屈螺酮与非致死性静脉血栓栓塞：雌二醇剂量是否存在风险差异？

Drospirenone and non-fatal venous thromboembolism: is there a risk difference by dosage of ethinyl-estradiol?

机构信息

Pharmaceutical Outcomes and Policy, College of Pharmacy and Epidemiology, University of Florida, Gainesville, FL 32611, USA.

出版信息

J Thromb Haemost. 2013 Jun;11(6):1059-68. doi: 10.1111/jth.12224.

DOI:10.1111/jth.12224

PMID:23574590

Abstract

BACKGROUND

Previous studies concluded that there was an increased risk of non-fatal venous thromboembolism (VTE) with drospirenone. It is unknown whether the risk is differential by ethinyl-estradiol dosage.

OBJECTIVES

To assess the risk of VTE with drospirenone and to determine whether drospirenone and ethinyl-estradiol 20 μg (DRSP/EE20) has a lower VTE risk than drospirenone and ethinyl-estradiol 30 μg (DRSP/EE30).

METHODS

Our cohort included women aged 18-46 years taking drospirenone or levonorgestrel (LNG)-containing combined oral contraceptives (COCs) in the IMS claims database between 2001 and 2009. VTE was defined using ICD-9-CM coding and anticoagulation. The hazard ratio (HR) from Cox proportional hazards models was used to assess the VTE relative risk (RR) with drospirenone compared with levonorgestrel, adjusted by a propensity score used to control for baseline co-morbidity and stratified by EE dosage and user-type (new/current).

RESULTS

The study included 238 683 drospirenone and 193,495 levonorgestrel users. Among new and current users, a 1.90-fold (95% CI, 1.51-2.39) increased VTE relative risk was observed for drospirenone (18.0 VTE/10,000 women-years) vs. levonorgestrel (8.9 VTE/10,000 women-years). In analysis of new users, DRSP/EE20 had a 2.35-fold (95% CI, 1.44-3.82) VTE RR versus LNG/EE20. New users of DRSP/EE30 observed an increased RR versus LNG/EE30 among women starting to use COCs between 2001 and 2006 (2.51, 95% CI, 1.12-5.64) but not between 2007 and 2009 (0.76, 95% CI, 0.42-1.39), attributable to an increased incidence rate with LNG/EE30 from 2007 to 2009. In direct comparison, DRSP/EE20 had an elevated risk of VTE compared with DRSP/EE30 (RR, 1.55; 95% CI, 0.99-2.41).

CONCLUSIONS

We observed a modestly elevated risk of VTE with drospirenone, compared with levonorgestrel. The larger VTE incidence rate observed in DRSP/EE20 than in DRSP/EE30 and the increasing VTE incidence rate with levonorgestrel between 2007 and 2009 were unexpected.

摘要

背景

先前的研究表明，屈螺酮增加了非致命性静脉血栓栓塞（VTE）的风险。但目前尚不清楚这种风险是否与乙炔雌二醇的剂量有关。

目的

评估屈螺酮引起 VTE 的风险，并确定屈螺酮与乙炔雌二醇 20μg（DRSP/EE20）是否比屈螺酮与乙炔雌二醇 30μg（DRSP/EE30）的 VTE 风险更低。

方法

我们的队列纳入了 2001 年至 2009 年间 IMS 索赔数据库中年龄在 18-46 岁之间使用屈螺酮或左炔诺孕酮（LNG）的含屈螺酮或左炔诺孕酮的复方口服避孕药（COC）的女性。使用 ICD-9-CM 编码和抗凝治疗来定义 VTE。使用 Cox 比例风险模型评估的风险比（RR），以评估与左炔诺孕酮相比，屈螺酮引起 VTE 的相对风险，通过倾向评分来控制基线合并症，并按 EE 剂量和使用者类型（新/现用）分层。

结果

本研究共纳入了 238683 例屈螺酮使用者和 193495 例左炔诺孕酮使用者。在新使用者和现使用者中，与左炔诺孕酮（8.9 VTE/10000 女性年）相比，屈螺酮（18.0 VTE/10000 女性年）的 VTE 相对风险增加了 1.90 倍（95%CI，1.51-2.39）。在新使用者的分析中，DRSP/EE20 的 VTE RR 比 LNG/EE20 高 2.35 倍（95%CI，1.44-3.82）。与 2001 年至 2006 年开始使用 COC 的女性相比，2007 年至 2009 年开始使用 DRSP/EE30 的女性 VTE RR 增加（2.51，95%CI，1.12-5.64），但与 2007 年至 2009 年开始使用 LNG/EE30 的女性相比，这一比值并未增加（0.76，95%CI，0.42-1.39），这归因于 2007 年至 2009 年 LNG/EE30 的发生率增加。直接比较发现，DRSP/EE20 比 DRSP/EE30 发生 VTE 的风险更高（RR，1.55；95%CI，0.99-2.41）。