Prospective ARNI vs. ACE inhibitor trial to DetermIne Superiority in reducing heart failure Events after Myocardial Infarction (PARADISE-MI): design and baseline characteristics.

Publisher: Wiley Country of Publication: England NLM ID: 100887595 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1879-0844 (Electronic) Linking ISSN: 13889842 NLM ISO Abbreviation: Eur J Heart Fail Subsets: MEDLINE

Publication: 2014- : Chichester : Wiley
Original Publication: Amsterdam ; New York : Elsevier Science, c1999-

Heart Failure*/drug therapy ; Heart Failure*/epidemiology ; Myocardial Infarction*/drug therapy ; Myocardial Infarction*/epidemiology; Aged ; Aminobutyrates/therapeutic use ; Angiotensin Receptor Antagonists/therapeutic use ; Angiotensin-Converting Enzyme Inhibitors/therapeutic use ; Drug Combinations ; Female ; Humans ; Middle Aged ; Prospective Studies ; Stroke Volume ; Tetrazoles/therapeutic use ; Ventricular Function, Left

Aims: Patients surviving an acute myocardial infarction (AMI) are at risk of developing symptomatic heart failure (HF) or premature death. We hypothesized that sacubitril/valsartan, effective in the treatment of chronic HF, prevents development of HF and reduces cardiovascular death following high-risk AMI compared to a proven angiotensin-converting enzyme (ACE) inhibitor. This paper describes the study design and baseline characteristics of patients enrolled in the Prospective ARNI vs. ACE inhibitor trial to DetermIne Superiority in reducing heart failure Events after Myocardial Infarction (PARADISE-MI) trial.
Methods and Results: PARADISE-MI, a multinational (41 countries), double-blind, active-controlled trial, randomized patients within 0.5-7 days of presentation with index AMI to sacubitril/valsartan or ramipril. Transient pulmonary congestion and/or left ventricular ejection fraction (LVEF) ≤40% and at least one additional factor augmenting risk of HF or death (age ≥70 years, estimated glomerular filtration rate <60 mL/min/1.73 m ² , diabetes, prior myocardial infarction, atrial fibrillation, LVEF <30%, Killip class ≥III, ST-elevation myocardial infarction without reperfusion) were required for inclusion. PARADISE-MI was event-driven targeting 708 primary endpoints (cardiovascular death, HF hospitalization or outpatient development of HF). Randomization of 5669 patients occurred 4.3 ± 1.8 days from presentation with index AMI. The mean age was 64 ± 12 years, 24% were women. The majority (76%) qualified with ST-segment elevation myocardial infarction; acute percutaneous coronary intervention was performed in 88% and thrombolysis in 6%. LVEF was 37 ± 9% and 58% were in Killip class ≥II.
Conclusions: Baseline therapies in PARADISE-MI reflect advances in contemporary evidence-based care. With enrollment complete PARADISE-MI is poised to determine whether sacubitril/valsartan is more effective than a proven ACE inhibitor in preventing development of HF and cardiovascular death following AMI.
(© 2021 European Society of Cardiology.)

Comment in: Turk Kardiyol Dern Ars. 2021 Jul;49(5):353-356. (PMID: 34308868)
Comment in: Eur J Heart Fail. 2022 Jul;24(7):1324. (PMID: 35118775)

O'Gara PT, Kushner FG, Ascheim DD, Casey DE, Chung MK, de Lemos JA, Ettinger SM, Fang JC, Fesmire FM, Franklin BA, Granger CB, Krumholz HM, Linderbaum JA, Morrow DA, Newby LK, Ornato JP, Ou N, Radford MJ, Tamis-Holland JE, Tommaso CL, Tracy CM, Woo YJ, Zhao DX. 2013 ACCF/AHA guideline for the management of ST-elevation myocardial infarction: executive summary: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol 2013;61:485-510.
Amsterdam EA, Wenger NK, Brindis RG, Casey DE, Ganiats TG, Holmes DR, Jaffe AS, Jneid H, Kelly RF, Kontos MC, Levine GN, Liebson PR, Mukherjee D, Peterson ED, Sabatine MS, Smalling RW, Zieman SJ. 2014 AHA/ACC guideline for the management of patients with non-ST-elevation acute coronary syndromes: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol 2014;64:e139-e228.
Ibanez B, James S, Agewall S, Antunes MJ, Bucciarelli-Ducci C, Bueno H, Caforio AL, Crea F, Goudevenos JA, Halvorsen S, Hindricks G, Kastrati A, Lenzen MJ, Prescott E, Roffi M, Valgimigli M, Varenhorst C, Vranckx P, Widimský P; ESC Scientific Document Group. 2017 ESC Guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation: The Task Force for the management of acute myocardial infarction in patients presenting with ST-segment elevation of the European Society of Cardiology (ESC). Eur Heart J 2018;39:119-177.
Collet JP, Thiele H, Barbato E, Barthélémy O, Bauersachs J, Bhatt DL, Dendale P, Dorobantu M, Edvardsen T, Folliguet T, Gale CP, Gilard M, Jobs A, Jüni P, Lambrinou E, Lewis BS, Mehilli J, Meliga E, Merkely B, Mueller C, Roffi M, Rutten FH, Sibbing D, Siontis GC; ESC Scientific Document Group. 2020 ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation. Eur Heart J 2021;42:1289-1367.
Van Diepen S, Chen AY, Wang TY, Alexander KP, Ezekowitz JA, Peterson ED, Roe MT. Influence of heart failure symptoms and ejection fraction on short- and long-term outcomes for older patients with non-ST-segment elevation myocardial infarction. Am Heart J 2014;167:267-273.e1.
Pfeffer MA, Braunwald E, Moyé LA, Basta L, Brown EJ, Cuddy TE, Davis BR, Geltman EM, Goldman S, Flaker GC, Klein M, Lamas GA, Packer M, Rouleau J, Rouleau JL, Rutherford J, Wertheimer JH, Hawkins CM. Effect of captopril on mortality and morbidity in patients with left ventricular dysfunction after myocardial infarction. Results of the Survival and Ventricular Enlargement Trial. The SAVE Investigators. N Engl J Med 1992;327:669-677.
The Acute Infarction Ramipril Efficacy (AIRE) Study Investigators. Effect of ramipril on mortality and morbidity of survivors of acute myocardial infarction with clinical evidence of heart failure. Lancet 1993;342:821-828.
Kober L, Torp-Pedersen C, Carlsen JE, Bagger H, Eliasen P, Lyngborg K, Videbaek J, Cole DS, Auclert L, Pauly NC. A clinical trial of the ACE inhibitor trandolapril in patients with left ventricular dysfunction after myocardial infarction. TRACE Study Group. N Engl J Med 1995;333:1670-1676.
Flather MD, Yusuf S, Køber L, Pfeffer M, Hall A, Murray G, Torp-Pedersen C, Ball S, Pogue J, Moyé L, Braunwald E. Long-term ACE-inhibitor therapy in patients with heart failure or left-ventricular dysfunction: a systematic overview of data from individual patients. Lancet 2000;355:1575-1581.
Goodfriend TL, Elliott ME, Catt KJ. Angiotensin receptors and their antagonists. N Engl J Med 1996;334:1649-1655.
Dickstein K, Kjekshus J. Effects of losartan and captopril on mortality and morbidity in high-risk patients after acute myocardial infarction: the OPTIMAAL randomised trial. Lancet 2002;360:752-760.
Pfeffer MA, McMurray JJ, Velazquez EJ, Rouleau J-L, Køber L, Maggioni AP, Solomon SD, Swedberg K, Van de Werf F, White H, Leimberger JD, Henis M, Edwards S, Zelenkofske S, Sellers MA, Califf RM; Valsartan in Acute Myocardial Infarction Trial Investigators. Valsartan, captopril, or both in myocardial infarction complicated by heart failure, left ventricular dysfunction, or both. N Engl J Med 2003;349:1893-1906.
McMurray JJ. Neprilysin inhibition to treat heart failure: a tale of science, serendipity, and second chances. Eur J Heart Fail 2015;17:242-247.
McMurray JJ, Packer M, Desai AS, Gong J, Lefkowitz MP, Rizkala AR, Rouleau JL, Shi VC, Solomon SD, Swedberg K, Zile MR; PARADIGM-HF Investigators and Committees. Angiotensin-neprilysin inhibition versus enalapril in heart failure. N Engl J Med 2014;371:993-1004.
Velazquez EJ, Morrow DA, DeVore AD, Duffy CI, Ambrosy AP, McCague K, Rocha R, Braunwald E; PIONEER-HF Investigators. Angiotensin-neprilysin inhibition in acute decompensated heart failure. N Engl J Med 2019;380:539-548.
Solomon SD, McMurray JJ, Anand IS, Ge J, Lam CS, Maggioni AP, Martinez F, Packer M, Pfeffer MA, Pieske B, Redfield MM, Rouleau JL, van Veldhuisen DJ, Zannad F, Zile MR, Desai AS, Claggett B, Jhund PS, Boytsov SA, Comin-Colet J, Cleland J, Düngen HD, Goncalvesova E, Katova T, Kerr Saraiva JF, Lelonek M, Merkely B, Senni M, Shah SJ, Zhou J, Rizkala AR, Gong J, Shi VC, Lefkowitz MP; PARAGON-HF Investigators and Committees. Angiotensin-neprilysin inhibition in heart failure with preserved ejection fraction. N Engl J Med 2019;381:1609-1620.
Prospective ARNI vs ACE Inhibitor Trial to DetermIne Superiority in Reducing Heart Failure Events After MI (PARADISE-MI). https://clinicaltrials.gov/ct2/show/NCT02924727 (25 February 2021).
Mozaffarian D, Benjamin EJ, Go AS, Arnett DK, Blaha MJ, Cushman M, De Ferranti S, Després JP, Fullerton HJ, Howard VJ, Huffman MD, Judd SE, Kissela BM, Lackland DT, Lichtman JH, Lisabeth LD, Liu S, Mackey RH, Matchar DB, McGuire DK, Mohler ER, Moy CS, Muntner P, Mussolino ME, Nasir K, Neumar RW, Nichol G, Palaniappan L, Pandey DK, Reeves MJ, Rodriguez CJ, Sorlie PD, Stein J, Towfighi A, Turan TN, Virani SS, Willey JZ, Woo D, Yeh RW, Turner MB; American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Heart disease and stroke statistics - 2015 update: a report from the American Heart Association. Circulation 2015;131:e29-e322.
Chung SC, Gedeborg R, Nicholas O, James S, Jeppsson A, Wolfe C, Heuschmann P, Wallentin L, Deanfield J, Timmis A, Jernberg T, Hemingway H. Acute myocardial infarction: a comparison of short-term survival in national outcome registries in Sweden and the UK. Lancet 2014;383:1305-1312.
Aissaoui N, Puymirat E, Delmas C, Ortuno S, Durand E, Bataille V, Drouet E, Bonello L, Bonnefoy-Cudraz E, Lesmeles G, Guerot E, Schiele F, Simon T, Danchin N. Trends in cardiogenic shock complicating acute myocardial infarction. Eur J Heart Fail 2020;22:664-672.
Curry LA, Spatz E, Cherlin E, Thompson JW, Berg D, Ting HH, Decker C, Krumholz HM, Bradley EH. What distinguishes top-performing hospitals in acute myocardial infarction mortality rates? Ann Intern Med 2011;154:384-390.
Jhund PS, McMurray JJ. Heart failure after acute myocardial infarction: a lost battle in the war on heart failure? Circulation 2008;118:2019-2021.
Sulo G, Igland J, Vollset SE, Nygård O, Ebbing M, Sulo E, Egeland GM, Tell GS. Heart failure complicating acute myocardial infarction; burden and timing of occurrence: a nation-wide analysis including 86 771 patients from the Cardiovascular Disease in Norway (CVDNOR) project. J Am Heart Assoc 2016;5:e002667.
Lewis EF, Moye LA, Rouleau JL, Sacks FM, Arnold JM, Warnica JW, Flaker GC, Braunwald E, Pfeffer MA. Predictors of late development of heart failure in stable survivors of myocardial infarction: the CARE study. J Am Coll Cardiol 2003;42:1446-1453.
Arnold JM, Yusuf S, Young J, Mathew J, Johnstone D, Avezum A, Lonn E, Pogue J, Bosch J. Prevention of heart failure in patients in the Heart Outcomes Prevention Evaluation (HOPE) study. Circulation 2003;107:1284-1290.
Lewis EF, Velazquez EJ, Solomon SD, Hellkamp AS, McMurray JJ, Mathias J, Rouleau JL, Maggioni AP, Swedberg K, Kober L, White H, Dalby AJ, Francis GS, Zannad F, Califf RM, Pfeffer MA. Predictors of the first heart failure hospitalization in patients who are stable survivors of myocardial infarction complicated by pulmonary congestion and/or left ventricular dysfunction: a VALIANT study. Eur Heart J 2008;29:748-756.
Dargie HJ. Effect of carvedilol on outcome after myocardial infarction in patients with left-ventricular dysfunction: the CAPRICORN randomised trial. Lancet 2001;357:1385-1390.
Pitt B, Remme W, Zannad F, Neaton J, Martinez F, Roniker B, Bittman R, Hurley S, Kleiman J, Gatlin M; Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study Investigators. Eplerenone, a selective aldosterone blocker, in patients with left ventricular dysfunction after myocardial infarction. N Engl J Med 2003;348:1309-1321.
Entresto. US Prescribing Information. Novartis Pharmaceuticals, East Hanover, NJ, USA. https://www.novartis.us/sites/www.novartis.us/files/entresto.pdf?source=news_body_link (9 March 2021).
Hansen ML, Gislason GH, Køber L, Schramm TK, Folke F, Buch P, Abildstrom SZ, Madsen M, Rasmussen S, Torp-Pedersen C. Different angiotensin-converting enzyme inhibitors have similar clinical efficacy after myocardial infarction. Br J Clin Pharmacol 2008;65:217-223.
Yusuf S, Sleight P, Pogue J, Bosch J, Davies R, Dagenais G; Heart Outcomes Prevention Evaluation Study Investigators. Effects of an angiotensin-converting-enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients. N Engl J Med 2000;342:145-153.
Yusuf S, Teo KK, Pogue J, Dyal L, Copland I, Schumacher H, Dagenais G, Sleight P, Anderson C; ONTARGET Investigators. Telmisartan, ramipril, or both in patients at high risk for vascular events. N Engl J Med 2008;358:1547-1559.

T32 HL007604 United States HL NHLBI NIH HHS

Keywords: Acute myocardial infarction; Angiotensin receptor-neprilysin inhibitor; Angiotensin-converting enzyme inhibitor; Heart failure; Sacubitril/valsartan

0 (Aminobutyrates)
0 (Angiotensin Receptor Antagonists)
0 (Angiotensin-Converting Enzyme Inhibitors)
0 (Drug Combinations)
0 (Tetrazoles)

Date Created: 20210413 Date Completed: 20210810 Latest Revision: 20220909

20231215

10.1002/ejhf.2191

33847047