BACKGROUND: Vericiguat, a direct stimulator of soluble guanylate cyclase, has 
been developed as a first-in-class therapy for symptomatic chronic heart failure 
(HF) and ejection fraction < 45%.
METHODS: Safety, pharmacodynamic (PD), and pharmacokinetic (PK) interactions 
between vericiguat and drugs used in HF (sacubitril/valsartan [SV] and aspirin 
[acetylsalicylic acid]) or with a narrow therapeutic index (warfarin) were 
evaluated in three phase I studies.
RESULTS: Vericiguat 15 mg (single dose [SD]) had no effect on bleeding time or 
platelet aggregation when coadministered with aspirin 1000 mg versus aspirin 
alone: estimated differences in least squares means 2.7% (95% confidence 
interval [CI] - 90.4 to 95.8) and 2.4% (95% CI - 7.0 to 11.8) turbidimetry, 
respectively. Vericiguat 10 mg (once daily) had no effect on coagulation 
inhibition elicited by warfarin 25 mg (SD; mean ratios of area under the 
concentration-time curve from time zero to 96 h for clotting parameter treatment 
comparisons approximated 100.0%). There were no clinically relevant PD changes 
whether SV 97/103 mg was administered with single or multiple doses of 
vericiguat 2.5 mg or placebo (differences in systolic blood pressure 
[BP] - 1.66 mmHg [90% CI - 4.22 to 0.90]; diastolic BP - 1.80 mmHg [90% 
CI - 3.24 to - 0.36]; heart rate - 0.33 beats/min [90% CI - 2.25 to 1.60]). 
Vericiguat demonstrated no PK interactions when coadministered with aspirin, 
warfarin, or SV at steady state. Treatments were well tolerated.
CONCLUSIONS: Coadministration of vericiguat with SV, aspirin, or warfarin was 
well tolerated. No clinically relevant PD or PK interactions were observed, 
supporting concomitant use of these drugs, commonly used by patients with HF, 
with vericiguat and no dose adjustment.
EUDRACT NUMBER: 2014-000765-52; 2014-004880-19; 2015-004809-16.