November 05, 2013
By MD Will Boggs
NEW YORK - Calcium channel blockers improve exercise capacity in patients with permanent atrial fibrillation (AF), but beta-blockers have the opposite effect, according to a new study from Norway.
Researchers also found that calcium channel blockers reduced N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels, whereas beta-blockers increased them.
"The most striking finding in this research was how levels of NT-proBNP were influenced in the opposite direction by treatment with beta-blockers versus calcium channel blockers," Dr. Sara R. Ulimoen from Baerum Hospital, Rud, Norway, told Reuters Health by email.
"The reduction in NT-proBNP caused by the calcium channel blockers is of special interest as it has recently been shown in other studies that NT-proBNP levels are independently associated with an increased risk of stroke and mortality in patients with atrial fibrillation."
In a pre-defined substudy of the RATAF cross-over trial, Dr. Ulimoen and colleagues compared exercise capacity and NT-proBNP levels at rest and during exercise in 60 patients with permanent AF.
The mean peak oxygen uptake (VO2) during exercise was significantly lower with metoprolol and carvedilol than at baseline or with diltiazem and verapamil, according to the findings, online October 17 in the European Heart Journal. For instance, peak VO2 was 21.1 mL/kg/min with metoprolol vs. 23.7 with diltiazem and 23.1 at baseline (both p<0.001).
All treatments reduced peak heart rate at maximal exercise, but treatment with carvedilol brought significantly lower peak heart rates than did calcium channel inhibitors.
Treatment with diltiazem and verapamil significantly reduced NT-proBNP levels at rest and at peak exercise compared with baseline, whereas treatment with metoprolol and carvedilol significantly increased NT-proBNP levels at rest and at peak exercise.
For example, NT-proBNP at rest was 831 pg/mL with diltiazem vs. 1,332 pg/mL with metoprolol and1,039 pg/mL at baseline (both p<0.001).
Moreover, diltiazem and verapamil reduced the exercise-induced increases in NT-proBNP levels, whereas metoprolol augmented the increases and carvedilol had no impact.
NT-proBNP levels throughout the study were inversely correlated with peak oxygen uptake.
"Beta-blockers are often used as first line treatment for rate control in AF patients," the researchers note. "However, in this study, calcium channel blockers had similar effects on heart rate during exercise, without the negative impact on exercise capacity."
"We believe that rate control treatment should be individualized and that calcium channel blockers could be considered more often in patients that do not have comorbidities mandating treatment with beta-blockers," Dr. Ulimoen concluded.
Dr. Isabelle C. van Gelder, who was not involved in the study, said she was surprised that the researchers hadn't reported data on symptoms or outcomes.
"We do not treat NT-proBNP levels or peak VO2, but symptoms of patients," Dr. van Gelder, chair of University Medical Center Groningen's Department of Electrophysiology in The Netherlands, told Reuters Health by email. "This may only be of importance if it is associated with an impaired prognosis which warrants a large randomized controlled trial."
"In any patient with AF the most important thing is to evaluate symptoms and to choose which drug might be best for your patient," she said. "I think these data show you can give verapamil/diltiazem or beta-blockers if your patient has a good left ventricular function with the beneficial side-effect that peak VO2 is slightly better under verapamil/diltiazem without knowing what it will do on symptoms/outcome."
"Although the study has an important and clear message, there remains a lot unknown," Dr. van Gelder added. "By what mechanism, for example, does NT-proBNP decrease by using verapamil and diltiazem? ... We don't know the role and meaning of NT-proBNP in patients with permanent AF. Is it a sign for worse to come in patients with AF?"
Dr. van Gelder concluded that this is a "study with a lot of limitations and no implications for clinical practice now."
The Norwegian researchers reported ties to several pharmaceutical companies, including manufacturers of some of the drugs studied. Their study was supported by the South-Eastern Norway Regional Health Authority and by the Medical Research Foundation, Baerum Hospital, Norway. Roche provided most of the NT-proBNP assays free of charge.
Eur Heart J 2013.
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