Vericiguat
Overview:
Vericiguat is a novel agent that belongs to a class of drugs called soluble guanylate cyclase (sGC) stimulators.
- It has earned recognition as the “Fifth Pillar” of Guideline Directed Medical Treatment (GDMT) for Heart Failure with reduced ejection fraction (HFrEF).
- It was the first oral (sGC) approved in US by FDA in January (2021) and later approved in India on February (2022), based on the results of pivotal phase III VICTORIA trial.
Victoria Trial
It was a global, randomized, double-blind, parallel study that evaluated the effectiveness of vericiguat in
reducing cardiovascular death or hospitalization for heart failure in patient with chronic heart failure due to reduced
ejection fraction (EF).
Trial Design
- Patients with symptomatic chronic HFrEF (LVEF < 45%) who have recent heart failure hospitalization or need IV
- Randomization: Patient were randomized to receive vericiguat (n=2,5526) or placebo (n=2,524).
- Dosing: Vericiguat started at 2.5mg daily, increased to 5mg daily, and then 10mg daily.
- Follow-up: Patients were followed for a median of 10.8 months.
- Guideline-Directed Therapy: Patient were already receiving optimal heart failure therapy, including beta blockers, ACE
- Inhibitors/ARB
Mechanism of Action
Vericiguat directly stimulates the sGC receptor through a binding site which is independent of nitric oxide. It also increases sensitivity of sGC to endogenous nitric oxide by stabilizing the nitric oxide binding site leading to smooth muscle relation and vasodilation that may improve cardiac function.
Resistance concerns: There’s no current documented evidence of resistance or tolerance development to Vericiguat.
Embryo-Fetal Toxicity
Animal reproduction studies suggest that vericiguat may cause fetal harm to a pregnant woman.
Females of reproductive age are to be counselled on the potential hazard to a fetus. Clinicians should order pregnancy
tests before treatment with vericiguat. Advise females to use contraception during treatment and at least one month after
the final dose of vericiguat.
Drug-Drug Interactions
Administration of omeprazole with vericiguat reduces the absorption of vericiguat. Magnesium
hydroxide and aluminum hydroxide also decreased the absorption of vericiguat. Drug-drug interaction study indicated
that vericiguat is a suitable drug for managing patients with heart failure with multiple comorbidities requiring
polypharmacy.
