Da Silva Barbara, Tschampa Jean, Beron Jörg, Fredrick Linda, Patwardhan Meenal, Zachry Woodie, Woodward William C, Norton Michael, Nilius Angela
Abbott, Abbott Park, IL 60046-6145, USA.
Int J Clin Pharmacol Ther. 2012 Jun;50(6):391-402. doi: 10.5414/CP201606.
There is growing interest in studying age-related diseases, such as coronary artery disease (CAD) and resulting myocardial infarction (MI) in HIV-infected patients. While some cohort studies indicate that several antiretrovirals (ARVs), including the protease inhibitor lopinavir/ ritonavir (LPV/r), are associated with an increased relative risk (RR) of MI, other studies show a reduction of MI and CAD in subjects taking ARVs when compared with HIV+ patients not taking ARV therapy. This manuscript reviews data from Abbott-sponsored clinical trials and pharmacovigilance reporting system.
A systematic search was performed to retrieve cases of MI and CAD in Abbott’s clinical trial and pharmacovigilance safety databases. The rates of MI and CAD, and risk factors for the events were reviewed in detail.
The rate of MI and CAD per 1,000 patient treatment years (PTY) was 1.24 (95% CI = 0.40 - 2.90) and 2.74 (95% CI = 1.37 - 4.90), respectively, for subjects taking LPV/r during clinical trials. The frequency of pharmacovigilance reports of MI and CAD were 2.9 per 100,000 PTY and 3.6 per 100,000 PTY, respectively. Most subjects who had MI and CAD events had multiple baseline risk factors.
Relatively few subjects experienced MI or CAD during Abbott-sponsored clinical trials of LPV/r. Analysis of clinical trial and pharmacovigilance data did not indicate an increased risk of MI or CAD associated with LPV/r compared with the general population. In general, the subjects that experienced MI or CAD had known traditional risk factors suggesting that addressing modifiable risk factors could decrease the risk of MI or CAD. ARVs have not been thoroughly studied in subjects at high risk for MI and CAD, and further studies of this population could identify whether starting ARVs affects the incidences of cardic events in subjects with many traditional risk factors
对研究与年龄相关疾病的兴趣日益增加，如在感染人类免疫缺陷病毒（HIV）的患者中研究冠状动脉疾病（CAD）及由此导致的心肌梗死（MI）。虽然一些队列研究表明，包括蛋白酶抑制剂洛匹那韦/利托那韦（LPV/r）在内的几种抗逆转录病毒药物（ARV）与MI相对风险（RR）增加相关，但其他研究显示，与未接受抗逆转录病毒治疗的HIV阳性患者相比，接受ARV治疗的受试者中MI和CAD有所减少。本手稿回顾了雅培公司赞助的临床试验和药物警戒报告系统的数据。
进行系统检索，以获取雅培公司临床试验和药物警戒安全数据库中的MI和CAD病例。详细回顾了MI和CAD的发生率以及这些事件的风险因素。
在临床试验期间服用LPV/r的受试者中，每1000患者治疗年（PTY）的MI和CAD发生率分别为1.24（95%置信区间 = 0.40 - 2.90）和2.74（95%置信区间 = 1.37 - 4.90）。MI和CAD的药物警戒报告频率分别为每100,000 PTY 2.9例和每100,000 PTY 3.6例。大多数发生MI和CAD事件的受试者有多个基线风险因素。
在雅培公司赞助的LPV/r临床试验期间，相对较少的受试者发生MI或CAD。对临床试验和药物警戒数据的分析未表明与普通人群相比，LPV/r会增加MI或CAD的风险。一般来说，发生MI或CAD的受试者有已知的传统风险因素，这表明控制可改变的风险因素可能会降低MI或CAD的风险。尚未在MI和CAD高危受试者中对ARV进行全面研究，对该人群的进一步研究可能会确定开始使用ARV是否会影响有许多传统风险因素的受试者发生心脏事件的发生率。
