Vericiguat for Heart Failure with Reduced Ejection Fraction
Vericiguat is indicated specifically for high-risk patients with symptomatic chronic heart failure and ejection fraction less than 45% who have recently experienced worsening heart failure (hospitalization within 6 months or outpatient IV diuretics within 3 months) while already on guideline-directed medical therapy. 1, 2
Patient Selection Criteria
You should prescribe vericiguat only when ALL of the following criteria are met:
- Left ventricular ejection fraction <45% 1, 3
- NYHA Class II-IV symptoms 3
- Recent worsening heart failure event:
- Already on guideline-directed medical therapy (beta-blocker, RAS inhibitor/ARNI, and MRA when tolerated) 4, 2
- Elevated natriuretic peptides 2
Dosing Protocol
Start vericiguat at 2.5 mg once daily with food, then double the dose approximately every 2 weeks to reach the target maintenance dose of 10 mg once daily. 1, 4
The titration schedule is:
- Week 0-2: 2.5 mg once daily
- Week 2-4: 5 mg once daily
- Week 4+: 10 mg once daily (target dose) 1
In clinical trials, 90% of patients achieved the 10 mg target dose, with a mean daily dose of 9.2 mg. 4, 1
For patients with difficulty swallowing, tablets may be crushed and mixed with water. 1
Absolute Contraindications
Do not prescribe vericiguat in the following situations:
- Pregnancy (causes fetal harm - BLACK BOX WARNING) 1
- Concomitant use with other soluble guanylate cyclase stimulators 1
- Systolic blood pressure <100 mmHg 2
- eGFR <15 mL/min/1.73 m² 2
Clinical Efficacy Data
Vericiguat reduces the composite endpoint of cardiovascular death or heart failure hospitalization by 10% compared to placebo (HR 0.90,95% CI 0.82-0.98, p=0.019). 2, 3
Specific outcomes from the VICTORIA trial:
- Primary composite endpoint: 35.5% vs 38.5% (4.2% absolute risk reduction per year) 1, 3
- Heart failure hospitalization: 27.4% vs 29.6% (HR 0.90) 1, 3
- Cardiovascular death: 16.4% vs 17.5% (HR 0.93, not statistically significant) 1, 3
Important nuance: Vericiguat showed greater benefit in patients with lower NT-proBNP levels and was less effective in those with very recent hospitalization. 4
Common Adverse Effects
The most common adverse reactions (≥5%) are:
Drug Interactions
Concomitant use with PDE-5 inhibitors (sildenafil, tadalafil) is not recommended. 1
No clinically significant interactions occur with:
Vericiguat can be safely combined with short-acting nitroglycerin for acute angina, though blood pressure monitoring is warranted. 6
Mechanism of Action
Vericiguat directly stimulates soluble guanylate cyclase (sGC), increasing cyclic GMP production independently of nitric oxide availability. 5, 7 This leads to vasodilation, improved endothelial function, and decreased cardiac fibrosis and remodeling. 2, 7
The critical distinction is that vericiguat works even when the NO-sGC-cGMP pathway is impaired, which is common in heart failure. 5, 7
Place in Therapy
Vericiguat currently has uncertain placement in guideline-directed medical therapy and is not considered first-line. 4
The 2022 ACC/AHA guidelines position vericiguat as:
- An add-on therapy for selected high-risk patients already on optimal GDMT (beta-blocker, ARNI/ACEi/ARB, MRA, and ideally SGLT2 inhibitor) 4
- Most appropriate after recent decompensation despite standard therapy 2, 8
Critical pitfall: Do not use vericiguat as a substitute for foundational HFrEF therapies (ARNI/ACEi/ARB, beta-blockers, MRAs, SGLT2 inhibitors), which have stronger mortality benefits and Class I recommendations. 4
Special Populations
Females of reproductive potential: Exclude pregnancy before starting treatment and use effective contraception during treatment and for one month after stopping. 1
Breastfeeding: Not recommended. 1
Renal impairment: Vericiguat was safe and well-tolerated in patients with renal impairment in clinical trials, though avoid if eGFR <15 mL/min/1.73 m². 4, 2 Urinary excretion is low, and no dose adjustment is needed for mild-moderate renal dysfunction. 5