Cardiac arrhythmias and pacing.

Clinical trials. In the last two years, a number of landmark clinical trials have been published which further our understanding and clinical management of patients with atrial fibrillation (AF). Two of the major goals in the treatment of this condition include reducing progression or recurrence of the arrhythmia and decreasing the risk of cardiovascular events, thereby improving quality of life and decreasing morbidity. Following on from a large body of evidence from pre-clinical studies, small clinical trials and meta-analyses suggesting that blockade of the renin-angiotensin system has beneficial effects on the pathophysiology of AF,1 two large multi-centre, placebo-controlled, randomised trials were conducted to determine the effects of angiotensin IIreceptor blockers (ARBs) on AF. The first of these trials, published in 2009, tested the hypothesis that the ARB valsartan could reduce the recurrence of AF in patients with underlying cardiovascular disease, diabetes or left atrial enlargement and a history of documented AF, in addition to established therapies.2 A total of 1442 patients were enrolled into the study-722 assigned to the valsartan group (target dose 320 mg) and 720 to the placebo group. The investigators found that treatment with valsartan had no significant effect on AF recurrence (AF recurred 51.4% in the valsartan group and 52.1% in the placebo group, p = 0.73) over a relatively short follow up-period of one year. The second large ARB randomised-controlled trial published this year evaluated whether irbesartan would reduce the risk of cardiovascular events in patients with AF.3 Patients with a history of risk factors for stroke and a systolic blood pressure of at least 110 mmHg were randomly assigned to receive either irbesartan (target dose of 300 mg once daily) or placebo. Patients for this study were already enrolled in one of two other AF trials looking at clopidogrel plus aspirin versus aspirin alone or versus oral anticoagulants. Essentially, the investigators found that irbesartan did not reduce cardiovascular events or hospitalization rates for AF (total of 9016 enrolled with a mean follow up of 4.1 years) and that, not surprisingly, more patients in the irbesartan group had symptomatic hypotension and renal dysfunction compared with the placebo group. Although the main findings from both of these large RCTs were negative, it should be noted that they were secondary prevention studies, i.e. patients already had established AF, and also had more advanced stages of disease (over 80% of patients in both studies had a history of persistent or permanent AF), implying that the substrate for AF