Antithrombotic Therapy and Risk of Sudden Coronary Death in Heart Failure

ABSTRACT & COMMENTARY

Synopsis: After a multivariate analysis that adjusted for relevant covariates, antiplatelet therapy was still associated with a 24% reduction in sudden death risk, and anticoagulant therapy was associated with a 32% reduction in risk.

Source: Dries DL, et al. Am J Cardiol 1997;79:909-913.

Dries and colleagues performed a retrospective analysis of the Studies of Left Ventricular Dysfunction (SOLVD) database to assess the effects of antithrombotic therapy on risk for sudden cardiac death. The SOLVD trials evaluated the effects of the angiotensin converting enzyme (ACE) inhibitor enalapril on total cardiac mortality. There were more than 4200 asymptomatic patients in the SOLVD prevention trial and more than 2500 patients with symptoms in the SOLVD treatment trial. All patients in both trials had a left ventricular ejection fraction of less than 35%. There were 424 deaths in SOLVD that were classified as probably due to an arrhythmia without preceding coronary heart failure. The influence of a number of clinical factors, including antiplatelet or anticoagulant therapy, on the incidence of these deaths was then analyzed.

In SOLVD, 46% of patients received antiplatelet monotherapy, 13% received anticoagulant monotherapy, and 2% received both antiplatelet and anticoagulant therapy. Antithrombotic therapy was not randomized but was prescribed at the discretion of the patient’s physician. Antiplatelet therapy and anticoagulant therapy reduced the crude relative risk for sudden death by 0.66 (CI = 0.50-0.81) and 0.70 (95% CI = 0.50-0.98), respectively. Cardiovascular mortality was also improved. Other variables associated with increased sudden death risk included ejection fraction, diabetes, antiarrhythmic drugs, diuretic use, and digoxin use. After a multivariate analysis that adjusted for relevant covariates, antiplatelet therapy was still associated with a 24% reduction in sudden death risk, and anticoagulant therapy was associated with a 32% reduction in risk. Antiplatelet therapy was not associated with a reduction in sudden death risk in a subset of 923 thought to have nonischemic heart failure, but anticoagulant therapy was still associated with a reduced risk in this group.

COMMENT BY JOHN P. DiMARCO, MD, PhD

This interesting database report strongly suggests that ischemia plays a major, if not the major, role in the pathogenesis of sudden death in individuals. This has been noted in prior reports. It was estimated that 58% of arrhythmic deaths in the Multicenter Post Infarction Program were preceded by acute ischemia (Am J Cardiol 1988;61:875). In the Cardiac Arrhythmia Pilot Study, the estimate was 35% (Am J Cardiol 1989;63:1-6).

Most ventricular arrhythmias identified in cardiac arrest survivors are rapid and often polymorphic tachycardias. It appears that these arrhythmias are strongly influenced by, if not totally dependent on, ischemia. This is in contrast to the situation in patients with stable monomorphic ventricular tachycardia in whom scar without ischemia is the predominant finding.

This report suffers from all the problems inherent in a retrospective database study. The use of antiplatelet and anticoagulant therapy was not randomized, and other clinical factors not examined in the analysis may have influenced sudden death risk. However, in view of other data implicating ischemia as a major factor in the pathophysiology of sudden death, the data are persuasive.

Prevention of sudden death remains an important goal. It now seems clear that any effective strategy should be directed at treatment of ischemia, as well as the use of antiarrhythmic devices or drugs where appropriate.