Research eyes MI risk in oral contraceptive use
The association between the use of oral contraceptives (OCs) and the risk of myocardial infarction (MI) continues to be reviewed, with data just in from a European study.1
How should U.S. clinicians interpret the results? A commentary that accompanies the latest research suggests the focus should be placed on counseling women to discontinue cigarette smoking, a chief factor in MI risk.2 According to statistics from the Bethesda, MD-based National Heart, Lung, and Blood Institute, women who smoke are two to six times more likely to suffer a heart attack than nonsmoking women, with the risk increased with the number of cigarettes smoked each day.3
"The risk of MI due to cigarette smoking alone remains striking, and it’s substantially higher than the risk from any generation of progestin," says commentary co-author Lynn Chasan-Taber, ScD, assistant professor of epidemiology in the department of biostatistics and epidemiology at the University of Massachusetts in Amherst.
Review the findings
The new research follows the findings of European studies on oral contraceptives and venous thrombosis,4,5 reports Frits Rosendaal, MD, chairman of the department of clinical epidemiology at the Leiden (Netherlands) University Medical Center and lead author of the study.
According to Rosendaal, these studies indicate no benefit of lower estrogen doses on risk of deep-vein thrombosis and pulmonary embolism, and an excess risk with third-generation progestins over second-generation progestins.
Rosendaal’s research looks at the OC-MI risk association according to the OCs’ type of progestin, estrogen dose, and the presence or absence of prothrombotic mutations in the women who used them. The population-based, case-control study enrolled 248 women ages 18-49 who had had a first MI between 1990 and 1995 and 925 women who had not had a MI and who were matched for age, calendar year of the index event, and area of residence. Oral contraceptives were categorized into three groups based on progestin content: first-generation pills with lynestrenol or norethindrone, second-generation pills with levonorgestrel, and third-generation formulations with desogestrel or gestodene.
"Our main findings are that MI risk is not lower with lower estrogen dose," says Rosendaal. "As for third vs. second generation, we considered our results inconclusive; we found for third generation half the risk of second generation, but there was considerable statistical uncertainty around that result."
Andrew Kaunitz, MD, professor and assistant chair in the obstetrics and gynecology department at the University of Florida Health Science Center in Jacksonville, asks why U.S. studies6,7 have failed to find a similar link between OC use and MI risk.
The difference may lie in differences in prescribing practice, as U.S. providers are cautioned not to prescribe OCs to women smokers who are age 35 or older, says Kaunitz. Responses to the 2001 Contraceptive Technology Update Contraception Survey bear out this observation, as 72.2% said they would withhold pills from women ages 35-39 who smoke 10 cigarettes a day, and almost 90% said they would refuse OCs to women older than age 40. (Results of the 2001 Survey were reported in the September 2001 issue.)
Many of the women included in the most recent European research were smokers, notes Kaunitz. Even a slightly more permissive approach to prescribing OCs to high-risk women could explain why European, but not U.S. investigators, have found an elevated risk, he notes.
Focus on care
The debate about the safety of oral contraceptives containing third-generation progestins desogestrel or gestodene shows no sign of fading away in the European medical community, as evidenced in a recent commentary in the British Medical Journal.8 The controversy has not ignited in the United States because few pills contain the progestins in question.
What is the overriding message for clinicians? Kaunitz points to the need for discouraging smoking in all women patients.
"For patients who continue to smoke, OC use should not be continued beyond age 35," he states. "In this group, intrauterine or progestin-only methods represent sound contraceptive choices."
References
1. Tanis BC, van den Bosch MAAJ, Kemmeren JM, et al. Oral contraceptives and the risk of myocardial infarction. N Engl J Med 2001; 345:1,787-1,793.
2. L Chasan-Taber, M Stampfer. Oral contraceptives and myocardial infarction — the search for the smoking gun. N Engl J Med 2001; 345:1,841-1,842.
3. National Heart, Lung, and Blood Institute. Facts About Heart Disease and Women: Kicking the Smoking Habit. Bethesda, MD; 1996.
4. Kemmeren JM, Algra A, Grobbee DE. Third-generation oral contraceptives and risk of venous thrombosis: Meta-analysis. BMJ 2001; 323:131-134.
5. Vandenbroucke JP, Rosing J, Bloemenkamp KW, et al. Oral contraceptives and the risk of venous thrombosis. N Engl J Med 2001; 344:1,527-1,535.
6. Sidney S, Siscovick DS, Petitti DB, et al. Myocardial infarction and use of low-dose oral contraceptives: A pooled analysis of 2 U.S. studies. Circulation 1998; 98:1,058-1,063.
7. Rosenberg L, Palmer JR, Rao RS, et al. Low-dose oral contraceptive use and the risk of myocardial infarction. Arch Intern Med 2001; 161:1,065-1,070.
8. Drife JO. The third-generation pill controversy ("continued"). BMJ 2001; 323:119-120.
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