Calcium Channel Blockade Versus Beta-Blockade for Hypertension in Heart Failure With Preserved Ejection Fraction: A Randomized Crossover Trial

BACKGROUND: Hypertension is present in 90% of individuals with heart failure with preserved ejection fraction (HFpEF) and is a major modifiable risk factor for the development of HFpEF. However, randomized controlled trial evidence for hypertension management in HFpEF is limited. METHODS: In a double-blind, randomized, crossover trial, we studied the effect of amlodipine 5 to 10 mg versus metoprolol succinate 100 to 200 mg (doses previously demonstrated to have comparable antihypertensive efficacy) for 4 weeks among adults with HFpEF and hypertension, without contraindications to initiating or withholding either drug. The primary outcome was the difference in mean home systolic BP during the final week of each treatment. RESULTS: The mean age of the 50 enrolled participants was 72±9 years, 34 (68%) were women, 33 (66%) were of Black race, mean blood pressure was 144±15/78±9 mm Hg, and 23 (46%) were receiving β-blockers before enrollment. Compared with metoprolol, systolic blood pressure was 4 (95% CI, −7 to −1; P =0.017) mm Hg lower with amlodipine. In addition, peak oxygen uptake during exercise was 1.2 (95% CI, 0.3–2.0; P =0.008) mL/min per kg higher, physical activity was 0.1 (95% CI, 0.01–0.1; P =0.019) metabolic equivalents of task/d higher, and NT-proBNP (N-terminal pro-B-type natriuretic peptide) was 200 (95% CI, −291 to −109; P <0.0001) pg/mL lower with amlodipine versus metoprolol. There was no significant difference in septal E/e′, myocardial strain, or systemic vasodilatory reserve. The frequency and severity of adverse events were similar across treatments. CONCLUSIONS: Our findings support the use of dihydropyridine calcium channel blockers as a preferred alternative to β-blockers for the management of hypertension in HFpEF. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT04434664.