The oral dihydropyridine calcium channel blocker (CCB) amlodipine appears more beneficial than the beta-blocker metoprolol for managing hypertension in patients with heart failure with preserved ejection fraction (HFpEF), with greater effects on blood pressure (BP) control and exercise capacity, as shown in a randomized crossover trial.
Mean systolic home BP, the primary outcome, was lower by 4 mm Hg (95 percent confidence interval [CI], −7 to −1) during treatment with amlodipine vs metoprolol (131 vs 135 mm Hg; p=0.017). [Hypertension 2026;doi:10.1161/HYPERTENSIONAHA.126.26801]
Compared with metoprolol, amlodipine treatment also led to a 1.2-mL/min/kg increase in peak oxygen uptake during exercise (12 vs 11 mL/min/kg; p=0.008), a 0.1-metabolic equivalent of task (MET) per day increase in physical activity (1.5 vs 1.4 MET per day; p=0.019), a 200-pg/mL reduction in N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels (133 versus 344 pg/mL; p<0.0001), and an 8-mm Hg drop in central systolic BP (124 vs 129 mm Hg; p=0.013).
The severity and frequency of adverse events did not significantly differ across treatments, with headaches, dizziness, and bradycardia more common during treatment with metoprolol.
“Our findings suggest several mechanistic advantages of using dihydropyridine CCBs over beta-blockers for treating hypertension in patients with HFpEF,” the investigators said. “These challenge the common clinical practice of favouring beta-blockers in this population and support re-evaluation of antihypertensive strategies in HFpEF.”
A preferred alternative
Although the most recent HF guidelines removed the recommendation for beta-blockers, these agents remain more commonly used than CCBs in HFpEF, the investigators noted. This pattern of prescribing reflects previous guidelines, which recommended beta-blockers rather than CCBs based on extrapolation from HF with reduced EF data, they added. [Circulation 2022;145:e895-e1032; Circulation 2017;136:e137-e161; Circulation 2013;128:e240-e327; Cochrane Database Syst Rev 2018;6:CD012721]
For HFpEF patients with hypertension who do not have a compelling indication for beta-blockers, dihydropyridine CCBs offer a more favourable therapeutic profile by more effectively lowering home and central systolic BP, while also improving aerobic capacity and markers of LV function, according to the investigators.
The systolic BP effects observed with amlodipine vs metoprolol in the study population were comparable to those seen with spironolactone vs placebo and sacubitril/valsartan vs placebo in prior HFpEF trials. [Eur J Heart Fail 2018;20:483-490; J Am Coll Cardiol 2020;75:1644-1656]
The present data “support the use of dihydropyridine CCBs as a preferred alternative to beta-blockers for the management of hypertension in HFpEF,” the investigators said.
Study overview
A total of 50 HFpEF patients with hypertension participated in this double-blind, randomized, crossover trial. Their mean age was 72 years, 68 percent were female, 66 percent were Black, and 46 percent were receiving beta-blockers before enrolment. At baseline, mean BP levels were 144/78 mm Hg, and patients were receiving a mean of three antihypertensive medications.
The patients underwent a 4-week treatment with amlodipine and metoprolol, with a 1-week washout period before starting each medication. Amlodipine was initiated on 5-mg daily dosing schedule and titrated up to 10 mg daily after 1 week. Metoprolol, on the other hand, was initiated on 100-mg daily dosing schedule and titrated up to 200 mg daily. Criteria for uptitration for both medications included home systolic BP of ≥130 mm Hg and heart rate of ≥50 bpm after the first week of use.
Results for other outcomes showed no significant difference in septal E/e′, myocardial strain, or systemic vasodilatory reserve across treatments.
“Participants in our trial represent an obesity- and resistant hypertension-predominant HFpEF phenotype frequently encountered in contemporary practice,” the investigators said. “Our findings therefore inform comparative BP management in patients with HFpEF who are often already treated with multiple agents rather than initial therapy in untreated hypertension.”