Baseline characteristics and treatment of patients in prospective comparison of ARNI with ACEI to determine impact on global mortality and morbidity in heart failure trial (PARADIGM-HF).
OBJECTIVE
To describe the baseline characteristics and treatment of the patients randomized in the PARADIGM-HF (Prospective comparison of ARNi with ACEi to Determine Impact on Global Mortality and morbidity in Heart Failure) trial, testing the hypothesis that the strategy of simultaneously blocking the renin-angiotensin-aldosterone system and augmenting natriuretic peptides with LCZ696 200 mg b.i.d. is superior to enalapril 10 mg b.i.d. in reducing mortality and morbidity in patients with heart failure and reduced ejection fraction.


METHODS
Key demographic, clinical and laboratory findings, along with baseline treatment, are reported and compared with those of patients in the treatment arm of the Studies Of Left Ventricular Dysfunction (SOLVD-T) and more contemporary drug and device trials in heart failure and reduced ejection fraction.


RESULTS
The mean age of the 8442 patients in PARADIGM-HF is 64 (SD 11) years and 78% are male, which is similar to SOLVD-T and more recent trials. Despite extensive background therapy with beta-blockers (93% patients) and mineralocorticoid receptor antagonists (60%), patients in PARADIGM-HF have persisting symptoms and signs, reduced health related quality of life, a low LVEF (mean 29 ± SD 6%) and elevated N-terminal-proB type-natriuretic peptide levels (median 1608 inter-quartile range 886-3221 pg/mL).


CONCLUSIONS
PARADIGM-HF will determine whether LCZ696 is more beneficial than enalapril when added to other disease-modifying therapies and if further augmentation of endogenous natriuretic peptides will reduce morbidity and mortality in heart failure and reduced ejection fraction.
BHF Cardiovascular Research Centre, University of Glasgow, Glasgow, Scotland, UK.
John J V
JJ
McMurray
Milton
M
Packer
Akshay S
AS
Desai
Jianjian
J
Gong
Martin
M
Lefkowitz
Adel R
AR
Rizkala
Jean L
JL
Rouleau
Victor C
VC
Shi
Scott D
SD
Solomon
Karl
K
Swedberg
Michael R
MR
Zile
D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use; D000368:Aged; D000613:Aminobutyrates / Q000627:therapeutic use*; D057911:Angiotensin Receptor Antagonists / Q000627:therapeutic use*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D001713:Biphenyl Compounds; D004232:Diuretics / Q000627:therapeutic use; D004338:Drug Combinations; D004656:Enalapril / Q000627:therapeutic use*; D005260:Female; D006333:Heart Failure / Q000188:drug therapy* / Q000401:mortality / Q000503:physiopathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D000451:Mineralocorticoid Receptor Antagonists / Q000627:therapeutic use; D020097:Natriuretic Peptide, Brain / Q000097:blood; D018579:Patient Selection; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use; D011788:Quality of Life; D016032:Randomized Controlled Trials as Topic; D013318:Stroke Volume; D013777:Tetrazoles / Q000627:therapeutic use*; D016896:Treatment Outcome; D000068756:Valsartan
D000319:Adrenergic beta-Antagonists; D000613:Aminobutyrates; D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D001713:Biphenyl Compounds; D004232:Diuretics; D004338:Drug Combinations; D000451:Mineralocorticoid Receptor Antagonists; D010975:Platelet Aggregation Inhibitors; D013777:Tetrazoles; D020097:Natriuretic Peptide, Brain; D004656:Enalapril; D000068756:Valsartan; C549068:sacubitril and valsartan sodium hydrate drug combination
Heart failure; Natriuretic peptides; Neutral endopeptidase; Renin-angiotensin system