Vericiguat in Combination with Short-Acting Nitroglycerin in Patients With Chronic Coronary Syndromes: The Randomized, Phase Ib, VENICE Study
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Vericiguat in Combination with Short-Acting Nitroglycerin in Patients With Chronic Coronary Syndromes: The Randomized, Phase Ib, VENICE Study. / Boettcher, Michael; Düngen, Hans-Dirk; Donath, Frank; Mikus, Gerd; Werner, Nikos; Thuermann, Petra A; Karakas, Mahir; Besche, Nina; Koch, Tanja; Gurniak, Matthias; Becker, Corina.
In: CLIN PHARMACOL THER, Vol. 111, No. 6, 06.2022, p. 1239-1247.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Vericiguat in Combination with Short-Acting Nitroglycerin in Patients With Chronic Coronary Syndromes: The Randomized, Phase Ib, VENICE Study
AU - Boettcher, Michael
AU - Düngen, Hans-Dirk
AU - Donath, Frank
AU - Mikus, Gerd
AU - Werner, Nikos
AU - Thuermann, Petra A
AU - Karakas, Mahir
AU - Besche, Nina
AU - Koch, Tanja
AU - Gurniak, Matthias
AU - Becker, Corina
N1 - © 2022 Bayer AG. Clinical Pharmacology & Therapeutics published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.
PY - 2022/6
Y1 - 2022/6
N2 - 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.
AB - 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.
KW - Adult
KW - Double-Blind Method
KW - Heart Failure/drug therapy
KW - Heterocyclic Compounds, 2-Ring/adverse effects
KW - Humans
KW - Nitroglycerin/adverse effects
KW - Pyrimidines
KW - Stroke Volume/physiology
KW - Syndrome
U2 - 10.1002/cpt.2574
DO - 10.1002/cpt.2574
M3 - SCORING: Journal article
C2 - 35258101
VL - 111
SP - 1239
EP - 1247
JO - CLIN PHARMACOL THER
JF - CLIN PHARMACOL THER
SN - 0009-9236
IS - 6
ER -