Antiplatelet therapy and anticoagulation in patients with hypertension

Elevated systemic blood pressure results in high intravascular pressure. The main complications, coronary heart disease, ischemic strokes, and peripheral vascular disease, are related to thrombosis rather than hemorrhage. Some complications related to elevated blood pressure, heart failure, and atrial fibrillation are associated with stroke and thromboembolism. It seems plausible that antithrombotic therapy may be particularly useful in preventing thrombosis-related complications of elevated blood pressure.

To conduct a systematic review of the role of antiplatelet therapy and anticoagulation in patients with hypertension, including those with elevations in systolic and diastolic blood pressure and those with isolated elevations of systolic or diastolic blood pressure. The following hypotheses were addressed: (1) antiplatelet agents reduce total deaths and major thrombotic events compared with other active treatment or placebo; and (2) oral anticoagulants reduce total deaths and major thromboembolic events compared with other active treatment or placebo.

The authors' studied reference lists of articles found by searching electronic databases (MEDLINE, EMBASE, DARE) and abstracts from national and international cardiovascular meetings. Relevant authors of these studies were contacted to obtain further data.

Randomized controlled trials (RCTs) in patients with elevated blood pressure were included if they were of at least three months' duration and compared antithrombotic therapy with other active treatment or placebo.

Data were independently collected and verified by two reviewers. Data from different trials were pooled when appropriate.

The Antiplatelet Trialists' Collaboration meta-analysis of antiplatelet therapy for secondary prevention in patients with elevated blood pressure reported a 4.1 percent absolute reduction in vascular events compared with placebo. Data on the patients with elevated blood pressure from the 29 individual trials were requested but could not be obtained. Three additional trials met the inclusion criteria and were included. Acetylsalicylic acid (ASA) did not reduce stroke or "all cardiovascular events" compared with placebo in primary prevention patients with elevated blood pressure and no prior cardiovascular disease. In one large trial (the Hypertension Optimal Treatment trial), ASA taken for five years reduced rates of myocardial infarction (MI) (absolute risk reduction, 0.5 percent; number needed to treat [NNT], 200 for five years), increased rates of major hemorrhage (absolute risk increase, 0.7 percent; NNT, 154), and did not reduce all-cause mortality or cardiovascular mortality. In the Clopidogrel vs. Aspirin in Patients at Risk of Ischemic Events trial, there was no significant difference between ASA and clopidogrel for the composite end point of stroke, MI, or vascular death. In two small trials, warfarin alone or in combination with ASA did not reduce rates of stroke or coronary events.

Antiplatelet therapy with ASA cannot be recommended for primary prevention of vascular events in patients with elevated blood pressure, because the magnitude of benefit--a reduction in rates of MI--is negated by a harm of similar magnitude, an increase in rates of major hemorrhage. Antiplatelet therapy is recommended for secondary prevention in patients with elevated blood pressure because the magnitude of the absolute benefit is many times greater. Warfarin therapy alone or in combination with aspirin in patients with elevated blood pressure cannot be recommended because of lack of demonstrated benefit. Glycoprotein IIb/IIIa inhibitors, as well as ticlopidine and clopidogrel, have not been evaluated sufficiently in patients with elevated blood pressure. Further trials of antithrombotic therapy with complete documentation of all benefits and harms are needed in patients with elevated blood pressure.