Nitrates have been used for many years in the treatment of heart failure. Their therapeutic mechanism was based on the supply of an exogenous source of nitric oxide, capable of binding to soluble guanylate cyclase thus obtaining a modulation of vascular tone.
However, the effectiveness of these drugs was limited by the appearance of tolerance phenomena.
In recent years, new drugs capable of modulating soluble guanylate cyclase have become available, even in the absence of nitric oxide. One of them is vericiguat which acts, in particular, by increasing the affinity of guanylate cyclase at low levels of nitric oxide.
The efficacy of this new drug in patients with heart failure and reduced ejection fraction was assessed in the VICTORIA trial.
This phase 3 study, recently published in the New England Journal of Medicine, randomized 5,050 patients with an ejection fraction of less than 45%, at 616 experimental centers.
Enrolled subjects were treated with vericiguat or placebo.
The primary outcome of the study was a composite of death from cardiovascular causes or first hospitalization for heart failure.
The mean age of the enrolled patients was 67 years and 24% were women; the median level of NT-proBNP was 2816 pg / ml.
During a median follow-up of 10.8 months, the composite endpoint occurred in 37.9% of patients treated with vericiguat and in 40.9% of those treated with placebo.
Hospitalizations for heart failure were registered in 27.4% of patients on active treatment and in 29.6% of those in the control group.
Cardiovascular death occurred in 16.4% of patients included in the vericiguat group and in 17.5% of those included in the placebo group.
Regarding safety, the study prespecified two adverse events: symptomatic hypotension and syncope. The first occurred in 9.1% of patients in the vericiguat group and in 7.9% of patients in the placebo group. The second occurred in 4% and 3.5% of cases, respectively.
Anemia developed more frequently in patients in the vericiguat group.
Looking at the clinical characteristics of the patients included in the study, the therapeutic success of vericiguat involves most subgroups. The only exceptions concern patients with particularly high NT-proBNP values), an ejection fraction greater than or equal to 40%, an age greater than or equal to 75 years and with an estimated glomerular filtration rate less than or equal to 30.
Therefore, thanks to the results of this important study, a new treatment for heart failure appears to be on the horizon, able to improve the clinical prognosis of patients, reducing mortality and hospitalizations.
The authors remember that in heart failure, endothelial dysfunction and reactive oxygen species reduce the bioavailability of nitric oxide, resulting in a relative deficiency of soluble guanylate cyclase and a reduction in the cyclic generation of GMP. Vericiguat improves this pathway by directly stimulating soluble guanylate cyclase, as an alternative to the most common drugs used in patients with heart failure, which mainly aim to antagonize the neurohormonal pathways.
Vericiguat acts according to a therapeutic mechanism already used in the past by other drugs, but in a more efficient way, providing an additional treatment to contrast heart failure.
This post is also available in: Chinese (Simplified)