What are the side effects of Vericiguat (vericiguat)?

Side Effects of Vericiguat

The most common side effects of vericiguat include symptomatic hypotension (9.1%), syncope (4.0%), and anemia, with hypotension being the most clinically significant adverse effect requiring monitoring during therapy. 1, 2

Common Side Effects

• Hypotension-related effects:

  • Symptomatic hypotension (9.1% vs 7.9% with placebo)
  • Syncope (4.0% vs 3.5% with placebo)
  • Dizziness
  • Presyncope

• Other reported adverse effects:

  • Anemia
  • Headache
  • Dyspepsia (digestive discomfort)
  • Peripheral edema

Incidence and Risk Factors

The VICTORIA trial, which studied vericiguat in high-risk heart failure patients with reduced ejection fraction (HFrEF), demonstrated that while hypotension-related side effects were more common with vericiguat than placebo, the differences were not statistically significant 2:

• Symptomatic hypotension: 9.1% vs 7.9% (p=0.12)
• Syncope: 4.0% vs 3.5% (p=0.30)

Patients at higher risk for hypotension include:

• Those with systolic blood pressure <100 mmHg
• Patients on concomitant long-acting nitrates
• Patients with severe renal impairment (eGFR <15 mL/min/1.73m²)

Contraindications and Drug Interactions

• Absolute contraindications:

  • Concomitant use with PDE-5 inhibitors (sildenafil, tadalafil) due to risk of severe hypotension 3
  • Pregnancy due to teratogenic potential

• Drug interactions:

  • Limited experience with long-acting nitrates (potential for additive hypotension)
  • Phosphodiesterase type-5 inhibitors (combination not recommended due to increased risk of symptomatic hypotension) 4

Monitoring and Management

1. Blood pressure monitoring:

   • Essential during dose titration
   • Starting dose is 1 mg three times daily
   • Titrate by 0.5 mg increments at 2-week intervals
   • Maximum dose of 2.5 mg three times daily

2. Special populations:

   • Assess smoking status (smoking increases vericiguat metabolism, potentially requiring higher doses) 3
   • No dose adjustments needed for age, sex, race, or hepatic/renal impairment in adult HFrEF patients 4

3. Management of hypotension:

   • Temporary dose reduction or discontinuation if symptomatic hypotension occurs
   • Ensure adequate hydration status
   • Review and potentially adjust other antihypertensive medications

Efficacy Considerations

The 2022 AHA/ACC/HFSA Heart Failure Guidelines note that vericiguat has shown a 10% relative risk reduction in the primary outcome of cardiovascular death or heart failure hospitalization compared to placebo 1. However, this benefit was not observed in patients with the highest NT-proBNP levels (>5314 pg/mL) 1.

A recent 2024 American Heart Association scientific statement notes that vericiguat is well tolerated without meaningful effects on blood pressure, but it did not improve quality of life in its landmark clinical trial, which may prompt consideration of deprescribing in palliative care settings 1.

Clinical Pearls

• Vericiguat should be initiated and monitored at specialized centers by physicians experienced in treating heart failure 3
• The drug has a half-life of approximately 20 hours in healthy volunteers and 30 hours in patients with HFrEF 4
• Most drug metabolism is achieved by glucuronidation 4
• Vericiguat has high oral bioavailability (93%) when taken with food 4

Careful patient selection and monitoring can help minimize the risk of side effects while maximizing the potential benefits of vericiguat therapy in appropriate heart failure patients.