Vericiguat (1) – Verquvo®

• Clinical trials
  • The pharmaceutical manufacturer presents the placebo-controlled, double-blind, randomised VICTORIA trial, in which patients with chronic heart failure in NYHA classes II to IV and a reduced left ventricular ejection fraction (LVEF) of ≤ 45 per cent.

Adults with symptomatic, chronic heart failure with reduced ejection fraction who have been stabilised following a recent episode of decompensation requiring intravenous therapy

• Hint for a minor additional benefit
• Overall, a hint of a minor additional benefit is derived.
• Due to the uncertainties described above, the certainty of the evidence is classified in the ‘hint’ category.
• mortality
  • There are no statistically significant differences between the treatment arms for either the endpoint ‘all-cause mortality’ or the additional endpoint ‘cardiovascular death’.
• Morbidity – total hospitalisation
  • The endpoint ‘total hospitalisation’ was not planned in the VICTORIA trial; no further details on its operationalisation are available.
  • The data submitted subsequently during the commenting procedure show a statistically significant advantage for vericiguat compared with the control arm in terms of ‘total hospitalisation’.
• Morbidity – Hospitalisation due to heart failure
  • The endpoint ‘hospitalisation due to heart failure’ is presented here as supplementary information.
  • This shows a statistically significant advantage for vericiguat compared with the control arm.
  • Furthermore, an effect modification with respect to age has been observed: for adults younger than 75 years, there were statistically significantly fewer hospitalisations due to heart failure in the vericiguat arm compared with the control arm, whilst for adults aged 75 years or older, there were no statistically significant differences between the treatment arms.
• Morbidity – myocardial infarction and stroke
  • For the endpoints ‘myocardial infarction’ and ‘stroke’, no statistically significant differences were observed between the treatment arms.
• Morbidity – Health status
  • Health status was assessed in the study using the visual analogue scale (VAS) of the EQ-5D questionnaire.
  • No statistically significant difference was observed between the treatment arms in terms of an improvement of ≥ 15 points by week 32.
• Quality of life – Kansas City Cardiomyopathy Questionnaire (KCCQ)
  • The KCCQ questionnaire was used for the endpoint category of health-related quality of life.
  • For the clinical total score (KCCQ-OSS), operationalised as an improvement of ≥ 15 %, there were no statistically significant differences between the treatment arms.
  • The pharmaceutical manufacturer has provided analyses of responder data using the criterion of an improvement of ≥ 5 points compared with baseline at week 32.
  • This results in a statistically significant advantage for vericiguat compared with the comparator arm.
• Side effects – Serious adverse events (SAEs)
  • There are no statistically significant differences between the treatment groups for the SAE endpoint.
• Side effects – Discontinuation due to adverse events (AE)
  • There were no statistically significant differences between the treatment groups for the endpoint of discontinuation due to AEs.
• Side effects – Hypotension
  • In detail, there were no statistically significant differences between the treatment groups for the specific AEs of hypotension (PT, SAE).
• Side effects – disorders of the blood and lymphatic system
  • In detail, for the endpoint ‘disorders of the blood and lymphatic system’ (SOC, SAE), there was a statistically significant difference between the treatment groups, with a disadvantage for vericiguat compared with the comparator arm.
• Side effects – atrial fibrillation
  • In detail, a statistically significant advantage was observed between the treatment groups for the endpoint ‘atrial fibrillation’ (PT, SAE), favouring vericiguat over the comparator arm.
• Overall assessment / Conclusion
  • For the mortality category, for the endpoint ‘all-cause mortality’ and for the additionally reported endpoint ‘cardiovascular mortality’, no statistically significant difference was observed between the treatment arms in either case.
  • In the morbidity category, a statistically significant advantage of vericiguat over the comparator arm was observed for the endpoint ‘total hospitalisations’.
  • For other endpoints in the morbidity category – myocardial infarction, stroke and health status, as assessed using the EQ-5D VAS – there were no statistically significant differences between the treatment arms.
  • In the health-related quality of life category, data are available for the KCCQ-OSS clinical total score in two operationalisations, which show different effects depending on the operationalisation used.
  • For the operationalisation defined as an improvement of ≥ 15%, no statistically significant differences were found.
  • For an improvement of ≥ 5 points, a statistically significant advantage was observed in favour of vericiguat.
  • In the ‘side effects’ category, no statistically significant differences were found between the groups for the overall rate of SAEs or discontinuations due to AEs.
  • With regard to specific AEs, a statistically significant disadvantage compared with the control was found for the endpoint ‘disorders of the blood and lymphatic system’ (SOC, SAE), whilst for the endpoint ‘atrial fibrillation’ (PT, SAE), a statistically significant advantage was observed in favour of vericiguat.
  • Taking an overall view of the results, based on the positive effects of vericiguat in preventing total hospitalisations and improving quality of life (operationalised as an improvement of ≥ 5 points on the KCCQ-OSS:) a minor additional benefit for vericiguat compared with the appropriate comparator therapy is inferred.

Courtesy translation only, please refer to the German original.