What are the cardiovascular risks associated with Abacavir (nucleoside reverse transcriptase inhibitor) therapy?

Cardiovascular Risks Associated with Abacavir Therapy

Abacavir should be used with caution or avoided in patients who have or are at high risk of cardiovascular disease due to its association with increased risk of myocardial infarction, though evidence remains inconclusive. 1

Evidence on Abacavir and Cardiovascular Risk

• The association between abacavir and increased risk of myocardial infarction remains controversial with conflicting data across studies 1
• Recent cohort studies have demonstrated that abacavir exposure is associated with over a 2-fold increased risk of cardiovascular disease events, which was not explained by renal dysfunction or other cardiovascular risk factors 2
• Abacavir has been linked to a 1.43-fold increased hazard of cardiovascular events with current exposure and 1.18-fold increased hazard per year of cumulative exposure 3
• The FDA drug label for abacavir notes that in observational studies, abacavir use within the previous 6 months was correlated with increased risk of myocardial infarction 4

Mechanism and Risk Patterns

• The exact mechanism by which abacavir may increase cardiovascular risk has not been established 1
• Risk appears to follow a bell-shaped dose-response curve, peaking at approximately 24 months of exposure 3
• Hypertension risk may be elevated with abacavir use, particularly in specific populations including:
  • Patients with poor antiretroviral therapy adherence 5
  • Men and individuals aged ≥40 years 5
  • Patients requiring prophylactic antibiotics 5

Conflicting Evidence

• Meta-analyses of randomized controlled trials have not supported an increased risk of myocardial infarction or major cardiovascular events with abacavir-containing regimens 6
• Some observational studies show significant associations between abacavir and cardiovascular disease while others do not 4
• The 2016 and 2018 International Antiviral Society-USA guidelines acknowledge this controversy but recommend caution 1

Clinical Recommendations

• Perform cardiovascular risk assessment before initiating abacavir therapy 4
• Consider alternative antiretroviral agents for patients with established cardiovascular disease or multiple risk factors 1
• Among patients at moderate to high risk for cardiovascular events or those who have experienced a cardiovascular event, switching from abacavir-based regimens is recommended (evidence rating: AIIa) 1
• HLA-B*5701 testing must be performed prior to abacavir use to prevent hypersensitivity reactions (evidence rating AIa), which is a separate safety concern from cardiovascular risk 1

Alternative Options

• Tenofovir alafenamide (TAF) may be preferred over abacavir in patients with cardiovascular risk factors, though it has its own considerations for renal function 1
• For patients with both cardiovascular and renal concerns, integrase inhibitor-based regimens with appropriate nucleoside/nucleotide reverse transcriptase inhibitors should be considered 1
• In patients with chronic kidney disease where tenofovir is contraindicated, the cardiovascular risk of abacavir must be weighed against its benefit of not requiring dose adjustment in renal impairment 1

Monitoring Recommendations

• Regular cardiovascular risk assessment and monitoring of blood pressure is recommended for all patients on antiretroviral therapy, especially those on abacavir 1
• Documentation of weight and body mass index at baseline and every 6 months is recommended for all patients on antiretroviral therapy 1
• Patients with 10-year atherosclerotic cardiovascular disease risk above 20% should receive a high-intensity statin regardless of antiretroviral regimen 1