The Efficacy and Safety of Sacubitril/Valsartan in Heart Failure Patients: A Review

Heart failure (HF) is one of the leading causes of morbidity and mortality worldwide. Sacubitril/valsartan, an angiotensin receptor-neprilysin inhibitor, has been approved for the treatment of HF. At present, there have been few systematic and detailed reviews discussing the efficacy and safety of sacubitril/valsartan in HF. In this review, we first introduced the pharmacological mechanisms of sacubitril/valsartan, including the reduction in the degradation of natriuretic peptides in the natriuretic peptide system and inhibition of the renin-angiotensin system. Then, we summarized the efficacy of sacubitril/valsartan in HF patients with reduced ejection fraction (HFrEF) or preserved ejection fraction (HFpEF) including the reduction in risks of mortality and hospitalization, reversal of cardiac remodeling, regulation of biomarkers of HF, improvement of the quality of life, antiarrhythmia, improving renal dysfunction and regulation of metabolism. Finally, we discussed the safety and tolerability of sacubitril/valsartan in the treatment of HFrEF or HFpEF. Compared with ACEIs/ARBs or placebo, sacubitril/valsartan showed good safety and tolerability, although the risk of hypotension might be high. In conclusion, the overwhelming majority of studies show that sacubitril/valsartan is effective and safe in the treatment of HFrEF patients but that it has little benefit in HFpEF patients. Sacubitril/valsartan will probably be a promising anti-HF drug in the near future.

Efficacy of angiotensin receptor neprilysin inhibitor in Asian patients with refractory hypertension

Background Angiotensin receptor neprilysin inhibitor, concomitantly inhibits neprilysin and angiotensin type 1 receptor shown an effect of reducing blood pressure. We aimed to study whether it can be used as an antihypertensive agent in patients with resistant hypertension who has already been treated. Methods This is a multiple center prospective study. Thirty-five Chinese patients with refractory hypertension were enrolled. Resistant hypertension was defined as on the basis of improved lifestyle when the application of the three reasonable and tolerable dose of antihypertensive drugs including thiazide diuretics at least four weeks after treatment, the inadequate control of BP is confirmed by ambulatory BP monitoring, or at least four drugs are needed to achieve the BP standard. Refractory hypertensive patient received sacubitil/valsartan 200 mg instead of their angiotensin type 1 receptor blocker while other agents were continued. If blood pressure was uncontrolled, the sacubitil/valsartan dose was increased to 400 mg after 4 weeks. ABPM were evaluated at 8 weeks follow up. Results Reductions in office SBP/DBP at week 8 were 37/17 mmHg. the average baseline ABPM were 154/90 mmHg of 24-h, and daytime BP and nighttime BP were 157/92 mmHg and 145/83 mmHg respectively. he average endpoint ABPM were 134/80 mmHg of 24-h, and daytime BP and nighttime BP were 136/82 mmHg and 125/73 mmHg respectively. Reductions in 24-h ABPM at week 8 were 20/9 mmHg while 20/10 mmHg in daytime and 20/9 mmHg in nighttime. Conclusion The sacubitil/valsartan provided a strategy therapy for refractory hypertension in Chinese patients in reducing SBP and DBP. FUNDunding Acknowledgement Type of funding sources: None.

Looking for a Tailored Therapy for Heart Failure: Are We Capable of Treating the Patient Instead of the Disease?

After almost a decade of stagnation in clinical research for HF treatment, five large randomized trials recently published have supported the use of four new classes of drugs, namely: angiotensin receptor/neprilysin inhibitor, sodium–glucose co-transporters 2 inhibitors, soluble guanylate cyclase modulators, and myosin activators. Each treatment has proved to be beneficial for both long-term outcomes and quality of life. Beside their clinical relevance, all these novel treatments have a different mechanism of action beyond the usual neuro-hormonal blockage. These different pathways, together with the unquestionable clinical evidence, advocate a re-thinking of HF treatment and of the appropriate drug to integrate with the existing standard therapy, according to different characteristics of HFrEF patients. This study aimed to offer a synthetic overview of the mechanisms of action of the new drugs and to propose a more personalized approach, considering patients’ characteristics and safety profiles. To this end, we have identified seven profiles for patients with chronic heart failure with reduced ejection fraction and two for pre-discharge patients.