Key result
Targeting cyclic GMP via sacubitril/valsartan and vericiguat demonstrates clinical efficacy in HFrEF.
Why the study?
The significant morbidity and mortality associated with HFrEF or HFpEF justify the search for novel therapeutic agents targeting reduced cyclic guanosine monophosphate levels, which contribute to HF progression.
This review summarizes therapeutic strategies targeting the cGMP pathway in heart failure, highlighting the success of sacubitril/valsartan and vericiguat in HFrEF while noting remaining questions regarding their combination and efficacy in HFpEF.
Supports cGMP targeting in HFrEF; leaves open questions on combination and HFpEF testing.
The significant morbidity and mortality associated with heart failure with reduced ejection fraction (HFrEF) or heart failure with preserved ejection fraction (HFpEF) justify the search for novel therapeutic agents. Reduced cyclic guanosine monophosphate levels contribute to HF progression. Among molecules modulating the nitric oxide (NO)-GMP-phosphodiesterase (PDE) pathway, the evaluation of nitrates, synthetic natriuretic peptides (NP), and NP analogs has yielded mixed results. Conversely, sacubitril/valsartan, combining NP degradation inhibition through neprilysin and angiotensin receptor blockade, has led to groundbreaking findings in HFrEF. Other strategies to increase tissue cyclic guanosine monophosphate have been attempted, such as PDE-3 or PDE-5 inhibition (with negative or neutral results), NO-independent soluble guanylate cyclase (sGC) activation, or enhancement of sGC sensitivity to endogenous NO. Following the positive results of the phase 3 VICTORIA (A Study of Vericiguat in Participants With Heart Failure With Reduced Ejection Fraction) trial on the sGC stimulator vericiguat in HFrEF, the main open questions are the efficacy of the sacubitril/valsartan-vericiguat combination in HFrEF and of vericiguat in HFpEF.
No takes yet. Share an insight, caveat, or question.
Emdin et al. (2020) conducted a review in Heart failure (HFrEF and HFpEF). Molecules modulating the nitric oxide (NO)-GMP-phosphodiesterase (PDE) pathway (including sacubitril/valsartan and vericiguat) was evaluated. Targeting cyclic GMP via sacubitril/valsartan and the sGC stimulator vericiguat (in the phase 3 VICTORIA trial) has demonstrated positive efficacy in heart failure with reduced ejection fraction.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: