Use of antioxidant vitamins for the prevention of cardiovascular disease: meta-analysis of randomised trials.

INTRODUCTION: Oxidised LDL is thought to play an important part in the pathogenesis of atherosclerosis. Observational studies have associated alpha tocopherol (vitamin E), beta carotene, or both, with reductions in cardiovascular events, but not clinical trials. We did a meta-analysis to assess the effect of these compounds on long-term cardiovascular mortality and morbidity. METHODS: We analysed seven randomised trials of vitamin E treatment and, separately, eight of beta carotene treatment; all trials included 1000 or more patients. The dose range for vitamin E was 50-800 IU, and for beta carotene was 15-50 mg. Follow-up ranged from 1.4 to 12.0 years. FINDINGS: The vitamin E trials involved a total of 81788 patients and the beta carotene trials 138113 in the all-cause mortality analyses. Vitamin E did not provide benefit in mortality compared with control treatment (11.3 vs 11.1%, odds ratio 1.02 [95% CI 0.98-1.06] p=0.42) or significantly decrease risk of cardiovascular death (6.0 vs 6.0%, p=0.86) or cerebrovascular accident (3.6 vs 3.5%, p=0.31). Beta carotene led to a small but significant increase in all-cause mortality (7.4 vs 7.0%, 1.07 [1.02-1.11] p=0.003) and with a slight increase in cardiovascular death (3.4 vs 3.1%, 1.1 [1.03-1.17] p=0.003). No significant heterogeneity was noted for any analysis. INTERPRETATION: The lack of a salutary effect was seen consistently for various doses of vitamins in diverse populations. Our results, combined with the lack of mechanistic data for efficacy of vitamin E, do not support the routine use of vitamin E.

Heart rate recovery after exercise is a predictor of mortality, independent of the angiographic severity of coronary disease.

OBJECTIVES: We sought to determine whether abnormal heart rate recovery predicts mortality independent of the angiographic severity of coronary disease. BACKGROUND: An attenuated decrease in heart rate after exercise, or heart rate recovery (HRR), has been shown to predict mortality. There are few data on its prognostic significance once the angiographic severity of coronary artery disease (CAD) is ascertained. METHODS: For six years we followed 2,935 consecutive patients who underwent symptom-limited exercise testing for suspected CAD and then had a coronary angiogram within 90 days. The HRR was abnormal if < or =12 beats/min during the first minute after exercise, except among patients undergoing stress echocardiography, in whom the cutoff was < or =18 beats/min. Angiographic CAD was considered severe if the Duke CAD Prognostic Severity Index was > or =42 (on a scale of 0 to 100), which corresponds to a level of CAD where revascularization is associated with better long-term survival. RESULTS: Severe CAD was present in 421 patients (14%), whereas abnormal HRR was noted in 838 patients (29%). There were 336 deaths (11%). Mortality was predicted by abnormal HRR (hazard ratio [HR] 2.5, 95% confidence interval [CI] 2.0 to 3.1; p < 0.0001) and by severe CAD (HR 2.0, 95% CI 1.6 to 2.6; p < 0.0001); both variables provided additive prognostic information. After adjusting for age, gender, standard risk factors, medications, exercise capacity, and left ventricular function, abnormal HRR remained predictive of death (adjusted HR 1.6, 95% CI 1.2 to 2.0; p < 0.0001); severe CAD was also predictive (adjusted HR 1.4, 95% CI 1.1 to 1.9; p = 0.008). CONCLUSIONS: Even after taking into account the angiographic severity of CAD, left ventricular function, and exercise capacity, HRR is independently predictive of mortality.

Effect of clopidogrel pretreatment on periprocedural rise in C-reactive protein after percutaneous coronary intervention.

This study sought to determine the effect of clopidogrel pretreatment on the increase in C-reactive protein (CRP) after percutaneous coronary intervention. Clopidogrel pretreatment attenuated the periprocedural increase in CRP by 65% and was independently associated with an attenuation in the CRP increase in a multivariate model.

Glycoprotein IIb/IIIa combination therapy in acute myocardial infarction: tailoring therapies to optimize outcome.

Numerous randomized trials have unequivocally shown that fibrinolytic therapy in the treatment of ST-segment elevation myocardial infarction substantially reduces mortality when administered within 12 hours of symptom-onset. Although fibrinolytic therapy initially restores antegrade flow in the infarct vessel in the majority of patients, sustained tissue-level reperfusion occurs in only approximately 25% of patients. Thrombin and platelets are two additional constituents of a coronary thrombus that contribute to the tendency for vessel reocclusion after initially successful reperfusion. Therefore, adjunctive therapy with potent antithrombins and antiplatelets is essential in the successful treatment of a coronary thrombus. Recent studies including GUSTO-V and ASSENT-III have studied the use of combination drug therapy with glycoprotein IIb/IIIa inhibition and reduced-dose fibrinolytics in the treatment of acute myocardial infarction. These studies demonstrated that combination therapy reduces reinfarction rates. However, this therapy is associated with increased bleeding complications especially in elderly patients. This article reviews the results and clinical implications of these major trials of combination drug therapy in acute myocardial infarction and provides recommendations for tailoring their use in clinical practice.

Glycoprotein IIb/IIIa antagonism and fibrinolytic therapy for acute myocardial infarction.

Fibrinolytic therapy for the treatment of ST-segment elevation myocardial infarction unquestionably reduces mortality when administered within 12 hours of symptom onset. By promptly restoring antegrade perfusion, infarct size is limited, ventricular function is less compromised, and mortality rates are lowered. Although fibrinolytic therapy initially restores antegrade flow in the infarct vessel in the majority of patients, sustained, tissue-level reperfusion occurs in only approximately one fourth of patients. Thrombin and platelets associated with a coronary thrombus are not specifically targeted by fibrinolytic agents, but rather have paradoxically increased activity. These components contribute to the tendency for vessel reocclusion after initially successful reperfusion. Thus, adjunctive therapy with antithrombins and antiplatelet agents are essential in the successful treatment of a coronary thrombus. Although aspirin has been shown to reduce mortality in acute myocardial infarction, it is a weak antiplatelet agent that is pathway specific. Glycoprotein IIb/IIIa inhibitors are potent antiplatelet agents that block the final common pathway for platelet aggregation. Thus, the growing evidence of platelet preeminence in the pathophysiology of failed thrombolysis has lead to the study of combination drug therapy with glycoprotein IIb/IIIa inhibition and reduced dose fibrinolytic agents in the treatment of acute ST-segment elevation myocardial infarction. This article reviews the rationale, results, and clinical implications of the major trials of combination drug therapy in acute myocardial infarction.