Copyright ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Cardiol. Oct 26, 2020; 12(10): 501-512
Published online Oct 26, 2020. doi: 10.4330/wjc.v12.i10.501
Safety and efficacy of soluble guanylate cyclase stimulators in patients with heart failure: A systematic review and meta-analysis
Waqas Ullah, Maryam Mukhtar, Aws Al-Mukhtar, Rehan Saeed, Margot Boigon, Donald Haas, Eduardo Rame
Waqas Ullah, Rehan Saeed, Margot Boigon, Donald Haas, Department of Internal Medicine, Abington Jefferson Health, Abington, PA 19001, United States
Maryam Mukhtar, Department of Cardiology, Rawalpindi Institute of Cardiology, Rawalpindi 44000, Punjab, Pakistan
Aws Al-Mukhtar, Department of Surgery and Cancer, Imperial College London, London SW7 2AZ, United Kingdom
Eduardo Rame, Department of Cardiology, Thomas Jefferson University, Philadelphia, PA 19001, United States
Author contributions: Ullah W contributed to the conceptualization, writing, data analysis; Al-Mukhtar A contributed to the data curation; Mukhtar M contributed to the investigation; Al-Mukhtar A and Mukhtar M wrote the original draft; Saeed R and Ullah W contributed to the review and editing; Ullah W and Boigon M contributed to the project administration; Haas D and Rame E contributed to the supervision and validation.
Conflict-of-interest statement: The authors deny any conflict of interest.
PRISMA 2009 Checklist statement: The authors have read the PRISMA 2009 Checklist, and the manuscript was prepared and revised according to the PRISMA 2009 Checklist.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Corresponding author: Waqas Ullah, MD, Doctor, Department of Internal Medicine, Abington Jefferson Health, 1200 Old York Road, Abington, PA 19001, United States.
Received: May 7, 2020
Peer-review started: May 7, 2020
First decision: May 24, 2020
Revised: May 31, 2020
Accepted: September 11, 2020
Article in press: September 11, 2020
Published online: October 26, 2020
Research background

Despite treatment with traditional pharmacologic management, patients with heart failure (HF) have a dismal prognosis, with approximately 1 million HF-related hospitalizations (HHF) occurring annually, accounting for over 6.5 million hospital days and $37.2 billion each year.

Research motivation

This has led researchers to study the efficacy of alternate drugs in preventing HF exacerbations, which include soluble guanylate cyclase (sGC) stimulators vericiguat and riociguat. Multiple clinical trials have attempted to explore the utility of vericiguat and riociguat in patients with HF. However, there a lack of large scale studies to determine the true merits of sGC stimulators in patients with HF.

Research objectives

Therefore, we performed this meta-analysis to determine the efficacy and safety of sGC stimulators in HF patients.

Research methods

The MEDLINE (PubMed, Ovid), Embase, and Cochrane databases were queried with various combinations of medical subject headings (MeSH) to identify relevant articles. All randomized control trials (RCT) until March 31, 2020, comparing the safety and efficacy of sGC in HF were evaluated for inclusion. The primary efficacy endpoint was a composite of the first hospitalization for HF and death from cardiovascular causes. The secondary efficacy endpoints were the components of the primary outcome, total HF-related hospitalizations, cardiovascular and all-cause mortality. The statistical analysis was performed using the Cochran–Mantel–Haenszel test on a random-effect model to calculate relative risk (RR) for the dichotomous outcomes of RCTs. The overall quality of the included RCTs was high.

Research results

Six RCTs comprising 5604 patients (2801 sGC stimulator and 2803 placebo) were included. The primary endpoint (a composite of cardiovascular mortality and first HF-related hospitalization) was reduced in patients receiving sGC stimulators compared to placebo [RR 0.92, 95% confidence interval (CI): 0.85-0.99, P = 0.02]. The incidence of total HF-related hospitalizations were also lower in sGC group (RR 0.91, 95%CI: 0.86-0.96, P = 0.0009), however, sGC stimulators had no impact on all-cause and cardiovascular mortality (RR 0.96, 95%CI: 0.86-1.07, P = 0.45) and (RR 0.94, 95%CI: 0.83-1.06, P = 0.29), respectively. The overall safety endpoints (composite of hypotension and syncope) were also identical between the two groups (RR 1.50, 95%CI: 0.93-2.42, P = 0.10). For the primary composite endpoint, the number needed to treat was 35, the number needed to harm was -44 and the overall net clinical benefit was -9.

Research conclusions

Data published in literature revealed no additional benefits to guideline-based medical therapy in reducing incidence of HF hospitalization and mortality with sGC stimulator use. Large scale studies are required to determine the efficacy of sGC stimulators in patients with HF.

Research perspectives

As it is unclear whether sGC stimulators have any additional benefit in improving the prognosis of HF patients due to a lack of substantial research, large scale studies are needed to determine their efficacy in reducing HF related hospitalization rates.