Risk of Myocardial Infarction in Women Taking Diane Pills
Women taking combined oral contraceptives like Diane (ethinyl estradiol and cyproterone acetate) have an increased risk of myocardial infarction compared to non-users, with the risk amplified substantially by the presence of cardiovascular risk factors, particularly smoking, hypertension, and age over 35 years.
Baseline Risk in Healthy Women
- Current users of combined oral contraceptives have a 1.6-fold increased risk of myocardial infarction compared to non-users 1, 2.
- The FDA drug labeling confirms that the relative risk of myocardial infarction for current oral contraceptive users ranges from 2 to 6-fold 3.
- This risk is not related to duration of use and disappears after discontinuation 3.
- The risk is dose-dependent, with higher estrogen doses (>50 mcg) conferring greater risk 1.
- The risk is not related to the dose, generation, or type of progestogen 1.
Risk Amplification with Comorbidities
Hypertension
- Women with adequately controlled hypertension using combined oral contraceptives face a relative contraindication (WHO MEC Category 3) 1, 4.
- Women with moderate hypertension (SBP 140-159 or DBP 90-99 mmHg) have an odds ratio of 6-68 for myocardial infarction when using combined oral contraceptives 1.
- Women with severe hypertension (SBP ≥160 or DBP ≥100 mmHg) have an absolute contraindication to combined oral contraceptives 1, 4, 5.
Smoking
- The risk of myocardial infarction is primarily in smokers or women with other cardiovascular risk factors 3.
- Heavy smokers (≥15 cigarettes/day) using combined oral contraceptives have a relative risk of 20.8 compared to non-smokers not using contraceptives 6.
- Women age ≥35 years who smoke ≥15 cigarettes daily have an absolute contraindication to combined oral contraceptives 4, 5.
Other Risk Factors
- Women with dyslipidemia using combined oral contraceptives have an increased risk of myocardial infarction compared to non-users 1.
- Women with diabetes mellitus have a 6.9-fold increased risk of myocardial infarction, which is further amplified by combined oral contraceptive use 6.
- Women with a history of hypertension during pregnancy using combined oral contraceptives have approximately 2-times the absolute risk of myocardial infarction compared to those without this history 1.
Clinical Decision Algorithm
Absolute Contraindications (Do Not Prescribe)
- Age ≥35 years AND smoking ≥15 cigarettes daily 4, 5
- Severe hypertension (SBP ≥160 or DBP ≥100 mmHg) 1, 4, 5
- Current or history of ischemic heart disease 4, 5
- Current or history of stroke 4, 5
- Multiple cardiovascular risk factors that substantially increase cardiovascular disease risk 1
Relative Contraindications (Risks Usually Outweigh Benefits)
- Moderate hypertension (SBP 140-159 or DBP 90-99 mmHg) 1, 4
- Adequately controlled hypertension 1, 4
- Age >35 years with any cardiovascular risk factors 3
Acceptable Use (Benefits Outweigh Risks)
- Age <35 years, non-smoker, normotensive, no other cardiovascular risk factors 1
- Use lowest effective estrogen dose (≤35 mcg) 3
Important Caveats
- Blood pressure must always be measured before initiating combined oral contraceptives 4, 5.
- The risk of myocardial infarction is thrombotic, not atherosclerotic in mechanism 7.
- Discontinuation of combined oral contraceptives in hypertensive women may improve blood pressure control 1, 5.
- The absolute risk of myocardial infarction remains small in young, healthy women without risk factors 3, 8.
- Modern low-dose formulations (≤35 mcg estrogen) have lower cardiovascular risk than older high-dose preparations 3, 2.