Killip Class III/IV Doubles Risk of Sudden Cardiac Death

MUNICH — Killip class is a powerful predictor of sudden cardiac death risk in post-MI patients with heart failure, according to a secondary analysis of the landmark EPHESUS trial results.

The double-blind EPHESUS (Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study) involved 6,632 patients who were randomized to 25-50 mg/day of the selective aldosterone blocker eplerenone (Inspra) or placebo, in addition to standard background medical therapy, beginning 3-14 days after an MI complicated by left ventricular systolic dysfunction. All subjects had a left ventricular ejection fraction (LVEF) of 40% or less at randomization.

During a mean follow-up of 16 months, sudden cardiac death (SCD) occurred in 9.2% of the 1,298 participants who were baseline Killip class III or IV. In contrast, the incidence of SCD in patients who were Killip class I/II at baseline was 4.6%, Dr. Bertram Pitt reported at the annual congress of the European Society of Cardiology.

After adjustment for treatment and LVEF in a Cox proportional hazards model, patients who were baseline Killip class III, defined as severe heart failure with frank pulmonary edema, or Killip class IV, which is cardiogenic shock, had a twofold higher risk of SCD than those who were Killip class I/II, added Dr. Pitt, professor of internal medicine at the University of Michigan, Ann Arbor.

A lower baseline LVEF was also associated with an increased rate of SCD, with an LVEF of 30% proving to be a useful cutoff. The 1,105 patients who were baseline Killip class I/II with an LVEF of less than 30% had a 7.7% rate of SCD, compared with a 3.8% rate in those with a baseline LVEF of 30% or more. Among patients who were Killip class III/IV with an LVEF below 30%, the rate of SCD was 11.1%, compared with 8.5% in Killip class III/IV patients with an LVEF of 30% or above.

These findings underscore the importance of determining LVEF and Killip class in order to predict SCD risk in patients with heart failure following an MI, Dr. Pitt stressed.

EPHESUS is considered a landmark study because it resulted in the addition of aldosterone blockade with eplerenone to the short list of lifesaving therapies in patients with heart failure. During 16 months of follow-up, eplerenone reduced all-cause mortality by 15%, cardiovascular mortality by 17%, and SCD by 21%.

A particularly striking finding was the 37% reduction in the risk of SCD within the first 30 days post randomization; the importance of that result lies in the fact that one-quarter of all deaths in the placebo arm during the entire study occurred in the 30 days after randomization (J. Am. Coll. Cardiol. 2005;46:425-31).

Dr. Pitt led EPHESUS and has served as a consultant to Pfizer Inc., which sponsored the main trial as well as the new post hoc analysis.