Drospirenone Associated With Increased Risk for VTE

Emma Hitt, PhD

April 26, 2011

April 26, 2011 (UPDATED April 29, 2011) — Women without risk factors for venous thromboembolism (VTE) who are taking the third-generation oral contraceptive drospirenone have an increased risk for nonfatal VTE compared with women taking the second-generation contraceptive levonorgestrel, according to the findings of 2 new case-control studies.

Susan S. Jick, Dsc, from the Boston Collaborative Drug Surveillance Program at the Boston School of Medicine, in Massachusetts, and colleagues reported their findings in 2 separate articles published online April 21 in the BMJ.

Oral contraceptives

According to the researchers, a series of case reports beginning in 2002 first raised concerns about an increased risk for VTE in users of oral contraceptives containing drospirenone. This risk has since been assessed in several studies that included women with risk factors for VTE. However, the risk attributable to oral contraceptives in the absence of other causes was unknown.

In the current studies, one conducted in the United Kingdom and the other in the United States, the study populations, both consisting of women aged 15 to 44 years, was restricted to patients with idiopathic VTE, each matched with up to 4 control case patients by age and calendar time of drug exposure.

Data for the UK cohort came from the UK General Practice Research Database, which contains data from more than 3 million people. Data for the US cohort were acquired from the PharMetrics database, which contains prescription data on 55 million people reaching back to 1995.

The UK study included 61 cases of idiopathic VTE among current users of drospirenone and levonorgestrel; these patients were matched with 215 control patients. All patients were receiving oral contraceptives containing 30 μg of estrogen in combination with either drospirenone or levonorgestrel. The US study included 186 cases of idiopathic VTE; these patients were matched with 681 control patients, with contraceptives including either drospirenone or levonorgestrel.

Although the absolute risk was low, both studies showed a 2- to 3-fold increased risk for nonfatal VTE with drospirenone compared with levonorgestrel. The UK study showed an odds ratio (OR) of 3.3 (95% confidence interval [CI], 1.4 - 7.6), and the US study showed an OR of 2.4 (95% CI, 1.7 - 3.4).

In the UK study, the incidence rates for idiopathic VTE were 23 (95% CI, 13.4 - 36.9) per 100,000 woman/years with drospirenone and 9.1 (95% CI, 6.6 - 12.2) per 100,000 woman/years with levonorgestrel. The corresponding incidence rates in the US study were 30.8 (95% CI, 25.6 - 36.8) per 100,000 woman/years with drospirenone and 12.5 (95% CI, 9.61 - 15.9) per 100,000 woman/years with levonorgestrel.

"This study adds to emerging evidence that use of the oral contraceptive containing drospirenone is associated with a higher risk of [VTE] than are preparations containing levonorgestrel," Dr. Jick and colleagues conclude.

"In the meantime, as no clear evidence exists to show that the use of the drospirenone pill confers benefits above those of other oral contraceptives in preventing pregnancy, treating acne, alleviating premenstrual syndrome, or avoiding weight gain," they add, "prescribing lower risk levonorgestrel preparations as the first line choice in women wishing to take an oral contraceptive would seem prudent."

Comment: Factors Examined in These 2 Studies

"These findings will likely reduce enthusiasm for routine use of these oral contraceptives in otherwise healthy young women who are taking pills for no other reason except contraception," said Nanette Santoro, MD, with the University of Colorado School of Medicine, in Aurora.

"There have been several concepts that have allayed concerns until today," Dr. Santoro told Medscape Medical News. "Drospirenone has been recommended for women with polycystic ovary syndrome and hirsutism, and these women are at higher risk for VTE than others. So a finding of higher incidence of VTEs in these women is not a great surprise," she said. "Moreover, there is the 'new user' effect that tends to result in more women with VTEs in the group taking the newer contraceptive. These two new studies have examined those factors and still find a greater risk with drospirenone."

Dr. Santoro points out, however, that the risk for VTE is low for young women, and the need for contraception is huge. "The risk of VTE associated with pregnancy is about 6-fold greater than the risk for non-pregnant women, so the risk of VTE linked to oral contraceptives must always be balanced against the alternative: a 6-fold increased risk of VTE and an unwanted pregnancy."

The studies were not commercially funded. The study authors and Dr. Santoro have disclosed no relevant financial relationships.

BMJ. Published online April 21, 2011. Full text Full text


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