SusanS. Jick

Risk of idiopathic cardiovascular death and rionfatal venous thromboembolism in women using oral contraceptives with differing progestagen components

Concern about the risks of cardiovascular illness in women using combined oral contraceptives (OC) containing the progestagens desogestrel and gestodene prompted two studies of data from the UK General Practice Research Database. We compared the risks of certain cardiovascular illnesses in otherwise healthy women exposed to one of three OCs containing < 35 micrograms oestrogen plus levonorgestrel, desogestrel, or gestodene. In the first study, based on some 470 general practices, there were 15 cases of unexpected idiopathic cardiovascular death among 303,470 women who were current users of one of the study OCs. The estimated incidence rates were 8/184,536 (4.3 per 100,000) woman-years at risk for users of combined OCs containing levonorgestrel, 2/135,567 (1.5 per 100,000) for desogestrel users, and 5/105,201 (4.8 per 100,000) for gestodene users. The relative risk (RR) estimates were 0.4 (95% CI 0.1-2.1) and 1.4 (CI 0.5-4.5) for desogestrel and gestodene, respectively, compared with levonorgestrel. In the second study, derived from some 370 general practices, there were 80 cases of nonfatal venous thromboembolism (VTE) in a cohort of 238,130 otherwise healthy women. The incidence rates of VTE per 100,000 woman-years at risk were 16.1 for levonorgestrel users, 29.3 for desogestrel, and 28.1 for gestodene. The adjusted RR estimates from the cohort analysis were 1.9 (1.1-3.2) and 1.8 (1.0-3.2) for desogestrel and gestodene users, respectively, compared with users of levonorgestrel. In a nested case-control analysis the adjusted matched RR estimates were 2.2 (1.1-4.4) and 2.1 (1.0-4.4) for desogestrel and gestodene users, respectively, compared with users of levonorgestrel. The excess risk for nonfatal VTE associated with the new generation of combined OCs containing low-dose oestrogen and the progestagens desogestrel or gestodene compared with levonorgestrel is estimated to be 16 per 100,000 woman-years.

Acute respiratory-tract infections and risk of first-time acute myocardial infarction

BACKGROUND There is growing interest in the role of infections in the aetiology of acute myocardial infarction (AMI). We undertook a large, population-based study to explore the association between risk of AMI and recent acute respiratory-tract infection. METHODS We used data from general practices in the UK (General Practice Research Database). Potential cases were people aged 75 years or younger, with no history of clinical risk factors, who had a first-time diagnosis of AMI between Jan 1, 1994, and Oct 31, 1996. Four controls were matched to each case on age, sex, and the practice attended. The date of the AMI in the case was defined as the index date. For both cases and controls the date of the last respiratory-tract infection before the index date was identified. We also did a case-crossover analysis of cases who had an acute respiratory-tract infection either before the index date or before an arbitrarily chosen date (1 year before AMI). FINDINGS In the case-control analysis of 1922 cases and 7649 matched controls, significantly more cases than controls had an acute respiratory-tract infection in the 10 days before the index date (54 [2.8%] vs 72 [0.9%]). The odds ratios, adjusted for smoking and body-mass index, for first-time AMI in association with an acute respiratory-tract infection 1-5, 6-10, 11-15, or 16-30 days before the index date (compared with participants who had no such infection during the preceding year) were 3.6 (95% CI 2.2-5.7), 2.3 (1.3-4.2), 1.8 (1.0-3.3), and 1.0 (0.7-1.6); (test for trend p<0.01). The case-crossover analysis showed a relative risk of 2.7 (1.6-4.7) for AMI in relation to an acute respiratory-tract infection in the 10 days before the index date. INTERPRETATION Our findings suggest that in people without a history of clinical risk factors for AMI, acute respiratory-tract infections are associated with an increased risk of AMI for a period of about 2 weeks. We cannot, however, completely exclude the possibility of misdiagnosis bias, if prodromal symptoms of AMI were mistaken for respiratory-tract infection.

First trimester topical tretinoin and congenital disorders

We used information from the Group Health Cooperative of Puget Sound, Washington, USA, to evaluate the risk of birth defects in mothers exposed to topical tretinoin--a retinoid preparation used to treat acne--in the first trimester of pregnancy. We identified 215 women who delivered live or stillborn infants at Group Health Cooperative hospitals and who were exposed to topical tretinoin early in pregnancy, and 430 age-matched nonexposed women who delivered live or stillborn infants at the same hospitals. The prevalence of major anomalies among babies born to the exposed women was 1.9% and among babies born to the nonexposed women was 2.6%. The relative risk estimate for having a baby with a major congenital anomaly for exposed versus nonexposed women was 0.7 (95% CI 0.2-2.3). We conclude that topical tretinoin is not associated with an increased risk for major congenital disorders.

Non-steroidal anti-inflammatory drugs and hospital admission for perforated peptic ulcer

The frequency of hospital admission for perforated ulcer was not measurably affected by concurrent use of non-steroidal anti-inflammatory drugs (NSAID) during nearly 30 million person-days of NSAID use at Group Health Cooperative of Puget Sound. Whether patients had ever used cimetidine or antacids, drugs which indicate the presence of ulcer disease or symptoms, was strongly predictive of perforation in the same population (rate ratio 5.1; 95% CI 2.6-10.0). Perforation rates increased sharply with age but were similar for men and women.

Risk of acute myocardial infarction and low-dose combined oral contraceptives

Researchers from Boston University Medical Center assessed 303470 women who had used combined low estrogen oral contraceptives (OCs) containing levonorgestrel desogestrel or gestodene between January 1991 and October 1994 to investigate the risk of myocardial infarction. 11 women had experienced an acute myocardial infarction or sudden death. Each myocardial infarction case was matched to four controls by age index date of the case and general practice. The relative risk for desogestrel gestodene and past use compared with levonorgestrel stood at 0.7 0.6 and 0.9 respectively (95% confidence interval: 0.1-8.2 0.1-6.4 and 0.2-4.5 respectively). 6 of the 11 cases were either current smokers or past smokers. Based on these findings the researchers concluded that users of low-dose OCs were at low risk of myocardial infarction and any risk was limited to smokers. Further these findings support the findings of earlier studies that also found the risk of acute myocardial infarction to be very low in otherwise healthy users of low-dose OCs.

Oral contraceptives and breast cancer.

A population-based case-control study of oral contraceptive use and breast cancer was carried out among young women (less than 43 years of age) at Group Health Cooperative of Puget Sound, Seattle, Washington. Use of oral contraceptives before first pregnancy did not materially differ between cases or controls. The rate ratio estimate of breast cancer incidence in women who had used oral contraceptives before first pregnancy compared to those who had not was 0.9 (95% CI = 0.4, 2.1). There were no meaningful patterns of association between breast cancer and duration of use or formulation of oral contraceptive used before first pregnancy.