The FDA (sort of) addresses blood clot risks with Yaz

The lawyers have been advertising about it for years now, so it’s nice to see the FDA finally begin to address the issue of Yaz and blood clot risks.

The reason is the recent publication of two more studies suggesting that birth control pills containing the progestin drosperineone (Yaz and its generics) may have a higher blood clot risk than other pills.

From the FDA –

Two recent articles in the British Medical Journal have raised the question as to whether there is greater risk of DVT and PE in women taking combination oral contraceptives containing the progestin drospirenone as compared to the risk in women taking oral contraceptives containing the progestin levonorgestrel.1,2 These two new studies reported a two- to three-fold greater risk of venous thromboembolic events or VTEs (VTEs include DVTs and PEs) in women using oral contraceptives containing drospirenone rather than levonorgestrel.

Previously published studies have also addressed the risk of blood clots in women using birth control pills containing drospirenone. These studies had conflicting findings. Two were postmarketing studies required by the FDA or European regulatory agencies. These studies did not report any difference in VTE risk between drospirenone-containing products and products containing levonorgestrel or other progestins.4,5 However, two other publications from 2009 reported a 1.5- to 2-fold higher VTE risk in women who use drospirenone-containing contraceptives as compared to the risk in women who use levonorgestrel-containing contraceptives.6,7 Results of these latter four studies are described in the current labels for all the drospirenone-containing contraceptive products.

If you’re been keeping track, the score is now four studies suggesting a higher clot risk for Yaz vs two studies showing no increased risk.

That was enough to cause the European Medicines Association to issue a statement that drosperinone containing pills have a higher clot risk than levonorgestrel containing pills.

Which led our FDA to issue a statement basically saying that that they are looking into the matter, so stay tuned –

FDA is currently reviewing the two most recent studies and will be looking at all currently available information to assess whether there is a greater risk of VTE in women using oral contraceptives containing drospirenone. Data from an additional, large, FDA-funded, study on hormonal contraceptives is also being finalized and reviewed. This study includes over 800,000 US women and is designed to look at thrombotic and thromboembolic risks including VTE in a number of hormonal contraceptive products; results are expected later this summer. FDA will continue to communicate any new safety information to the public as it becomes available.

Just how high is the blood clot risk from Yaz?

It’s quite small – far, far less than a 1% chance or even a 1 in a thousand chance. According to the US Study, if 100,000 women were to use the pill for a year, clots would occur in 23 Yasmin vs 9.1 levonorgestel containing pill users. In the UK study, corresponding risks were 30.8 for drosperinone vs 12.5 for levonogrestrel-containing pills.

Remember that all estrogen-containing contraceptives carry a clot risk, on the order of a few per 10,000 women per year of use. Risks are highest in the first year of use and in women over 35 who smoke.

It’s worth noting that the Europeans are stating that the clot risks for Yaz and its generics are similar to those of pills containing desogestrol, which in the United States are marketed as Mircette, Desogen and their generics. So there’s really no reason to be singling out Yaz for blame.  It’s also worth noting that norgestimate-containing pills (Ortho-Cyclens and their generics) seem to have evaded much of the scrutiny when it comes to clot risks, although the patch version of norgestimate (Ortho-Evra) did come under fire for possible higher clot risks. One study to date ranks clot risks with norgestimate pills as similar to levonorgestrel. And the Nuvaring seems to have been completely left out of the mix…

The problem, of course, with all the studies comparing clot risks between pills is that no single study included all the pills being marketed, and all to date have had both very low overall clot incidence and  methodological issues that make firm conclusions difficult. I hope the study the FDA is awaiting will be more definitive. The fact that they are releasing this communication now, ahead of the results of that study, makes me wonder if they already know the outcome and are preparing us for it…

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FDA Communication on Yaz

• FDA Safety Announcemnt regarding drosperinone-containing oral contraceptives
• Questions and Answers from the FDA on the issue

My previous posts on Yaz and this issue

• Yaz and Blood Clots – Two More Studies Point to Higher Risks
• Clotting up Office Hours with talk of clots
• Yaz makers to Women – We Screwed Up
• CVS- Detailing Yaz for Bayer?

Links to studies referenced in the FDA communication

1. Parkin L, Sharples K, Hernandez RK, Jick SS. Risk of venous thromboembolism in users of oral contraceptives containing drospirenone or levonorgestrel: nested case-control study based on UK General Practice Research Database. BMJ 2011; 340:d2139.
2. Jick SS, Hernandez RK. Risk of non-fatal venous thromboembolism in women using oral contraceptives containing drospirenone compared with women using oral contraceptives containing levonorgestrel: case-control study using United States claims data. BMJ 2011; 340:d2151.
3. U.S. National Library of Medicine. National Institutes of Health. Health Topics monograph Deep Vein Thrombosis. Available athttp://www.nlm.nih.gov/medlineplus/deepveinthrombosis.html; Accessed April 28, 2011.
4. Seeger JD, Loughlin J, Eng PM, Clifford CR, Cutone J, Walker AM. Risk of thromboembolism in women taking ethinylestradiol/drospirenone and other oral contraceptives. Obstet Gynecol 2007; 110(3):587-93.
5. Dinger JC, Heinemann LA, Kühl-Habich D. The safety of a drospirenone-containing oral contraceptive: final results from the European Active Surveillance Study on oral contraceptives based on 142,475 women-years of observation. Contraception 2007; 75:344-54.
6. Lidegaard Ø, Løkkegaard E, Svendsen AL, Agger C. Hormonal contraception and risk of venous thromboembolism: national follow-up study. BMJ 2009; 339:b2890.
7. Van Hylckama V, Helmerhorst FM, Vandenbroucke JP, Doggen CJM, Rosendaal FR. The venous thrombotic risk of oral contraceptives, effects of oestrogen dose and progestogen type: results of the MEGA case-control study. BMJ 2009; 339:b2921.