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)?


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.


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).


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


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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