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Initiation of Statins for Primary Prevention in HFpEF
Quick Takes
- New statin use is associated with reductions in mortality, MACE, and hospitalizations in Veterans with HFpEF.
- Current HF guidelines recommend statin therapy for patients with a history of prior MI to prevent symptomatic HF and CVD events, but there are no specific recommendations for the primary prevention of future cardiac events.
Study Questions:
Is statin use associated with a lower risk of mortality and major adverse cardiovascular events (MACE) in patients who have heart failure with preserved ejection fraction (HFpEF)?
Methods:
The US Veteran’s Affairs clinical database was used to curate a cohort of HFpEF patients between 2002 and 2012. Patients with claims indicating prior coronary artery bypass grafting (CABG) or percutaneous coronary intervention (PCI), myocardial infarction (MI), stroke/transient ischemic attack (TIA), or peripheral vascular disease were excluded to conduct this study on primary prevention. Patients with any statin use prior to an HFpEF diagnosis were also excluded to remove the potential of historic statin use influencing study results. Primary exposure was new use of any approved statin in the United States and was calculated beginning with the first outpatient statin prescription fill following HFpEF diagnosis. The two coprimary outcomes included all-cause mortality and MACE, defined as CABG/PCI, incident MI, mortality due to MI, incident stroke/TIA, or mortality due to stroke. Secondary outcomes included all-cause hospitalizations and HF hospitalizations.
Results:
A total of 7,970 Veterans with HFpEF and no atherosclerotic cardiovascular disease (ASCVD) or prior statin use were identified in the database. Of these, 3,759 (47%) initiated a statin during the 6-year follow-up period. Patients had a mean age of 69 ± 12 years, 96% were male, 67% White, 14% Black, and mean EF was 60 ± 6%. The most prescribed statin was simvastatin (76%), followed by lovastatin (9%), atorvastatin (7%), and pravastatin (6%). Baseline characteristics were all matched after propensity score overlap weighting. There were 5,314 deaths and 4,859 major ASCVD events during the study period.
The weighted difference per 1,000 patient-years was -23.55 (95% confidence interval [CI], -29.87 to -17.23) for all-cause mortality and -46.33 (95% CI, -56.38 to -36.29) for MACE. Use of a statin was associated with a 22% reduction in all-cause mortality (hazard ratio [HR], 0.78; 95% CI, 0.73-0.83) and a 21% reduction in MACE (HR, 0.79; 95% CI, 0.74-0.84). Results were consistent across multiple subgroups for mortality. For MACE, there were significant interactions by sex and ASCVD risk category. Statin use also reduced the risk of all-cause hospitalizations (relative risk [RR], 0.69; 95% CI, 0.60-0.80) and HF hospitalizations (RR, 0.72; 95% CI, 0.59-0.88).
Conclusions:
Among Veterans with HFpEF and no known ASCVD, new statin use was associated with reduced all-cause mortality, MACE, and hospitalization.
Perspective:
Early landmark studies evaluating efficacy of statins largely excluded patients with HF and two randomized controlled trials of statins specifically in subjects with pre-existing HF did not show improvement in outcomes. These trials, CORONA and GISSI-HF, primarily included HF patients with reduced EF. Consequently, this trial was designed to evaluate the potential benefit of statin therapy in HF with preserved EF. The mechanism for potential benefit of statins in HFpEF is not yet clear, but results of this study in patients with no prior ASCVD suggest benefit beyond their impact on atherosclerosis. Despite positive results from this study, enrollment of predominantly male Veterans limits generalizability to other populations, which requires further study in broader cohorts as well as investigations into mechanistic theories.
Clinical Topics: Prevention, Heart Failure and Cardiomyopathies
Keywords: Heart Failure, Preserved Ejection Fraction, Primary Prevention, Statins
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