Sildenafil for improving outcomes in patients with corrected valvular heart disease and persistent pulmonary hypertension: a multicenter, double-blind, randomized clinical trial


Por: Bermejo, J, Yotti, R, Garcia-Orta, R, Sanchez-Fernandez, PL, Castano, M, Segovia-Cubero, J, Escribano-Subias, P, San Roman, JA, Borras, X, Alonso-Gomez, A, Botas, J, Crespo-Leiro, MG, Velasco, S, Bayes-Genis, A, Lopez, A, Munoz-Aguilera, R, de Teresa, E, Gonzalez-Juanatey, JR, Evangelista, A, Mombiela, T, Gonzalez-Mansilla, A, Elizaga, J, Martin-Moreiras, J, Gonzalez-Santos, JM, Moreno-Escobar, E, Fernandez-Aviles, F

Publicada: 14 abr 2018
Resumen:
Aims We aimed to determine whether treatment with sildenafil improves outcomes of patients with persistent pulmonary hypertension (PH) after correction of valvular heart disease (VHD). Methods and results The sildenafil for improving outcomes after valvular correction (SIOVAC) study was a multricentric, randomized, parallel, and placebo-controlled trial that enrolled stable adults with mean pulmonary artery pressure >= 30 mmHg who had undergone a successful valve replacement or repair procedure at least 1 year before inclusion. We assigned 200 patients to receive sildenafil (40 mg three times daily, n = 104) or placebo (n = 96) for 6 months. The primary endpoint was the composite clinical score combining death, hospital admission for heart failure (HF), change in functional class, and patient global self-assessment. Only 27 patients receiving sildenafil improved their composite clinical score, as compared with 44 patients receiving placebo; in contrast 33 patients in the sildenafil group worsened their composite score, as compared with 14 in the placebo group [odds ratio 0.39; 95% confidence interval (Cl) 0.22-0.67; P < 0.001]. The Kaplan-Meier estimates for survival without admission due to HF were 0.76 and 0.86 in the sildenafil and placebo groups, respectively (hazard ratio 2.0, 95% Cl = 1.0-4.0; log-rank P = 0.044). Changes in 6-min walk test distance, natriuretic peptides, and Doppler-derived systolic pulmonary pressure were similar in both groups. Conclusion Treatment with sildenafil in patients with persistent PH after successfully corrected VHD is associated to worse clinical outcomes than placebo. Off-label usage of sildenafil for treating this source of left heart disease PH should be avoided.

Filiaciones:
Bermejo, J:
 Univ Complutense Madrid, Hosp Gen Univ Gregorio Maranon, Fac Med, Inst Invest Sanitaria Gregorio Marano,Dept Cardio, Dr Esquerdo 46, Madrid 28007, Spain

 CIBERCV, Dr Esquerdo 46, Madrid 28007, Spain

Yotti, R:
 Univ Complutense Madrid, Hosp Gen Univ Gregorio Maranon, Fac Med, Inst Invest Sanitaria Gregorio Marano,Dept Cardio, Dr Esquerdo 46, Madrid 28007, Spain

 CIBERCV, Dr Esquerdo 46, Madrid 28007, Spain

Garcia-Orta, R:
 Hosp Virgen Nieves, Granada, Spain

Sanchez-Fernandez, PL:
 Univ Salamanca, Hosp Clin, Salamanca, Spain

 CIBERCV Salamanca, Salamanca, Spain

Castano, M:
 Hosp Univ Leon, Leon, Spain

Segovia-Cubero, J:
 Hosp Puerta Hierro Majadahonda, Majadahonda, Spain

 CIBERCV, Majadahonda, Spain

Escribano-Subias, P:
 Hosp 12 Octubre, Madrid, Spain

 CiberCV, Madrid, Spain

San Roman, JA:
 Hosp Clin Valladolid, Valladolid, Spain

 CIBERCV, Valladolid, Spain

Borras, X:
 Hosp Santa Creu & Sant Pau, Barcelona, Spain

 CIBERCV, Barcelona, Spain

Alonso-Gomez, A:
 Hosp Univ Araba Txagorritxu, Vitoria, Spain

Botas, J:
 Hosp Univ Fdn Alcorcon, Alcorcon, Spain

Crespo-Leiro, MG:
 Complejo Hosp Univ A Coruna, La Coruna, Spain

 CIBERCV, La Coruna, Spain

Velasco, S:
 Hosp Galdakao Usansolo, Usansolo, Spain

Bayes-Genis, A:
 Hosp Badalona Germans Trias & Pujol, Badalona, Spain

 CIBERCV, Badalona, Spain

Lopez, A:
 Hosp Univ Reina Sofia, Cordoba, Spain

Munoz-Aguilera, R:
 Hosp Infanta Leonor, Madrid, Spain

de Teresa, E:
 Hosp Virgen Victoria, Malaga, Spain

 CIBERCV, Malaga, Spain

Gonzalez-Juanatey, JR:
 Hosp Clin Santiago de Compostela, Santiago De Compostela, Spain

 CIBERCV, Santiago De Compostela, Spain

Evangelista, A:
 CIBERCV, Barcelona, Spain

 Hosp Univ Vall Hebron, Barcelona, Spain

Mombiela, T:
 Univ Complutense Madrid, Hosp Gen Univ Gregorio Maranon, Fac Med, Inst Invest Sanitaria Gregorio Marano,Dept Cardio, Dr Esquerdo 46, Madrid 28007, Spain

 CIBERCV, Dr Esquerdo 46, Madrid 28007, Spain

Gonzalez-Mansilla, A:
 Univ Complutense Madrid, Hosp Gen Univ Gregorio Maranon, Fac Med, Inst Invest Sanitaria Gregorio Marano,Dept Cardio, Dr Esquerdo 46, Madrid 28007, Spain

 CIBERCV, Dr Esquerdo 46, Madrid 28007, Spain

Elizaga, J:
 Univ Complutense Madrid, Hosp Gen Univ Gregorio Maranon, Fac Med, Inst Invest Sanitaria Gregorio Marano,Dept Cardio, Dr Esquerdo 46, Madrid 28007, Spain

 CIBERCV, Dr Esquerdo 46, Madrid 28007, Spain

Martin-Moreiras, J:
 Univ Salamanca, Hosp Clin, Salamanca, Spain

 CIBERCV Salamanca, Salamanca, Spain

Gonzalez-Santos, JM:
 Univ Salamanca, Hosp Clin, Salamanca, Spain

 CIBERCV Salamanca, Salamanca, Spain

Moreno-Escobar, E:
 Hosp Univ San Cecilio, Granada, Spain

Fernandez-Aviles, F:
 Univ Complutense Madrid, Hosp Gen Univ Gregorio Maranon, Fac Med, Inst Invest Sanitaria Gregorio Marano,Dept Cardio, Dr Esquerdo 46, Madrid 28007, Spain

 CIBERCV, Dr Esquerdo 46, Madrid 28007, Spain
ISSN: 0195668X





EUROPEAN HEART JOURNAL
Editorial
OXFORD UNIV PRESS, GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND, Reino Unido
Tipo de documento: Article
Volumen: 39 Número: 15
Páginas: 1255-1264
WOS Id: 000430715700009
ID de PubMed: 29281101
imagen Green Published, Hybrid Gold

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