Risk of stroke and bleeding in relation to hypertension in anticoagulated patients with atrial fibrillation: a meta-analysis of randomised controlled trials

Abstract

Background and purpose

Hypertension is common in patients with atrial fibrillation (AF) and carries an additional risk for complications, most notably stroke and bleeding. We assessed the history of hypertension, level of blood pressure control, and an interaction with the choice of oral anticoagulants on clinical outcomes

Methods

We performed a systematic review and meta-analysis of studies that randomised patients to novel oral anticoagulants (NOACs) or vitamin K antagonists (VKAs) and reported outcomes stratified by presence of hypertension. Collected outcomes were: ischaemic stroke or systemic embolism (SE), haemorrhagic stroke, intracranial haemorrhage and major bleeding. Log adjusted hazard ratios (HR) and corresponding standard error were calculated, and HRs were compared using Mantel-Haenszel random effects. Quality of the evidence was assessed with Cochrane risk of bias tool.

Results

Five high-quality studies were eligible, including 71.527 participants who received NOACs (apixaban, dabigatran, edoxaban, rivaroxaban) or VKAs, with median follow-up of 1.8–2.8 years. Compared with patients without hypertension, those with hypertension had higher adjusted risk for ischaemic stroke/SE (HR: 1.25, 95%-CI:1.09, 1.43) and haemorrhagic stroke (HR:1.98, 1.24–3.16). On a continuous scale, the risk of ischaemic stroke/SE increased 6–7% per 10 mmHg increase in systolic blood pressure. No interactions were found between the efficacy or safety of NOACs versus VKAs in the presence or absence of hypertension. In both groups, the use of NOACs led to a lower risk of ischaemic stroke/SE, haemorrhagic stroke and intracranial haemorrhage compared with patients that used VKAs.

Conclusions

Adequate blood pressure management is vital to optimally reduce the risk of stroke in patients with atrial fibrillation. The benefits of NOACs over VKAs, also apply to patients with elevated blood pressure.

Keywords:

• Stroke
• bleeding
• direct oral anticoagulants
• hypertension
• atrial fibrillation

Disclosure statement

Dr Harskamp reported receiving grants from the Dutch Research Council outside the submitted work. Prof. Lopes reported receiving consulting fees from Bayer, Boehringer Ingelheim, Daiichi Sankyo, Merck, and Portola Pharmaceuticals; and grants and consulting fees from Bristol-Myers Squibb, GlaxoSmithKline, Medtronic, Pfizer, and Sanofi outside the submitted work.

Additional information

Funding

Salary support for Dr. Harskamp was provided by a Rubicon fellowship provided by the Netherlands Organisation for Scientific Research (NWO). The authors are solely responsible for the design and conduct of this study, all study analyses, the drafting and editing of the paper, and its final contents.