Antiplatelet agents and anticoagulants for hypertension.

BACKGROUND: Elevated systemic blood pressure results in high intravascular pressure but the main complications, coronary heart disease (CHD), ischaemic strokes and peripheral vascular disease (PVD), are related to thrombosis rather than haemorrhage. Some complications related to elevated blood pressure, heart failure or atrial fibrillation, are themselves associated with stroke and thromboembolism. Therefore it is important to investigate if antithrombotic therapy may be useful in preventing thrombosis-related complications in patients with elevated blood pressure.

OBJECTIVES: To conduct a systematic review of the role of antiplatelet therapy and anticoagulation in patients with high blood pressure, including those with elevations in both systolic and diastolic blood pressure, isolated elevations of either systolic or diastolic blood pressure, to address the following hypotheses: (i) antiplatelet agents reduce total deaths and/or major thrombotic events when compared to placebo or other active treatment; and (ii) oral anticoagulants reduce total deaths and/or major thromboembolic events when compared to placebo or other active treatment.

SEARCH METHODS: Electronic databases (MEDLINE, EMBASE, DARE, CENTRAL, Hypertension Group specialised register) were searched up to January 2011. The reference lists of papers resulting from the electronic searches and abstracts from national and international cardiovascular meetings were hand-searched to identify missed or unpublished studies. Relevant authors of studies were contacted to obtain further data.

SELECTION CRITERIA: Randomised controlled trials (RCTs) in patients with elevated blood pressure were included if they were of at least 3 months in duration and compared antithrombotic therapy with control or other active treatment.

DATA COLLECTION AND ANALYSIS: Data were independently collected and verified by two reviewers. Data from different trials were pooled where appropriate.

MAIN RESULTS: Four trials with a combined total of 44,012 patients met the inclusion criteria and are included in this review. Acetylsalicylic acid (ASA) did not reduce stroke or 'all cardiovascular events' compared to placebo in primary prevention patients with elevated blood pressure and no prior cardiovascular disease. In one large trial ASA taken for 5 years reduced myocardial infarction (ARR 0.5%, NNT 200), increased major haemorrhage (ARI 0.7%, NNT 154), and did not reduce all cause mortality or cardiovascular mortality. In one trial there was no significant difference between ASA and clopidogrel for the composite endpoint of stroke, myocardial infarction or vascular death. In two small trials warfarin alone or in combination with ASA did not reduce stroke or coronary events. The ATC meta-analysis of antiplatelet therapy for secondary prevention in patients with elevated blood pressure reported an absolute reduction in vascular events of 4.1% as compared to placebo. Data on the 10,600 patients with elevated blood pressure from the 29 individual trials included in the ATC meta-analysis was requested but could not be obtained.

AUTHORS' CONCLUSIONS: Antiplatelet therapy with ASA for primary prevention in patients with elevated blood pressure provides a benefit, reduction in myocardial infarction, which is negated by a harm of similar magnitude, increase in major haemorrhage.The benefit of antiplatelet therapy for secondary prevention in patients with elevated blood pressure is many times greater than the harm.Benefit has not been demonstrated for warfarin therapy alone or in combination with aspirin in patients with elevated blood pressure. Ticlopidine, clopidogrel and newer antiplatelet agents such as prasugrel and ticagrelor have not been sufficiently evaluated in patients with high blood pressure. Newer antithrombotic oral drugs such as dabigatran, rivaroxaban, apixaban and endosaban are yet to be tested in patients with high blood pressure.Further trials of antithrombotic therapy including with newer agents and complete documentation of all benefits and harms are required in patients with elevated blood pressure.