Individuals with nonalcoholic steatohepatitis or elevated liver enzymes have increased cardiovascular mortality but are often excluded from prevention trials. We investigated the effectiveness of fixed-dose combination therapy in prevention of major cardiovascular events (MCVE) among individuals with and without presumed nonalcoholic steatohepatitis (pNASH).

2400 Participants over 50 were randomized into intervention and control. Consent was taken post-randomization. Participants in the intervention group were given a combination pill containing aspirin, atorvastatin, hydrochlorothiazide, and valsartan (Polypill). Participants were followed for 5 years. pNASH was diagnosed by ultrasonography and elevated liver enzymes. The primary outcome was MCVE. ClinicalTrials.gov ID: NCT01245608.

892 participants did not consent or meet enrollment criteria and 1508 entered the study. During 5-years of follow-up, 63/787 (8.0%) intervention group participants and 86/721 (11.9%) controls had MCVE (adjusted RR 0.61, 95%CI 0.44 to 0.83). Although the adjusted relative risk of MCVE in participants with pNASH (0.35, 95%CI 0.17 to 0.74) was under half that for participants without pNASH (0.73, 95%CI 0.49 to 1.00), the difference did not reach statistical significance. Outcomes were also evaluated for the pre-consent population. 138/1249 in the intervention group (11.0%) and 137/1017 controls (13.5%) had MCVE during the 5-year follow-up (unadjusted RR 0.83, 95%CI 0.66-1.03). Participants with pNASH in the intervention group had a significant decrease in liver enzyme levels after 60 months of follow-up (intragroup -12.0 IU/L, 95%CI -14.2 to -9.6).

Fixed-dose combination therapy is safe and effective for prevention of MCVE even among participants with fatty liver and increased liver enzymes.