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- Armstrong, Paul W, et al.
(författare)
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Vericiguat in Patients with Heart Failure and Reduced Ejection Fraction.
- 2020
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Ingår i: New England Journal of Medicine. - 0028-4793 .- 1533-4406. ; 382:20, s. 1883-1893
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The effect of vericiguat, a novel oral soluble guanylate cyclase stimulator, in patients with heart failure and reduced ejection fraction who had recently been hospitalized or had received intravenous diuretic therapy is unclear.METHODS: In this phase 3, randomized, double-blind, placebo-controlled trial, we assigned 5050 patients with chronic heart failure (New York Heart Association class II, III, or IV) and an ejection fraction of less than 45% to receive vericiguat (target dose, 10 mg once daily) or placebo, in addition to guideline-based medical therapy. The primary outcome was a composite of death from cardiovascular causes or first hospitalization for heart failure.RESULTS: Over a median of 10.8 months, a primary-outcome event occurred in 897 of 2526 patients (35.5%) in the vericiguat group and in 972 of 2524 patients (38.5%) in the placebo group (hazard ratio, 0.90; 95% confidence interval [CI], 0.82 to 0.98; P = 0.02). A total of 691 patients (27.4%) in the vericiguat group and 747 patients (29.6%) in the placebo group were hospitalized for heart failure (hazard ratio, 0.90; 95% CI, 0.81 to 1.00). Death from cardiovascular causes occurred in 414 patients (16.4%) in the vericiguat group and in 441 patients (17.5%) in the placebo group (hazard ratio, 0.93; 95% CI, 0.81 to 1.06). The composite of death from any cause or hospitalization for heart failure occurred in 957 patients (37.9%) in the vericiguat group and in 1032 patients (40.9%) in the placebo group (hazard ratio, 0.90; 95% CI, 0.83 to 0.98; P = 0.02). Symptomatic hypotension occurred in 9.1% of the patients in the vericiguat group and in 7.9% of the patients in the placebo group (P = 0.12), and syncope occurred in 4.0% of the patients in the vericiguat group and in 3.5% of the patients in the placebo group (P = 0.30).CONCLUSIONS: Among patients with high-risk heart failure, the incidence of death from cardiovascular causes or hospitalization for heart failure was lower among those who received vericiguat than among those who received placebo. (Funded by Merck Sharp & Dohme [a subsidiary of Merck] and Bayer; VICTORIA ClinicalTrials.gov number, NCT02861534.).
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| 2. |
- Gheorghiade, Mihai, et al.
(författare)
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Effect of Vericiguat, a Soluble Guanylate Cyclase Stimulator, on Natriuretic Peptide Levels in Patients With Worsening Chronic Heart Failure and Reduced Ejection Fraction : The SOCRATES-REDUCED Randomized Trial.
- 2015
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Ingår i: Journal of the American Medical Association (JAMA). - : American Medical Association (AMA). - 0098-7484 .- 1538-3598. ; 314:21, s. 2251-2262
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Tidskriftsartikel (refereegranskat)abstract
- IMPORTANCE: Worsening chronic heart failure (HF) is a major public health problem.OBJECTIVE: To determine the optimal dose and tolerability of vericiguat, a soluble guanylate cyclase stimulator, in patients with worsening chronic HF and reduced left ventricular ejection fraction (LVEF).DESIGN, SETTING, AND PARTICIPANTS: Dose-finding phase 2 study that randomized 456 patients across Europe, North America, and Asia between November 2013 and January 2015, with follow-up ending June 2015. Patients were clinically stable with LVEF less than 45% within 4 weeks of a worsening chronic HF event, defined as worsening signs and symptoms of congestion and elevated natriuretic peptide level requiring hospitalization or outpatient intravenous diuretic.INTERVENTIONS: Placebo (n = 92) or 1 of 4 daily target doses of oral vericiguat (1.25 mg [n = 91], 2.5 mg [n = 91], 5 mg [n = 91], 10 mg [n = 91]) for 12 weeks.MAIN OUTCOMES AND MEASURES: The primary end point was change from baseline to week 12 in log-transformed level of N-terminal pro-B-type natriuretic peptide (NT-proBNP). The primary analysis specified pooled comparison of the 3 highest-dose vericiguat groups with placebo, and secondary analysis evaluated a dose-response relationship with vericiguat and the primary end point.RESULTS: Overall, 351 patients (77.0%) completed treatment with the study drug with valid 12-week NT-proBNP levels and no major protocol deviation and were eligible for primary end point evaluation. In primary analysis, change in log-transformed NT-proBNP levels from baseline to week 12 was not significantly different between the pooled vericiguat group (log-transformed: baseline, 7.969; 12 weeks, 7.567; difference, -0.402; geometric means: baseline, 2890 pg/mL; 12 weeks, 1932 pg/mL) and placebo (log-transformed: baseline, 8.283; 12 weeks, 8.002; difference, -0.280; geometric means: baseline, 3955 pg/mL; 12 weeks, 2988 pg/mL) (difference of means, -0.122; 90% CI, -0.32 to 0.07; ratio of geometric means, 0.885, 90% CI, 0.73-1.08; P = .15). The exploratory secondary analysis suggested a dose-response relationship whereby higher vericiguat doses were associated with greater reductions in NT-proBNP level (P < .02). Rates of any adverse event were 77.2% and 71.4% among the placebo and 10-mg vericiguat groups, respectively.CONCLUSIONS AND RELEVANCE: Among patients with worsening chronic HF and reduced LVEF, compared with placebo, vericiguat did not have a statistically significant effect on change in NT-proBNP level at 12 weeks but was well-tolerated. Further clinical trials of vericiguat based on the dose-response relationship in this study are needed to determine the potential role of this drug for patients with worsening chronic HF.TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01951625.
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