New Brunswick, NJ - New data from the SCD-HeFT trial have helped to better characterize the risk of thromboembolism (TE) in patients with chronic heart failure, revealing for the first time that ejection fraction (EF) is an independent predictor of risk and that amiodarone and ICD therapy appear to halve the incidence of such events [1].

Dr Ronald S Freudenberger (Robert Wood Johnson Medical School, New Brunswick, NJ) and colleagues report their findings online May 7, 2007 in Circulation. Freudenberger told heartwire that prior to these results, the rate of TE in patients with chronic heart failure "was poorly characterized," and there has been a long-standing controversy about whether the risk is significantly high enough to warrant the use of anticoagulants or aspirin.

"The present analysis represents the most extensive published experience enumerating thromboembolism events in stable patients with moderately symptomatic systolic HF undergoing contemporary medical therapy," say Freudenberger et al.

They found no reduction in risk of TE associated with use of either warfarin or aspirin but say this was a post hoc analysis, so the results must still be considered "exploratory." Optimal prevention strategies are currently being studied in the ongoing Warfarin Versus Aspirin in Reduced Cardiac Ejection Fraction (WARCEF) trial [2], Freudenberger told heartwire.

Freudenberger and colleagues analyzed 2114 of the original 2521 SCD-HeFT patients, excluding 407 who had a history of atrial fibrillation (AF) or flutter at baseline. Overall, 71 patients (3.4%) experienced TE over a median follow-up of 4.5 months, to yield an approximate annual rate of TE of 1.0%.

Those who were receiving optimum medical therapy but were not assigned to amiodarone or an ICD had a higher rate of TE of around 1.7% per year, with those who received the antiarrhythmic drug or device having around half that risk, a result Freudenberger told heartwire he found "curious and somewhat surprising."

Given the large numbers of patients in this trial, this may be a finding of significance, and the clinical relevance will need to be assessed in another study, say the researchers.

In addition, they showed that hypertension at baseline and lower LVEF were independent predictors of the risk of TE. Freudenberger said this is "the first study that has found that EF is directly related to TE."

The 4-year Kaplan Meier rate of TE was 3.5% in patients with an LVEF of at least 30% but not over 35%, 3.6% in those with an EF >20% but <30%, and 4.6% in those with an EF 20% or less.

At baseline, 28% of the patients were taking warfarin and 59% were taking aspirin; antithrombotic therapy changed during follow-up, however, with 42% of those not taking an anticoagulant at baseline beginning therapy subsequently, 13% of those taking an anticoagulant at entry discontinuing therapy, and 14% switching from one antithrombotic to another over the course of the study. In the multivariate analysis, neither warfarin nor aspirin use were significantly associated with reduced TE risk.

Freudenberger told heartwire that although a number of trials have looked at the issue of preventive strategies for TE in HF, none have provided a definitive answer. He hopes that the ongoing WARCEF trial, with which he is involved, will shed more light on optimal therapy.

WARCEF is a US National Institutes of Health-funded, randomized, double-blind trial designed to test the hypothesis that there is no difference between warfarin (INR 2.5-3.0) and aspirin (325 mg) in three- to five-year event-free survival for the composite end point of death or stroke (ischemic or hemorrhagic) among patients with cardiac ejection fraction <35% who do not have AF or mechanical valves.

Secondary analyses will compare warfarin and aspirin for reduction of all-cause mortality, ischemic stroke, and MI balanced against the risk of intracerebral hemorrhage; among women and African Americans; and compare warfarin and aspirin for prevention of stroke alone.

Freudenberger says the study has enrolled approximately half of the planned 3000 participants.