BACKGROUNDFrail and polypathological patients (PP) are often undertreated with evidence-based cardiovascular drugs, as their benefits are uncertain in this population.OBJECTIVESTo determine the effects of treatment with renin-angiotensin system blockers/inhibitors (ACEI/ARB), statins and/or beta-blockers on survival rates and functional decline in PP with evidence-based clinical indications for treatment with any of these drug families.METHODProspective observational multicentre cohort study with a 12-month follow-up period. We selected PP with any condition of the following: chronic heart failure, coronary heart disease, chronic renal disease, cerebrovascular disease, peripheral artery disease, diabetes mellitus with any visceral involvement, hypertension, and dyslipidaemia. Clinical, functional (Barthel index), socio-familial risk data and drug prescriptions were measured at baseline. Multivariate Cox proportional hazards and logistic regression models were used to identify variables independently associated with survival and functional decline.RESULTSThe analysis included 1260 PP. The mean age was 79±9.5 years. The mortality rate was 34.5%. Statin (aHR 0.671; P=0.001), beta-blocker plus statin (aHR 0.645; P=0.007), ACEI/ARB plus statin (aHR 0.680; P=0.002), or combined ACEI/ARB plus statin plus beta-blocker (aHR 0.541; P=0.000) prescriptions were associated with longer survival times. Additionally, PP whose Barthel index was ≥60 showed a lower risk of disability progression if treated with statins (aOR=0.476; P=0.000), or their combinations, mainly with ACEI/ARB plus beta-blockers (aOR 0.563; P=0.031).CONCLUSIONSThe prescription of statins, alone or in combination with other drugs, may impact the survival and functional decline in polypathological patients. Further prospective blinded randomised assays are needed to confirm these observations.