Calcium Channel Blockers Improve Exercise Capacity and Reduce N-Terminal Pro-B-Type Natriuretic Peptide Levels Compared With Beta-Blockers in Patients With Permanent Atrial Fibrillation

Study Questions:

What are the comparative effects of beta-blockers or non-dihydropyridine calcium channel blockers on exercise capacity and levels of N-terminal pro-B-type natriuretic peptide (NT-proBNP) in patients with permanent atrial fibrillation (AF)?

Methods:

This was a predefined substudy of the RATAF (RATe control in Atrial Fibrillation) study. This was conducted as a randomized, crossover, investigator-blinded study in which 60 patients without heart failure received one of the following once daily: diltiazem 360 mg, verapamil 240 mg, metoprolol 100 mg, and carvedilol 25 mg (for at least 3 weeks). At baseline (i.e., with no rate-reducing drug) and on the last day of each treatment period, participants underwent cardiopulmonary exercise testing on a bicycle ergometer. Venous blood samples were obtained for measurement of NT-proBNP at rest, at peak exercise, and 15 minutes after exercise termination.

Results:

Compared with no treatment or treatment with verapamil or diltiazem, treatment with metoprolol and carvedilol significantly reduced exercise capacity (peak VO2, p < 0.001 for all). Compared with baseline, treatment with diltiazem and verapamil significantly reduced NT-proBNP levels both at rest and peak exercise; however, treatment with metoprolol and carvedilol increased the levels at rest and exercise (p < 0.05 for all). All treatments reduced peak heart rate compared with baseline (p < 0.001 for all), but treatment with carvedilol results in lower peak heart rate than treatment with calcium channel antagonists (p < 0.001 for both).

Conclusions:

Compared to no rate-reducing treatment or beta-blockade, treatment with verapamil or diltiazem preserved exercise capacity and reduced NT-proBNP levels.

Perspective:

The limitations of this small, prespecified substudy of RATAF aside, the authors presented valuable information on the comparative effects of rate-reducing drugs in patients with permanent AF without heart failure. Although these findings will need to be confirmed in larger and longer-term studies, the authors presented information that may broaden the appeal of non-dihydropyridine calcium channel antagonists as preferred rate control therapy in permanent AF. Select previous studies have also demonstrated that beta-blocker treatment may reduce exercise capacity; by demonstrating an inverse relationship between exercise capacity and NT-proBNP levels, the authors suggested that the deleterious impact of beta-blockade on exercise capacity may be mediated through negative lusitropy.

Clinical Topics: Diabetes and Cardiometabolic Disease, Heart Failure and Cardiomyopathies, Prevention, Statins, Acute Heart Failure, Heart Failure and Cardiac Biomarkers, Exercise

Keywords: Dihydropyridines, Exercise, Propanolamines, Heart Rate, Calcium Channel Blockers, Natriuretic Peptides, Carbazoles, Biological Markers, Troponin I, Cardiology, Heart Failure


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