Pulmonary vasodilation by sildenafil in acute intermediate-high risk pulmonary embolism: a randomized explorative trial

Asger Andersen, Farhad Waziri, Jacob Gammelgaard Schultz, Sarah Holmboe, Søren Warberg Becker, Tage Jensen, Hanne Maare Søndergaard, Karen Kaae Dodt, Ole May, Ulrik Markus Mortensen, Won Yong Kim, Søren Mellemkjær, Jens Erik Nielsen-Kudsk, Asger Andersen, Farhad Waziri, Jacob Gammelgaard Schultz, Sarah Holmboe, Søren Warberg Becker, Tage Jensen, Hanne Maare Søndergaard, Karen Kaae Dodt, Ole May, Ulrik Markus Mortensen, Won Yong Kim, Søren Mellemkjær, Jens Erik Nielsen-Kudsk

Abstract

Background: To investigate if acute pulmonary vasodilation by sildenafil improves right ventricular function in patients with acute intermediate-high risk pulmonary embolism (PE).

Methods: Single center, explorative trial. Patients with PE were randomized to a single oral dose of sildenafil 50 mg (n = 10) or placebo (n = 10) as add-on to conventional therapy. The time from hospital admission to study inclusion was 2.3 ± 0.7 days. Right ventricular function was evaluated immediately before and shortly after (0.5-1.5 h) randomization by right heart catheterization (RHC), trans-thoracic echocardiography (TTE), and cardiac magnetic resonance (CMR). The primary efficacy endpoint was cardiac index measured by CMR.

Results: Patients had acute intermediate-high risk PE verified by computed tomography pulmonary angiography, systolic blood pressure of 135 ± 18 (mean ± SD) mmHg, increased right ventricular/left ventricular ratio 1.1 ± 0.09 and increased troponin T 167 ± 144 ng/L. Sildenafil treatment did not improve cardiac index compared to baseline (0.02 ± 0.36 l/min/m2, p = 0.89) and neither did placebo (0.00 ± 0.34 l/min/m2, p = 0.97). Sildenafil lowered mean arterial blood pressure (- 19 ± 10 mmHg, p < 0.001) which was not observed in the placebo group (0 ± 9 mmHg, p = 0.97).

Conclusion: A single oral dose of sildenafil 50 mg did not improve cardiac index but lowered systemic blood pressure in patients with acute intermediate-high risk PE. The time from PE to intervention, a small patient sample size and low pulmonary vascular resistance are limitations of this study that should be considered when interpreting the results.

Trial registration: The trial was retrospectively registered at www.clinicaltrials.gov (NCT04283240) February 2nd 2020, https://ichgcp.net/clinical-trials-registry/NCT04283240?term=NCT04283240&draw=2&rank=1 .

Keywords: PDE5 inhibition; Pulmonary embolism; Pulmonary vasodilation; Sildenafil.

Conflict of interest statement

AA have received travel grants and lecturing fees from MSD, Medtronic, Abbot, Astra Zenica, Boehringer Ingelheim. JS has received lecturing fees from MSD. SB have received travel grants from Pfizer/BMS and Boehringer Ingelheim. HMS have received travel grants and lecturing fees from Astra Zeneca. SM, WYK, OM, SH, KKD, FW, JENK, TJ, UMM report no competing interests.

Figures

Fig. 1
Fig. 1
Study design. CMR cardiac magnetic resonance imaging. TTE trans-thoracic echocardiography. RCH right heart catheterization. R randomisation sildenafil 50 mg or placebo. *Measurement of blood pressure
Fig. 2
Fig. 2
a Primary efficacy endpoint. CI cardiac index measured by cardiac magnetic resonance imaging, b safety endpoint. MAP mean arterial blood pressure. ***p < 0.001

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