Lisinopril heart failure

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-... 

Nitrates and hydralazine have been used in patients with congestive heart failure. An angiotensinconverting enzyme inhibitor such as lisinopril increases the left ventricular ejection fraction in... 

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. 

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. 

Packer M, Poole-Whson PA, Armstrong PW, Cleland JG, Horowitz JD, Massie BM, Ryden L, Thygesen K, Uretsky BF. Comparative effects of low and high doses of the angiotensin-converting enzyme inhibitor, lisinopril, on morbidity and mortality in chronic heart failure. ATLAS Study Group. Circulation 1999 100(23) 2312-18. 

Lewis GR. Comparison of lisinopril versus placebo for congestive heart failure. Am J Cardiol 1989 63(8) D12-16. 

In the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT), over 40 000 participants aged 55 years or older with hypertension and at least one other risk factor for coronary heart disease were randomized to chlortalidone, amlodipine, doxazosin, or lisinopril (1,2). Doxazosin was discontinued prematurely because chlortalidone was clearly superior in preventing cardiovascular events, particularly heart failure (2). Otherwise, mean follow-up was 4.9 years. There were no differences between chlortalidone, amlodipine, and lisinopril in the primary combined outcome or allcause mortality. Compared with chlortalidone, heart failure was more common with amlodipine and lisinopril, and chlortalidone was better than lisinopril at preventing stroke. 

Lisinopril is a non-sulfhydryl ACE inhibitor. It has been used in patients with hypertension, heart failure, myocardial infarction, and diabetic nephropathy. 

The results of the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) was the deciding evidence that the JNC7 used to justify thiazide diuretics as first-line therapy." It was designed to test the hypothesis that newer antihypertensive agents (an a-blocker, ACE inhibitor, and dihydropyridine CCB) would be superior to thiazide diuretic therapy. The primary objective was to compare the combined end point of fatal coronary heart disease and nonfatal myocardial infarction. Other hypertension-related complications (e.g., heart failure and stroke) were evaluated as secondary end points. This was the largest hypertension trial ever conducted and included 42,418 patients aged 55 years and older with hypertension and one additional cardiovascular risk factor. This prospective, double-blind trial randomized patients to chlorthalidone (a thiazide diuretic), amlodipine (dihydropyridine CCB), doxazosin (a-blocker), or lisinopril (ACE inhibitor) for a mean follow-up of 4.9 years. 

The doxazosin arm was terminated early when a significantly higher risk of heart failure compared with chlorthalidone was observed." The other arms were continued as scheduled, and no significant differences in the primary end point were seen between chlorthalidone and either lisinopril or amlodipine. However, chlorthalidone had statistically fewer secondary end points than amlodipine (heart failure) and lisinopril (combined cardiovascular disease, heart failure, and stroke). The study conclusions were that chlorthalidone was superior in preventing one or more major forms of cardiovascular disease and was less expensive than amlodipine and lisinopril. 

ACE inhibitors are considered second-line therapy to diuretics in most patients with hypertension. The ALLHAT demonstrated less heart failure and stroke with chlorthalidone versus lisinopril. This difference in stroke is consistent with another outcomes trial, the Captopril Prevention Project (CAPPP). However, other outcome studies have demonstrated similar, if not better, outcomes with ACE inhibitors versus thiazide diuretics." " In the elderly, one study found that they were at least as effective when compared with diuretics and P-blockers, and another study found that they were more effective." In addition, ACE inhibitors have many roles for patients with hypertension and coexisting conditions. Nonetheless, most clinicians will agree that if ACE inhibitors are not first-line therapy in most patients with hypertension, they are a very close second to diuretics. 

Ryden L., Armstrong P.W., Cleland J.G., Horowitz J.D., Massie B.M., Packer M., Poole-Wilson P.A. Efficacy and safety of high-dose lisinopril in chronic heart failure patients at high cardiovascular risk, including those with diabetes mellitus. Results from the ATLAS trial. Eur. Heart J. 21 (2000) 1967-1978. 

Lisinopril is an angiotensin I-converting enzyme (ACE) inhibitor. It competitively inhibits ACE, prevents angiotensin I conversion to angiotensin II, and is a potent vasoconstrictor that also stimnlates aldosterone secretion. Results are a decrease in sodinm and fluid retention, a decrease in BP, and increase in dinresis. It is indicated in the treatment of hypertension treatment of heart failure not responding to dinretics and digitalis and treatment of acute MI within 24 honrs in hemodynamically stable patients. 

Lisinopril (prinivil, zestril) Lisinopril is the Lys analog of enalaprilat unUke enalapril, lisinopiil itself is active. Lisinopril is slightly more potent than enalaprilat. Lisinopril is absorbed slowly, variably, and incompletely (about 30%) after oral administration (bioavailability is not reduced by food) peak concentrations in plasma are achieved in -7 hours. It is cleared intact by the kidney, and its tj, in plasma is about 12 hours. The oral dosage of lisinopril ranges from 5 to 40 mg daily (single or divided dosage), with 5 and 10 mg daily being appropriate for the initiation of therapy for heart failure and hypertension, respectively. A daily dose of 2.5 mg is recommended for patients with heart failure who are Na+-depleted or have renal impairment. 

Angiotensin-Converting Enzyme Inhibitors Six ACE inhihilots-captopril (Capoten), enalapril (VASOTEC), ramipril (altace), lisinopril (prinivil, zestril), quinapril (accupril), and/oi-inopril (monopril)—are currently EDA-approved for the treatment of heart failure. Data from... 

There is no precisely defined relationship between dose and long-term clinical effectiveness of these drugs, but it is reasonable to use doses comparable to those used in studies that established efficacy in patients with heart failure. On this basis, target doses of these drugs would be 50 mg three times/day for captopril 10 mg twice daily for enalapril 10 mg once daily for lisinopril or 5 mg twice daily for ramipril. In patients who have not achieved an adequate clinical response at these doses, further increases, as tolerated, may be of value high-dose lisinopril (32.5 or 35 mg) reduced the combined endpoint of mortality and hospitalization when compared to lower doses of this agent. 

Vandenbuig MJ, Kelly JG, Wiseman HT, Mannering D, Loi C, Glover DR. The effect of lisinopril on digoxin pharmacokinetics in patients with cor estive heart failure. BrJ Clin Pharmacol 9ZZ) 21,656P-657P. 

ACE inhibitors can raisie lithium levels, and in some individuals two to fourfold increases have been recorded. Cases of lithium toxicity have been reported in patients when given captopril, enal-april or lisinopril (and possibly perindopril). One analysis found an increased relative risk of 7.6 for lithium toxicity requiring hos-pitaUsation in elderly patients newly started on an ACE inhibitor. Risk factors for this interaction seem to be poor renal function, heart failure, volume depletion, and increased age. 

Risk factors for increased lithium toxicity include advanced age, " congestive heart failure, "" renal insufficiency " and volume depletion. " Some consider these to be contraindications to the use of lithi-um. " " Only captopril, enalapril, lisinopril (and possibly perindopril) have been reported to interact, but it seems likely, given the proposed mechanism, that this interaction will occur with any other ACE inhibitor. 

Lisinopril [76547-98-3], angiotensin-converting enzyme inhibitor (for use as antihypertensive and in congestive heart failure), 149. Phosgenation is employed to activate N -(trifluoroacetyl)-L-lysine 146 as N -carboxy anhydride 147, a key intermediate in the acylation of L-proline [114, 115]. Alternative processes have also been described [116-119]. 

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