Atorvastatin Effect on Aortic Dilatation and Valvular Calcification Progression in Bicuspid Aortic Valve (BICATOR): A Randomized Clinical Trial.

Francisco Calvo-Iglesias, Jose F Rodríguez-Palomares, Augusto Sao-Avilés, Hug Cuellar-Calabria, Marina Huguet, María Ángeles Carmona, Lydia Dux-Santoy, Aroa Ruiz-Muñoz, Elena Ferrer-Sistach, Juan M Robledo Carmona, Violeta Sánchez, Javier Bermejo, Gisela Teixido-Tura, Laura Galian-Gay, Ignacio Ferreira-González, Andrea Guala, Josep M Alegret, Arturo Evangelista, Irene Méndez, Daniel Saura, Teresa Sevilla

Journal: Circulation 2024;149(25):1938-1948

PMID: 38804148

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Abstract

BACKGROUND

Ascending aorta dilation and aortic valve degeneration are common complications in patients with bicuspid aortic valve. Several retrospective studies have suggested the benefit of statins in reducing these complications. This study aimed to determine whether atorvastatin treatment is effective in reducing the growth of aortic diameters in bicuspid aortic valve and if it slows the progression of valve calcification.

METHODS

In a randomized clinical trial, 220 patients with bicuspid aortic valve (43 women; 46±13 years of age) were included and treated with either 20 mg of atorvastatin per day or placebo for 3 years. Inclusion criteria were ≥18 years of age, nonsevere valvular dysfunction, nonsevere valve calcification, and ascending aorta diameter ≤50 mm. Computed tomography and echocardiography studies were performed at baseline and after 3 years of treatment.

RESULTS

During follow-up, 28 patients (12.7%) discontinued medical treatment (15 on atorvastatin and 13 taking placebo). Thus, 192 patients completed the 36 months of treatment. Low-density lipoprotein cholesterol levels decreased significantly in the atorvastatin group (median [interquartile range], -30 mg/dL [-51.65 to -1.75 mg/dL] versus 6 mg/dL [-4, 22.5 mg/dL]; <0.001). The maximum ascending aorta diameter increased with no differences between groups: 0.65 mm (95% CI, 0.45-0.85) in the atorvastatin group and 0.74 mm (95% CI, 0.45-1.04) in the placebo group (=0.613). Similarly, no significant differences were found for the progression of the aortic valve calcium score (=0.167) or valvular dysfunction.

CONCLUSIONS

Among patients with bicuspid aortic valve without severe valvular dysfunction, atorvastatin treatment was not effective in reducing the progression of ascending aorta dilation and aortic valve calcification during 3 years of treatment despite a significant reduction in low-density lipoprotein cholesterol levels.

REGISTRATION

URL: https://www.clinicaltrialsregister.eu; Unique identifier: 2015-001808-57. URL: https://www.clinicaltrials.gov; Unique identifier: NCT02679261.

Address: Servei de Cardiologia (A.E., L.G.-G., G.T.-T., A.R.-M., M.A.C., H.C.-C., I.F.-G., J.F.R.-P.), Hospital Universitari Vall d´Hebron, Barcelona, Spain.; CIBER-CV (A.E., A.G., G.T.-T., T.S., J.B., I.M., V.S., J.M.R.-C., E.F., D.S., A.R.-M., J.F.R.-P.), Instituto de Salud Carlos III, Madrid, Spain.; Vall d'Hebron Institut de Recerca (VHIR), Barcelona, Spain (A.E., L.G.-G., A.G., G.T.-T., A.R.-M., L.D.-S., A.S.-A., I.F.-G., J.F.R.-P.).; Servei de Cardiologia (A.E., L.G.-G., G.T.-T., A.R.-M., M.A.C., H.C.-C., I.F.-G., J.F.R.-P.), Hospital Universitari Vall d´Hebron, Barcelona, Spain.; Vall d'Hebron Institut de Recerca (VHIR), Barcelona, Spain (A.E., L.G.-G., A.G., G.T.-T., A.R.-M., L.D.-S., A.S.-A., I.F.-G., J.F.R.-P.).; CIBER-CV (A.E., A.G., G.T.-T., T.S., J.B., I.M., V.S., J.M.R.-C., E.F., D.S., A.R.-M., J.F.R.-P.), Instituto de Salud Carlos III, Madrid, Spain.; Vall d'Hebron Institut de Recerca (VHIR), Barcelona, Spain (A.E., L.G.-G., A.G., G.T.-T., A.R.-M., L.D.-S., A.S.-A., I.F.-G., J.F.R.-P.).; Hospital Alvaro Cunqueiro, Vigo, Spain (F.C.-I.).; CIBER-CV (A.E., A.G., G.T.-T., T.S., J.B., I.M., V.S., J.M.R.-C., E.F., D.S., A.R.-M., J.F.R.-P.), Instituto de Salud Carlos III, Madrid, Spain.; Hospital Clínico Universitario de Valladolid, Spain (T.S.).; CIBER-CV (A.E., A.G., G.T.-T., T.S., J.B., I.M., V.S., J.M.R.-C., E.F., D.S., A.R.-M., J.F.R.-P.), Instituto de Salud Carlos III, Madrid, Spain.; Hospital Gregorio Marañón, Madrid, Spain (J.B.).; CIBER-CV (A.E., A.G., G.T.-T., T.S., J.B., I.M., V.S., J.M.R.-C., E.F., D.S., A.R.-M., J.F.R.-P.), Instituto de Salud Carlos III, Madrid, Spain.; Hospital Universitario Virgen del Macarena, Sevilla, Spain (I.M.).; CIBER-CV (A.E., A.G., G.T.-T., T.S., J.B., I.M., V.S., J.M.R.-C., E.F., D.S., A.R.-M., J.F.R.-P.), Instituto de Salud Carlos III, Madrid, Spain.; Hospital 12 de Octubre, Madrid, Spain (V.S.).; CIBER-CV (A.E., A.G., G.T.-T., T.S., J.B., I.M., V.S., J.M.R.-C., E.F., D.S., A.R.-M., J.F.R.-P.), Instituto de Salud Carlos III, Madrid, Spain.; UGC Corazón Hospital Clinico Universitario Virgen de la Victoria, IBIMA, UMA, Málaga, Spain (J.M.R.-C.).; Hospital Universitari de Sant Joan, Departament de Medicina i Cirurgia, Universitat Rovira i Virgili, Reus, Spain (J.M.A.).; CIBER-CV (A.E., A.G., G.T.-T., T.S., J.B., I.M., V.S., J.M.R.-C., E.F., D.S., A.R.-M., J.F.R.-P.), Instituto de Salud Carlos III, Madrid, Spain.; Hospital Germans Trias i Pujol, Badalona, Spain (E.F.).; CIBER-CV (A.E., A.G., G.T.-T., T.S., J.B., I.M., V.S., J.M.R.-C., E.F., D.S., A.R.-M., J.F.R.-P.), Instituto de Salud Carlos III, Madrid, Spain.; Hospital Clínico Universitario Virgen de la Arrixaca-IMIB, Murcia, Spain (D.S.).; Vall d'Hebron Institut de Recerca (VHIR), Barcelona, Spain (A.E., L.G.-G., A.G., G.T.-T., A.R.-M., L.D.-S., A.S.-A., I.F.-G., J.F.R.-P.).; Servei de Cardiologia (A.E., L.G.-G., G.T.-T., A.R.-M., M.A.C., H.C.-C., I.F.-G., J.F.R.-P.), Hospital Universitari Vall d´Hebron, Barcelona, Spain.; Instituto del Corazón, Centro Médico Teknon, Quirón-Salud, Barcelona, Spain (M.H.).; Servei de Cardiologia (A.E., L.G.-G., G.T.-T., A.R.-M., M.A.C., H.C.-C., I.F.-G., J.F.R.-P.), Hospital Universitari Vall d´Hebron, Barcelona, Spain.; Servei de Radiodiagnòstic (H.C.-C.), Hospital Universitari Vall d´Hebron, Barcelona, Spain.; Servei de Cardiologia (A.E., L.G.-G., G.T.-T., A.R.-M., M.A.C., H.C.-C., I.F.-G., J.F.R.-P.), Hospital Universitari Vall d´Hebron, Barcelona, Spain.; CIBERESP (I.F.-G.), Instituto de Salud Carlos III, Madrid, Spain.; Vall d'Hebron Institut de Recerca (VHIR), Barcelona, Spain (A.E., L.G.-G., A.G., G.T.-T., A.R.-M., L.D.-S., A.S.-A., I.F.-G., J.F.R.-P.).

DOI: 10.1161/CIRCULATIONAHA.123.067537

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MeSH Terms: Humans, Atorvastatin, Female, Male, Middle Aged, Aortic Valve, Disease Progression, Calcinosis, Bicuspid Aortic Valve Disease, Heart Valve Diseases, Adult, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Dilatation, Pathologic, Follow-Up Studies, Double-Blind Method, Treatment Outcome, Aorta, Aortic Valve Disease, Aortic Valve Stenosis