Efficacy of Sildenafil in Patients with Severe COVID-19 and Pulmonary Arterial Hypertension

Oleksandr Valentynovych Oliynyk; Marta Rorat; Olena Vadymivna Strepetova; Serhij Oleksandrovych Dubrov; Vitaliy Grygorovych Guryanov; Yanina Volodymyrivna Oliynyk; Oleksii Serhijovych Kulivets; Anna Ślifirczyk; Wojciech Barg

doi:10.3390/v15051157

Efficacy of Sildenafil in Patients with Severe COVID-19 and Pulmonary Arterial Hypertension

Viruses. 2023 May 11;15(5):1157. doi: 10.3390/v15051157.

Affiliations

¹ Department of Anaesthesiology and Intensive Care, Bogomolets National Medical University, 01601 Kyiv, Ukraine.
² Department of Emergency Medicine, Rzeszow University, 35-310 Rzeszow, Poland.
³ Department of Forensic Medicine, Wroclaw Medical University, 50-367 Wroclaw, Poland.
⁴ Commercial Hospital "Manufaktura", 08173 Kyiv, Ukraine.
⁵ Commercial Hospital "Raiering", 02121 Kyiv, Ukraine.
⁶ Department of Medical Statistics, Bogomolets National Medical University, 01601 Kyiv, Ukraine.
⁷ Nursing Department, Siedlce University of Natural Sciences and Humanities, 08-110 Siedlce, Poland.
⁸ Department of Human Physiology, Rzeszow University, 35-310 Rzeszow, Poland.

Abstract

Pulmonary arterial hypertension (PAH) is common in severe coronavirus disease 2019 (COVID-19) and worsens the prognosis. Sildenafil, a phosphodiesterase-5 inhibitor, is approved for PAH treatment but little is known about its efficacy in cases of severe COVID-19 with PAH. This study aimed to investigate the clinical efficacy of sildenafil in patients with severe COVID-19 and PAH. Intensive care unit (ICU) patients were randomly assigned to receive sildenafil or a placebo, with 75 participants in each group. Sildenafil was administered orally at 0.25 mg/kg t.i.d. for one week in a placebo-controlled, double-blind manner as an add-on therapy alongside the patient's routine treatment. The primary endpoint was one-week mortality, and the secondary endpoints were the one-week intubation rate and duration of ICU stay. The mortality rate was 4% vs. 13.3% (p = 0.078), the intubation rate was 8% and 18.7% (p = 0.09), and the length of ICU stay was 15 vs. 19 days (p < 0.001) for the sildenafil and placebo groups, respectively. If adjusted for PAH, sildenafil treatment significantly reduced mortality and intubation risks: OR = 0.21 (95% CI: 0.05-0.89) and OR = 0.26 (95% CI: 0.08-0.86), respectively. Sildenafil demonstrated some clinical efficacy in patients with severe COVID-19 and PAH and should be considered as an add-on therapy in these patients.

Keywords: SARS-CoV-2; pulmonary artery pressure; respiratory failure; sildenafil.

Publication types

Randomized Controlled Trial
Research Support, Non-U.S. Gov't

MeSH terms

COVID-19*
Humans
Hypertension, Pulmonary* / drug therapy
Pulmonary Arterial Hypertension* / drug therapy
Sildenafil Citrate / therapeutic use
Treatment Outcome

Substances

Sildenafil Citrate

Grants and funding

The study was a part of the clinical research “Optimisation of respiratory support methods for patients with severe forms of respiratory insufficiency, including acute respiratory distress syndrome”, conducted in the Department of Anaesthesiology and Intensive Care, Bohomolets National Medical University, Kyiv, Ukraine, and registered in the Clinical Trials Register of the State Expert Centre of the Ministry of Health of Ukraine (registration number 0119U100684). This work was also carried out according to the subject register in Simple system SUBZ.A120.23.071 and supported by a statutory subsidy granted by the Ministry of Science and Higher Education in Poland.