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Association Between Atazanavir-Induced Hyperbilirubinemia and Cardiovascular Disease in Patients Infected with HIV.
- Source :
-
Journal of the American Heart Association [J Am Heart Assoc] 2020 Oct 20; Vol. 9 (19), pp. e016310. Date of Electronic Publication: 2020 Sep 15. - Publication Year :
- 2020
-
Abstract
- Background: Serum bilirubin is inversely associated with cardiovascular risk. Atazanavir, an HIV protease inhibitor that competitively inhibits bilirubin conjugation, provides a unique opportunity to examine whether selectively increasing bilirubin is cardioprotective. We sought to determine whether patients receiving atazanavir manifest a reduced risk of cardiovascular disease compared with those receiving darunavir, an HIV protease inhibitor that does not increase serum bilirubin.<br />Methods and Results: This was a retrospective cohort study of 1020 patients with HIV. The main outcome was time to myocardial infarction or ischemic stroke. Mean follow-up was 6.6±3.4 years, with 516 receiving atazanavir and 504 darunavir. Atazanavir patients exhibited significantly higher serum total bilirubin (1.7 versus 0.4 mg/dL; P <0.001) and longer mean time to ischemic event (10.2 versus 9.4 years; P <0.001). On Cox regression, atazanavir treatment (hazard ratio [HR], 0.38; 95% CI, 0.21-0.71; P =0.002) and serum bilirubin (HR, 0.60; 95% CI, 0.41-0.89; P =0.011) were independently associated with a lower risk of an ischemic event. Notably, when atazanavir and bilirubin were included together in the Cox regression model, atazanavir lost significance (HR, 0.55; 95% CI, 0.24-1.29; P =0.169) consistent with bilirubin being an intermediate variable on the causal pathway between atazanavir and its effect on cardiovascular disease. Patients on atazanavir also had a significantly lower risk of developing new cardiovascular disease (HR, 0.53; 95% CI, 0.33-0.86; P =0.010) and longer mean time to death (12.2 versus 10.8 years; P <0.001).<br />Conclusions: Patients with HIV on atazanavir manifest a decreased risk of cardiovascular disease when compared with those on darunavir, an effect that appears to be mediated by serum bilirubin.
- Subjects :
- Atazanavir Sulfate therapeutic use
Bilirubin blood
Darunavir therapeutic use
Female
HIV Infections complications
Humans
Ischemic Stroke epidemiology
Kaplan-Meier Estimate
Male
Middle Aged
Myocardial Infarction epidemiology
Proportional Hazards Models
Retrospective Studies
Time Factors
Atazanavir Sulfate adverse effects
Cardiovascular Diseases prevention & control
HIV Infections drug therapy
HIV Protease Inhibitors therapeutic use
Hyperbilirubinemia chemically induced
Subjects
Details
- Language :
- English
- ISSN :
- 2047-9980
- Volume :
- 9
- Issue :
- 19
- Database :
- MEDLINE
- Journal :
- Journal of the American Heart Association
- Publication Type :
- Academic Journal
- Accession number :
- 32930032
- Full Text :
- https://doi.org/10.1161/JAHA.120.016310