Appropriateness of Sildenafil Prescribing in Pulmonary Hypertension with Valvular Heart Disease: A Single Centre Study

Document Type : Original Article

Authors

Pharmacy Department, Serdang Hospital, Selangor, Malaysia

10.30476/tips.2021.92905.1115

Abstract

Oral sildenafil has proven efficacy in pulmonary hypertension in current clinical practice. However, there is a research gap in sildenafil prescribing among patients with valvular heart disease (VHD) and pulmonary hypertension (PH) in Malaysia. This study aimed to determine the appropriateness of sildenafil prescribing and rehospitalization rate in patients with corrected VHD and PH. This is a retrospective descriptive study using universal sampling with a calculated sampling size of 123. Patients who were diagnosed with VHD and PH in Hospital Serdang were recruited from 2014 - 2018. Patients' demographic and clinical characteristics were retrieved from Electronic Hospital Information System (eHIS) and recorded using a pre-designed data collection form. Appropriateness prescribing of sildenafil included appropriate dose(20mg to 80mg three times daily) and duration(total of eight weeks of sildenafil treatment that started before and continued after surgery). Rehospitalization is defined as any hospitalization within six months after surgery. Data were analyzed using descriptive and inferential statistics. From 123 patients (44.7% male, 55.3% female), 41% (n=51) and 61.8%(n=76) received appropriate dose and duration of Sildenafil respectively. Rehospitalization rate within six months after valve surgery was 55.3%(n=68). Univariate analysis showed that patients more than 65 years old (p=0.039), atrial fibrillation (AF) (p=0.04) and female (p=0.002) received appropriate prescribing of sildenafil. Only female patients and patients with AF were the predictors of appropriate prescribing of sildenafil. The role of sildenafil in VHD and PH remains unclear and needs further research in different perspectives such as short term and long-term duration with different doses.

Keywords


1. Galiè N, Humbert M, Vachiery JL, Gibbs S, Lang I, Torbicki A, et al. 2015 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension. Eur Respir J. 2015 Oct;46(4):903-75. doi: 10.1183/13993003.01032-2015
2. 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 Nov 25;21(12):151. doi: 10.1007/s11886-019-1240-7.
3. Weitsman T, Weisz G, Farkash R, Klutstein M, Butnaru A, Rosenmann D, Hasin T. Pulmonary Hypertension with Left Heart Disease: Prevalence, Temporal Shifts in Etiologies and Outcome. Am J Med. 2017 Nov;130(11):1272-1279. doi: 10.1016/j.amjmed.2017.05.003.
4. Mehra P, Mehta V, Sukhija R, Sinha AK, Gupta M, Girish MP, et al. Pulmonary hypertension in left heart disease.
Arch Med Sci.2019;15(1):262-273. doi:10.5114/aoms.2017.68938
5. Zolty R. Challenges in pulmonary hypertension associated with left heart disease. Expert Rev Cardiovasc Ther. 2019 Jun;17(6):461-472. doi: 10.1080/14779072.2019.1615885.
6. 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 May;13(5):e005993. doi: 10.1161/CIRCOUTCOMES.119.005993.
7. Otto CM, Nishimura RA, Bonow RO, Carabello BA, Erwin JP 3rd, Gentile F, et al. 2020 ACC/AHA Guideline for the Management of Patients With Valvular Heart Disease: Executive Summary: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Circulation. 2021 Feb 2;143(5):e35-e71. doi: 10.1161/CIR.0000000000000932.
8. Barnett CF, Machado RF. Sildenafil in the treatment of pulmonary hypertension. Vasc Health Risk Manag. 2006;2(4):411-422. doi:10.2147/vhrm.2006.2.4.411
9. 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 Dec 24;62(25 Suppl):D100-8. doi: 10.1016/j.jacc.2013.10.033.
10. Revatio- Sildenafil citrate tablet, film coated [package insert on the Internet]. New York: Pfizer Inc; 2014 Jan [updated 2020 April; cited 2020 December 20]. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/021845s011,022473s004,0203109s002lbl.pdf
11. Maron BA, Ryan JJ. A Concerning Trend for Patients With Pulmonary Hypertension in the Era of Evidence-Based Medicine. Circulation. 2019 Apr 16;139(16):1861-1864. doi: 10.1161/CIRCULATIONAHA.118.037613.
12. Rosenkranz S, Lang IM, Blindt R, Bonderman D, Bruch L, Diller GP, et al. Pulmonary hypertension associated with left heart disease: Updated Recommendations of the Cologne Consensus Conference 2018. Int J Cardiol. 2018 Dec 1;272S:53-62. doi: 10.1016/j.ijcard.2018.08.080.
13. Cahir C, Bennett K, Teljeur C, Fahey T. Potentially inappropriate prescribing and adverse health outcomes in community dwelling older patients. Br J Clin Pharmacol. 2014 Jan;77(1):201-10. doi: 10.1111/bcp.12161.
14. Pollock M, Bazaldua OV, Dobbie AE. Appropriate prescribing of medications: an eight-step approach. Am Fam Physician. 2007 Jan 15;75(2):231-6.
15. 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 May-Jun;46(3):281-5. doi: 10.4103/0253-7613.132158.
16. Bermejo J, Yotti R, García-Orta R, Sánchez-Fernández PL, Castaño M, Segovia-Cubero J, et al. Sildenafil for Improving Outcomes after VAlvular Correction (SIOVAC) investigators. 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 Apr 14;39(15):1255-1264. doi: 10.1093/eurheartj/ehx700.
17. Chapman TH, Wilde M, Sheth A, Madden BP. Sildenafil therapy in secondary pulmonary hypertension: Is there benefit in prolonged use? Vascul Pharmacol. 2009 Aug-Sep;51(2-3):90-5. doi: 10.1016/j.vph.2009.04.002.
18. 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 Jun;33(6):1648-1656. doi: 10.1053/j.jvca.2018.12.023.
19. 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 Dec;132(6):1420-5. doi: 10.1016/j.jtcvs.2006.08.035.
20. Mickey RM, Greenland S. The impact of confounder selection criteria on effect estimation. Am J Epidemiol. 1989 Jan;129(1):125-37. doi: 10.1093/oxfordjournals.aje.a115101.
21. Podolec P, Kopec G, Rubis P, KabÅ‚ak-Ziembicka A, Rokita E, Tracz W. Calcific and degenerative aortic stenosis—pathogenesis and new possibilities of treatment. Przegl Lek. 2004; 61(6):604–8. pmid:15724645
22. Walker AM, Langleben D, Korelitz JJ, Rich S, Rubin LJ, Strom BL, et al. Temporal trends and drug exposures in pulmonary hypertension: an American experience. Am Heart J. 2006 Sep;152(3):521-6. doi: 10.1016/j.ahj.2006.02.020.
23. Frost AE, Badesch DB, Barst RJ, Benza RL, Elliott CG, Farber HW, et al. The changing picture of patients with pulmonary arterial hypertension in the United States: how REVEAL differs from historic and non-US contemporary registries. Chest. 2011. January; 139 1: 128– 37. 10.1378/chest.10-0075
24. Pugh ME, Hemnes AR. Pulmonary hypertension in women. Expert Rev Cardiovasc Ther. 2010;8(11):1549-1558. doi:10.1586/erc.10.137
25. Berra G, Noble S, Soccal PM, Beghetti M, Lador F. Pulmonary hypertension in the elderly: a different disease?. Breathe (Sheff). 2016;12(1):43-49. doi:10.1183/20734735.0034161
26. Wanamaker B, Cascino T, McLaughlin V, Oral H, Latchamsetty R, Siontis KC. Atrial Arrhythmias in Pulmonary Hypertension: Pathogenesis, Prognosis and Management. Arrhythm Electrophysiol Rev. 2018 Mar;7(1):43-48. doi: 10.15420/aer.2018.3.2.
27. Nabar A, Pathan I. Professor of Cardiology, SGPGIMS, Lucknow, Uttar Pradesh. J Assoc Physicians India. 2016 Aug;64(8 Suppl):11-15. PMID: 28812335.
28. Pourafkari L, Ghaffari S, Bancroft GR, Tajlil A, Nader ND. Factors associated with atrial fibrillation in rheumatic mitral stenosis. Asian Cardiovasc Thorac Ann. 2015 Jan;23(1):17-23. doi: 10.1177/0218492314530134.
29. Nishimura RA, Otto CM, Bonow RO, Carabello BA, Erwin JP 3rd, Fleisher LA, et al. 2017 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. Circulation. 2017 Jun 20;135(25):e1159-e1195. doi: 10.1161/CIR.0000000000000503.