LCZ696: The Next Step in Improving RAS Inhibition?

Current Hypertension Reports

Volumn 17, Issue 5, 2015, Pages

  Gradman, Alan H ^a  

^a TEMPLE UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

Heart failure; Hypertension; LCZ696; Natriuretic peptides; Neprilysin

Indexed keywords

3 (1 BIPHENYL 4 YLMETHYL 3 ETHOXYCARBONYL 1 BUTYLCARBAMOYL)PROPIONIC ACID PLUS VALSARTAN; ANGIOTENSIN RECEPTOR ANTAGONIST; DIPEPTIDYL CARBOXYPEPTIDASE INHIBITOR; MEMBRANE METALLOENDOPEPTIDASE; AMINOBUTYRIC ACID DERIVATIVE; RAS PROTEIN; SACUBITRIL PLUS VALSARTAN; TETRAZOLE DERIVATIVE;

ANGIONEUROTIC EDEMA; BLOOD PRESSURE MONITORING; CLINICAL TRIAL (TOPIC); DIABETES MELLITUS; ENZYME INHIBITION; HEART FAILURE; HIGH RISK POPULATION; HUMAN; HYPERTENSION; PHASE 2 CLINICAL TRIAL (TOPIC); PROTEINURIA; RENIN ANGIOTENSIN ALDOSTERONE SYSTEM; REVIEW; ANIMAL; ANTAGONISTS AND INHIBITORS; DRUG EFFECTS;

AMINOBUTYRATES; ANGIOTENSIN-CONVERTING ENZYME INHIBITORS; ANIMALS; HEART FAILURE; HUMANS; HYPERTENSION; RAS PROTEINS; RENIN-ANGIOTENSIN SYSTEM; TETRAZOLES;

EID: 84926327784     PISSN: 15226417     EISSN: 15343111     Source Type: Journal    
DOI: 10.1007/s11906-015-0548-y     Document Type: Review

References (43)

1. ALLHAT Collaborative Research Group. Major outcomes in high-risk hypertensive patients randomized to angiotensin-converting enzyme inhibitor or calcium channel blocker vs diuretic the antihypertensive and lipid-lowering treatment to prevent heart attack trial (ALLHAT). JAMA. 2002;288:2981–97.
2. Julius S, Kjeldsen S, Weber M, Brunner H. Outcomes in hypertension patients at high cardiovascular risk treated with regimens based on valsartan or amlodipine: the VALUE randomised trial. Lancet. 2004;363:2022–31.
3. SOLVD The Investigators. Effect of enalapril on survival in patients with reduced left ventricular ejection fractions and congestive heart failure. N Engl J Med. 1991;325:293–302.
4. Cohn JN, Tognoni G. A randomized trial of the angiotensin-receptor blocker valsartan in chronic heart failure. N Engl J Med. 2001;345:1667–75.
5. Zannad F, McMurray JJ, Krum H, et al. Eplerenone in patients with systolic heart failure and mild symptoms. N Engl J Med. 2011;364:11–21.
6. Pitt B, Zannad F, Remme WJ, et al. The effect of spironolactone on morbidity and mortality in patients with severe heart failure. N Engl J Med. 1999;341:709–17.
7. Lewis EJ, Hunsicker LG, Bain RP, et al. The effect of angiotensin converting-enzyme inhibition on diabetic nephropathy. The collaborative study group. N Engl J Med. 1993;329:1456–62.
8. Lewis EJ, Hunsicker LG, Clarke WR, et al. Renoprotective effect of the angiotensin-receptor antagonist irbesartan in patients with nephropathy due to type 2 diabetes. N Engl J Med. 2001;345:851–60.
9. Brenner BM, Cooper ME, de Zeeuw D, et al. Effects of losartan on renal and cardiovascular outcomes in patients with type 2 diabetes and nephropathy. N Engl J Med. 2001;345:861–9.
10. Pfeffer MA, Braunwald E, Moye LA, et al. Effect of captopril on mortality and morbidity in patients with left ventricular dysfunction after myocardial infarction: results of the survival and ventricular enlargement trial. N Engl J Med. 1992;327:669–77.
11. Yusuf S, Teo KK, Pogue J, et al. Telmisartan, ramipril, or both in patients at high risk for vascular events. N Engl J Med. 2008;358:1547–59.
12. Parving HH, Brenner BM, McMurray JJ, et al. Cardiorenal end points in a trial of aliskiren for type 2 diabetes. N Engl J Med. 2012;367:2204–13.
13. McMurray J, Packer M, Desai A, Gong J, et al. PARADIGM-HF investigators and committees. Angiotensin-neprilysn inhibition versus enalapril in heart failure. N Engl J Med. 2014;371:993–1004. Landmark clinical trial demonstrating superiority of LCZ696 compared to enalapril in patients with systolic dysfunction heart failure.
14. 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;50:401–14. Comprehensive presentation of the pharmacokinetics and pharmacodynamics of LCZ696 by investigators at Novartis.
15. Vardeny O, Miller R, Solomon S. Combined neprilysin and renin–angiotensin system inhibition for the treatment of heart failure. JACC Heart Fail. 2014;2:663–70.
16. 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;34:886–893c.
17. 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;8:79–84.
18. Bevan EG, Connell JM, Doyle J, Carmichael HA, Davies DL, Lorimer AR, et al. Candoxatril, a neutral endopeptidase inhibitor: efficacy and tolerability in essential hypertension. J Hypertens. 1992;10:607–13.
19. Ando S, Rahman MA, Butler GC, Senn BL, Floras JS. Comparison of candoxatril and atrial natriuretic factor in healthy men. Effects on hemodynamics, sympathetic activity, heart rate variability, and endothelin. Hypertension. 1995;26:1160–6.
20. Campese VM, Lasseter KC, Ferrario CM, Smith WB, et al. Omapatrilat versus lisinopril: efficacy and neurohormonal profile in salt-sensitive hypertensive patients. Hypertension. 2001;38:1342–8.
21. 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;17:103–11.
22. Solomon SD, Zile M, Pieske B, et al. The angiotensin receptor neprilysin inhibitor LCZ696 in heart failure with preserved ejection fraction: a phase 2 double-blind randomised controlled trial. Lancet. 2012;380:1387–95. Preliminary study examining the efficacy of LCZ696 in patients with heart failure and preserved systolic function.
23. Trippodo NC, Fox M, Monticello TM, Panchal BC, Asaad MM. Vasopeptidase inhibition with omapatrilat improves cardiac geometry and survival in cardiomyopathic hamsters more than does ACE inhibition with captopril. J Cardiovasc Pharmacol. 1999;34:782–90.
24. O’Connor CM, Starling RC, Hernandez AF, et al. Effect of nesiritide in patients with acute decompensated heart failure. N Engl J Med. 2011;365:32–43.
25. Packer M, Califf RM, Konstam MA, Krum H, et al. Comparison of omapatrilat and enalapril in patients with chronic heart failure: the Omapatrilat Versus Enalapril Randomized Trial of Utility in Reducing Events (OVERTURE). Circulation. 2002;106:920–6.
26. Yusuf S, Pfeffer MA, Swedberg K, et al. Effects of candesartan in patients with chronic heart failure and preserved left ventricular ejection fraction: the CHARM Preserved Trial. Lancet. 2003;362:777–8.
27. Massie BM, Carson PE, McMurray JJ, et al. Irbesartan in patients with heart failure and preserved ejection fraction. N Engl J Med. 2008;359:2456–67.
28. Cleland JG, Tendera M, Adamus J, Freemantle N, Polonski L, Taylor J. The perindopril in elderly people with chronic heart failure (PEP-CHF) study. Eur Heart J. 2006;27:2338–45.
29. Pitt B, Pfeffer MA, Assmann SF, Boineau R, Anand IS, Claggett B, et al. Spironolactone for heart failure with preserved ejection fraction. N Engl J Med. 2014;370:1383–92.
30. Ruilope L, Dukat A, Bohm 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;375:1255–66. Largest hypertension trial conducted to date using LCZ696; includes an ABPM sub-study and neurohormonal measurements after 8 weeks of treatment.
31. 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;63:698–705. Hypertension trial examining the safety and efficacy of LCZ696 in Asian hypertensive patients.
32. Package Insert, Norvasc (amlodipine)
33. Packer M, Coats AJ, Fowler MB, et al. Effect of carvedilol on survival in severe chronic heart failure. N Engl J Med. 2001;344:1651–8.
34. Hjalmarson A, Goldstein S, Fagerberg B, et al. Effects of controlled release metoprolol on total mortality, hospitalizations, and well-being in patients with heart failure: the Metoprolol CR/XL Randomized Intervention Trial in congestive heart failure (MERIT-HF). JAMA. 2000;283:1295–302.
35. CIBIS-II Investigators and Committees. The Cardiac Insufficiency Bisoprolol Study II (CIBIS-II): a randomised trial. Lancet. 1999;353:9–13.
36. McMurray JJ, Ostergren J, Swedberg K, et al. Effects of candesartan in patients with chronic heart failure and reduced left-ventricular systolic function taking angiotensin-converting-enzyme inhibitors: the CHARM-Added trial. Lancet. 2003;362:767–71.
37. Packer M, Carson P, Elkayam U, Konstam MA, Moe G, et al. Effect of amlodipine on the survival of patients with severe chronic heart failure due to a nonischemic cardiomyopathy: results of the PRAISE-2 study (Prospective Randomized Amlodipine Survival Evaluation-2). JACC Heart Fail. 2013;1(4):308–14.
38. Cao Z, Burrell LM, Tikkanen I, et al. Vasopeptidase inhibition attenuates the progression of renal injury in subtotal nephrectomised rats. Kidney Int. 2001;60:715–21.
39. Taal MW, Nenov VD, Wong W, et al. Vasopeptidase inhibition affords greater renoprotection than angiotensin-converting enzyme inhibition alone. J Am Soc Nephrol. 2001;12:2051–9.
40. Judge P, Haynes R, Landray M, Baigent C. Neprilysin inhibition in chronic kidney disease. Neph Dialysis Transpl. 2014. 0:1-6
41. Yusuf S, Sleight P, Pogue J, et al. Effects of an angiotensin-converting enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients. N Engl J Med. 2000;342:145–53.
42. PEACE the Trial Investigators. Angiotensin converting enzyme inhibition in stable coronary artery disease. N Engl J Med. 2004;351:2058–68.
43. Yusuf S, Teo K, Anderson C, et al. Effects of the angiotensin-receptor blocker telmisartan on cardiovascular events in high-risk patients intolerant to angiotensin-converting enzyme inhibitors: a randomised controlled trial. Lancet. 2008;372(9644):1174–83.