sacubitril and vericiguat

Heart failure is associated with notable morbidity and mortality, and therefore, novel therapies are needed. This minireview focused on the effects and mechanisms of action of sacubitril/valsartan, sodium-glucose cotransporter 2 inhibitors and vericiguat in heart failure patients. A systematic review of the current literature was conducted. Seventeen randomised clinical trials regarding the effects of these drug classes were included. The mechanism of action of each treatment could improve pathophysiological imbalances present in heart failure. All three drug classes revealed a reduction in hospitalisations for heart failure or death from cardiovascular causes in patients with reduced ejection fraction. Sacubitril/valsartan also reduced hospitalisations and death from cardiovascular causes in patients with mid-range ejection fraction, but not in patients with preserved ejection fraction. The sodium-glucose cotransporter 2 inhibitors, sotagliflozin and empagliflozin, reduced hospitalisations and death from cardiovascular causes in heart failure patients with preserved ejection fraction. None of the three drug classes was associated with a higher prevalence of treatment discontinuation due to increases in adverse effects in large-scale randomised clinical trials compared with placebo. Further studies are required to clarify the extent of effects of these medications in different subpopulations-especially in patients with mid-range and preserved ejection fraction.

Topics: Aminobutyrates; Angiotensin Receptor Antagonists; Biphenyl Compounds; Drug Combinations; Glucose; Heart Failure; Heterocyclic Compounds, 2-Ring; Humans; Pyrimidines; Sodium; Tetrazoles; Treatment Outcome; Valsartan

The significant morbidity and mortality associated with heart failure with reduced (HFrEF) or preserved ejection fraction (HFpEF) justify the search for novel therapeutic agents. The nitric oxide (NO)-soluble guanylate cyclase (sGC)-cyclic guanosine monophosphate (cGMP) pathway plays an important role in the regulation of cardiovascular function. This pathway is disrupted in HF resulting in decreased protection against myocardial injury. The sGC activator cinaciguat increases cGMP levels by direct, NO-independent activation of sGC, and may be particularly effective in conditions of increased oxidative stress and endothelial dysfunction, and then reduced NO levels, but this comes at the expense of a greater risk of hypotension. Conversely, sGC stimulators (riociguat and vericiguat) enhance sGC sensitivity to endogenous NO, and then exert a more physiological action. The phase 3 VICTORIA trial found that vericiguat is safe and effective in patients with HFrEF and recent HF decompensation. Therefore, adding vericiguat may be considered in individual patients with HFrEF, particularly those at higher risk of HF hospitalization; the efficacy of the sacubitril/valsartan-vericiguat combination in HFrEF is currently unknown.

Topics: Aminobutyrates; Biphenyl Compounds; Cyclic GMP; Heart Failure; Heterocyclic Compounds, 2-Ring; Humans; Nitric Oxide; Pyrimidines; Soluble Guanylyl Cyclase; Stroke Volume

We assessed a subset of the 5040 patients in VICTORIA receiving sacubitril/valsartan, either at randomization (n = 731) or post-randomization drop-in use (n = 425), to evaluate the relationship between the efficacy and safety of combination therapy with vericiguat.. The efficacy of vericiguat on the primary composite endpoint, heart failure (HF) hospitalization, and all-cause mortality was assessed. Safety outcomes included symptomatic hypotension, syncope, worsening renal function, and hyperkalaemia. At randomization, 731 patients received sacubitril/valsartan; they were more frequently from Western Europe or North America, had lower ejection fraction and systolic blood pressure, and more use of triple background HF therapy (65.9% vs. 58.6%), biventricular pacemakers (17.9% vs. 14.1%), or implantable cardioverter defibrillators (42.3% vs. 25.3%). For patients on versus not on sacubitril/valsartan at randomization, adjusted hazard ratios (95% confidence intervals) for vericiguat's treatment effect on the primary composite outcome, cardiovascular death, and HF hospitalization were 0.92 (0.71-1.19) versus 0.89 (0.80-0.98), 0.71 (0.45-1.12) versus 0.95 (0.82-1.11), and 0.98 (0.74-1.29) versus 0.87 (0.78-0.98), respectively. No significant interaction existed between sacubitril/valsartan and vericiguat's treatment effect (p-values for interaction: 0.81, 0.23 and 0.47, respectively). Post-randomization, more drop-in sacubitril/valsartan use occurred in those assigned to placebo (n = 238) versus vericiguat (n = 187) (p = 0.007). Symptomatic hypotension (21.0% vs. 23.1%; p = 0.41), renal dysfunction (29.9% vs. 31.9%; p = 0.50), and hyperkalaemia (10.3% vs. 7.9%; p = 0.20) in patients receiving sacubitril/valsartan (n = 992) for ≥3 months were not different by treatment arm.. Concomitant use of sacubitril/valsartan for at least 3 months did not alter the efficacy of vericiguat and was similarly safe and tolerated in both study arms. Sacubitril/valsartan was initiated more frequently after randomization in patients assigned to placebo versus vericiguat.. ClinicalTrials.gov NCT02861534.

Topics: Aminobutyrates; Biphenyl Compounds; Drug Combinations; Heart Failure; Heterocyclic Compounds, 2-Ring; Humans; Hyperkalemia; Hypotension; Pyrimidines; Stroke Volume; Treatment Outcome; Valsartan; Ventricular Dysfunction, Left

Topics: Aminobutyrates; Angiotensin Receptor Antagonists; Biphenyl Compounds; Drug Combinations; Heart Failure; Heterocyclic Compounds, 2-Ring; Humans; Pyrimidines; Stroke Volume; Tetrazoles; Valsartan

Topics: Aminobutyrates; Angiotensin Receptor Antagonists; Biphenyl Compounds; Drug Combinations; Heart Failure; Heterocyclic Compounds, 2-Ring; Humans; Hypertension; Neprilysin; Pyrimidines; Stroke Volume; Tetrazoles; Valsartan