Liu Wei, Antonelli Patrick J, Dahm Philipp, Gerhard Tobias, Delaney Joseph A C, Segal Richard, Crystal Stephen, Winterstein Almut G
Department of Pharmaceutical Outcomes and Policy, College of Pharmacy, University of Florida, Gainesville, FL, USA.
Department of Otolaryngology, College of Medicine, University of Florida, Gainesville, FL, USA.
Pharmacoepidemiol Drug Saf. 2018 Jun;27(6):587-595. doi: 10.1002/pds.4405. Epub 2018 Mar 7.
The objective of the study was to determine the risk of sudden sensorineural hearing loss (SNHL) associated with use of phosphodiesterase type 5 (PDE5) inhibitors.
We conducted a retrospective cohort study in the MarketScan Commercial Claims and Encounters Database including adult men who initiated a PDE5 inhibitor (n = 377,722) and 1,957,233 nonusers between 1998 and 2007. Periods of drug exposure were assessed on a weekly basis based on pharmacy billing records, assuming use of 1 dose per week (current use). Incident sudden SNHL was defined based on inpatient or outpatient visits with International Classification of Diseases, Ninth Revision, Clinical Modification codes 389.1x, 389.2x, or 388.2 plus ≥2 procedure codes for audiometric hearing testing within ±30 days of sudden SNHL diagnosis. We used age- and propensity score-adjusted Cox proportional hazards model to evaluate the risk of sudden SNHL during periods of current or recent use compared with that of nonuse. We conducted sensitivity analyses by varying the assumed drug utilization frequency and sudden SNHL case definition.
We evaluated 1233 sudden SNHL cases, resulting in an incidence of 4.35, 5.58, and 2.38 per 10,000 person-years for current, recent, and nonuse of PDE5 inhibitors, respectively. Compared with nonuse, the adjusted hazard ratio was 1.25 (1.01-1.55) for current use with a risk difference of 1.97 (1.12-2.82) per 10,000 person-years. For recent use, the adjusted hazard ratio was 1.60 (1.33-1.94) and risk difference was 3.19 (2.24-4.14). Estimates were consistent across the sensitivity analyses.
Use of PDE5 inhibitors is associated with a small but significantly increased risk of sudden SNHL.
本研究的目的是确定与使用5型磷酸二酯酶（PDE5）抑制剂相关的突发性感音神经性听力损失（SNHL）风险。
我们在MarketScan商业索赔和病历数据库中进行了一项回顾性队列研究，纳入了1998年至2007年间开始使用PDE5抑制剂的成年男性（n = 377,722）和1,957,233名未使用者。根据药房计费记录每周评估药物暴露期，假设每周使用1剂（当前使用）。根据国际疾病分类第九版临床修订版代码389.1x、389.2x或388.2加上在突发SNHL诊断±30天内进行听力测试的≥2个程序代码的住院或门诊就诊情况定义新发突发SNHL。我们使用年龄和倾向评分调整的Cox比例风险模型来评估当前或近期使用期间与未使用相比突发SNHL的风险。我们通过改变假设的药物使用频率和突发SNHL病例定义进行敏感性分析。
我们评估了1233例突发SNHL病例，当前、近期和未使用PDE5抑制剂的发病率分别为每10,000人年4.35、5.58和2.38例。与未使用相比，当前使用的调整后风险比为1.25（1.01 - 1.55），每10,000人年的风险差异为1.97（1.12 - 2.82）。对于近期使用，调整后风险比为1.60（1.33 - 1.94），风险差异为3.19（2.24 - 4.14）。敏感性分析的估计结果一致。
使用PDE5抑制剂与突发SNHL的风险虽小但显著增加相关。
