BACKGROUND
The risk of sudden death has changed over time among patients with symptomatic
heart failure and reduced ejection fraction with the sequential introduction of medi
-
cations including angiotensin-converting–enzyme inhibitors, angiotensin-receptor
blockers, beta-blockers, and mineralocorticoid-receptor antagonists. We sought to
examine this trend in detail.
METHODS
We analyzed data from 40,195 patients who had heart failure with reduced ejection
fraction and were enrolled in any of 12 clinical trials spanning the period from
1995 through 2014. Patients who had an implantable cardioverter–defibrillator at
the time of trial enrollment were excluded. Weighted multivariable regression was
used to examine trends in rates of sudden death over time. Adjusted hazard ratios
for sudden death in each trial group were calculated with the use of Cox regression
models. The cumulative incidence rates of sudden death were assessed at different
time points after randomization and according to the length of time between the
diagnosis of heart failure and randomization.
RESULTS
Sudden death was reported in 3583 patients. Such patients were older and were
more often male, with an ischemic cause of heart failure and worse cardiac function,
than those in whom sudden death did not occur. There was a 44% decline in the rate
of sudden death across the trials (P
= 0.03). The cumulative incidence of sudden
death at 90 days after randomization was 2.4% in the earliest trial and 1.0% in
the most recent trial. The rate of sudden death was not higher among patients
with a recent diagnosis of heart failure than among those with a longer-standing
diagnosis.
CONCLUSIONS
Rates of sudden death declined substantially over time among ambulatory patients
with heart failure with reduced ejection fraction who were enrolled in clinical trials,
a finding that is consistent with a cumulative benefit of evidence-based medica
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tions on this cause of death. (Funded by the China Scholarship Council and the
University of Glasgow.)