Low-dose OCs don’t add to heart attack risk

The evidence grows for the safety of low-dose (under 50 mcg estrogen) oral contraceptives (OCs) following release of new data showing no increased risk for heart attack among women with no previous risk of coronary heart disease.1

Researchers with the northern and southern California units of Kaiser Permanente Medical Care Program in Oakland and Pasadena and the University of Washington in Seattle conducted separate population-based case-control studies and pooled the data for the comprehensive report.

The studies were designed to be combined from the beginning to confirm consistent findings between the two sites, as well as to gain a greater degree of precision in determining the estimated risk associated with OCs, says Stephen Sidney, MD, MPH, associate director for clinical research at Kaiser-Permanente’s Oakland site.

As cases, the studies included women 18 to 44 with incidents of heart attack but no prior incident of ischemic heart disease or cerebrovascular disease. Women in the case and control groups were interviewed about OC use and cardiovascular risk factors. The analysis included 271 cases and 993 controls.

In the pooled analysis, there was no evidence of an increased risk of heart attack associated with the use of OCs, a finding consistent with most other recent studies.2-6

Results from a recent multinational study from the World Health Organization (WHO) in Geneva, Switzerland, also showed minimal risk for young women who have no previous identified risk.7 However, the WHO study did report an elevated risk of heart attack among pill users who smoke or have high blood pressure. (See Contraceptive Technology Update, July 1997, p. 85, for full results of the WHO study.)

One of the biggest differences in the design of the WHO study is its inclusion of women who were not screened for cardiovascular risk factors, Sidney says. The WHO study did find that nonsmoking women who had had a blood pressure check prior to taking OCs had no increased risk of heart attack, a finding that is consistent with the U.S. study.

One intriguing finding from the U.S. study is the association of past OC use with a statistically significant decrease in the risk of heart attack, says Ramona Slupik, MD, assistant professor of OB/GYN at Northwestern University in Chicago. Is it possible there was a selection bias in the study, and people with different risk factors received different pills or didn’t receive the pill at all? The answer is no, because the cardiovascular risk factors were similar in cases and controls, she notes. Unmeasured factors, such as a healthy lifestyle, may have confounded the results, researchers say. Other studies are needed to tease out associated factors, she says.

While the U.S. study showed no increased risk of heart attack among current OC users who smoke, the body of previously published evidence clearly supports the dangers of combining the two, says Sidney. "Providers should absolutely counsel women who are smokers that they need to stop. I would not prescribe OCs to a woman who is a smoker and is not going to stop."

The researchers note the limitations of the study, which include possible response, recall, and diagnostic bias, Slupik points out. Until further evidence to support the OC/smoking finding becomes available, Slupik agrees with Sidney that providers should continue to counsel heavily for smoking cessation prior to OC use.

For women with high blood pressure, provid ers should use clinical judgment in assessing OC use, Sidney states. High blood pressure does not automatically rule out pill use, he says. Providers must take into account a number of factors, including the risk of pregnancy and the medical problems that may arise from it.

"I think blood pressure certainly should be considered, with a tendency probably to not put somebody on OCs if they have untreated high blood pressure," Sidney observes. "I don’t think we know a lot about treated blood pressure, so it really comes down to individual judgment."

What’s next in research?

Researchers at Kaiser-Permanente are now looking at OC use and venous thromboembolism, an issue that has captured the interest of investigators around the world. (Such investigations have looked at risks associated with estrogen dose and differences in second- and third-generation progestins. For details, see CTU: January 1996, p. 6; April 1996, p. 41, p. 47; November 1996, p. 142; and December 1996, p. 149.)

"I think all the studies that have been done thus far suggest that there really is an increased risk with OC use, and we are studying that now in the same Kaiser population," Sidney reports. "I think clearly there is evidence coming out that there’s a genetic component to this risk, that women who have genetic predisposing conditions may be at higher risk of blood clots."

References

1. 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.

2. Rosenberg L, Palmer JR, Lesko SM, et al. Oral contraceptive use and the risk of myocardial infarction. Am J Epidemiol 1990; 131:1,009-1,016.

3. Croft P, Hannaford PC. Risk factors for acute myocardial infarction in women: Evidence from the Royal College of General Practitioners’ oral contraception study. BMJ 1989; 298:165-168.

4. Thorogood M, Mann J, Murphy M, et al. Is oral contraceptive use still associated with an increased risk of fatal myocardial infarction? Br J Obstet Gynaecol 1991; 98:1,245-1,253.

5. D’Avanzo B, La Vecchia C, Negri E, et al. Oral contraceptive use and risk of myocardial infarction: An Italian case-control study. J Epidemiol Community Health 1994; 48:324-325.

6. Sidney S, Petitti DB, Quesenberry CP Jr, et al. Myocardial infarction in users of low-dose oral contraceptives. Obstet Gynecol 1996; 88:939-944.

7. WHO Collaborative Study of Cardiovascular Disease and Steroid Hormone Contraception. Acute myocardial infarction and combined oral contraceptives: Results of an international multicentre case-control study. Lancet 1997; 349:1,202-1,209.