Sacubitril/valsartan in therapy of hypertension
Abstract
In recent years a new very promising drug was introduced for the treatment of chronic heart failure. This drug, sacubitril/valsartan, prevents the clinical progression of surviving patients with heart failure more effectively than enalapril and it reduces the need for hospitalization by more than 20%. At the same time it has been shown that it reduces blood pressure particularly in patients with essential hypertension. This drug is an inhibitor of neprilysin, an enzyme that degrades natriuretic factors. Natriuretic factors (ANP, BNP, CNP) increase diuresis and natriuresis, reduce the activity of the sympathetic system, relax the blood vessels and inhibit fibrosis. Several studies have shown that sacubitril/valsartan therapy more significantly reduces blood pressure in patients with salt-sensitive or refractory to treatment hypertension than is observed with valsartan or amlodipine. Furthermore, beneficial effects of this drug on central blood pressure and renal function have been demonstrated in patients with chronic renal failure. More rarely than enalapril it leads to hyperkalaemia in patients treated simultaneously with mineralocorticoid receptor inhibitors. Sacubitril/valsartan is the first representative of a new class of drugs that inhibit neprilysin, which probably in the future will be frequently used in hypertension.
Keywords: hypertensionnatriuretic factorssacubitril/valsartan
References
- Packer M, McMurray JJV, Desai AS, et al. PARADIGM-HF Investigators and Coordinators. Angiotensin receptor neprilysin inhibition compared with enalapril on the risk of clinical progression in surviving patients with heart failure. Circulation. 2015; 131(1): 54–61.
- Kobalava Z. The role of natriuretic peptides in the pathogenesis of cardiovascular diseases. J Hypertens. 2016; 34(Suppl 1 ISH2016 Abstract Book): e377.
- Benigni A, Zoja C, Zatelli C, et al. Vasopeptidase inhibitor restores the balance of vasoactive hormones in progressive nephropathy. Kidney Int. 2004; 66(5): 1959–1965.
- Mangiafico S, Costello-Boerrigter LC, Andersen IA, et al. Neutral endopeptidase inhibition and the natriuretic peptide system: an evolving strategy in cardiovascular therapeutics. Eur Heart J. 2013; 34(12): 886–893c.
- Gardner DG, Chen S, Glenn DJ, et al. Molecular biology of the natriuretic peptide system: implications for physiology and hypertension. Hypertension. 2007; 49(3): 419–426.
- Potter LR, Abbey-Hosch S, Dickey DM. Natriuretic peptides, their receptors, and cyclic guanosine monophosphate-dependent signaling functions. Endocr Rev. 2006; 27(1): 47–72.
- Voors AA, Gori M, Liu LCY, et al. PARAMOUNT Investigators. Renal effects of the angiotensin receptor neprilysin inhibitor LCZ696 in patients with heart failure and preserved ejection fraction. Eur J Heart Fail. 2015; 17(5): 510–517.
- Melo LG, Veress AT, Chong CK, et al. Salt-sensitive hypertension in ANP knockout mice: potential role of abnormal plasma renin activity. Am J Physiol. 1998; 274(1 Pt 2): R255–R261.
- Lin KF, Chao J, Chao L. Atrial natriuretic peptide gene delivery reduces stroke-induced mortality rate in Dahl salt-sensitive rats. Hypertension. 1999; 33(1 Pt 2): 219–224.
- Bayés-Genís A, Barallat J, Galán A, et al. Soluble neprilysin is predictive of cardiovascular death and heart failure hospitalization in heart failure patients. J Am Coll Cardiol. 2015; 65(7): 657–665.
- McDowell G, Nicholls DP. The endopeptidase inhibitor, candoxatril, and its therapeutic potential in the treatment of chronic cardiac failure in man. Expert Opin Investig Drugs. 1999; 8(1): 79–84.
- Kostis JB, Packer M, Black HR, et al. Omapatrilat and enalapril in patients with hypertension: the Omapatrilat Cardiovascular Treatment vs. Enalapril (OCTAVE) trial. Am J Hypertens. 2004; 17(2): 103–111.
- Kusaka H, Sueta D, Koibuchi N, et al. LCZ696, Angiotensin II Receptor-Neprilysin Inhibitor, Ameliorates High-Salt-Induced Hypertension and Cardiovascular Injury More Than Valsartan Alone. Am J Hypertens. 2015; 28(12): 1409–1417.
- Miura SI, Suematsu Y, Matsuo Y, et al. The angiotensin II type 1 receptor-neprilysin inhibitor LCZ696 blocked aldosterone synthesis in a human adrenocortical cell line. Hypertens Res. 2016; 39(11): 758–763.
- Gu J, Noe A, Chandra P, et al. Pharmacokinetics and pharmacodynamics of LCZ696, a novel dual-acting angiotensin receptor-neprilysin inhibitor (ARNi). J Clin Pharmacol. 2010; 50(4): 401–414.
- Gan Lu, Langenickel T, Petruck J, et al. Effects of age and sex on the pharmacokinetics of LCZ696, an angiotensin receptor neprilysin inhibitor. J Clin Pharmacol. 2016; 56(1): 78–86.
- Williams B, Cockcroft JR, Kario K, et al. Effects of Sacubitril/Valsartan Versus Olmesartan on Central Hemodynamics in the Elderly With Systolic Hypertension: The PARAMETER Study. Hypertension. 2017; 69(3): 411–420.
- Wang TD, Tan RS, Lee H, et al. Treatment with LCZ696 compared to AT-1 receptor blockade is associated with non-sustained increases of natriuresis and diuresis in Asian patients with salt-sensitive hypertension. J Hypertens. 2015; 33 Suppl 1: e124.
- Kario K, Tamaki Y, Okino N, et al. LCZ696, a First-in-Class Angiotensin Receptor-Neprilysin Inhibitor: The First Clinical Experience in Patients With Severe Hypertension. J Clin Hypertens (Greenwich). 2016; 18(4): 308–314.
- Kario K, Sun N, Chiang FT, et al. Efficacy and safety of LCZ696, a first-in-class angiotensin receptor neprilysin inhibitor, in Asian patients with hypertension: a randomized, double-blind, placebo-controlled study. Hypertension. 2014; 63(4): 698–705.
- Ruilope LM, Dukat A, Böhm M, et al. Blood-pressure reduction with LCZ696, a novel dual-acting inhibitor of the angiotensin II receptor and neprilysin: a randomised, double-blind, placebo-controlled, active comparator study. Lancet. 2010; 375(9722): 1255–1266.
- Supasyndh O, Sun N, Kario K, et al. Long-term (52-week) safety and efficacy of Sacubitril/valsartan in Asian patients with hypertension. Hypertens Res. 2017; 40(5): 472–476.
- Wang JG, Yukisada K, Sibulo A, et al. Efficacy and safety of sacubitril/valsartan (LCZ696) add-on to amlodipine in Asian patients with systolic hypertension uncontrolled with amlodipine monotherapy. J Hypertens. 2017; 35(4): 877–885.
- Konta T, Ikeda A, Ichikawa K, et al. Blood pressure control in a Japanese population with chronic kidney disease: a baseline survey of a nationwide cohort. Am J Hypertens. 2012; 25(3): 342–347.
- Ito S, Satoh M, Tamaki Y, et al. Safety and efficacy of LCZ696, a first-in-class angiotensin receptor neprilysin inhibitor, in Japanese patients with hypertension and renal dysfunction. Hypertens Res. 2015; 38(4): 269–275.
- Voors AA, Gori M, Liu LCY, et al. PARAMOUNT Investigators. Renal effects of the angiotensin receptor neprilysin inhibitor LCZ696 in patients with heart failure and preserved ejection fraction. Eur J Heart Fail. 2015; 17(5): 510–517.
- Lofton CE, Newman WH, Currie MG. Atrial natriuretic peptide regulation of endothelial permeability is mediated by cGMP. Biochem Biophys Res Commun. 1990; 172(2): 793–799.
- Battle T, Michel JB, Corman B. Effect of atrial natriuretic factor on the water permeability of endothelial cells. Biochem Biophys Res Commun. 1992; 185(1): 386–391.
- Huxley VH, Tucker VL, Verburg KM, et al. Increased capillary hydraulic conductivity induced by atrial natriuretic peptide. Circ Res. 1987; 60(2): 304–307.
- Bodey F, Hopper I, Krum H. Neprilysin inhibitors preserve renal function in heart failure. Int J Cardiol. 2015; 179: 329–330.
- Judge P, Haynes R, Landray MJ, et al. Neprilysin inhibition in chronic kidney disease. Nephrol Dial Transplant. 2015; 30(5): 738–743.
- Jordan J, Stinkens R, Jax T, et al. Improved Insulin Sensitivity With Angiotensin Receptor Neprilysin Inhibition in Individuals With Obesity and Hypertension. Clin Pharmacol Ther. 2017; 101(2): 254–263.
- Desai AS, Vardeny O, Claggett B, et al. Reduced Risk of Hyperkalemia During Treatment of Heart Failure With Mineralocorticoid Receptor Antagonists by Use of Sacubitril/Valsartan Compared With Enalapril: A Secondary Analysis of the PARADIGM-HF Trial. JAMA Cardiol. 2017; 2(1): 79–85.
- Vodovar N, Paquet C, Mebazaa A, et al. Neprilysin, cardiovascular, and Alzheimer's diseases: the therapeutic split? Eur Heart J. 2015; 36(15): 902–905.