Department of Radiology, Penn State Milton S. Hershey Medical Center, 500 University Drive, Hershey, PA, 17033-0850, USA.
Drugs R D. 2017 Dec;17(4):623-629. doi: 10.1007/s40268-017-0213-9.
Real-world evidence of statin side effects is potentially biased because statin use is neither randomized nor unblinded. An innovative study design can mitigate these biases. For example, in the recent ASCOT-LLA trial, patient-reported adverse events such as muscle pain and weakness were higher in the non-randomized and non-blinded setting than in the randomized, blinded setting. Less optimally, secondary re-analysis of clinical trials in which statin use is recorded and in which serious adverse events (SAEs) are adjudicated may be conducted.
The objective of this study was to evaluate SAEs by statin use at baseline among participants in the SPRINT blood pressure (BP) management trial.
Unadjusted overall SAE and treatment-related SAE rates by statin use as well as adjusted hazard ratios for statin use were computed in four cohorts [by baseline clinical cardiovascular disease (CVD), by intervention arm].
Statin use at baseline was not associated with higher overall or treatment-related SAE rates among (1) those without pre-existing CVD, regardless of BP arm, nor among (2) those randomized to standard BP management, regardless of pre-existing CVD. Among higher risk patients with existing clinical CVD randomized to intensive BP management, a small but significant increase in overall SAE rate was found among those taking statin at baseline.
In SPRINT, generally statin use was not associated with increased risk of reporting SAEs. Only statin use by higher risk patients was associated with more overall SAEs. Confounding by clinical CVD and the polytherapy of intensive BP management may explain this.
他汀类药物副作用的真实世界证据可能存在偏差,因为他汀类药物的使用既不是随机的,也不是盲目的。创新的研究设计可以减轻这些偏差。例如,在最近的 ASCOT-LLA 试验中,在非随机和非盲法环境中,与随机、盲法环境相比,患者报告的不良反应(如肌肉疼痛和无力)更高。不太理想的是,可能会对他汀类药物使用有记录且严重不良事件(SAE)已裁决的临床试验进行二次重新分析。
本研究旨在评估 SPRINT 血压(BP)管理试验中参与者在基线时的他汀类药物使用与 SAE 之间的关系。
根据基线临床心血管疾病(CVD)和干预臂,计算了按他汀类药物使用情况的未调整总体 SAE 和治疗相关 SAE 发生率以及他汀类药物使用的调整后的危险比。
基线时使用他汀类药物与(1)无论 BP 臂如何,无预先存在 CVD 的人群中的总体或治疗相关 SAE 发生率增加无关,也与(2)无论预先存在 CVD 如何,随机接受标准 BP 管理的人群中的总体或治疗相关 SAE 发生率增加无关。在随机接受强化 BP 管理的存在临床 CVD 的高风险患者中,基线时使用他汀类药物的患者的总体 SAE 发生率略有增加。
在 SPRINT 中,他汀类药物的使用通常与报告 SAE 的风险增加无关。只有高风险患者的他汀类药物使用与更多的总体 SAE 相关。强化 BP 管理的临床 CVD 和多种药物联合治疗的混杂可能解释了这一点。