Incidence of myocardial infarction in randomized clinical trials of protease inhibitor-based antiretroviral therapy: An analysis of four different protease inhibitors
Incidence of myocardial infarction in randomized clinical trials of protease inhibitor-based antiretroviral therapy: An analysis of four different protease inhibitors
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DOI：
10.1089/088922203766774487
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发表时间：
2003-06-01
影响因子：
1.5
通讯作者：
DiNubile, MJ
中科院分区：
文献类型：
--
作者：
Coplan, PM;Nikas, A;DiNubile, MJ
对感染人类免疫缺陷病毒的患者进行蛋白酶抑制剂（PI）治疗与血脂紊乱和胰岛素抵抗有关。我们在 1999 年之前针对前 4 种 PI 药物进行的 30 项 II/III 期双盲随机研究中，比较了接受 PI 治疗（联合或不联合核苷逆转录酶抑制剂 (nRTI)）与单独 nRTI 治疗的参与者的心肌梗死 (MI) 发生率。在本次分析中包含的大多数试验中，参与者可以在盲法阶段结束后在开放标签扩展中接受 PI 加 nRTI 的联合治疗。随访人年 (PY) 的计算范围为从治疗开始到 MI 诊断，或仅 nRTI 治疗的随机阶段结束，或含 PI 方案的研究结束。对随机阶段和随机加延伸阶段进行了单独的分析。在 10,986 名参与者中，7951 名（72%）在某个时间点接受了 PI 药物，平均持续时间为 12 个月。随机阶段有 10 例 MI（1.31/1000 PY），随机加扩展阶段有 19 例 MI（1.63/1000 PY）。含 PI 方案（1.82 MI/1000 PY）与仅使用 nRTI（1.05 MI/1000 PY）方案相比，MI 总体分层相对风险为 1.69，并未显着增加（95% 置信区间 [CI]，0.54 至 7.48）。 MI 风险的绝对差异为 +0.77（95% CI，-0.71 至 +2.26）MIs/1000 PY。与仅接受 NRTI 治疗相比，接受含 PI 治疗方案平均 1 年的患者并未出现明显更多的 MI，但 95% CI 的上限表明每 1000 PY 可能会出现多达 2.3 次额外的 MI。尽管正在进行较长 PI 治疗持续时间的研究，以评估 MI 发病率是否会在后期增加，但我们的分析并未表明 PI 治疗第一年期间 MI 风险显着增加。
Protease inhibitor (PI) therapy for patients infected with the human immunodeficiency virus has been associated with lipid disorders and insulin resistance. We compared the incidence of myocardial infarction (MI) among participants receiving treatment with PIs with or without nucleoside reverse transcriptase inhibitors (nRTIs) to nRTI therapy alone in 30 phase II/III double-blind, randomized studies conducted before 1999 for the first 4 PI drugs. In most trials included in this analysis, participants could receive combination therapy with a PI plus nRTIs in open-label extensions after the blinded phase concluded. Person-years (PY) of follow-up were calculated from treatment initiation to the diagnosis of MI, or to the end of the randomized phases for nRTI-only therapy or to the conclusion of the studies for PI-containing regimens. Separate analyses were conducted for the randomized and the randomized-plus-extension phases. Among 10,986 participants, 7951 (72%) received PI drugs at some point for an average duration of 12 months. There were 10 MIs (1.31/1000 PY) in the randomized phases and 19 MIs (1.63/1000 PY) in the randomized-plus-extension phases. The overall stratified relative risk of MI for PI-containing (1.82 MI/1000 PY) versus nRTI-only (1.05 MI/1000 PY) regimens of 1.69 was not significantly increased (95% confidence interval [CI], 0.54 to 7.48). The absolute difference in MI risk was +0.77 (95% CI, -0.71 to +2.26) MIs/1000 PY. Compared with NRTI-only therapy, patients receiving PI-containing regimens for an average of 1 year did not have significantly more MIs, but the upper bound of the 95% CI indicates there may be up to 2.3 additional MIs per 1000 PY. Although studies with a longer duration of PI therapy are in progress to assess whether a later increase in MI incidence occurs, our analysis did not demonstrate a dramatic increase in MI risk during the first year of PI therapy.