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VERQUVO (vériciguat) (insuffisance cardiaque chronique symptomatique)

Opinions on drugs - Posted on Mar 18 2022

Reason for request

First assessment

Key points

Favourable opinion for reimbursement in the treatment of symptomatic chronic heart failure, in addition to optimised standard of care therapy, in adult patients with reduced ejection fraction who are stabilised after a recent decompensation event requiring IV therapy and who remain symptomatic (NYHA class II to IV) despite this treatment.

 What therapeutic improvement?

No clinical added value in the therapeutic strategy.

Role in the care pathway?

According to the European and international guidelines, updated in 2021, in addition to lifestyle and dietary measures and control of cardiovascular risk factors, the management of adults with symptomatic (NYHA class II to IV) heart failure with reduced ejection fraction is based on optimised standard of care therapy, which includes:

  • an angiotensin converting enzyme (ACE) inhibitor, or an angiotensin receptor blocker (ARB) in the event of contraindication or intolerance to ACE inhibitors.

For ACE inhibitor naïve patients, the initiation of treatment with the sacubitril/valsartan fixed-dose combination should be considered, in the event of contraindication or intolerance;

  • a beta-blocker, in clinically stable patients only;
  • a mineralocorticoid receptor antagonist (MRA) (spironolactone or eplerenone) in patients who remain symptomatic with an LVEF ≤ 35%, despite optimal ACE inhibitor (or ARB) / beta-blocker treatment;
  •  ± a loop diuretic in the event of signs and symptoms of congestion.

In the event of persistent symptoms and an LVEF ≤ 35% despite optimal ACE inhibitor (or ARB) / beta-blocker / mineralocorticoid receptor antagonist (MRA) treatment, the sacubitril/valsartan fixed-dose combination is recommended in place of the ACE inhibitor (or ARB).

It should be noted that the Committee considers that the proprietary medicinal product ENTRESTO (sacubitril/valsartan) may be proposed to patients with NYHA class II or III heart failure with an LVEF ≤ 35%, who remain symptomatic despite ACE inhibitor or ARB treatment and require treatment modification (opinion following the re-evaluation on 11 January 2017).

The addition of a sodium-glucose co-transporter 2 inhibitor (SGLT-2) (empagliflozin or dapagliflozin) to optimised standard of care therapy with an ACE inhibitor (or ARB) or sacubitril/valsartan fixed-dose combination / beta-blocker / mineralocorticoid receptor antagonist (MRA) is now recommended, in the absence of contraindications, irrespective of diabetes status (Committee opinion for the indication extension for FORXIGA (dapagliflozin) of 24 March 2021 and JARDIANCE (empagliflozin) of 05 January 2022).

According to the latest guidelines, ivabradine should be considered in symptomatic patients with an LVEF ≤ 35%, in sinus rhythm with a resting heart rate ≥ 70 bpm, despite optimised standard of care therapy with an ACE inhibitor (or ARB) / beta-blocker / mineralocorticoid receptor antagonist (MRA). It should be noted that the Committee considered that the proprietary medicinal product PROCORALAN (ivabradine) should be reserved for patients with NYHA class II or III heart failure with a reduced LVEF, in sinus rhythm, with a heart rate ≥ 77 bpm despite optimised treatment and in whom beta-blockers are contraindicated or poorly tolerated (opinion for renewal of inclusion on 19 July 2017).

In the event of resistant symptoms, intolerance or contraindications, the addition of other treatments (digoxin, hydralazine / isosorbide dinitrate), a left ventricular assist device (LVAD) or heart transplantation should be envisaged.

Cardiac resynchronisation and implantation of a cardiac defibrillator may also be envisaged depending on the patient’s profile.

Role of VERQUVO (vericiguat) in the care pathway

In the medicinal strategy, VERQUVO (vericiguat) may be proposed in addition to optimised standard of care therapy, in adults with chronic heart failure with reduced ejection fraction (LVEF ≤ 45%) who are stabilised after a recent decompensation event requiring IV therapy, i.e., patients hospitalised in the past 6 months or treated with diuretics (without hospitalisation) in the past 3 months, and who remain symptomatic (NYHA class II to IV) despite this treatment.

The Committee considers that optimisation of treatment prior to the prescription of VERQUVO (vericiguat) implies having used medicinal products in accordance with the recommended strategy and at the maximum tolerated dose.

In the absence of comparison with gliflozins, VERQUVO (vericiguat) cannot be positioned compared to these medicinal products.


Clinical Benefit
Moderate

The Committee deems that the clinical benefit of VERQUVO (vericiguat) is moderate, in addition to optimised standard of care therapy, in adults with chronic heart failure with reduced ejection fraction who are stabilised after a recent decompensation event requiring IV therapy, and who remain symptomatic (NYHA class II to IV) despite this treatment.

Clinical Added Value
no clinical added value

Considering:

  • demonstration of the superiority of vericiguat in combination with optimised standard of care therapy compared to placebo, in a randomised, double-blind study having included adult patients with chronic heart failure with reduced ejection fraction (LVEF ≤ 45%) having been recently hospitalised for HF in the past 6 months or treated with IV diuretics in the past 3 months, in terms of:
    • reduction in the number of cardiovascular events, a composite primary endpoint combining cardiovascular death and hospitalisation for heart failure (HR=0.90; CI95% [0.82; 0.98]; p=0.019);
    • time to occurrence of HF hospitalisation (ranked secondary endpoint) (first and recurrent) (HR=0.91; CI95% [0.84; 0.99]; p=0.023);
  • the good safety profile of vericiguat based on the available study data and current pharmacovigilance data;

but in view of:

  • the modest effect size of the results demonstrated for the primary endpoint and the ranked secondary endpoints;
  • the absence of a demonstrated impact on cardiovascular mortality (exploratory analysis), and on all-cause mortality (non-significant ranked secondary endpoint);
  • the absence of robust data enabling a conclusion to be reached relative to quality of life, which is particularly impacted in this disease;
  • the absence of direct comparative data versus gliflozins, nonetheless considered to be developed concomitantly in this indication,

the Committee considers that the addition of VERQUVO (vericiguat) to optimised standard of care therapy provides no clinical added value (CAV V), in the care pathway for the treatment of adults with chronic heart failure with reduced ejection fraction (LVEF ≤ 45%) who are stabilised after a recent decompensation event requiring IV therapy.

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