Association of Nondihydropyridine Calcium Channel Blockers Versus β-Adrenergic Receptor Blockers With Risk of Heart Failure Hospitalization

Abstract

Heart failure (HF) with preserved ejection fraction (HFpEF) and atrial fibrillation (AF) are interrelated and often coexisting conditions in older adults. Although equally recommended, nondihydropyridine calcium channel blockers (non-DHP CCBs), such as diltiazem and verapamil, are less often used than β blockers. Because recent studies suggested that β-blocker use in both HFpEF and AF may increase the risk for HF, we tested whether non-DHP CCBs were associated with lower HF hospitalization risk than β blockers. We examined fee-for-service Medicare beneficiaries who were aged ≥66 years, had HFpEF or AF, and newly initiated a β blocker (n = 83,458) or non-DHP CCB (n = 18,924) from 2014 to 2018. The outcomes of HF hospitalization and all-cause mortality were analyzed using multivariable-adjusted Cox regression in the full cohort and, separately, in the subset without a recent hospital or skilled nursing discharge. Follow-up was analyzed using 2 frameworks: intention-to-treat and censored-at-drug-switch-or-discontinuation. There was a modestly protective association of non-DHP CCBs for the risk of HF hospitalization. Before drug switch or discontinuation, the use of diltiazem or verapamil was associated with decreased risk of HF hospitalization in the full cohort (hazard ratio [HR] 0.90, 95% confidence interval [CI] 0.81 to 1.00, p = 0.05) and in the subgroup (HR 0.70, 95% CI 0.56 to 0.89, p = 0.003). However, the association with all-cause mortality tended to favor β blockers, including in the intention-to-treat analysis (HR 1.21, 95% CI 1.17 to 1.25, p <0.001). In conclusion, compared with β blockers, the initiation of diltiazem or verapamil in patients with HFpEF or AF may be associated with fewer HF hospitalization events but also with more all-cause deaths.