Pathophysiology of heart failure with reduced ejection fraction (HFrEF) is characterised by the chronic activation of deleterious neurohormonal systems, such as the renin-angiotensin-aldosterone system and the sympathetic nervous system, along with suppression of protective pathways, including natriuretic peptides and the nitric oxide (NO)-soluble guanylate cyclase (sGC)-cyclic guanosine monophosphate (cGMP) pathway. Current treatments do not comprehensively target all these mechanisms, allowing disease progression. Therefore, an ideal therapeutic approach should combine inhibition of harmful pathways with stimulation of protective ones.
Vericiguat is a recently approved drug for the treatment of symptomatic HFrEF in patients who have experienced a recent episode of decompensation despite optimised standard therapy. Its mechanism of action is based on stimulation of the impaired NO-sGC-cGMP pathway, which plays a key role in heart failure pathophysiology. Under physiological conditions, NO activates sGC, leading to increased production of cGMP, a second messenger involved in the regulation of vascular tone, myocardial contractility, and cardiac remodelling. Reduced NO bioavailability, sGC dysfunction, and impaired cGMP signalling contribute to disease progression. Vericiguat acts through a dual mechanism: it sensitises sGC to low levels of NO and directly stimulates sGC even in the absence of NO, thereby restoring cGMP synthesis and improving cardiovascular function.
We present a retrospective review of our experience with this drug in patients with HFrEF. In all cases, treatment was initiated at a dose of 2.5 mg per day. We observed that most patients reached a dose of 5 mg, but did not tolerate the maximum dose of 10 mg. Despite not reaching the full dose, clinical outcomes were favourable in most cases, with a reduction in the number of hospital admissions due to heart failure.
In conclusion, our preliminary experience suggests that vericiguat is a safe and effective addition to the therapeutic arsenal for patients with symptomatic HFrEF. Earlier implementation and broader use may be warranted to confirm these potential benefits.