Combination antiretroviral therapy was independently associated with a relative increase of about a quarter in the rate of myocardial infarction per year of exposure during the first four to six years of use. The absolute risk of myocardial infarction, however, was low and must be balanced against the marked benefits from antiretroviral treatment.
In this prospective observational study, researchers from the Data Collection on Adverse Events of Anti-HIV Drugs Study Group enrolled 23 468 patients in Europe, the United States and Australia, from December 1999 to April 2001 and collected follow up data until February 2002. They collected data on infection with HIV and on risk factors for and the incidence of myocardial infarction (New England Journal of Medicine 2003;349:1993-2003).
Combination antiretroviral therapy was defined as any combination regimen of antiretroviral drugs that included a protease inhibitor or a non-nucleoside reverse transcriptase inhibitor.
Over a period of 36 199 person years, 126 patients had a myocardial infarction. The overall event rate in the study was 3.5 per 1,000 and the incidence of myocardial infarction increased with longer exposure to combination antiretroviral therapy (adjusted relative rate per year of exposure 1.26 (95% confidence interval 1.12 to 1.41; P<0.001).
Other factors significantly associated with myocardial infarction were older age, current or former smoking, previous cardiovascular disease, and male sex, but not a family history of coronary heart disease. A higher total serum cholesterol level, a higher triglyceride level, and the presence of diabetes were also associated with an increased incidence of myocardial infarction.
In the study population, the median known duration of HIV infection was 3.5 years, and 26% of the patients had previously been found to have AIDS. At baseline, 81% of the study population had been exposed to at least one antiretroviral drug and 75% to combination antiretroviral therapy. Overall, the median cumulative exposure to combination antiretroviral therapy was 1.9 years.
In this population, which was relatively young, the prevalence of previous cardiovascular disease was only 1.5%. However, many of the subjects had cardiovascular risk factors: current or previous smoking (56%); diabetes (3%), hypertension (7%), and dyslipidaemia (46%).
Although the absolute event rate was low, the increase in cardiac events associated with combination antiretroviral therapy was plausible because combination antiretroviral therapy can cause adverse metabolic changes that are known risk factors for cardiovascular disease. However, the authors of the study note that only randomised trials might be able to prove whether the observed association reflects a causal relation. In addition, the relative increase in the risk of myocardial infarction per year cannot be extrapolated beyond the duration of follow up in the study.
In an accompanying editorial (p 2065), Dr Peter Sklar of the division of HIV/AIDS medicine at Drexel University College of Medicine, Philadelphia, and Dr Henry Masur of the critical care medicine department at Warren Grant Magnuson Clinical Center, National Institutes of Health, Bethesda, Maryland, recommend that patients taking antiretroviral therapy should introduce changes in their lifestyle, such as stopping smoking, and that those with atherogenic lipid profiles should be treated through diet and drugs, as well as with lipid lowering drugs.