LOS ANGELES – In terms of preserving exercise capacity and lowering elevated N-terminal pro-B-type natriuretic peptide levels, calcium channel blockers outperformed beta-blockers for rate control in patients with permanent atrial fibrillation.
The findings were noted in the RATAF (Norwegian Rate Control in Atrial Fibrillation) trial, a randomized, crossover, investigator-blinded study. RATAF also showed that diltiazem and verapamil significantly reduced arrhythmia-related symptoms, while carvedilol and metoprolol did not. Moreover, mean 24-hour ventricular heart rate was significantly lower during calcium channel blocker therapy than when subjects were on beta-blockers, according to Dr. Sarah Reinvik Ulimoen, of Baerum Hospital in Rud, Norway.
"Treatment with calcium channel blockers for rate control in atrial fibrillation should be considered more often in patients not needing a beta-blocker – that is, in patients without systolic heart failure or coronary heart disease," she said at the annual scientific sessions of the American Heart Association.
She reported on 60 RATAF participants with permanent AF, a normal left ventricular ejection fraction, and no coronary heart disease. The subjects received for 3 weeks each and in random sequence, once-daily diltiazem at 360 mg, verapamil at 240 mg, metoprolol at 100 mg, and carvedilol at 25 mg. At baseline and on the final day of each 3-week-long treatment period, the patients performed a bicycle ergometer maximal cardiopulmonary exercise test with measurement of peak oxygen uptake.
Blood samples for measurement of N-terminal pro-B-type natriuretic peptide (NT-proBNP) were taken at rest, peak exercise, and recovery. NT-proBNP is a biomarker widely utilized in the diagnosis and monitoring of heart failure. In addition, NT-proBNP is known to be elevated in patients with AF, even if they have normal systolic function.
The two calcium channel blockers preserved patients’ exercise capacity: Mean VO2max on the bike was 23.1 mL/kg per minute at baseline, 23.7 mL/kg per minute while subjects were on diltiazem, and 23.1 mL/kg per minute when they were on verapamil.
In contrast, mean VO2max was significantly reduced relative to baseline when patients were on beta-blocker therapy: 21.1 mL/kg per minute with metoprolol and 20.0 mL/kg per minute with carvedilol.
Mean NT-proBNP levels at rest were 1,039 pg/mL at baseline and significantly lower during calcium channel blocker therapy: 831 pg/mL while patients were on diltiazem and 897 pg/mL on verapamil. When patients were on a beta-blocker, however, their resting NT-proBNP was significantly greater than at baseline: 1,332 pg/mL for metoprolol and 1,205 pg/mL for carvedilol.
The same relationships seen when NT-proBNP was measured at rest held true when the biomarker was measured at peak exercise or during recovery: Mean levels were significantly reduced compared with baseline if patients were on calcium channel blockers for rate control, and significantly elevated above baseline while they were on beta-blockers. An inverse relationship was evident between exercise capacity and NT-proBNP: As maximum oxygen uptake went down, NT-proBNP levels went up.
Dr. Ulimoen noted that the exact mechanism underlying the increased levels of NT-proBNP in AF is unknown. Possibilities include myocardial stretching, oxidative stress in the atrial wall, and local ischemia. It’s believed that the major source of the NT-proBNP present in AF is the atria, not the ventricles as in heart failure.
As to why beta-blocker therapy was associated with higher levels of the cardiac biomarker, Dr. Ulimoen speculated that perhaps the drugs interfere with relaxation of the heart and thus diastolic filling; it is thought that NT-proBNP levels may reflect left ventricular filling pressure.
The findings she presented at the meeting regarding peak exercise capacity and changes in NT-proBNP were secondary end points in RATAF. The primary outcomes – the four rate control drugs’ effects on arrhythmia-related symptoms and mean 24-hour heart rate – were recently published (Am. J. Cardiol. 2012 [doi: 10.1016/j.amjcard.2012.09.020]).
Dr. Ulimoen reported having no financial conflicts.