Abstract
Abstract Background Randomised evidence showing that pharmacological blood pressure (BP) lowering can reduce cardiovascular risk of patients with atrial fibrillation (AF) is limited. Purpose This study aimed to compare the effect of BP-lowering treatment on fatal and non-fatal cardiovascular outcomes in patients with and without AF overall and by major drug classes. Methods We extracted individual participant data from all trials with over 1,000 person-years of follow-up that had randomly assigned patients to different classes of BP-lowering drugs, BP-lowering drugs vs placebo, or to more vs less intensive BP-lowering regimens. We investigated the effects of BP-lowering treatment on a composite endpoint of major cardiovascular events (stroke, ischaemic heart disease or heart failure) according to AF status at baseline using fixed-effect one-stage individual participant data meta-analyses based on Cox proportional hazards models stratified by trial. Findings Twenty-two trials were included with 188,570 patients, of whom 13,266 (7%) had AF at baseline. Patients with AF had lower BP at baseline than patients without AF (143/84 mmHg, SD 21/12mmHg) versus 155/88 mmHg, SD 21/13 mmHg, respectively). Meta-regression showed that relative risk reductions were proportional to trial-level intensity of BP lowering, both in patients with and without AF. The hazard ratio for major cardiovascular events was 0.91 in patients with AF (95% confidence interval [0.83–1.00]) and 0.91 without AF (95% confidence interval [0.88–0.93]) for each 5-mmHg reduction in systolic BP, with no difference between subgroups (p=0.91) (Figure 1). Similar patterns were observed for individual components of the composite primary outcome. In patients with AF, there was no evidence that treatment effects varied according to baseline systolic BP or use of specific drug classes. Conclusion This study demonstrated that BP-lowering treatment reduces the risk of major cardiovascular events in patients with AF to a similar extent to that of patients without AF, even when baseline BP is below recommended treatment thresholds. Owing to their higher absolute cardiovascular risk, treatment in patients with AF is likely to result in greater absolute risk reduction than in patients without AF. Guidelines should be updated to clearly recommend pharmacological BP lowering for prevention of cardiovascular events in patients with AF. Figure 1. Forest plot Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): British Heart Foundation
Highlights
Atrial fibrillation (AF) is the most common clinically relevant cardiac arrhythmia and its incidence and prevalence are on the rise across the globe [1,2], mainly due to population ageing and an increase in other cardiometabolic risk factors [3]
Over 4.5 years of median follow-up, a 5-mm Hg systolic blood pressure (BP) (SBP) reduction lowered the risk of major cardiovascular events both in patients with AF and in patients without AF at baseline (HR 0.91, 95% confidence interval (CI) 0.88 to 0.93), with no difference between subgroups
The findings of this study need to be interpreted in light of its potential limitations, such as the limited number of trials, limitation in ascertaining AF cases due to the nature of the arrhythmia and measuring BP in patients with AF. In this meta-analysis, we found that BP-lowering treatment reduces the risk of major cardiovascular events in individuals with and without AF
Summary
Atrial fibrillation (AF) is the most common clinically relevant cardiac arrhythmia and its incidence and prevalence are on the rise across the globe [1,2], mainly due to population ageing and an increase in other cardiometabolic risk factors [3]. High blood pressure (BP) is the most common cardiovascular risk factor in patients with AF [8,9], whether BP lowering reduces the risk of cardiovascular events in patients with AF remains uncertain. The complex structural, neurohumoral, and metabolic changes in the cardiovascular system that underpin the development and progression of AF may interfere with BP-lowering treatment [11]. This uncertainty is further compounded by the fact that the only randomised controlled trial (RCT) conducted in patients with AF failed to detect a risk reduction in cardiovascular events using an angiotensin receptor blocker [12]. This study aimed to compare the effects of BP-lowering drugs in patients with and without AF at baseline
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