Vericiguat in Combination with Short-Acting Nitroglycerin in Patients With Chronic Coronary Syndromes: The Randomized, Phase Ib, VENICE Study.

Abstract

Vericiguat is a soluble guanylate cyclase stimulator indicated to reduce the risk of cardiovascular death and heart failure (HF) hospitalization in adults with symptomatic chronic HF and ejection fraction less than 45%. Guidelines recommend short-acting nitrates, such as sublingual nitroglycerin, for the treatment of acute angina pectoris in patients with chronic coronary syndromes (CCSs), common comorbidities in HF. We evaluated safety, tolerability, and the pharmacodynamic interaction between vericiguat and nitroglycerin, coadministered in patients with CCSs. In this phase Ib, double-blind, randomized, multicenter study, 36 patients with CCSs received either vericiguat 2.5 mg (up-titrated every 2 weeks to 5 mg and 10 mg) or placebo. Patients also received nitroglycerin (0.4 mg sublingual). In total, 31 patients completed the study (vericiguat + nitroglycerin, n = 21; placebo + nitroglycerin, n = 10). There was no increase in treatment-emergent adverse events (TEAEs) with vericiguat + nitroglycerin vs. placebo + nitroglycerin; three patients discontinued due to TEAEs (vericiguat + nitroglycerin, n = 1; placebo + nitroglycerin, n = 2). Decreases in mean blood pressure (BP; 6-10 mmHg systolic BP (SBP); 4-6 mmHg diastolic BP (DBP)) were independent of vericiguat exposure and occurred to a similar extent at trough and peak concentrations with all vericiguat doses and placebo. Coadministration of vericiguat with nitroglycerin in patients with CCSs was well tolerated, and the combination is unlikely to cause significant adverse effects beyond those known for nitroglycerin.

• Authors: Michael Boettcher, Hans-Dirk Düngen, Frank Donath, Gerd Mikus, Nikos Werner, Petra A Thuermann, Mahir Karakas, Nina Besche, Tanja Koch, Matthias Gurniak, Corina Becker
• Journal: Clinical pharmacology and therapeutics (Clin Pharmacol Ther) Vol. 111 Issue 6 Pg. 1239-1247 (06 2022) ISSN: 1532-6535 [Electronic] United States
• PMID: 35258101 (Publication Type: Clinical Trial, Phase I, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: © 2022 Bayer AG. Clinical Pharmacology & Therapeutics published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.

Chemical References

• Heterocyclic Compounds, 2-Ring
• Pyrimidines
• Nitroglycerin
• vericiguat

Topics

• Adult
• Double-Blind Method
• Heart Failure (drug therapy)
• Heterocyclic Compounds, 2-Ring (adverse effects)
• Humans
• Nitroglycerin (adverse effects)
• Pyrimidines
• Stroke Volume (physiology)
• Syndrome