Polypill protects MAFLD patients from cardiovascular events and mortality: a prospective trial.

BACKGROUND: Metabolic dysfunction-associated fatty liver disease (MAFLD) is a novel term that distinguishes patients at risk of adverse clinical outcomes with higher accuracy than those with non-alcoholic fatty liver disease (NAFLD). Cardiovascular mortality is the leading cause of death in MAFLD. The current literature lacks large-scale prospective studies that address preventive approaches for cardiovascular health in MAFLD. We investigated whether MAFLD patients benefit from a fixed-dose combination therapy (Aspirin, hydrochlorothiazide, atorvastatin, valsartan), known as a Polypill. METHODS: Analysis was performed (stratified based on MAFLD status) of a clinical trial that included 1596 individuals randomly allocated to an intervention (polypill) or a control (usual care) group. Patients were followed up for five years for any adverse drug reaction, major cardiovascular events, and mortality. Univariable and multivariable survival analyses were performed, and the interaction level was assessed by R programming. RESULTS: Patients who consumed the polypill had significantly lower hazard ratios of major cardiovascular events incidence (HR 0.56, 95% CI 0.41-0.78) and cardiovascular mortality (HR 0.41, 95% CI 0.2-0.86) compared to the control group. Polypill showed significantly better results in lowering cardiovascular events in MAFLD patients than in the general population. (p-value for interaction: 0.028). Moreover, comparing those patients who had high adherence to the Polypill, with the control group, further enhanced the results. CONCLUSIONS: Major cardiovascular events are prevented in MAFLD patients who consume the Polypill. MAFLD patients benefit from the Polypill more than the general population.

Polypill for prevention of cardiovascular diseases with focus on non-alcoholic steatohepatitis: the PolyIran-Liver trial.

AIMS: Individuals with non-alcoholic 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 for the prevention of major cardiovascular events (MCVE) among individuals with and without presumed non-alcoholic steatohepatitis (pNASH). METHODS AND RESULTS: Two thousand four hundred participants over 50 were randomized into the intervention and control groups. Consent was obtained post-randomization. Consenting participants in the intervention group were given a pill containing aspirin, atorvastatin, hydrochlorothiazide, and valsartan (polypill). Participants were followed for 5 years. Presumed non-alcoholic steatohepatitis was diagnosed by ultrasonography and elevated liver enzymes. The primary outcome was MCVE. ClinicalTrials.gov: NCT01245608. Among the originally randomized population, 138 of 1249 in the intervention group (11.0%) and 137 of 1017 controls (13.5%) had MCVE during the 5-year follow-up [unadjusted risk ratio (RR) 0.83, 95% confidence interval (CI) 0.66-1.03]. Of the 1508 participants who consented to additional measurements and treatment, 63 of 787 (8.0%) intervention group participants and 86 of 721 (11.9%) controls had MCVE (adjusted RR 0.61, 95% CI 0.44-0.83). Although the adjusted relative risk of MCVE in participants with pNASH (0.35, 95% CI 0.17-0.74) was under half that for participants without pNASH (0.73, 95% CI 0.49-1.00), the difference did not reach statistical significance. There was no change in liver enzymes in participants taking polypill but among those with pNASH, there was a significant decrease after 60 months of follow-up (intragroup -12.0 IU/L, 95% CI -14.2 to -9.6). CONCLUSION: Among patients consenting to receive fixed-dose combination therapy, polypill is safe and effective for the prevention of MCVE, even among participants with fatty liver and increased liver enzymes.