Materia Medica

Vericiguat (Verquvo®)

lauRen siTTaRD, PhaRmD anD William BeaThaRD, PhaRmD, BCPs

Background: Verquvo (vericiguat) is a soluble guanylate cyclase (sGC) stimulator recently FDA approved indicated for use in adults with symptomatic chronic heart failure with an ejection fraction less than 45% (HFrEF) to reduce the risk of cardiovascular death and heart failure hospitalization following a hospitalization for heart failure or need for outpatient IV diuretics. By supplementing cardiac tissue with intracellular cyclic guanosine monophosphate, Verquvo contributes to both vasodilation and smooth muscle relaxation that may lead to a reduction in myocardial dysfunction thought to be associated with decreased sGC activity.1

Safety: Verquvo is contraindicated in patients who are currently taking other sGC stimulators or those who are pregnant. Due to the potential for embryo-fetal toxicity, it is recommended to obtain a pregnancy test prior to initiating treatment in women of reproductive potential. Furthermore, it is recommended for these patients to use contraception during therapy and for at least one month following the final dose of Verquvo.1While not mentioned in the prescribing information for Verquvo, it is important to note that for the medication Adempas (riociguat), another sGC stimulator, the concomitant use of nitrates, nitric oxide donors, and phosphodiesterase inhibitors are contraindicated due to the risk of hypotension.2

Tolerability: In a phase 3, randomized, double-blind, placebo-controlled trial 32.8% of patients receiving Verquvo experienced serious adverse effects as compared to 34.8% in the placebo group. Similarly, adverse effects, both serious and nonserious in nature, occurred to a lesser extent (80.5%) in the vericiguat group compared to placebo (81%). The most common adverse events in the treatment arm consisted of hypotension (15.4%), cardiac failure (8.9%), skin and subcutaneous tissue disorders (8.7%), anemia (7.6%), dizziness (6.7%), pneumonia (6.4%), acute kidney injury (5.3%), dyspnea (5.3%), and diarrhea (5.2%). The difference between symptomatic hypotension in the vericiguat group (9.1%) was not found to be significantly different from that of the placebo group (7.9%) (95% CI: -0.3 to 2.8%, P= 0.121). Additionally, syncope was also not found to occur at a significantly different incidence in the vericiguat group compared to the placebo group (estimated percent difference: 0.6; 95% CI: -0.5 to 1.6).3 A multicenter, randomized, double-blind, placebo-controlled, dose-finding trial observed an incidence of adverse events that differed independently with dosing ranging from 70.3% to 78.9% compared to placebo with an incidence of 77.2%. Hypotension occurred at a rate of 15.4% for those on doses of 2.5 mg to 10 mg with 11% being symptomatic hypotension. Among this same group syncope occurred in 4.4% of patients and acute kidney injury in 3.3% of patients, these rates were 1.1% and 3.3% in the placebo group, respectively.4

Efficacy: The evidence put forth by the Vericiguat Global Study in Subjects with Heart Failure with Reduced Ejection Fraction (VICTORIA) trial largely contributed to the approval of vericiguat. Approximately 60% of the 5050 study participants studied with worsening heart failure were on triple therapy of a beta blocker, mineralocorticoid antagonist, and either and ACE inhibitor, ARB, or sacubitril/ valsartan. The study included 3 subgroups; patient hospitalized within 3 months prior to randomization, those hospitalized 3-6 months prior to randomization, and those who were not hospitalized but required IV diuretics within the last three months. These patients also had to have had an elevated natriuretic peptide. The researchers defined this as an elevated natriuretic peptide was defined as a BNP ≥ 300 pg/mL or a NT-proBNP ≥ 1000 pg/ mL for patients in normal sinus rhythm and a BNP ≥ 500 pg/mL or NT-proBNP ≥ 1600 pg/ mL for patients in atrial fibrillation. This study demonstrated that in patients with HFrEF and an elevated natriuretic peptide level, over a median period of 10.8 months, vericiguat was associated with a lower incidence of a composite of death from cardiovascular causes and first hospitalization for heart failure when compared to placebo (HR: 0.90; 95% CI: 0.82 to 0.98; P= 0.02). Total hospitalizations for heart failure were found to be lower in the treatment arm when compared to placebo (HR: 0.91; 95% CI: 0.84 to 0.99; P= 0.02) as well as a composite of death from any cause and hospitalization for heart failure (HR: 0.90; 95% CI: 0.83 to 0.98; P= 0.02).3

Price: Currently, there are no generic equivalents to Verquvo on the U.S. market. The estimated retail price for a 30-day supply (30 tablets) is around $700.5

Simplicity: Vericiguat is currently available as 2.5 mg, 5 mg, and 10 mg oral tablets. The current dosing and administration recommendations per the manufacturer are a starting dose of 2.5 mg once daily with food. The recommended titration schedule increases the dose every 2 weeks, doubling the strength as tolerated until the target maintenance dose of 10 mg once daily is achieved.1 This tolerability is based on blood pressure and clinical symptoms.3

Bottom Line: Data suggests a mortality benefit with using vericiguat in select patients with worsening symptoms of HFrEF that had recently required either hospitalization or urgent treatment (IV diuretic therapy).3 Safety and tolerability data was found to be relatively similar between Verquvo and placebo, apart

from hypotension.3,4 At the present time, given no generic equivalents available, the cost of this medication may limit its use.5

At the time of authorship Lauren Sittard, PharmD is a PGY-1 Pharmacy Resident at UPMC St. Margaret and can be reached at sittardl@upmc.edu. William A. Beathard, PharmD is a PGY-2 Geriatric Pharmacy Resident at UPMC St. Margaret and can be reached at beathardwa@upmc.edu. Heather Sakely, PharmD, BCPS, BCGP provided editing and mentoring for this article and can be reached at sakelyh@upmc.edu.

References:

1. VERQUVO® (vericiguat) tablets, for oral use [prescribing information]. Available at: https://www.merck.com/product/usa/ pi_circulars/v/verquvo/verquvo_pi.pdf.

Accessed 24 October 2021.

2. ADEMPAS (riociguat) tablets, for oral use [prescribing information]. Available at: https:// labeling.bayerhealthcare.com/html/products/ pi/Adempas_PI.pdf. Accessed 3 November 2021.

3. Armstrong PW, Pieske B, Anstrom KJ, et al. Vericiguat in Patients with Heart Failure and Reduced Ejection Fraction. N Engl J

Med. 2020;382(20):1883-1893. doi:10.1056/

NEJMoa1915928

4. Gheorghiade M, Greene SJ, Butler J, et al.

Effect of Vericiguat, a Soluble Guanylate

Cyclase Stimulator, on Natriuretic Peptide

Levels in Patients With Worsening

Chronic Heart Failure and Reduced

Ejection Fraction: The SOCRATES-

REDUCED Randomized Trial. JAMA. 2015;314(21):2251-2262.

5. GoodRx. FDA Approves Verquvo for

Treatment of Heart Failure. Available at: https://www.goodrx.com/blog/fda-approvesverquvo-for-heart-failure/. Accessed 3

November 2021.

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