Cardiovascular risk in chronic hepatitis B patients treated with tenofovir disoproxil fumarate or tenofovir alafenamide
0
조회
0
다운로드
3
인용
0
참고문헌
키워드
초록
Background/Aims: Tenofovir disoproxil fumarate (TDF) is known to have a lipid-lowering effect. This is in contrast to tenofovir alafenamide (TAF), which has a lipid-neutral effect. Therefore, concerns have been raised as to whether these differences affect long-term cardiovascular risk. Here, we aimed to evaluate the long-term risk of cardiovascular events in chronic hepatitis B (CHB) patients treated with TAF or TDF. Methods: We retrospectively analyzed 4,124 treatment-naïve CHB patients treated with TDF (n=3,186) or TAF (n=938) between 2012 and 2022. The primary outcome was a composite endpoint of major adverse cardiovascular events (MACE), including myocardial infarction, ischemic stroke, and hospitalization for unstable angina or heart failure. Serial changes in lipid profiles between two treatments were also explored. Results: The median age of the patients was 50.6 years, and 60.6% of the patients were male. At baseline, 486 (11.8%) and 637 (15.4%) of the patients had dyslipidemia and fatty liver, respectively. A total of 42 MACE occurred, with an annual incidence of 0.2%/100 person-years (PYs). At 1, 3, and 5 years, the cumulative risk of MACE was 0.4%, 0.8%, and 1.2% in patients treated with TDF, and 0.2%, 0.7%, and 0.7% in patients treated with TAF, respectively (P=0.538). No significant differences in the risk of MACE were observed between TDF and TAF. A multivariable analysis found that current smoker and a history of cardiovascular events were risk factors associated with an increased risk of MACE. Conclusions: Patients treated with TAF had comparable risks of cardiovascular outcomes, defined as MACE, as patients treated with TDF.
Abstract
Background/Aims: Tenofovir disoproxil fumarate (TDF) is known to have a lipid-lowering effect. This is in contrast to tenofovir alafenamide (TAF), which has a lipid-neutral effect. Therefore, concerns have been raised as to whether these differences affect long-term cardiovascular risk. Here, we aimed to evaluate the long-term risk of cardiovascular events in chronic hepatitis B (CHB) patients treated with TAF or TDF. Methods: We retrospectively analyzed 4,124 treatment-naïve CHB patients treated with TDF (n=3,186) or TAF (n=938) between 2012 and 2022. The primary outcome was a composite endpoint of major adverse cardiovascular events (MACE), including myocardial infarction, ischemic stroke, and hospitalization for unstable angina or heart failure. Serial changes in lipid profiles between two treatments were also explored. Results: The median age of the patients was 50.6 years, and 60.6% of the patients were male. At baseline, 486 (11.8%) and 637 (15.4%) of the patients had dyslipidemia and fatty liver, respectively. A total of 42 MACE occurred, with an annual incidence of 0.2%/100 person-years (PYs). At 1, 3, and 5 years, the cumulative risk of MACE was 0.4%, 0.8%, and 1.2% in patients treated with TDF, and 0.2%, 0.7%, and 0.7% in patients treated with TAF, respectively (P=0.538). No significant differences in the risk of MACE were observed between TDF and TAF. A multivariable analysis found that current smoker and a history of cardiovascular events were risk factors associated with an increased risk of MACE. Conclusions: Patients treated with TAF had comparable risks of cardiovascular outcomes, defined as MACE, as patients treated with TDF.
참고문헌 (22)
- Liaw YF, "Lamivudine for patients with chronic hepatitis B and advanced liver disease", N Engl J Med, 351, pp.1521~1531 (2004)
- Kim GA, "HBsAg seroclearance after nucleoside analogue therapy in patients with chronic hepatitis B : clinical outcomes and durability", Gut, 63, pp.1325~1332 (2014)
- Korean Association for the Study of the Liver(KASL), "KASL clinical practice guidelines for management of chronic hepatitis B", Clin Mol Hepatol, 28, pp.276~331 (2022)
- Terrault NA, "AASLD guidelines for treatment of chronic hepatitis B", Hepatology, 63, pp.261~283 (2016)
- European Association for the Study of the Liver, "EASL 2017 Clinical Practice Guidelines on the management of hepatitis B virus infection", J Hepatol, 67, pp.370~398 (2017)
- Oh H, "Increasing comorbidities in a South Korea insured population-based cohort of patients with chronic hepatitis B", Aliment Pharmacol Ther, 52, pp.371~381 (2020)
- Lee YB, "Association of metabolic risk factors with risks of cancer and all-cause mortality in patients with chronic hepatitis B", Hepatology, 73, pp.2266~2277 (2021)
- Buti M, "Tenofovir alafenamide versus tenofovir disoproxil fumarate for the treatment of patients with HBeAg-negative chronic hepatitis B virus infection : a randomised, double-blind, phase 3, non-inferiority trial", Lancet Gastroenterol Hepatol, 1, pp.196~206 (2016)
- Chan HL, "Tenofovir alafenamide versus tenofovir disoproxil fumarate for the treatment of HBeAg-positive chronic hepatitis B virus infection : a randomised, double-blind, phase 3, non-inferiority trial", Lancet Gastroenterol Hepatol, 1, pp.185~195 (2016)
- Agarwal K, "96 weeks treatment of tenofovir alafenamide vs. tenofovir disoproxil fumarate for hepatitis B virus infection", J Hepatol, 68, pp.672~681 (2018)
- Byun KS, "Tenofovir alafenamide for drug-resistant hepatitis B : A randomized trial for switching from tenofovir disoproxil fumarate", Clin Gastroenterol Hepatol, 20, pp.427~437 (2022)
- Lim J, "Efficacy and safety of tenofovir alafenamide versus tenofovir disoproxil fumarate in treatment-naïve chronic hepatitis B", Liver Int, 42, pp.1517~1527 (2022)
- Santos JR, "The lipid-lowering effect of tenofovir", emtricitabine : a randomized, crossover, double-blind, placebo-controlled trial, 2015, pp.61, 403~408
- Jeong J, "Tenofovir alafenamide treatment may not worsen the lipid profile of chronic hepatitis B patients : A propensity score-matched analysis", Clin Mol Hepatol, 28, pp.254~264 (2022)
- Cid-Silva P, "Treatment with tenofovir alafenamide fumarate worsens the lipid profile of HIV-infected patients versus treatment with tenofovir disoproxil fumarate, each coformulated with elvitegravir, cobicistat, and emtricitabine", Basic Clin Pharmacol Toxicol, 124, pp.479~490 (2019)
- Levey AS, "A new equation to estimate glomerular filtration rate", Ann Intern Med, 150, pp.604~612 (2009)
- Bosco E, "Major adverse cardiovascular event definitions used in observational analysis of administrative databases : a systematic review", BMC Med Res Methodol, 21, pp.241~ (2021)
- Quispe R, "Total cholesterol", HDL-cholesterol ratio discordance with LDLcholesterol and non-HDL-cholesterol and incidence of atherosclerotic cardiovascular disease in primary prevention : The ARIC study, 2020, pp.27, 1597~1605
- Goff DC Jr, "2013 ACC", AHA guideline on the assessment of cardiovascular risk : a report of the American College of Cardiology, J Am Coll Cardiol, pp.2014, 63[DOI]
- Huhn GD, "Atherosclerotic cardiovascular disease risk profile of tenofovir alafenamide versus tenofovir disoproxil fumarate", Open Forum Infect Dis, 7, pp.ofz472~ (2019)
- Suzuki K, "Tenofovir-disoproxil-fumarate modulates lipid metabolism via hepatic CD36", PPAR-alpha activation in hepatitis B virus infection, 2021, pp.56, 168~180
- Shaheen AA, "Tenofovir disoproxil fumarate significantly decreases serum lipoprotein levels compared with entecavir nucleos(t)ide analogue therapy in chronic hepatitis B carriers", Aliment Pharmacol Ther, 46, pp.599~604 (2017)