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DAAs Cut Cardio Event Rate in HCV+ But Boost Arrhythmia Risk
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EASL International Liver Congress 2022, London, June 22-26, 2022
Mark Mascolini
Analysis of a big French HCV cohort linked direct-acting antiviral (DAA) therapy to a lower overall cardiovascular event rate in people with advanced fibrosis [1]. But in the whole study group-regardless of fibrosis stage-DAAs halved the risk of peripheral arterial disease while boosting risk of arrhythmias and other conduction disorders.
French investigators working with the prospective ANRS CO22 HEPATHER cohort noted that research has not clearly defined associations between DAA therapy and nonliver complications of chronic hepatitis C infection. To clarify the impact of DAAs on extrahepatic complications of chronic HCV, they analyzed HEPATHER cohort members through December 2018, enriching individual patient records with data from the French National Health Insurance Database, which collects information on ambulatory care and hospital admissions.
The ANRS team enrolled HEPATHER cohort members seeking care at 32 hepatology centers from August 2012 through December 2015. The analysis included 8148 people with chronic HCV infection who had 12,905 person-years of follow-up with no DAA exposure and 22,326 person-years of follow-up after starting DAAs. The investigators defined cardiovascular events as stroke, acute coronary syndrome, pulmonary embolism, heart failure, arrhythmias and conduction disorders, and peripheral arterial disease. They defined nonliver cancer as colorectal, bladder, prostate, kidney, lung, pancreas, thyroid, head/neck, and breast cancer. To estimate associations between DAAs and nonliver events, the study team used marginal structural models adjusted for clinical and biological confounders, relevant medications, and frequency of visits to the physician.
The study group had a median age of 56.7 years, 54% were men, and 7037 (86%) had started DAAs. Median time since HCV diagnosis stood at 13.6 years in DAA-naive people and 14.5 years in people who took DAAs. Higher proportions who started DAA therapy had F3 fibrosis (16% vs 9%) or F4 fibrosis (35% vs 18%).
In the total population of 8148 people, modeling estimated that DAA therapy halved the risk of peripheral arterial disease (adjusted hazard ratio [aHR] 0.54, 95% confidence interval [CI] 0.33 to 0.89). But DAAs in this population independently boosted the risk of arrhythmias or conduction disorders (aHR 1.46, 95% CI 1.04 to 2.04), mostly after 1 year following DAA initiation (HR at 1 year 1.32, 95% CI 0.93 to 1.86; HR at 2 years 1.55, 95% CI 1.09 to 2.18; HR at 3 years 1.73, 95% CI 1.23 to 2.45). In the total population, DAA therapy had no impact on risk of major cardiovascular events (aHR 1.03, 95% CI 0.81 to 1.31), any cardiovascular event (aHR 1.10, 95% CI 0.90 to 1.36), or any extrahepatic solid cancer (aHR 1.23, 95% CI 0.50 to 3.03).
Further analysis linked four factors to a higher risk of arrhythmias or conduction disorders: sofosbuvir-based regimen versus no DAA exposure (HR 1.54, 95% CI 1.10 to 2.16), every 10 years of age (HR 1.66, 95% CI 1.38 to 2.00), body mass index at or above 30 kg/m2 (HR 1.68, 95% CI 1.08 to 2.60), and history of a major cardiovascular event (HR 3.43, 95% CI 1.91 to 6.16).
Analysis of 3586 cohort members with advanced fibrosis tied DAAs to a half lower risk of acute heart failure (aHR 0.47, 95% CI 0.27 to 0.81), a two thirds lower risk of peripheral arterial disease (aHR 0.36, 95% CI 0.17 to 0.73), a half lower risk of major cardiovascular events (aHR 0.50, 95% CI 0.36 to 0.71), and about a 40% lower risk of any cardiovascular event (aHR 0.58, 95% CI 0.42 to 0.79). But again DAA therapy had no impact on risk of any nonliver solid cancer (aHR 0.39, 95% CI 0.09 to 1.71).
The ANRS team believes the link between DAAs and heightened risk of arrhythmias and conduction disorders a year after DAA therapy begins underlines a need for long-term cardiovascular monitoring in people treated with these drugs.
EASL: Impact of Direct-Acting Antiviral Treatment for Hepatitis C on Cardiovascular Diseases and Extrahepatic Cancers - (06/24/22)
Reference
1. Lam L, Fontaine H, Lapidus N, et al. Impact of direct-acting antiviral treatment for hepatitis C on cardiovascular diseases and extrahepatic cancers. EASL International Liver Congress 2022, London, June 22-26, 2022. Abstract OS006.
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