No current treatment guidelines explicitly recommend statin therapy
for patients with systolic heart failure because no single
large-scale randomized trial of heart failure patients has demonstrated
a statistically significant reduction in cardiovascular disease
(CVD) incidence or mortality with statin use.1–3 According
to the most recent 2013 American College of Cardiology
(ACC)/American Heart Association (AHA) Guideline on the Treatment
of Blood Cholesterol, ‘statin therapy is not routinely recommended
for individuals with NYHA (New York Heart Association)
class II–IV heart failure’ because ‘available evidence suggests that
initiation of statin therapy might not achieve a significant reduction
of CVD risk in patients with higher classes of NYHA heart
failure’. This is perhaps surprising given the efficacy of statins in
reducing CVD event rates significantly and substantially in most
patient groups studied.4 –14
The Controlled Rosuvastatin Multinational Trial in Heart Failure
(CORONA) and the Effect of Rosuvastatin in Patients with Chronic
Heart Failure Trial (GISSI-HF) both assessed whether rosuvastatin
(compared with placebo) improved cardiovascular endpoints and
mortality in patients with heart failure who were not already taking
statins.15,16 CORONA included participants with systolic heart
failure of ischaemic aetiology only, whereas GISSI-HF included participants
with all causes and types of heart failure. For each trial, the
addition of rosuvastatin 10 mg once daily to background pharmacotherapy
did not significantly reduce incident CVD or all-cause
mortality. However, in light of the substantial number of study
participants in CORONA and GISSI-HF experiencing death from
arrhythmic causes, worsening heart failure, or non-cardiovascular
causes, and the relatively low number of myocardial infarctions
(MIs), the ability to detect a statistically significant benefit for statins
preventing MI and stroke may have been limited.
We anticipated that pooling data from CORONA and GISSI-HF
would improve our power to detect a statistically significant
difference in the risk of MI for rosuvastatin vs. placebo groups. We
also anticipated that applying competing risks methods to analysing
these data might provide additional ability to detect a significant
benefit in those who did not suffer death. A competing risks
approach examines joint and simultaneous risks for next occurring
events (such as non-fatal MI or stroke, death from cardiovascular
causes, and death from other causes); accordingly, it may be
useful in re-examining data from CORONA and GISSI-HF given
the high incidence of death from arrhythmic causes, worsening
heart failure, and non-cardiovascular causes observed among these
study participants. It is possible that heart failure confers such a
high burden of mortality from non-atherothrombotic causes that
segments of the heart failure population do not live long enough
to experience the benefit of preventing atherothrombotic events
with statins.
In the present analysis, we used data from CORONA and
GISSI-HF to examine competing risks for multiple cardiovascular
outcomes in the context of death from non-cardiovascular
causes for rosuvastatin compared with placebo. Our co-primary
outcomes were fatal and non-fatal MI and stroke, whereas the
other possible competing outcomes for this analysis were other
............................................................................................................................... ...................................................
CVD death (not caused by MI or stroke) and death from
non-cardiovascular causes. We hypothesized that the risks for MI
and stroke would be significantly lower for the rosuvastatin group
after accounting for other competing outcomes.