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Long-Term ART and Risk for Myocardial Infarction

Risk for myocardial infarction increased in the DAD study with longer duration of PI use but not NNRTI use.

Metabolic effects of HIV infection and antiretroviral therapy (ART) may lead to increased rates of cardiovascular disease. Previous data from the DAD study, a multinational collaboration involving 11 observational cohorts, suggested that increased duration of ART is associated with increased rates of myocardial infarction (MI). Now, with longer follow-up and more clinical events, DAD investigators have examined how particular classes of antiretroviral drugs affect MI risk.

Of 23,437 HIV-infected patients, 345 suffered MIs during almost 100,000 person-years of observation. Notably, 61% of all study participants were either former or current smokers. MI incidence was higher in patients exposed to protease inhibitors (PIs) for 6 years than in those not exposed to PIs (6.01 vs. 1.53 per 1000 person-years). The relative risk of MI per year of PI exposure was 1.16 after adjustment for exposure to nonnucleoside reverse-transcriptase inhibitors (NNRTIs) and for cardiovascular risk factors other than lipid levels (lipids can be affected directly by certain PIs). In a multivariate model that adjusted for lipid levels, the RR fell to 1.10 (95% confidence interval, 1.04–1.18). No association was seen between duration of NNRTI exposure and increased risk for MI (RR per year of exposure, 1.05; 95% CI, 0.98–1.13).

Comment: In this large observational cohort study, increased duration of PI exposure was associated with an increased risk for MI. No association was detected with NNRTI exposure, but the number of person-years of observation was smaller for NNRTI exposure than for PI exposure. Although these findings are important, editorialists note several noteworthy qualifications. First, the DAD investigators made a valiant attempt to adjust the analysis for any known confounders, but the results still could have been influenced by competing temporal effects or unknown confounding factors. Second, the incidence of MI in this study was low, even among patients exposed to PIs for 6 years (0.6% per year), and must be weighed against the incontestable benefits of ART. Finally, smoking cessation and diabetes prevention efforts would probably have greater effects on MI risk than would changing ART exposure. Nevertheless, the findings of the DAD study challenge us to further improve long-term therapy for HIV.

— Rajesh T. Gandhi, MD

Published in Journal Watch Infectious Diseases April 25, 2007

Citation(s):

The DAD Study Group. Class of antiretroviral drugs and the risk of myocardial infarction. N Engl J Med 2007 Apr 26; 356:1723-35.

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• Medline abstract (Free)

Stein JH. Cardiovascular risks of antiretroviral therapy. N Engl J Med 2007 Apr 26; 356:1773-5.

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• Medline abstract (Free)

Hughes MD and Williams PL. Challenges in using observational studies to evaluate adverse effects of treatment. N Engl J Med 2007 Apr 26; 356:1705-7.

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• Medline abstract (Free)