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

TY - JOUR

T1 - Pulmonary vasodilation by sildenafil in acute intermediate-high risk pulmonary embolism

T2 - a randomized explorative trial

AU - Andersen, Asger

AU - Waziri, Farhad

AU - Schultz, Jacob Gammelgaard

AU - Holmboe, Sarah

AU - Becker, Søren Warberg

AU - Jensen, Tage

AU - Søndergaard, Hanne Maare

AU - Dodt, Karen Kaae

AU - May, Ole

AU - Mortensen, Ulrik Markus

AU - Kim, Won Yong

AU - Mellemkjær, Søren

AU - Nielsen-Kudsk, Jens Erik

PY - 2021/12

Y1 - 2021/12

N2 - 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://clinicaltrials.gov/ct2/show/NCT04283240?term=NCT04283240&draw=2&rank=1.

AB - 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://clinicaltrials.gov/ct2/show/NCT04283240?term=NCT04283240&draw=2&rank=1.

KW - PDE5 inhibition

KW - Pulmonary embolism

KW - Pulmonary vasodilation

KW - Sildenafil

UR - http://www.scopus.com/inward/record.url?scp=85101841803&partnerID=8YFLogxK

U2 - 10.1186/s12890-021-01440-7

DO - 10.1186/s12890-021-01440-7

M3 - Journal article

C2 - 33639897

SN - 1471-2466

VL - 21

JO - BMC Pulmonary Medicine

JF - BMC Pulmonary Medicine

IS - 1

M1 - 72

ER -