Mostaza, José MSuárez-Fernández, CarmenCosín-Sales, JuanGómez-Huelgas, RicardoBrotons, CarlosAraujo, Francisco PestanaBorrayo, GabrielaRuiz, EmilioVULCANO investigators2023-05-032023-05-032022-12-22http://hdl.handle.net/10668/20264Cardiovascular (CV) polypills are a useful baseline treatment to prevent CV diseases by combining different drug classes in a single pill to simultaneously target more than one risk factor. The aim of the present trial was to determine whether the treatment with the CNIC-polypill was at least non-inferior to usual care in terms of low-density lipoprotein cholesterol (LDL-c) and systolic BP (SBP) values in subjects at high or very high risk without a previous CV event. The VULCANO was an international, multicentre open-label trial involving 492 participants recruited from hospital clinics or primary care centres. Patients were randomised to the CNIC-polypill -containing aspirin, atorvastatin, and ramipril- or usual care. The primary outcome was the comparison of the mean change in LDL-c and SBP values after 16 weeks of treatment between treatment groups. The upper confidence limit of the mean change in LDL-c between treatments was below the prespecified margin (10 mg/dL) and above zero, and non-inferiority and superiority of the CNIC-polypill (p = 0.0001) was reached. There were no significant differences in SBP between groups. However, the upper confidence limit crossed the prespecified non-inferiority margin of 3 mm Hg. Significant differences favoured the CNIC-polypill in reducing total cholesterol (p = 0.0004) and non-high-density lipoprotein cholesterol levels (p = 0.0017). There were no reports of major bleeding episodes. The frequency of non-serious gastrointestinal disorders was more frequent in the CNIC-polypill arm. The switch from conventional treatment to the CNIC-polypill approach was safe and appears a reasonable strategy to control risk factors and prevent CVD. Trial registration This trial was registered in the EU Clinical Trials Register (EudraCT) the 20th February 2017 (register number 2016-004015-13; https://www.clinicaltrialsregister.eu/ctr-search/search?query=2016-004015-13 ).enAttribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/Cardiovascular diseaseCardiovascular risk factorsFixed-dose combinationNon-inferiority trialPolypillPrimary preventionHumansAntihypertensive AgentsCholesterol, LDLDrug CombinationsCardiovascular DiseasesCholesterolHydroxymethylglutaryl-CoA Reductase Inhibitorsresearch article36550424open access10.1186/s12872-022-03013-w1471-2261PMC9773517https://bmccardiovascdisord.biomedcentral.com/counter/pdf/10.1186/s12872-022-03013-whttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC9773517/pdf