Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Randomized Controlled Trial
. 2008 Sep 12;22(14):F17-24.
doi: 10.1097/QAD.0b013e32830fe35e.

Use of nucleoside reverse transcriptase inhibitors and risk of myocardial infarction in HIV-infected patients

Strategies for Management of Anti-Retroviral Therapy/INSIGHT  1 ; DAD Study Groups
Collaborators, Affiliations
Randomized Controlled Trial

Use of nucleoside reverse transcriptase inhibitors and risk of myocardial infarction in HIV-infected patients

Strategies for Management of Anti-Retroviral Therapy/INSIGHT et al. AIDS. .

Abstract

Background: Two nucleos(t)ide reverse transcriptase inhibitors (NRTIs)--abacavir and didanosine--may each be associated with excess risk of myocardial infarction. The reproducibility of this finding in an independent dataset was explored and plausible biological mechanisms were sought.

Methods: Biomarkers, ischemic changes on the electrocardiogram, and rates of various predefined types of cardiovascular disease (CVD) events according to NRTIs used were explored in the Strategies for Management of Anti-Retroviral Therapy (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 antiretroviral therapy arm of SMART were included in all analyses (N = 2752); for the study of biomarkers, patients from the antiretroviral therapy interruption arm were also included.

Results: Current use of abacavir was associated with an excess risk of CVD compared with other NRTIs. Adjusted hazard ratios for clinical myocardial infarction (n = 19), major CVD (myocardial infarction, stroke, surgery for coronary artery disease, and CVD death; n = 70), expanded CVD (major CVD plus congestive heart failure, peripheral vascular disease, coronary artery disease 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 patients receiving abacavir (N = 175) compared with those receiving other NRTIs (N = 500). Didanosine was associated neither with altered risk of CVD nor with altered levels of biomarkers.

Conclusion: Abacavir was associated with an increased risk of CVD. The drug may cause vascular inflammation, which may precipitate a CVD event.

Trial registration: ClinicalTrials.gov NCT00027352.

PubMed Disclaimer

References

    1. D:A:D Study Group Combination antiretroviral therapy and the risk of myocardial infarction. N Engl J Med. 2003 Nov 20;349(21):1993–2003. - PubMed
    1. Mensah GA, Brown DW, Croft JB, et al. Major Coronary risk factors and death from coronary heart disease. Am J Prev Med. 2005;29:68–74. - PubMed
    1. Triant VA, Lee H, Hadigan C, Grinspoon SK. Increased acute myocardial infarction rates and cardiovascular risk factors among patients with human immunodeficiency virus disease. JCEM. 2007;92:2506–2512. - PMC - PubMed
    1. Phillips AN, Andrew Carr, Jacquie Neuhaus. Interruption of antiretroviral therapy and risk of cardiovascular disease in persons with HIV-1 infection: exploratory analyses from the SMART trial. Antiviral Therapy. 2008;13:177–187. - PubMed
    1. Currier J, Taylor A, Boyd F, et al. Coronary Heart Disease in HIV-infected individuals. JAIDS. 2003;33:506–512. - PubMed

Publication types

MeSH terms

Associated data