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Combination antiretroviral therapy and the risk of myocardial infarction.
Friis-Møller N, Sabin CA, Weber R, d'Arminio Monforte A, El-Sadr WM, Reiss P, Thiébaut R, Morfeldt L, De Wit S, Pradier C, Calvo G, Law MG, Kirk O, Phillips AN, Lundgren JD; Data Collection on Adverse Events of Anti-HIV Drugs (DAD) Study Group. N Engl J Med 2003 Nov 20;349(21):1993-2003.
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Reviewed by
Susa Coffey, MD
Summary
The question of whether HIV infection or - antiretroviral therapy (ART) may increase the risk of cardiovascular disease is an issue of active investigation, with studies, mostly retrospective, offering conflicting conclusions. The DAD study, a prospective observational study, seeks to define the relationship of combination ART to myocardial infarction (MI). This study includes more than 23,000 patients (76% men, median age 39) from 11 cohorts in 21 countries. At baseline, subjects had spent a median of 1.9 years on combination ART (defined as regimens containing a protease inhibitor (PI) or a nonnucleoside reverse transcriptase inhibitor (NNRTI)). During 36,000 person-years of follow-up, 126 patients experienced MI. The incidence of MI increased with increasing exposure to combination ART, with an adjusted relative rate of 1.26 per year of exposure (p < .001). No distinction was made between regimens containing PIs and those containing NNRTIs. Other risk factors for MI included traditional cardiovascular risk factors such as age, male sex, smoking, and previous cardiovascular disease. Markers of HIV disease such as baseline CD4, CD4 nadir, and HIV RNA did not appear to confer risk of MI.
Commentary
This large study suggests that the rate of MI is increased by 26% per year of exposure to combination antiretroviral therapy. The DAD cohort is a group of young subjects with limited exposure to antiretroviral medications and with a very short time of follow-up (<2 years for most); the effect of ART on the development of atherosclerotic heart disease may become clearer as this cohort is followed over time.
It should be noted that the cardiovascular risk conferred by antiretroviral medications was much less significant than the risk conferred by other factors such as smoking (present at very high rates in this and other cohorts), hypertension, dyslipidemia, and diabetes. Much additional work is needed to define the role of ART, and of specific medications or classes, in the development of premature cardiovascular disease. In the meantime, it is important to continue to work closely with patients to identify and reduce their modifiable cardiovascular risk factors.
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