Antithrombotic Therapy for Cerebrovascular Disorders: Primary Stroke Prevention
The British physicians study asked 5,139 male physicians to take 300-500 mg of aspirin daily or to avoid aspirin (unblinded, no placebo administration). Mean follow-up was 5.5 years. The rate of death in the British study was 10.3 times that of the US trial. There were no differences between treatment arms in the rates of fatal or nonfatal MI. While TIAs were significantly reduced (0.28%/year vs 0.16%/year), the rates of disabling or fatal stroke were 75% higher (0.20%/ year vs 0.35%/year). Overall, the outcome in the aspirin-treated patients was worse due to the increased rate of disabling and fatal strokes. While the number of enrolled physicians was smaller than in the US trial, the vascular event rates were 5-10 times higher and were more serious.
These two large studies lead to the conclusion that the routine use of aspirin in healthy men may not be justified when the risks of a disabling or fatal storke are compared with the benefits in reducing nonfatal MI.
Cardiogenic Brain Emboli
Recent series report a distribution of cardioembolic sources similar to that previously summarized (Table 3 of initial task force report). Nonvalvular AF with or without associated ischemic heart disease accounts for 40-50% of cardioembolic strokes, followed by acute and chronic ischemic heart disease and valvular heart disease (rheumatic and prosthetic). fully
Nonvalvular Atrial Fibrillation
Three recent epidemiologic studies confirm the results of the Framingham Heart Study, indicating a 6-fold increase risk of stroke associated with nonrheumatic AF (Table 2). In addition to clinical strokes, AF has been associated with an undue risk of subclin-ical “silent” strokes.* Silent infarctions detected by CT have been found in 35-37% of nonrheumatic AF patients with no prior history of stroke. In a preliminary report including patients with rheumatic and nonrheumatic AF but without prior stroke, CT evidence of previous stroke was 2.9-4.5 times more frequent than non-AF patients. While these CT-defined infarctions are labeled as asymptomatic or “silent,” it is likely that they take a subtle but cumulative toll on cognition in elderly people. Considering the combined risk of clinical and subclinical stroke, AF is associated with a substantial threat to the brain.
Table 2—Stroke Risk and Atrial Fibrillation: Epidemiologic Studies
|Study||Stroke Incidence, %/yr||RiskRatio|
|Framingham,® USA, 1978||4.2||5.6:1|
|Shibata, Japan, 1985||5.0||5.6:1|
|Whitehall, UK, 1987*||1.8||6.9:1|
|Reykjavik,® Iceland, 1987||–||7.5:1|
Table 3—Heparin and Anterior Myocardial Infarction: Randomized Trials
|Reference||Heparin||No.||% LV thrombi||% Emboli||% Bleeding||% Mortality|
|Nordrehaug et al||–||25||28||4||0||16|
|Gueret et al||-t||25||52||4||?||4|
|+ (23,800 U)||21||38||5||5||15|
|Arvan and Boscha||-t||18||33||11||0||6|
|Turpie et al||+ (5,000 bid)||109||32||4||4||12|
|+ (12,000 bid)||112||11||1||5||10|
|Aggregate||— low dose||177||35||5||2||11|
Category: Antithrombotic Therapy
Tags: antithrombotic therapy, cardioembolic source, cerebrovascular disorders