Background-Epidemiological studies suggest a decreased risk of coronary heart disease (CHD) in healthy women taking hormonal replacement therapy (HRT). Whether this effect is shared by oral and transdermal preparations is unknown. Methods and Results-We conducted a population-based case-control study nested in a cohort of women 50 to 74 years of age without cardiovascular disease history in the United Kingdom. Among 164 769 women from the General Practice Research Database (January 1, 1991, to December 31, 1995), we identified 1242 first acute myocardial infarctions (AMI) and confirmed 1013 after medical record review. We randomly selected 5000 age-frequency-matched control subjects. AMI incidence was 1.6 per 1000 person-years; 13% and 17% of cases and control subjects used HRT within 6 months before the index date. Risk factor and comorbidity-adjusted OR of AMI for current-recent HRT users compared with nonusers was 0.72 (95% CI 0.59 to 0.89). The OR was similar within 30 days before the index date. The beneficial effect was present after 1 year of use (OR 0. 68; 95% CI 0.53 to 0.86), with no increase in risk within the first year. ORs for unopposed and opposed therapy were 0.52 (95% CI 0.35 to 0.78) and 0.79 (95% CI 0.59 to 1.08); 79% and 21% used oral and transdermal therapy. The protective effect was present at medium-high doses of estrogens with ORs for oral and transdermal therapy of 0.63 (95% CI 0.46 to 0.86) and 0.62 (95% CI 0.37 to 1.06) and ceased after 2 to 3 years since stopping HRT. Conclusions-Results are consistent with those previously reported in women without CHD who were taking oral HRT and, although based on few users, suggest that transdermal therapy might have similar cardioprotective effects.

The risk of a newly diagnosed episode of upper gastrointestinal bleeding, acute liver and renal failure, agranulocytosis, aplastic anemia, severe skin disorders, and anaphylaxis was examined within 30 days after the first prescription for a low dose of diclofenac, naproxen, or ibuprofen in a cohort in the United Kingdom. We identified 22,146 persons using diclofenac (< or = 75 mg), 46,919 using naproxen (< or = 750 mg), and 54,830 using ibuprofen (< or = 1200 mg). Age, gender, and comorbidity were similar in the three cohorts. Overall 64 potential cases were identified, and 20 were confirmed by medical record review. Incidence rates (95% CI) of upper gastrointestinal bleeding/10,000 people using diclofenac, naproxen, and ibuprofen were 1.8 (0.5-4.6), 2.3 (1.2-4.2), and 0.4 (0.04-1.3), respectively. There were three cases of hepatic injury, one with naproxen and two with ibuprofen. Although low, the incidence of gastrointestinal toxicity remains the main serious adverse event for all study drugs.