Association between calcium channel blockers prescription and outcome according to left ventricular ejection fraction: data from a real-world heart failure population

Abstract Background Controversy exists on the safety of dihydropyridine calcium channel blockers (CCB) in heart failure (HF), especially in patients with reduced ejection fraction (HFrEF). We aimed to evaluate CCB prescription trends over time and related outcomes across the spectrum of EF. Methods We screened for inclusion outpatients with chronic HF prospectively enrolled in the nationwide observational IN-HF registry from 1998 to 2022. We used Cox regression methods to analyze time-to-event outcomes in patients on dihydropyridine CCB. The primary outcome was the composite of all-cause mortality and cardiovascular hospitalization at 1-year. Results We included 15785 outpatients. 10829 had an EF ≤40% (HFrEF, 69%) and 4956 had an EF40% (HFmrEF/HFpEF, 31%). The median age was 69; 26.6% were females. Overall, a DHP CCB was prescribed to 1458 patients (9.1%). CCB administration was twice as prevalent in patients with HFmrEF/HFpEF (n=771) than in those with HFrEF (n=687) (respectively 13.9% vs 7.1%, p0.001). CCB prescription rates increased over time (p0.001). Patients who received CCB were older, more comorbid, and had a higher EF than those who were not prescribed CCB. After multivariable adjustment, CCB prescription was associated with a higher risk of the primary outcome among the overall cohort (HR 1.19, 95% CI 1.05-1.36, p=0.008), and HFrEF patients (HR 1.20, 95% CI 1.02-1.41, p=0.025), while no adverse effect was observed in HFmrEF/HFpEF patients (p=0.159). Conclusion In HFmrEF/HFpEF, CCB use was twice as likely than in HFrEF and appeared to be safe. In HFrEF, CCB use was not rare and was associated with worse outcomes.central illustration forest plot