Physicians' Academy for Cardiovascular Education

Polypill for the prevention of major CV events in individuals with and without NASH

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

Literature - Merat S, Jafari E, Radmard AR et al., - Eur Heart J 2022,

Introduction and methods


Individuals with fatty liver (non-alcoholic fatty liver disease) and especially those with non-alcoholic steatohepatitis (NASH) and elevated liver enzymes are at higher risk of CVD [1,2] and may benefit from primary prevention. However, these are not much data on primary or secondary prevention in individuals with increased liver enzyme levels [3].

This study was an extension of the PolyIran trial [4], a pragmatic cluster-randomized study in a rural population in Iran in which the effect of a four-component pill including aspirin, atorvastatin, hydrochlorothiazide and either enalapril or valsartan was investigated. Now, the effects of the same polypill on risk of major CV events were studied including participants with increased liver enzyme levels and individuals with fatty liver.


The PolyIran-Liver study is an open-label, individually randomized controlled trial. 2400 Participants ≥50 years from the Golestan cohort study who were resident of Gonbad city were randomized to receive polypill or no polypill. After randomization, participants were invited for participation and consent was obtained for those accepting (the Zelen design) [5]. Laboratory tests, ultrasonography and liver stiffness measurements were performed. Participants were identified as having presumed NAFLD (pNAFLD) and with elevated ALT levels participants were identified as presumed NASH (pNASH).

The polypill included 81 mg aspirin, 12.5 mg hydrochlorothiazide, 20 mg atorvastatin, and 40 mg valsartan.

Results were analyzed among the originally randomized population (n=2266) and among consenting participants who were eligible for polypill (n=1508).

Participants were visited every 6 months for 5 years.


Primary endpoint was the occurrence of major CV events (MCVE), a composite of fatal MI, sudden death, new-onset heart failure, coronary artery revascularization procedures, fatal and non-fatal stroke or hospitalization for an acute coronary event.

Main results

The randomized population

The consenting group


Secondary outcomes


The PolyIran-Liver study showed that in the randomized population a polypill did not significantly lower MCVE, but among subjects who consented to take polypill, polypill resulted in benefit. This benefit was similar in participants with and without pNASH. In addition, findings showed that polypill reduced ALT levels in individuals with pNASH.

The authors conclude: “Individuals with fatty liver and NASH are more likely to develop CVD. We do not have an effective medical treatment for the liver but preventing CVD, the main cause of death in this group, is an important management objective.”


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Find this article online at Eur Heart J

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