Antiplatelet agents and anticoagulants for hypertension

Although elevated systemic blood pressure results in high intravascular pressure, 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. It therefore seemed plausible that use of 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 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.

Reference lists of papers resulting from this search, electronic database searching (MEDLINE, EMBASE, DARE), and abstracts from national and international cardiovascular meetings were studied to identify unpublished studies. Relevant authors of these studies were contacted to obtain further data.

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

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 patients with elevated blood pressure from the 29 individual trials included in this meta-analysis was requested but could not be obtained. Three additional trials met the inclusion criteria and are reported on here. 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. Based on one large trial (HOT trial), ASA taken for 5 years reduced myocardial infarction (ARR, 0.5%, NNT 200 for 5 years), increased major haemorrhage (ARI, 0.7%, NNT 154), and did not reduce all cause mortality or cardiovascular mortality. There was no significant difference between ASA and clopidogrel for the composite endpoint of stroke, myocardial infarction or vascular death in one trial (CAPRIE 1996). In two small trials warfarin alone or in combination with ASA did not reduce stroke or coronary events.

For primary prevention in patients with elevated blood pressure, anti-platelet therapy with ASA cannot be recommended since the magnitude of benefit, a reduction in myocardial infarction, is negated by a harm of similar magnitude, an increase in major haemorrhage. For secondary prevention in patients with elevated blood pressure (ATC meta-analysis: APTC 1994) antiplatelet therapy is recommended 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 sufficiently evaluated in patients with elevated blood pressure. Further trials of antithrombotic therapy with complete documentation of all benefits and harms are required in patients with elevated blood pressure.