stratification, and different therapeutic options. For the diagnostic work-up in the acute phase, the ECG and the assessment of cardiac biomarkers play the central role. For patients with ST elevation myocardial infarction, primary interventional diagnostics and therapy are the first choice. For patients presenting with acute coronary syndromes without ST elevation, a risk-adapted therapeutic approach should be chosen. High-risk patients (elevated troponins, clinical, rhythmologic, and hemodynamic instability, ST depression, or diabetes mellitus) should be treated with an early invasive approach within 48-72 h. Low-risk patients can be treated primarily conservatively. For all patients who undergo interventional treatment, administration of an aggressive antiaggregatory therapy, including acetylsalicylic acid, clopidogrel, glycoprotein IIb/IIIa receptor antagonists, and heparin, is indicated in the acute phase. In the chronic phase, an adequate treatment of cardiovascular risk factors is of paramount importance.

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Am J Cardiol. 2006 Dec 1;98(11):1461-3. Epub 2006 Oct 12.
Safety and efficacy of short-term celecoxib before elective percutaneous coronary intervention for stable angina pectoris.
Pelliccia F, Pasceri V, Granatelli A, Pristipino C, Speciale G, Roncella A, Cianfrocca C, Mercuro G, Richichi G.
Department of Cardiovascular Diseases, San Filippo Neri Hospital, Rome, Italy. f.pelliccia@mclink.it

Fifty patients with stable angina pectoris entered a randomized, double-blind study and were assigned to receive celecoxib (200 mg 2 times daily) or placebo 7 days before percutaneous coronary intervention (PCI). Results showed that detection of markers of myocardial injury above the upper normal limit was significantly lower in the celecoxib than in the placebo group: 12% versus 35% for creatine kinase-MB (CK-MB; p = 0.001), 20% versus 48% for troponin I (p = 0.0004), and 22% versus 51% for myoglobin (p = 0.0005). Myocardial infarction by CK-MB determination was less commonly seen after PCI in the celecoxib than in the placebo group (5% vs 18%, p = 0.025). Postprocedural peak levels of CK-MB (2.9 +/- 18 vs 7.5 +/- 18 ng/ml, p = 0.0002) were also significantly lower in the celecoxib than in the placebo group. No significant side effect was reported by the 2 groups of patients. In conclusion, pretreatment with celecoxib 200 mg 2 times daily for 7 days significantly decreased procedural myocardial injury in elective PCI. These findings indicate that the antiphlogistic action of cyclo-oxygenase-2 inhibition may provide a friendly protection to ischemic cardiomyocytes.

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N Engl J Med. 2006 Nov 23;355(21):2203-16. Comment in: N Engl J Med. 2006 Nov 23;355(21):2249-50.
Bivalirudin for patients with acute coronary syndromes.
Stone GW, McLaurin BT, Cox DA, Bertrand ME, Lincoff AM, Moses JW, White HD, Pocock SJ, Ware JH, Feit F, Colombo A, Aylward PE, Cequier AR, Darius H, Desmet W, Ebrahimi R, Hamon M, Rasmussen LH, Rupprecht HJ, Hoekstra J, Mehran R, Ohman EM; ACUITY Investigators.
Columbia University Medical Center and the Cardiovascular Research Foundation, New York, NY 10022, USA. gs2184@columbia.edu

BACKGROUND: Current guidelines for patients with moderate- or high-risk acute coronary syndromes recommend an early invasive approach with concomitant antithrombotic therapy, including aspirin, clopidogrel, unfractionated or low-molecular-weight heparin, and glycoprotein IIb/IIIa inhibitors. We evaluated the role of thrombin-specific anticoagulation with bivalirudin in such patients. METHODS: We assigned 13,819 patients with acute coronary syndromes to one of three antithrombotic regimens: unfractionated heparin or enoxaparin plus a glycoprotein IIb/IIIa inhibitor, bivalirudin plus a glycoprotein IIb/IIIa inhibitor, or bivalirudin alone. The primary end points were a composite ischemia end point (death, myocardial infarction, or unplanned revascularization for ischemia), major bleeding, and the net clinical outcome, defined as the combination of composite ischemia or major bleeding. RESULTS: Bivalirudin plus a glycoprotein IIb/IIIa inhibitor, as compared with heparin plus a glycoprotein IIb/IIIa inhibitor, was associated with noninferior 30-day rates of the composite ischemia end point (7.7% and 7.3%, respectively), major bleeding (5.3% and 5.7%), and the net clinical outcome end point (11.8% and 11.7%). Bivalirudin alone, as compared with heparin plus a glycoprotein IIb/IIIa inhibitor, was associated with a noninferior rate of the composite ischemia end point (7.8% and 7.3%, respectively; P=0.32; relative risk, 1.08; 95% confidence interval [CI], 0.93 to 1.24) and significantly reduced rates of major bleeding (3.0% vs. 5.7%; P<0.001; relative risk, 0.53; 95% CI, 0.43 to 0.65) and the net clinical outcome end point (10.1% vs. 11.7%; P=0.02; relative risk, 0.86; 95% CI, 0.77 to 0.97). CONCLUSIONS: In patients with moderate- or high-risk acute coronary syndromes who were undergoing invasive treatment with glycoprotein IIb/IIIa inhibitors, bivalirudin was associated with rates of ischemia and bleeding that were similar to those with heparin. Bivalirudin alone was associated with similar rates of ischemia and significantly lower rates of bleeding. (ClinicalTrials.gov number, NCT00093158 [ClinicalTrials.gov].). Copyright 2006 Massachusetts Medical Society.

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Am Heart J. 2006 Nov;152(5):888-95. Comment in: Am Heart J. 2006 Nov;152(5):810-1.
Nonemergent coronary angioplasty without on-site surgical backup: a randomized study evaluating outcomes in low-risk patients.
Melberg T, Nilsen DW, Larsen A, Barvik S, Bonarjee V, Kuiper KK, Nordrehaug JE.
Division of Cardiology, Stavanger University Hospital, Stavanger, Norway.

BACKGROUND: Percutaneous coronary intervention (PCI) in nonemergent patients with coronary artery disease in hospitals without on-site cardiac surgery backup is still controversial. To prospectively evaluate a set of low procedural risk criteria for PCI, patients with stable or unstable angina were randomized to treatment in either a community hospital, which had all supportive services except for on-site cardiac surgery, or a regional surgical hospital 213 km away. METHODS AND RESULTS: During a 4-year period, 609 (57%) of 1064 consecutive patients with stable or unstable angina who underwent coronary angiography at a teaching community hospital in Norway fulfilled the predefined low-risk criteria for PCI. The patients were randomized to treatment at either the community hospital (n = 305) or at the regional hospital (n = 304). The angiographic success rate (96% at both hospitals) and number of major periprocedural complications (overall 0.3%) were equal at the 2 hospitals. In particular, there were no deaths or need for urgent transfer to cardiac surgery. At 6 months of clinical follow-up, there was a significant higher major adverse cardiac event rate rate at the community hospital, compared with the regional hospital (6.9% vs 2.3%, respectively, P = .03) because of more repeat target vessel revascularizations. Improvement in angina functional class and exercise capacity was similar in both groups. The excluded high-risk PCI patients had higher 6-month major adverse cardiac event compared with all low-risk patients (8.4% vs 4.3%, respectively, P = .01). CONCLUSION: Selected nonemergent patients can, based on angiography, safely undergo PCI at hospitals without cardiac surgery backup. The angiographic selection criteria identified high-risk patients, which had worsened outcome at 6 months of follow-up.

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Isr Med Assoc J. 2006 Oct;8(10):687-90.
The benefits and safety of external counterpulsation in symptomatic heart failure.
Kaluski E, Gabara Z, Uriel N, Milo O, Leitman M, Weisfogel J, Danicek V, Vered Z, Cotter G.
Department of Cardiology, Assaf Harofeh Medical Center, Zerifin, Israel. ekaluski@gmail.com

BACKGROUND: External counterpulsation is a safe and effective method of alleviating angina pectoris, but the mechanism of benefit is not understood. OBJECTIVES: To evaluate the safety and efficacy of external counterpulsation therapy in heart failure patients. METHODS: Fifteen symptomatic heart failure patients (subsequent to optimal medical and device therapy) underwent 35 hourly sessions of ECPT over a 7 week period. Before and after each ECPT session we performed pro-B-type natriuretic peptide and brachial artery function studies, administered a quality of life questionnaire, and assessed exercise tolerance and functional class. RESULTS: Baseline left ventricular ejection fraction was 28.1+/-5.8%. ECPT was safe and well tolerated and resulted in a reduction in pro-BNP levels (from 2,245+/- 2,149 pcg/ml to 1,558+/-1206 pcg/ml, P= 0.022). Exercise duration (Naughton protocol) improved (from 720+/-389 to 893+/-436 seconds, P= 0.0001), along with functional class (2.63+/-0.6 vs. 1.93+/-0.7, P= 0.023) and quality of life scores (54+/-22 vs. 67+/-23, P= 0.001). Nitroglycerine-mediated brachial vasodilatation increased (11.5+/-7.3% vs. 15.6+/-5.2%, P=0.049), as did brachial flow-mediated dilation (8.35+/-6.0% vs. 11.37+/-4.9%, P= 0.09). CONCLUSIONS: ECPT is safe for symptomatic heart failure patients and is associated with functional and neurohormonal improvement. Larger long-term randomized studies with a control arm are needed to confirm these initial encouraging observations.

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Am J Cardiovasc Drugs. 2006;6(5):357-9.
Spotlight on ranolazine in chronic stable angina pectoris.
Siddiqui MA, Keam SJ.
Wolters Kluwer Health/Adis, Auckland, New Zealand. demail@adis.com

Ranolazine (Ranexa), a piperazine derivative, is a new antianginal agent approved for the treatment of chronic stable angina pectoris for use as combination therapy when angina is not adequately controlled with other antianginal agents. While the exact mechanism of action of ranolazine is not known, its antianginal and anti-ischemic effects do not appear to depend upon changes in BP or heart rate. An extended-release (ER) oral formulation of ranolazine has been developed to facilitate twice-daily administration whilst maintaining therapeutically effective plasma concentrations. In patients with chronic stable angina, ranolazine ER monotherapy was shown to improve exercise duration at trough plasma drug concentration in a dose-dependent manner compared with placebo. The drug was effective as adjunctive therapy in patients with chronic stable angina whose condition was not controlled adequately with conventional antianginal therapy. In randomized clinical trials, ranolazine ER was well tolerated, with no overt effects on cardiovascular hemodynamics or conduction, apart from a modest increase in corrected QT interval (but no torsades de pointes). Importantly, the efficacy and tolerability of ranolazine ER were not affected by old age and co-morbid conditions (heart failure or diabetes mellitus). Comparative trials of ranolazine ER with other antianginal agents and trials examining its effects on long-term morbidity and mortality in patients with ischemic heart disease are required to determine with greater certainty the place of the drug in current antianginal therapy. Nevertheless, ranolazine ER may well prove to be a useful alternative and adjunct to conventional hemodynamic antianginal therapy in the treatment of chronic stable angina.
  
Previous Angina Research: 2002-2006   
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