The Lancet — Rothwell PM, et al. | July 20, 2018

In view of only modest benefits of a one-dose-fits-all approach to aspirin use for long-term prevention of cardiovascular events, researchers assessed aspirin in primary prevention of cardiovascular events by analyzing the modifying effects of bodyweight (10 kg bands) and height (10 cm bands) on the effects of low doses (≤100 mg) and higher doses (300–325 mg or ≥ 500 mg) of aspirin. Findings revealed only prevention of vascular events in patients weighing less than 70 kg in association with low doses of aspirin (75–100 mg). However, in the 80% of men and nearly 50% of all women weighing 70 kg or more, low doses of aspirin (75–100 mg) showed no beneficial effect. Interestingly, only among patients weighing 70 kg or more, higher doses of aspirin were effective. Given these results, a one-dose-fits-all approach to aspirin is unlikely to be optimal, indicating the need for a more tailored strategy.

Methods

• The findings were stratified in accordance to age, sex, and vascular risk factors, and were validated in trials of aspirin in secondary prevention of stroke.
• Furthermore, whether or not any weight or height dependence was evident for the effect of aspirin on 20-year risk of colorectal cancer or any in-trial cancer was assessed.

Results

• Researchers identified 10 eligible trials of aspirin in primary prevention including 117,279 participants.
• Among these trials, bodyweight varied four-fold and trial median weight ranged from 60.0 kg to 81.2 kg (p < 0.0001).
• With increasing weight, a reduction in the ability of 75-100 mg aspirin to reduce cardiovascular events was observed (p_interaction=0.0072), with benefit seen in people weighing 50–69 kg (hazard ratio [HR] 0.75 [95% CI 0.65–0.85]) but not in those weighing 70 kg or more (0.95 [0.86–1.04]; 1.09 [0.93–1.29] for vascular death).
• Furthermore, in people weighing 70 kg or more, case fatality of a first cardiovascular event was increased by low-dose aspirin (odds ratio 1.33 [95% CI 1.08–1.64], p=0.0082).
• Findings suggested an opposite interaction of higher doses of aspirin (≥325 mg) with bodyweight (difference p_interaction=0.0013), reducing cardiovascular events only at higher weight (p_interaction=0.017).
• Similar findings were noted in men and women, in people with diabetes, in trials of aspirin in secondary prevention, and in relation to height (p_interaction=0.0025 for cardiovascular events).
• Weight dependence was also observed in aspirin-mediated reductions in long-term risk of colorectal cancer (p_interaction=0.038).
• Harms due to excess dosing were also noted in stratification by body size: risk of sudden death was increased by aspirin in people at low weight for dose (p_interaction=0.0018) and risk of all-cause death was increased in people weighing less than 50 kg who were receiving 75–100 mg aspirin (HR 1.52 [95% CI 1.04–2.21], p=0.031).
• Increased 3-year risk of cancer by aspirin (1.20 [1.03–1.47], p=0.02) was also evident among participants aged 70 years or older; it was particularly noted in those weighing less than 70 kg (1.31 [1.07–1.61], p=0.009) and consequently in women (1.44 [1.11–1.87], p=0.0069).

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