迈阿密海滩——在国际黑人高血压学会主办的一次会议上，美国新奥尔良杜兰大学/杜兰心血管研究所的Keith C. Ferdinand博士报告称，一项纳入了将近160万例女性受试者的综合研究表明，高血压女性患者口服激素类避孕药与血栓性卒中和心肌梗死(MI)风险增加相关，虽然增幅较小但确实存在。

    在这项丹麦登记库研究中，研究者对1,626,158例既往无心血管病史的非妊娠期女性进行了评估，这基本上覆盖了整个年龄介于15~49岁的丹麦女性人群。这项历史队列研究表明，在总共超过1,400万人年的观察中共出现了3,311例血栓性卒中事件和1,725例首次MI事件。

    使用激素类避孕药与相对风险增加相关。Ferdinand博士说：“口服雌激素和孕激素类避孕药确实会增加患者出现卒中和MI的风险。”但用药剂量的效应存在差异。例如，大剂量雌激素会增加患者出现卒中的相对风险，但孕激素的剂量却几乎不会产生任何效应。

    具体来说，包括乙炔雌二醇在内的口服避孕药以20 μg给药时，患者出现MI和卒中的绝对风险为0.9~1.7；包括乙炔雌二醇在内的口服避孕药以30~40 μg给药时，绝对风险为1.3~2.3。

    如果患者合并糖尿病，其出现血栓性卒中的相对风险为2.73，出现MI的相对风险为4.66。如果患者患有高血压，其出现卒中的风险与糖尿病人群类似，相对风险为2.3，出现MI的相对风险为2.17。

    Ferdinand博士指出，即便是不吸烟的高血压女性患者，出现卒中和MI的风险也会增加，这提示医生在接受患者咨询时需要改变其关于口服避孕药方面的建议。“显然，这项研究表明如果患者正在使用口服避孕药，你不能告诉她们只要不吸烟就不会出现卒中或者心梗。”

    Ferdinand博士说：“这样的结果多少有点令人意外。从避孕药的产品说明书以及大部分临床医生的观点来看，我们过去的经验是只要年龄不超过35岁且不吸烟，那么使用口服避孕药基本上不会有问题。过去我们也一直这样告诉患者。”“然而，从这个丹麦登记库的数据来看，虽然归因危险度较低(41.5例/ 10,000 人年)，但它确实存在。”(N. Engl. J. Med. 2012;366:2257-66)。

    世界卫生组织指南建议，口服避孕药应绝对禁用于血压超过160/100 mmHg的女性。“你可以告诉患者，如果血压明显升高，可能需要选择另一种避孕方式。”Ferdinand博士还提醒道，即便血压只是轻度升高也会增加患者出现卒中和MI的风险。他补充道，好消息是停用口服避孕药可以逆转升高的MI和卒中风险。

    Ferdinand博士担任了阿斯利康、日本第一三共、Forest和诺华公司的顾问，也是阿斯利康、Forest、日本武田制药和诺华公司的讲演团成员。Ferdinand博士声明接受了礼来、日本第一三共、Forest和诺华公司提供的研究经费。

 

    By: DAMIAN MCNAMARA, Cardiology News Digital Network

    MIAMI BEACH – Results of a comprehensive study looking at almost 1.6 million women suggest a small but real elevated risk of thrombotic stroke and myocardial infarction associated with use of hormonal contraception among women who have hypertension.

    Even hypertensive women who do not smoke were at increased risk, which suggests that there needs to be a shift in how physicians counsel women regarding use of oral contraception, according to Dr. Keith C. Ferdinand, professor of clinical medicine at Tulane University, New Orleans, and a cardiologist at the Tulane Heart and Vascular Institute in that city.

    "Clearly this does suggest that if a patient is on oral contraceptives, you cannot tell them they won’t have a stroke or MI just because they don’t smoke," Dr. Ferdinand said at the meeting, which was sponsored by the International Society on Hypertension in Blacks.

    "I was a little surprised by the Danish study," Dr. Ferdinand said (N. Engl. J. Med. 2012;366:2257-66). "The rule of thumb is – if you look at the package insert and at what most clinicians believe – if you’re not over 35 and you don’t smoke, you’re [essentially] okay. That is what we tell patients."

    "The Danish registry suggests that although the attributable risk was low (41.5 cases out of 10,000 person-years), it’s really there."

    World Health Organization guidelines state that OCs are absolutely contraindicated in women with blood pressure greater than 160 mm Hg/100 mm Hg. "You may say to the patient that if their blood pressure is significantly elevated, they may need another form of contraception." Dr. Ferdinand urged additional caution because even milder blood pressure elevations could be associated with increased risks. The good news, he added, is that the increased risk for MI and stroke does reverse with cessation of OC use.

    In the Danish study, researchers assessed 1,626,158 nonpregnant women with no previous cardiovascular disease. This represented essentially the entire Danish female population aged 15-49 years, Dr. Ferdinand said. A total 3,311 thrombotic strokes and 1,725 first MIs occurred out of more than 14 million total person-years of observation in this historical cohort study.

    Relative risks increased with hormonal contraceptive use. "Using contraceptive pills with estrogen and progestin did indeed increase the risk of stroke and MI," Dr. Ferdinand said, but the variation by dosage was modest. For example, higher doses of estrogen did appear to increase the relative risk of stroke, but dosing of progestin had little effect, he added.

    Specifically, the absolute risks for MI and stroke were increased by a factor of 0.9 to 1.7 with oral contraceptives that included ethinyl estradiol at a dose of 20 mcg, and by a factor of 1.3 to 2.3 with OCs that included ethinyl estradiol at a dose of 30-40 mcg.

    Another finding was that if a woman had diabetes, her relative risk of thrombotic stroke was 2.73 and her relative risk for an MI was 4.66. If a woman had hypertension, there was almost an equivalent increased risk of stroke (RR, 2.3), Dr. Ferdinand said. The relative risk of MI associated with hypertension was 2.17.

    Dr. Ferdinand is a consultant to Astra Zeneca, Daiichi Sankyo, Forest, and Novartis. He is on the speakers bureau for Astra Zeneca, Forest, Takeda, and Novartis. He also receives grant research support from Eli Lilly, Daiichi Sankyo, Forest, and Novartis.