TY - JOUR
T1 - Dual angiotensin receptor and neprilysin inhibition as an alternative to angiotensin-converting enzyme inhibition in patients with chronic systolic heart failure
T2 - Rationale for and design of the Prospective comparison of ARNI with ACEI to Determine Impact on Global Mortality and morbidity in Heart Failure trial (PARADIGM-HF)
AU - McMurray, John J V
AU - Packer, Milton
AU - Desai, Akshay S.
AU - Gong, Jim
AU - Lefkowitz, Martin P.
AU - Rizkala, Adel R.
AU - Rouleau, Jean
AU - Shi, Victor C.
AU - Solomon, Scott D.
AU - Swedberg, Karl
AU - Zile, Michael R.
PY - 2013/9
Y1 - 2013/9
N2 - AimsAlthough the focus of therapeutic intervention has been on neurohormonal pathways thought to be harmful in heart failure (HF), such as the renin-angiotensin-aldosterone system (RAAS), potentially beneficial counter-regulatory systems are also active in HF. These promote vasodilatation and natriuresis, inhibit abnormal growth, suppress the RAAS and sympathetic nervous system, and augment parasympathetic activity. The best understood of these mediators are the natriuretic peptides which are metabolized by the enzyme neprilysin. LCZ696 belongs to a new class of drugs, the angiotensin receptor neprilysin inhibitors (ARNIs), which both block the RAAS and augment natriuretic peptides.MethodsPatients with chronic HF, NYHA class II-IV symptoms, an elevated plasma BNP or NT-proBNP level, and an LVEF of ≤40% were enrolled in the Prospective comparison of ARNI with ACEI to Determine Impact on Global Mortailty and morbidity in Heart Failure trial (PARADIGM-HF). Patients entered a single-blind enalapril run-in period (titrated to 10 mg b.i.d.), followed by an LCZ696 run-in period (100 mg titrated to 200 mg b.i.d.). A total of 8436 patients tolerating both periods were randomized 1:1 to either enalapril 10 mg b.i.d. or LCZ696 200 mg b.i.d. The primary outcome is the composite of cardiovascular death or HF hospitalization, although the trial is powered to detect a 15% relative risk reduction in cardiovascular death.
AB - AimsAlthough the focus of therapeutic intervention has been on neurohormonal pathways thought to be harmful in heart failure (HF), such as the renin-angiotensin-aldosterone system (RAAS), potentially beneficial counter-regulatory systems are also active in HF. These promote vasodilatation and natriuresis, inhibit abnormal growth, suppress the RAAS and sympathetic nervous system, and augment parasympathetic activity. The best understood of these mediators are the natriuretic peptides which are metabolized by the enzyme neprilysin. LCZ696 belongs to a new class of drugs, the angiotensin receptor neprilysin inhibitors (ARNIs), which both block the RAAS and augment natriuretic peptides.MethodsPatients with chronic HF, NYHA class II-IV symptoms, an elevated plasma BNP or NT-proBNP level, and an LVEF of ≤40% were enrolled in the Prospective comparison of ARNI with ACEI to Determine Impact on Global Mortailty and morbidity in Heart Failure trial (PARADIGM-HF). Patients entered a single-blind enalapril run-in period (titrated to 10 mg b.i.d.), followed by an LCZ696 run-in period (100 mg titrated to 200 mg b.i.d.). A total of 8436 patients tolerating both periods were randomized 1:1 to either enalapril 10 mg b.i.d. or LCZ696 200 mg b.i.d. The primary outcome is the composite of cardiovascular death or HF hospitalization, although the trial is powered to detect a 15% relative risk reduction in cardiovascular death.
KW - ACE inhibitor
KW - Angiotensin receptor blocker
KW - Angiotensin receptor neprilysin inhibitor
KW - Chronic heart failure
KW - LCZ696
KW - Natriuretic peptides
KW - Neprilysin
KW - Neutral endopeptidase
KW - Renin-angiotensin
UR - http://www.scopus.com/inward/record.url?scp=84880206504&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84880206504&partnerID=8YFLogxK
U2 - 10.1093/eurjhf/hft052
DO - 10.1093/eurjhf/hft052
M3 - Review article
C2 - 23563576
AN - SCOPUS:84880206504
SN - 1388-9842
VL - 15
SP - 1062
EP - 1073
JO - European Journal of Heart Failure
JF - European Journal of Heart Failure
IS - 9
ER -