Risk of Cardiovascular Events With Oral Contraceptives, Part 1 - Scope of the Problem

Oral contraceptives (OC) have been available since the 1960s, and it has been estimated that more than 100 million women use them throughout the world. They are also the most used contraceptive method in the US: over 70% of US women aged 20 to 44 years reported having ever used OC in 2011; 18.6% of those women were using OC when surveyed. However, soon after their introduction in the market, reports of cardiovascular events associated with the use of OC emerged. Even though OC have undergone numerous changes with respect to composition and strength of their active ingredients to improve their safety profile, all generations of OC have been consistently associated with an increased risk of cardiovascular events, including myocardial infarction, venous thromboembolic events, pulmonary embolism, and ischemic stroke.

The cardiovascular risks associated with OC vary across population subgroups. The risk of thromboembolic events increases substantially with age, and rises steeply after 39 years. Additionally, smokers using OC have an 8.8 fold higher risk of thromboembolic events in comparison with non-smokers who do not use OC. Despite knowledge about the synergic interaction between OC use and smoking, use of OC among smokers is still common. While the FDA set age limits for OC use as 35 years for smokers and 40 years for nonsmokers, the limit was removed in 1989 for healthy, nonsmoking women.

Among smokers and older women, OC—associated cardiovascular risk outweighs the risk of an unwanted pregnancy. With regard to genetic factors, OC use significantly interacts with factor V Leiden mutation. Factor V Leiden is a genetic variant of the factor V of coagulation and it is an important risk factor for venous thromboembolism. Users of OC carrying this mutation have a 30- to 50-fold greater risk of venous thromboembolism in comparison with non-carriers not using OC. The prevalence rates of factor V Leiden are highest for Caucasians, and between 3 and 7% of Europeans and white North Americans are estimated to carry this allele. Even though screening for this mutation has been clinically recommended before prescribing OC, it is not common practice.

In order to orient the prescription of OC, the World Health Organization compiled a list of medical eligibility criteria for contraceptive use and categorized several conditions according to the benefit/risk ratio of OC use among patients suffering from them. Recent studies have evaluated the compliance with these criteria in the US and estimated that among OC users, 23.7% had at least 1 high-risk condition and 9.3% had at least 1 condition of unacceptable risk.

This inappropriate use of OC can be due to several factors:

• Doctors may not be aware of these recommendations or may not comply with them. A survey conducted in Europe showed that around one third of the doctors surveyed were not aware of the WHO recommendations, many of whom expressed their unwillingness to change their prescription patterns after knowing them.
• Despite increased awareness of the risks of OC and recent studies showing a higher knowledge of OC than in the 1990s, many women remain unaware of the risks associated with oral contraception. This unawareness can be explained by two factors: OC users frequently do not receive appropriate counselling from their healthcare providers about the risks of OC. The results of an online survey showed that over 50% and 86.9% of OC users reported not having discussed the risks of OC with their healthcare provider and pharmacist, respectively. Many women may not be able to understand or interpret the information available on the risks of OC. A randomized study that exposed women to different information about contraceptives discovered that exposure to information on adverse effects did not change women’s preferences for contraceptive methods, compared with receiving basic information. This speaks to the difficulty with interpreting the information on the risk of adverse events associated with a pharmacological agent without the help of a health professional.

As a result of the physiopathological changes they induce, most effective pharmaceutical agents have side effects. It is therefore not possible to completely eradicate the occurrence of adverse events associated with OCs. However, a large proportion of these side effects are a result of amendable causes, such as the use of OC in women at high risk of OC-related events, for whom the benefit/risk ratio of other contraceptive methods is superior to that of OCs. In a following post, I will discuss potential policy solutions to increase the awareness of cardiovascular side effects among women using OCs, and to direct the prescription of this contraceptive method based on the risk of women for cardiovascular events.