Use of nucleoside reverse transcriptase inhibitors and risk of myocardial infarction in HIV-infected patients.
Use of nucleoside reverse transcriptase inhibitors and risk of myocardial infarction in HIV-infected patients.
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DOI：
10.1097/qad.0b013e32830fe35e
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发表时间：
2008-09-12
期刊：
影响因子：
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通讯作者：
DAD Study Groups
中科院分区：
文献类型：
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作者：
Strategies for Management of Anti-Retroviral Therapy/INSIGHT;DAD Study Groups
两种核苷-逆转录酶抑制剂(NRTIs)-阿巴卡韦和二腺苷-可能都与心肌梗死（MI）的过度风险相关。这一发现的再现性在一个独立的数据集进行了探索和合理的生物学机制寻求。SMART研究探讨了生物标志物、心电图上的缺血性变化以及根据nrti使用的各种预先定义的心血管疾病（CVD）事件的发生率。将接受阿巴卡韦而非二腺苷的患者与接受二腺苷的患者以及接受非阿巴卡韦或二腺苷的nrti患者（“其他nrti”）进行比较。随机分配到SMART持续ART组的患者被纳入所有分析（N=2752）；对于生物标志物的研究，来自ART中断组的患者也被纳入。与其他nrti相比，目前使用阿巴卡韦与CVD风险增加有关。临床心肌梗死（n=19）、主要心血管疾病（心肌梗死）、中风、冠状动脉疾病手术（CAD）和心血管疾病死亡的校正风险比；n=70)、扩张性CVD（主要CVD加充血性心力衰竭、周围血管疾病、需要药物治疗的CAD和未见死亡；n=112）分别为4.3（95%可信区间（CI）：1.4-13.0）、1.8（1.0-3.1）和1.9（1.3-2.9）。基线时，在一组有生物标志物数据的患者中，接受阿巴卡韦治疗的患者（N=175）的高敏c反应蛋白和白细胞介素-6比接受其他nrti治疗的患者（N=500）分别高出27% （p=0.02）和16% （p=0.02）。二腺苷与CVD风险的改变和生物标志物水平的改变无关。阿巴卡韦与心血管疾病的风险增加有关。该药可能引起血管炎症，从而引发心血管疾病。
Two nucleoside-reverse-transcriptase-inhibitors (NRTIs)-abacavir and didanosine-may each be associated with excess risk of myocardial infarction (MI). The reproducibility of this finding in an independent data set was explored and plausible biological mechanisms were sought. Biomarkers, ischemic changes on the electrocardiogram, and rates of various pre-defined types of cardiovascular disease (CVD) events according to NRTIs used were explored in the SMART study. Patients receiving abacavir and not didanosine were compared with those receiving didanosine, and to those receiving NRTIs other than abacavir or didanosine (“other NRTIs”). Patients randomly assigned to the continuous ART arm of SMART was included in all analyses(N=2752); for the study of biomarkers, patients from the ART interruption arm was also included. Current use of abacavir was associated with an excess risk of CVD compared to other NRTIs. Adjusted hazard ratios for clinical MI (n=19), major CVD (MI, stroke, surgery for coronary artery disease (CAD), and CVD death;n=70), expanded CVD (major CVD plus congestive heart failure, peripheral vascular disease, CAD requiring drug treatment, and unwitnessed deaths;n=112) were 4.3 (95% confidence interval (CI):1.4-13.0), 1.8(1.0-3.1), and 1.9(1.3-2.9). At baseline in a subset of patients with biomarker data, high sensitivity-C reactive protein and interleukin-6 were 27% (p=0.02) and 16% (p=0.02) higher for patient receiving abacavir (N=175) compared to other NRTIs (N=500). Didanosine was not associated with altered risk of CVD nor with altered levels of biomarkers. Abacavir was associated with an increased risk of CVD. The drug may cause vascular inflammation, which may precipitate a CVD event.