Enalapril heart failure

ACE inhibitors can be administered with diuretics (qv), cardiac glycosides, -adrenoceptor blockers, and calcium channel blockers. Clinical trials indicate they are generally free from serious side effects. The effectiveness of enalapril, another ACE inhibitor, in preventing patient mortaUty in severe (Class IV) heart failure was investigated. In combination with conventional dmgs such as vasodilators and diuretics, a 40% reduction in mortaUty was observed after six months of treatment using 2.5—40 mg/d of enalapril (141). However, patients complain of cough, and occasionally rash and taste disturbances can occur. 

The SOLVD Investigators, Effect of enalapril on survival in patients with reduced left ventricular ejection fractions and congestive heart failure, N. Engl.. Med., 325, 293-302,1991. 

Cohn IN, Johnson G, Ziesche S, et al. A comparison of enalapril with hydralazine-isosorbide dinitrate in the treatment of chronic congestive heart failure, [see comment]. N. Engl. J. Med. 1991 325 303-10. 

Willenheimer R, van Veldhuisen DJ, Silke B, et al. Effect on survival and hospitalization of initiating treatment for chronic heart failure with bisoprolol followed by enalapril, as compared with the opposite sequence results of the randomized Cardiac Insufficiency Bisoprolol Study (CIBIS) III. Circulation. Oct 18 2005 112(16) 2426-2435. 

CONSENSUS Trial Study Group. Effects of enalapril on mortality in severe congestive heart failure Results of the Cooperative North Scandinavian Enalapril Survival Study (CONSENSUS). N Engl J Med 1987 316 1429-1435. 

While essentially all ACE inhibitors have a similar mechanism of action and therefore exhibit similar efficacy in the treatment of hypertension and congestive heart failure, these drugs differ slightly in their pharmacokinetic profiles. Enalapril, lisinopril, and quinapril are excreted primarily by the kidney, with minimal liver metabolism, while the other prodrug compounds are metabolized by the liver and renally excreted. Thus, in patients with renal insufficiency, the half-life of renally excreted ACE inhibitors is prolonged. In addition, patients with impaired liver func-... 

Enalapril maleate is an orally active angiotensin converting enzyme (ACE) inhibitor, it lowers peripheral vascular resistance without causing an increase in heart rate. The maleate salt (enalapril) allows better absorption after oral administration. It is an ideal drug for hypertensive patients who are intolerant to beta-blocker therapy. It also shows promise in the treatment of congestive heart failure. Following oral adminishation, enalapril is rapidly absorbed and hydrolysed to... 

As noted earlier, lithium is contraindicated in patients with unstable congestive heart failure or the sick sinus node syndrome ( 307, 328). In older patients or those with prior cardiac histories, a pretreatment ECG should be obtained. Except for the potential adverse interactions with diuretics, the concomitant use of other cardiac drugs is generally safe. Because verapamil may lower serum levels of lithium, however, more careful monitoring may be required to assure continued therapeutic effects (329). Some data also indicate that verapamil may predispose to lithium neurotoxicity. Conversely, increased lithium levels leading to toxicity has occurred with methyidopa and enalapril. When antihypertensive therapy is necessary, b-blockers are a reasonable choice when lithium is coadministered. 

Vermes E et al Enalapril reduces the incidence of diabetes in patients with chronic heart failure Insight from the Studies Of Left Ventricular Dysfunction (SOLVD). Circulation 2003 107 1291. [PMID 12628950]... 

By reducing preload and afterload in asymptomatic patients, ACE inhibitors (eg, enalapril) slow the progress of ventricular dilation and thus slow the downward spiral of heart failure. Thus, ACE inhibitors are beneficial in all subsets of patients—from those who are asymptomatic to those in severe chronic failure. This benefit appears to be a class effect that is, all ACE inhibitors appear to be effective. 

An important class of orally active ACE inhibitors, directed against the active site of ACE, is now extensively used. Captopril and enalapril are examples of the many potent ACE inhibitors that are available. These drugs differ in their structure and pharmacokinetics, but in clinical use, they are interchangeable. ACE inhibitors decrease systemic vascular resistance without increasing heart rate, and they promote natriuresis. As described in Chapters 11 and 13, they are effective in the treatment of hypertension, decrease morbidity and mortality in heart failure and left ventricular dysfunction after myocardial infarction, and delay the progression of diabetic nephropathy. 

Enalapril Inhibits conversion of angiotensin I Arteriolar dilation decreased aldosterone Hypertension heart failure... 

Packer M 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. [PMID 12186794]... 

Drug Class Angiotensin-converting enzyme [ACE] inhibitors Suffix -pril Common Examples Captopril, enalapril Primary Indication or Desired Effect (Chapter in Parentheses) Antihypertensive [21], congestive heart failure [24]... 

It appears that all ACE inhibitors tested to date have beneficial effects in patients with chronic heart failure. Recent studies have documented these beneficial effects with enalapril, captopril, lisinopril, quinapril, and ramipril. Thus, this benefit appears to be a class effect. 

Abbreviations. AIRE, acute Infarction ramipril efficacy CONSENSUS, cooperative north Scandinavian enalapril sur/f/a study HF, heart failure LVEF, left ventricular ejection fraction NYHA. New York Heart Association SAVE, survival and ventricular enlargement SMILE, survival of myocardial infarction long-term evaluation SOLVD. studies of left ventricular dysfunction TRACE, trandolapril cardiac evaluation study group. 

Clinical benefits and effects on mortality and hospitalization Whether used alone or in combination, hydralazine and isosorbide dinitrate decrease the preload and afterload, decrease mitral regurgitation, improve cardiac output, increase exercise capacity, modestly increase LVEF and prolong survival in patients with HF (63,64). V-Heart Failure Trial (HeFT) II (64) showed that enalapril had a major benefit on survival when compared with the combination of hydralazine-isosorbide dinitrate with enalapril in patients with predominantly NYHA class ll-lll. The African Americans in Heart Failure Trial (A-HeFT) (65) showed a beneficial effect of adding vasodilator therapy to African-American patients already treated with ACE inhibitors, (3 blockers, and spironolactone. There are no results with the same strategy in other patient groups. 

Congestive heart failure (CHF), other high-risk patients Angiotensin-converting enzyme (ACE) inhibition Enalapril Captopril Ramipril Reduction in cardiovascular, all-cause mortality reduced hospitalizations and recurrent CHF in patients post-MI, with CHF and with decreased left ventricular ejection fraction (LVEF) CONSENSUS SAVE SOLVD AIRE HOPE >23,000 14... 

The phase I clinical testing of enalapril began in 1980 in a study in which its efficacy to inhibit intravenously administered angiotensin I was determined. Oral doses as low as 2.5 mg produced a substantial decrease in ACE, activity and lowering was evident even 21-24 hours after the drug was given (129). Phase II and phase III trials began in 1981, and the first approval to use enalapril in hypertension came in 1984 and in heart failure in 1986. 

The CONSENSUS study was performed in 253 patients with severe congestive heart failure. They were randomized to receive either placebo (n = 126) or enalapril (n = 127), from 2.5 mg bid to 20 mg bid with a follow-up period that averaged 182 days. By the end of the study, there had been 68 deaths in the placebo group and 50 in the enalapril group (p =. 003) (313). Later, enalapril was shown to be superior to hydralazine-isosorbide dinitrate (314, 315). 

With the data included in the overview of Garg et al. (316), it is possible to calculate that 18 patients need to be treated for 90 days to avoid one death or one hospitalization for congestive heart failure (95% confidence interval [Cl] 16-23). This meta-analysis includes 32 trials with the ACE inhibitors captopril, enalapril, lisinopril, quinapril, ramipril, and perindopril. It is likely that high doses (for instance, lisinopril 35 mg daily) are more effective than low doses (lisinopril 5 mg daily) (302). Treating 30 patients for 4 years with a high dose of lisinopril (95% Cl 16-509) will avoid one hospitalization for cardiovascular reasons or one death in comparison with a low dose, without increasing the number of adverse effects requiring withdrawal from treatment. 

The main argument in favor of a beneficial effect of ACE inhibition on coronary heart diseases comes from the pooled results of the SOLVE) treatment trial, the SOLVE) prevention trial, and the SAVE, AIRE, and TRACE studies, which indicate a 21% (95% Cl, 11-29%, p <. 001) relative risk reduction for myocardial infarction associated with ACE inhibitor therapy. Enalapril (SOLVE)) significantly reduced hospitalization for unstable angina, and captopril (SAVE) reduced revascularization procedures (291). In patients treated for 38 to 42 months with enalapril or captopril and selected on the basis of a reduction in ejection fraction with or without heart failure, it is necessary to treat 49 patients to avoid one myocardial infarction (95% Cl 32-117). 

Forster, C., Naik, G.O., and Larosa, G. 1994. Myocardial 3-adrenoceptors in pacing-induced heart failure regulation by enalapril Can. J. Physiol. Pharmacol. 72 667-672. 

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