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
José María Mostaza, Carmen Súarez-Fernández, Juan Cosı́n-Sales, Ricardo Gómez‐Huelgas, Carlos Brotons, Francisco Araújo, Gabriela Borrayo, Emilio Muñoz Ruiz, VULCANO investigators, Pablo Pérez, Jacinto Espinosa, Javier Sobrino, Antonio Posé, Juan Antonio Arroyo Díaz, Olga García Vallejo, Maria Pilar Cubo Romano, Sergio Jansen Chaparro, Jesús Cabezón Mariscal, Miguel Angel Rico Corral, José Abellán Alemán, Domingo Orozco Beltrán, Luis Escobar Jimenez, Pedro Valdivieso Felices, Juan Carlos Pedro-Botet Montoya, Luis Masana Marín, Carlos Guijarro, Ángel Díaz Rodríguez, José Luis Díaz Díaz, Andrés De la Peña Fernández, Emmanuel Coloma Bazán, Rafael Cuenca Acevedo, Carmen Suárez Fernández, Fernando Civeira, José María Castellano Vázquez, José María Mostaza Prieto, Manuel Suárez Tembra, Joaquín Alfonso Megido, Jesús Castiella Herrero, Juan José Tamarit, Miguel Ángel Martínez-Hervás Alonso, Francisco Javier Carrasco Franco, Luis Álvarez Sala, Enrique Calderón Sandubete, Eduardo Rovira Daudi, Fernando Bonilla Rovira, Juan Manuel Murcia Zaragoza, Lluís Cuixart Costa, José Luis Bianchi Llave, Carmen Álvarez Sánchez, Pedro Marqués Da Silva, Vitória Cunha, Catarina Santos, Francisco Araujo, José Moura, Martín Rosas Peralta
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 ).