Safety and efficacy of a cardiovascular polypill in people at high and very high risk without a previous cardiovascular event: the international VULCANO randomised clinical trial

BMC Cardiovasc Disord. 2022 Dec 22;22(1):560. doi: 10.1186/s12872-022-03013-w.

Abstract

Background: Cardiovascular (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.

Methods: 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.

Results: 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.

Conclusion: 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 ).

Keywords: Cardiovascular disease; Cardiovascular risk factors; Fixed-dose combination; Non-inferiority trial; Polypill; Primary prevention.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antihypertensive Agents / adverse effects
  • Cardiovascular Diseases* / diagnosis
  • Cardiovascular Diseases* / drug therapy
  • Cardiovascular Diseases* / prevention & control
  • Cholesterol
  • Cholesterol, LDL
  • Drug Combinations
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors* / adverse effects

Substances

  • Antihypertensive Agents
  • Cholesterol, LDL
  • Drug Combinations
  • Cholesterol
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors