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Risk of cardiovascular disease from antiretroviral therapy for HIV: a systematic review
Clay Bavinger1, Eran Bendavid, Katherine Niehaus
1Center for Primary Care and Outcomes Research, and Center for Health Policy, Stanford University, Stanford, California, United States of America. claybavinger@gmail.com
Insights
Certain antiretroviral therapy (ART) drugs like abacavir and protease inhibitors may increase myocardial infarction risk, based on observational studies. However, evidence is mixed, with randomized trials showing no increased cardiovascular risk.
Area of Science:
- HIV/AIDS research
- Cardiovascular epidemiology
- Pharmacovigilance
Background:
- Growing evidence links specific antiretroviral therapy (ART) drugs to increased cardiovascular disease (CVD) risk.
- Understanding these associations is crucial for patient management and drug safety.
Purpose of the Study:
- To conduct a systematic review and meta-analysis.
- To determine if specific ART drugs are associated with an elevated risk of myocardial infarction (MI).
Main Methods:
- Comprehensive literature search of major databases and conference abstracts up to June 2011.
- Inclusion of comparative studies reporting MI, stroke, or other cardiovascular events.
- Independent eligibility screening, data extraction, and quality assessment by two investigators.
Main Results:
- Observational studies (2) indicated increased MI risk with recent exposure to abacavir (RR 1.92) and protease inhibitors (PIs) (RR 2.13).
- Increased risk of MI was associated with longer exposure to indinavir (RR 1.11/year) and lopinavir (RR 1.22/year).
- Contrasting findings emerged from four meta-analyses of randomized controlled trials (RCTs), which found no increased CVD risk from abacavir or PIs.
Conclusions:
- Evidence linking specific ARTs to increased CVD risk is mixed.
- Meta-analyses of RCTs did not support an increased risk from abacavir or PIs.
- Observational data warrant further investigation into ART-associated cardiovascular risk.
Background:
Recent studies suggest certain antiretroviral therapy (ART) drugs are associated with increases in cardiovascular disease.
Purpose:
We performed a systematic review and meta-analysis to summarize the available evidence, with the goal of elucidating whether specific ART drugs are associated with an increased risk of myocardial infarction (MI).
Data Sources:
We searched Medline, Web of Science, the Cochrane Library, and abstract archives from the Conference on Retroviruses and Opportunistic Infections and International AIDS Society up to June 2011 to identify published articles and abstracts.
Study Selection:
Eligible studies were comparative and included MI, strokes, or other cardiovascular events as outcomes.
Data Extraction:
Eligibility screening, data extraction, and quality assessment were performed independently by two investigators.
Data Synthesis:
Random effects methods and Fisher's combined probability test were used to summarize evidence.
Findings:
Twenty-seven studies met inclusion criteria, with 8 contributing to a formal meta-analysis. Findings based on two observational studies indicated an increase in risk of MI for patients recently exposed (usually defined as within last 6 months) to abacavir (RR 1.92, 95% CI 1.51-2.42) and protease inhibitors (PI) (RR 2.13, 95% CI 1.06-4.28). Our analysis also suggested an increased risk associated with each additional year of exposure to indinavir (RR 1.11, 95% CI 1.05-1.17) and lopinavir (RR 1.22, 95% CI 1.01-1.47). Our findings of increased cardiovascular risk from abacavir and PIs were in contrast to four published meta-analyses based on secondary analyses of randomized controlled trials, which found no increased risk from cardiovascular disease.
Conclusion:
Although observational studies implicated specific drugs, the evidence is mixed. Further, meta-analyses of randomized trials did not find increased risk from abacavir and PIs. Our findings that implicate specific ARTs in the observational setting provide sufficient evidence to warrant further investigation of this relationship in studies designed for that purpose.
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