enalapril and Heart-Arrest

The addition of receptor-neprilysin inhibition to standard therapy, including a renin-angiotensin system blocker, has been demonstrated to improve outcomes in patients with heart failure with reduced ejection fraction (HFrEF) compared with standard therapy alone. The long-term absolute risk reduction from angiotensin receptor neprilysin inhibitor (ARNI) therapy, and whether it merits widespread use among diverse subpopulations, has not been well described.. To calculate estimated 5-year number needed to treat (NNT) values overall and for different subpopulations for the Prospective Comparison of ARNI with Angiotensin-Converting Enzyme Inhibitor (ACEI) to Determine Impact on Global Mortality and Morbidity in Heart Failure (PARADIGM-HF) cohort.. Overall and subpopulation 5-year NNT values were estimated for different end points using data from PARADIGM-HF, a double-blind, randomized trial of sacubitril-valsartan vs enalapril. This multicenter, international study included 8399 men and women with HFrEF (ejection fraction, ≤40%). The study began in December 2009 and ended in March 2014. Analyses began in March 2018.. Random assignment to sacubitril-valsartan or enalapril.. Cardiovascular death or HF hospitalization, cardiovascular death, and all-cause mortality.. The final cohort of 8399 individuals included 1832 women (21.8%) and 5544 white individuals (66.0%), with a mean (SD) age of 63.8 (11.4) years. The 5-year estimated NNT for the primary outcome of cardiovascular death or HF hospitalization with ARNI therapy incremental to ACEI therapy in the overall cohort was 14. The 5-year estimated NNT values were calculated for different clinically relevant subpopulations and ranged from 12 to 19. The 5-year estimated NNT for all-cause mortality in the overall cohort with ARNI incremental to ACEI was 21, with values ranging from 16 to 31 among different subgroups. Compared with imputed placebo, the 5-year estimated NNT for all-cause mortality with ARNI was 11. The 5-year estimated NNT values were also calculated for other HFrEF therapies compared with controls from landmark trials for all-cause mortality and were found to be 18 for ACEI, 24 for angiotensin receptor blockers, 8 for β-blockers, 15 for mineralocorticoid antagonists, 14 for implantable cardioverter defibrillator, and 14 for cardiac resynchronization therapy.. The 5-year estimated NNT with ARNI therapy incremental to ACEI therapy overall and for clinically relevant subpopulations of patients with HFrEF are comparable with those for well-established HF therapeutics. These data further support guideline recommendations for use of ARNI therapy among eligible patients with HFrEF.

Topics: Aged; Aminobutyrates; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Biphenyl Compounds; Cause of Death; Double-Blind Method; Drug Combinations; Enalapril; Female; Follow-Up Studies; Heart Arrest; Heart Failure; Hospitalization; Humans; Male; Middle Aged; Neprilysin; Prognosis; Prospective Studies; Quebec; Stroke Volume; Survival Rate; Sweden; Tetrazoles; Time Factors; United Kingdom; United States; Valsartan

none.

Topics: Adrenergic beta-Antagonists; Aged; Antihypertensive Agents; Enalapril; Heart Arrest; Humans; Hyperkalemia; Male; Spironolactone

There is strong evidence to suggest that angiotensin-converting enzyme inhibitors (ACEIs) protect against local myocardial ischemia/reperfusion (I/R) injury. This study was designed to explore whether ACEIs exert cardioprotective effects in a swine model of cardiac arrest (CA) and resuscitation. Male pigs were randomly assigned to three groups: sham‑operated group, saline treatment group and enalapril treatment group. Thirty minutes after drug infusion, the animals in the saline and enalapril groups were subjected to ventricular fibrillation (8 min) followed by cardiopulmonary resuscitation (up to 30 min). Cardiac function was monitored, and myocardial tissue and blood were collected for analysis. Enalapril pre‑treatment did not improve cardiac function or the 6-h survival rate after CA and resuscitation; however, this intervention ameliorated myocardial ultrastructural damage, reduced the level of plasma cardiac troponin I and decreased myocardial apoptosis. Plasma angiotensin (Ang) II and Ang‑(1‑7) levels were enhanced in the model of CA and resuscitation. Enalapril reduced the plasma Ang II level at 4 and 6 h after the return of spontaneous circulation whereas enalapril did not affect the plasma Ang‑(1‑7) level. Enalapril pre-treatment decreased the myocardial mRNA and protein expression of angiotensin-converting enzyme (ACE). Enalapril treatment also reduced the myocardial ACE/ACE2 ratio, both at the mRNA and the protein level. Enalapril pre‑treatment did not affect the upregulation of ACE2, Ang II type 1 receptor (AT1R) and MAS after CA and resuscitation. Taken together, these findings suggest that enalapril protects against ischemic injury through the attenuation of the ACE/Ang II/AT1R axis after CA and resuscitation in pigs. These results suggest the potential therapeutic value of ACEIs in patients with CA.

Topics: Angiotensin II; Angiotensin-Converting Enzyme Inhibitors; Animals; Blotting, Western; Cardiopulmonary Resuscitation; Cardiotonic Agents; Disease Models, Animal; Enalapril; Gene Expression; Heart; Heart Arrest; Humans; Immunohistochemistry; Male; Microscopy, Electron, Transmission; Myocardial Reperfusion Injury; Myocardium; Peptidyl-Dipeptidase A; Random Allocation; Receptor, Angiotensin, Type 1; Reverse Transcriptase Polymerase Chain Reaction; Swine; Time Factors; Ventricular Fibrillation

Topics: Aged; Airway Obstruction; Angioedema; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Diagnosis, Differential; Drug Combinations; Drug Hypersensitivity; Dyspnea; Enalapril; Heart Arrest; Humans; Hydrochlorothiazide; Male; Tongue Diseases

Angiotensin-converting-enzyme inhibitors are frequently used in conjunction with diuretics in the treatment of congestive cardiac failure. We report two cases in which use of a proprietary combination diuretic containing a loop diuretic and potassium sparing agent with an angiotensin converting enzyme inhibitor was associated with hyperkalaemic cardiac arrest. Successful resuscitation from the arrest permitted elucidation of its mechanism. We believe that this outcome has not previously been reported, and emphasise the importance of electrolyte monitoring in patients receiving angiotensin converting enzyme inhibitors particularly if prescribed in addition to fixed combination proprietary diuretics.

Topics: Aged; Amiloride; Angiotensin-Converting Enzyme Inhibitors; Diuretics; Drug Therapy, Combination; Enalapril; Female; Furosemide; Heart Arrest; Humans; Hyperkalemia

Topics: Adult; Angiotensin-Converting Enzyme Inhibitors; Captopril; Death, Sudden; Enalapril; Heart Arrest; Heart Failure; Humans; Hyperkalemia; Hypokalemia; Male; Middle Aged; Potassium; Resuscitation; Substance Withdrawal Syndrome