Stethoscope (Olivier Le Queinec | Dreamstime.com)
Strict control of heart rate in permanent atrial fibrillation (AF) is associated with the same cardiovascular morbidity or mortality as is lenient control. This is the conclusion of a prospective, open-label study carried out in the Netherlands (New England Journal of Medicine 2010;362:1363).
Researchers randomised 614 patients with permanent AF to be treated individually with one or more negative dromotropic medicines (ie, beta-blockers, non-dihydropyridine calcium-channel blockers and/or digoxin) to achieve either lenient (<110 beats/min) or aggressive (<80 beats/min) heart rate targets.
The cumulative incidence of the primary outcome — a composite of death from cardiovascular causes, admission to hospital for heart failure, and stroke, systemic embolism, bleeding and life-threatening arrhythmic events — was estimated to be 12.9% and 14.9% for the lenient control and strict control groups, respectively, at three years (P<0.001 for the prespecified non-inferiority margin).
However, the authors concede: “We cannot rule out the possiblity that we would have found significant differences between the two groups had we used a more effective means of strict rate control and had we kept heart rates just below 110 beats/min in the lenient-control group or if we had followed patients beyond three years.”
Sotiris Antoniou, principal clinical pharmacist for cardiac services at Barts and The London NHS Trust, told Clinical Pharmacist: “There seems to be a theme emerging in clinical trials within cardiovascular disease that aggressive control, for example of glucose or blood pressure, may actually be detrimental in comparison with a more lenient approach.”
He suggested that adverse effects — such as hypoglycaemia or hypoperfusion with the above examples, respectively — might negate the expected benefits.
“This may also be the case with this study. These results might seem surprising at the outset, since we know that for patients with ischaemic heart disease heart rate is a predictor of outcomes. However, although the rate of side effects was similar between the two groups, a quarter of those patients in the aggressive control group who failed to achieve their target heart rate did so because of drug side effects.”
He added: “Unsurprisingly, there was also a greater percentage of patients with heart rates found to be below 70 beats/min in the aggressive (22.1%) versus lenient (0.3%) group. It would have been helpful for the study to present the number of patients experiencing bradycardia, although the rate of syncope was found to be similar in the two groups.
“Until data are clearer we need to manage patients individually taking into consideration their symptoms and quality of life.”
