From the Guidelines
Variciguat, also known as a soluble guanylate cyclase stimulator, is a medication that has been shown to be effective in reducing the risk of cardiovascular death and heart failure hospitalization in patients with heart failure with reduced ejection fraction (HFrEF), as demonstrated in the VICTORIA trial 1.
Key Points About Variciguat
- It works by enhancing the body's nitric oxide pathway to improve heart function, providing a novel mechanism of action compared to traditional heart failure medications.
- The medication has been found to be safe and well-tolerated in high-risk HFrEF populations, including those with comorbidities such as renal impairment 1.
- Its benefit is greater in patients with lower N-terminal pro-brain natriuretic peptide levels and less effective in patients with a recent hospital admission 1.
Clinical Use and Considerations
- Variciguat has limited regulatory approval for reducing the risk of CV death and HF hospitalization following HF hospitalization or need for outpatient intravenous diuretic agents in adults with symptomatic HF and EF <45% 1.
- Given its current regulatory status and the uncertainty of its place in guideline-directed medical therapy (GDMT), its use is expected to be limited in contemporary clinical practice 1.
- As with any new medication, especially those affecting the cardiovascular system, careful patient selection, monitoring, and dose adjustment are crucial to maximize benefits while minimizing risks.
Important Considerations for Patient Care
- Patients on variciguat should be monitored for potential side effects such as hypotension and anemia.
- The medication should be used cautiously in patients with severe kidney impairment or those who are already hypotensive.
- Regular blood pressure checks are essential for patients taking variciguat to ensure safe use.
From the FDA Drug Label
Vericiguat is a stimulator of soluble guanylate cyclase (sGC), an important enzyme in the nitric oxide (NO) signaling pathway. By directly stimulating sGC, independently of and synergistically with NO, vericiguat augments levels of intracellular cGMP, leading to smooth muscle relaxation and vasodilation.
Variciguat is a soluble guanylate cyclase stimulator. It works by directly stimulating the soluble guanylate cyclase enzyme, which leads to an increase in intracellular cyclic guanosine monophosphate (cGMP) levels, resulting in smooth muscle relaxation and vasodilation 2.
From the Research
Definition and Mechanism of Action
- Vericiguat is a novel oral soluble guanylate cyclase (sGC) stimulator 3, 4, 5, 6, 7
- It works via stimulation of sGC in the critical NO-sGC-cGMP pathway, increasing cyclic guanosine monophosphate (cGMP) signaling 7
- This mechanism of action helps to reduce cardiovascular mortality and hospitalizations in patients with heart failure (HF) and reduced ejection fraction 3, 4, 5, 6
Clinical Efficacy
- Vericiguat has been shown to reduce the risk of death from cardiovascular causes or first hospitalization for heart failure in patients with symptomatic, chronic heart failure with reduced ejection fraction (HFrEF) 4, 5, 6
- The VICTORIA trial demonstrated a 10% relative reduction in the primary composite outcome of death from cardiovascular causes or first hospitalization for HF 4, 5, 6, 7
- Vericiguat was also associated with a reduction in the total number of hospitalizations for heart failure 6
Safety and Tolerability
- Vericiguat is generally well-tolerated, with the most common treatment-related adverse event being hypotension 4, 5, 6, 7
- Symptomatic hypotension and syncope occurred with low incidences, similar to those in the placebo group 4, 6, 7
- Vericiguat has a low drug-drug interaction potential, with no clinically relevant pharmacokinetic or pharmacodynamic interactions observed with common medications 7
Patient Population
- Vericiguat is approved for the treatment of adults with symptomatic, chronic heart failure with reduced ejection fraction (HFrEF) who have experienced a recent worsening event 5, 6, 7
- Patients with grossly elevated N-terminal pro-brain natriuretic peptide levels may not benefit from vericiguat therapy 6
- Vericiguat may be appropriate as add-on therapy for patients already on guideline-directed medical therapy with recent decompensated HFrEF to reduce hospitalization 5