Sildenafil is commonly used as off-label medication in Pulmonary Hypertension (PH) secondary to Valvular Heart Disease (VHD). Previously, published systematic review reported the efficacy of sildenafil for PH with VHD specifically in preoperative condition. We conducted this systematic review and meta-analysis to summarize the potential benefits of sildenafil at different treatment phases, namely acute or chronic. Articles available up to June 2020 were identified using Web of Science, Ovid & Medline, EBSCOHOST, the Cochrane Library, PubMed and Google scholar. Quality assessment and data analysis were conducted using Review Manager (RevMan) version 5.4 and Black and Downs’ Checklist. A total of nine studies (n = 614 patients) were eligible for analysis. Sildenafil improved systolic pulmonary arterial pressure (sPAP) (MD -5.89 mmHg ± 17.07), mean Pulmonary Arterial Pressure (mPAP) (MD -4.62 mmHg ± 12.24) and Pulmonary Vascular Resistance Index (PVRI) (MD -60.11 dynes.sec.cm5m2 ± 500.85) during acute and chronic phase in three studies. Data showed no changes in systemic hemodynamic during acute phase but improved in CO and Cl readings during chronic phase. Sildenafil reduced mechanical ventilation time and post-operative recovery room stay during acute and chronic phases. Patients required inotrope support were similar between placebo and sildenafil groups during acute phase (RR, 0.51%; 95% Cl, 0.21-1.27); P = 0.15: no heterogeneity). Sildenafil has little or no effect on pulmonary and systemic hemodynamic, perioperative monitoring, 6MWT and composite clinical score whether it is given as preoperative or postoperative during acute or chronic treatment phase.
1. Fernández AI, Yotti R, González-Mansilla A, Mombiela T, Gutiérrez- Ibanes E, Del Villar CP, et al. The biological bases of group 2 pulmonary hypertension. Int J Mol Sci. 2019;20(23):1-19.
2. Almuqati AL, Alluqmani MS, Balhareth SH, Alosaimi MA, Alosaimi MM, Alzughaibi AM, et al. Evaluation of role of family physicians in management and diagnosis of hypertension in primary health care centers: a simple literature review. Int J Pharm Res Allied Sci. 2020;9(1):105-9.
3. Mohamed AM, Badr NM, Hagag AA, Mohamed YM. Intra versus extra-thoracic oscillations in chronic obstructive pulmonary disease (a randomized clinical trial). J Adv Pharm Edu Res. 2019;9(3):85-90.
4. Weitsman T, Weisz G, Farkash R, Klutstein M, Butnaru A, Rosenmann D, et al. Pulmonary hypertension with left heart disease: prevalence, temporal shifts in etiologies and outcome. Am J Med. 2017;130(11):1272-9.
5. Fang JC, Demarco T, Givertz MM, Borlaug BA, Lewis GD, Rame JE, et al. World health organization pulmonary hypertension group 2: pulmonary hypertension due to left heart disease in the adult - a summary statement from the pulmonary hypertension council of the international society for heart and lung transplantation. J Heart Lung Transplant. 2012;31(9):913-33.
6. Nazzareno G, Marc H, Jean LV, Simon G, Irene L, Adam T. ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension. Eur Heart J. 2015;46:903-75.
7. Al-Omary MS, Sugito S, Boyle AJ, Sverdlov AL, Collins NJ. Pulmonary hypertension due to left heart disease. Hypertension. 2020;75(6):1397-408.
8. Kaple RK, Horn EM. Pulmonary hypertension due to valvular heart disease: aortic and mitral. Adv Pulm Hypertens. 2015;14(2):95-101.
9. Li M, Dumesnil JG, Mathieu P, Pibarot P. Impact of valve prosthesis-patient mismatch on pulmonary arterial pressure after mitral valve replacement. J Am Coll Cardiol. 2005;45:1034-40.
10. Martinez C, Tsugu T, Sugimoto T, Lancellotti P. Pulmonary hypertension with valvular heart disease: when to treat the valve disease and when to treat the pulmonary hypertension. Curr Cardiol Rep. 2019;21(151):1-7.
11. Vachiéry JL, Adir Y, Barberà JA, Champion H, Coghlan JG, Cottin V, et al. Pulmonary hypertension due to left heart diseases. J Am Coll Cardiol. 2013;62(25):D100-D8.
12. Ghoreishi M, Evans CF, Defilippi CR, Hobbs, G, Young CA, Griffith BP et al. Pulmonary hypertension adversely affects short- and long-term survival after mitral valve operation for mitral regurgitation: Implications for timing of surgery. J Thorac Cardiovasc Surg. 2011;142(6):1439-52.
13. Michelakis E, Tymchak W, Lien D, Webster L, Hashimoto K, Archer S. Oral sildenafil is and effective and specific pulmonary vasodilator in patients with pulmonary arterial hypertension: Comparison with inhaled nitric oxide. Circulation. 2002;105(2):2398-403.
14. Bermejo J, Yotti R, García-Orta R, Sánchez-Fernández PL, Castaño M, Segovia-Cubero J, et al. Sildenafil for improving outcomes in patients with corrected valvular heart disease and persistent pulmonary hypertension: A multicenter, double-blind, randomized clinical trial. Eur Heart J. 2018;39(15):1255-64.
15. Nishimura RA, Otto CM, Bonow RO, Carabello BA, Erwin JP, Fleisher LA, et al. AHA/ACC focused update of the 2014 AHA/ACC guideline for the management of patients with valvular heart disease: a report of the american college of cardiology/american heart association task force on clinical practice guidelines. J Am Coll Cardiol. 2017;70(2):252-89.
16. Gillmeyer KR, Rinne ST, Glickman ME, Lee KM, Shao Q, Qian SX, et al. Factors associated with potentially inappropriate phosphodiesterase-5 inhibitor use for pulmonary hypertension in the united states, 2006 to 2015. Circ Cardiovasc Qual Outcomes. 2020;13(5):216-27.
17. Jiang R, Wang L, Zhu CT, Yuan P, Pudasaini B, Zhao QH, et al. Comparative effectiveness of sildenafil for pulmonary hypertension due to left heart disease with HFrEF. Hypertens Res. 2015;38(12):829-39.
18. Villanueva DLE, Agustin RD, Llanes EJ. Pre-Operative sildenafil for patients with pulmonary hypertension undergoing mitral valve surgery: a systematic review and meta analysis. Cardiol Res. 2019;10(6):369-77.
19. Cao JY, Wales KM, Cordina R, Lau EMT, Celermajer DS. Pulmonary vasodilator therapies are of no benefit in pulmonary hypertension due to left heart disease: A meta-analysis. Int J Cardiol. 2018;273:213-20.
20. De Vecchis R, Cesaro A, Ariano C, Giasi A, Cioppa C. Phosphodiesterase-5 inhibitors improve clinical outcomes, exercise capacity and pulmonary hemodynamics in patients with heart failure with reduced left ventricular ejection fraction: a meta-analysis. Orig Artic J Clin Med Res. 2017;9(6):488-98.
21. Moher D, Liberati A, Tetzlaff J, Altman DG. Preferred reporting items for systematic reviews and meta-analyses: The PRISMA statement. Int J Surg. 2010;8(5):336-41.
22. Higgins JPT, Green S. Cochrane handbook for systematic reviews of interventions. cochrane handbook for systematic reviews of interventions. England: Wiley Blackwell; 2019. 187p.
23. Ayyad M, Abdel-Geleel A. Effect of immediate preoperative oral sildenafil administration for pulmonary hypertension undergoing valve replacement. J Eqyptian Soc Cardio-Thoracic Surg. 2012;20:113-7.
24. Shewale V, Jadhao M, Shah V, Raut C, Mishra P, Khandekar J. Effect of preoperative oral sildenafil on intraoperative hemodynamics in patients with severe pulmonary artery hypertension undergoing mitral valve replacement. J Med Sci Clin Res. 2020;8(4):279-84.
25. Chapman TH, Wilde M, Sheth A, Madden BP. Sildenafil therapy in secondary pulmonary hypertension: Is there benefit in prolonged use? Vascul Pharmacol. 2009;51(2-3):90-5.
26. Shim JK, Choi YS, Oh YJ, Kim DH, Hong YW, Kwak YL. Effect of oral sildenafil citrate on intraoperative hemodynamics in patients with pulmonary hypertension undergoing valvular heart surgery. J Thorac Cardiovasc Surg. 2006;132(6):1420-5.
27. Gandhi H, Shah B, Patel R, Toshani R, Pujara J, Kothari J, et al. Effect of preoperative oral sildenafil on severe pulmonary artery hypertension in patients undergoing mitral valve replacement. Indian J Pharmacol. 2014;46(3):281-5.
28. Ibrahim IM, Dokhan AL, Elsebaey RS, Abdellatif MG. Evaluation of the preoperative administration of sildenafil on operative and early postoperative outcome after mitral valve replacement in patients with pulmonary hypertension. Egypt Cardiothorac Surg. 2020;2(4):148-54.
29. Jiang G, Li B, Zhang G, Xu E, Liu Y, Xu Z. Effects of sildenafil on prognosis in patients with pulmonary hypertension after left-sided valvular surgery. Heart Lung Circ. 2014;23(7):680-5.
30. Ram E, Sternik L, Klempfner R, Eldar M, Goldenberg I, Peled Y, et al. Sildenafil for pulmonary hypertension in the early postoperative period after mitral valve surgery. J Cardiothorac Vasc Anesth. 2019;33(6):1648-56.
31. Barnett CF, Machado RF. Sildenafil in the treatment of pulmonary hypertension. Vasc Health Risk Manag. 2006;2(4):411-22.
32. Pfizer Inc. [Internet]. Revatio® (sildenafil). Medical information. Updated 2021 [cited 20 June 2021]. Available from: https://www.pfizermedicalinformation.com/en-us/revatio
33. Kaufmann J, Kung E. Factors affecting cardiovascular physiology in cardiothoracic surgery: implications for lumped-parameter modeling. Front Surg. 2019;6(62):1-7.
34. Papathanasiou M, Ruhparwar A, Kamler M, Rassaf T, Luedike P. Off-label use of pulmonary vasodilators after left ventricular assist device implantation: Calling in the evidence. Pharmacol Ther. 2020;214:107619.
35. Salem M, Diab A, Ateya A, Sanad O. Short term effects of sildenafil citrate therapy in secondary pulmonary hypertension. Egypt Hear J. 2014;66(1):49-53.
36. Lindman BR, Zajarias A, Madrazo JA, Shah J, Gage BF, Novak E, et al. Effects of phosphodiesterase type 5 inhibition on systemic and pulmonary hemodynamics and ventricular function in patients with severe symptomatic aortic stenosis. Circulation. 2012;125(19):2353-62.
37. Rassa A, Zahr F. Hypertension and aortic stenosis: A review. Curr Hypertens Rev. 2018;14(1):6-14.
38. Halliday SJ, Wang L, Yu C, Vickers BP, Newman JH, Fremont RD, et al. Six-minute walk distance in healthy young adults. Respir Med. 2020;165:105933.
39. Hao Y, Zhu Y, Mao Y, Xu J, He X, Huang S, et al. Efficacy and safety of Sildenafil treatment in pulmonary hypertension caused by chronic obstructive pulmonary disease: A meta-analysis. Life Sci. 2020;257:118001.
40. Cooper TJ, Guazzi M, Al-Mohammad A, Amir O, Bengal T, Cleland JG. et al. Sildenafil in heart failure (SilHF). an investigator-initiated multinational randomized controlled clinical trial: rationale and design. J Hear Fail. 2013;15(1):119-22.
41. Guazzi M, Vicenzi M, Arena R. Phosphodiesterase 5 inhibition with sildenafil reverses exercise oscillatory breathing in chronic heart failure: A long-term cardiopulmonary exercise testing placebo-controlled study. Eur J Heart Fail. 2012;14(1):82-90.
42. Magne J, Pibarot P, Sengupta PP, Donal E, Rosenhek R, Lancellotti P. Pulmonary hypertension in valvular disease: comprehensive review on pathophysiology to therapy from the HAVEC group. JACC Cardiovasc Imaging. 2015;8(1):83-99.
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