Bayer HealthCare Pharmaceuticals Inc. today announced that interim results from a large, prospective, observational cohort safety study offer insights into the increased risk of venous thromboembolism (VTE), or blood clots, which is a well-established risk in women who use combination oral contraceptives (COCs), also known as "the Pill".
Specifically, the new data provides healthcare providers with information regarding when the VTE risk associated with COCs is highest. The risk of VTE is highest during the first year of COC use and the new data suggest that this increased risk is greatest during the first six months. This risk is greatest when first starting the Pill and when restarting the same or a different Pill after a four week or greater break.
The new data are from the ongoing, Long-Term Active Surveillance Study for Oral Contraceptives (LASS) – a large, multinational, prospective cohort, five-year follow-up safety study to the European Active Surveillance (EURAS) study. Cardiovascular events, including VTE, were the main clinical outcomes studied in LASS. Together, these two studies will provide data for up to ten years on women using various COCs.
"As a leader in women's contraception, we believe it is important for Bayer to take the lead in studying and communicating the risks and benefits of COCs," said Leo Plouffe, MD, Vice President, US Medical Affairs, Women's Healthcare, Bayer HealthCare Pharmaceuticals. "The new information is helpful because while healthcare providers have long known about the risk of VTE associated with COCs, there was little information to indicate that there was an increased risk in women restarting COCs after a four week or greater period of non-use. This new information should provide both healthcare providers and women who choose a COC for contraception with additional information when making the decision to implement a pause in their COC routine."
Following the submission of the interim analysis, Bayer worked with the US Food and Drug Administration (FDA) and updated the Prescribing Information for YAZ® (3 mg drospirenone / 0.02 mg ethinyl estradiol) in the US. Bayer will continue to work with the FDA to update the Prescribing Information for all of its oral contraceptives in the US.
Like pregnancy, the use of COCs is associated with an increased risk of blood clots, which can be life-threatening. However, pregnancy increases the risk of blood clots as much or more than the use of COCs. These events are uncommon in healthy women using COCs.
Since 2001, Bayer commissioned independent investigators to conduct large-scale observational studies assessing the risk of VTE in women using COCs containing a variety of progestins, including drospirenone. The results from these studies have been shared with the FDA and other regulatory authorities.
"Increased VTE risk is associated with any COC, and Bayer is committed to studying the safety and efficacy of our products. Birth control pills are among the most systematically studied medicines available today," said Dr. Plouffe.
Several studies have investigated the relative risks of thromboembolism in women using drospirenone-containing COCs compared to women using COCs containing other progestins.
Bayer's post-marketing studies have shown that the risk of VTE in a COC formulation containing 3 mg drospirenone in combination with 0.03 mg ethinyl estradiol is comparable to that of any COCs in those studies.
Two other published studies – one case-control study and one retrospective cohort study – have suggested that the risk of VTE occurring in drospirenone/ethinyl estradiol users was between the risk associated with levonorgestrel-containing COCs and desogestrel/gestodene-containing COCs. In April 2010, the FDA approved an update to the YAZ Prescribing Information regarding these two studies and indicated that they may be unreliable, specifically:
- With regard to the case-control study, the Prescribing Information indicates that, "…the number of [3 mg drospirenone/0.03 mg ethinyl estradiol] cases was very small (1.2% of all cases) making the risk estimates unreliable."
- Concerning the retrospective cohort study, the Prescribing Information indicates that, "The relative risk for [3 mg drospirenone/0.03 mg ethinyl estradiol] users in the retrospective cohort study was greater than that for users of other COCs when considering women who used the products for less than one year. However, these one-year estimates may not be reliable because the analysis may include women of varying risk levels. Among women who used the product for one to four years, the relative risk was similar for users of [3 mg drospirenone/0.03 mg ethinyl estradiol] to that for users of other COC products."
Women should not use YAZ if they smoke and are over age 35. Smoking increases the risk of serious side effects from the Pill, which can be life-threatening, including blood clots, stroke or heart attack. This risk increases with age and number of cigarettes smoked.
YAZ increases the risk of serious conditions including blood clots, stroke, and heart attack. The risk of blood clots is highest during the first year of use.
In addition, YAZ contains drospirenone, a different kind of hormone that for some may increase potassium too much. Therefore, women should not take YAZ if they have kidney, liver, or adrenal disease because this could cause serious heart and health problems. Women who are on daily, long-term treatment for a chronic condition with medications that may also increase potassium (see below), should consult with their healthcare provider as they should have a blood test to check their potassium level during the first month of taking YAZ.
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