High affinity for angiotensin converting enzyme (ACE) competing with angiotensin I, the natural substrate, to block its conversion to angiotensin II. Angiotensin II is a potent vasoconstrictor and a negative feedback mediator for renin activity. Thus, as a result of lower angiotensin II plasma levels, plasma renin activity increases, reducing aldosterone secretion, and lowering BP.
Formulation (tab, caps, IV)
U.S. Cost per dose
Onset / time to peak
Hypertension alone or in combination with other medications
Benazepril / Losentin
HFrEF, diabetic nephropathy, hypertension and LVD after MI
1.7 hrs in healthy adults
3.3 hrs in heart failure
20-40 hrs in anuria
Onset: 15 min
Peak effect: 1 hr
Metabolism: 50% metabolized hepatically
Treatment of hypertension, asymptomatic left ventricular dysfunction and HFrEF
Enalaprilat inj 1.25 mg/mL
2.5 mg tab
Enalaprilat inj 1.25 mg/mL (2 mL vial) $3.41
Pro-drug (Enalapril) healthy adults 2 hrs; congestive heart failure 3.4-5.8
Treatment of heart failure and hypertension either alone or in combination with other medications
Active Metabolite (fosinoprilat)
Onset: 1 hr
Treatment of hypertension either alone or in combination with other medications, left ventricular dysfunction after MI, acute MI within 24 hrs in stable patients and adjunctive treatment with heart failure
Lisinopril / Zestril
Treatment of hypertension and reduce mortality/nonfatal MI in patients with stable CAD
Onset/time to peak: 1-2 hrs
Metabolism: Hepatically hydrolyzed to active metabolite perindoprilat and other active metabolites
Perindopril: 60%; Perindoprilat: 10% to 20%
Treatment of hypertension and heart failure
Quinapril / Accupril
Pro drug: (Quinapril) 0.8 hrs
Onset: 1 hr
Peak: 2-4 hr
Quinapril and quinaprilat: 97%;
Treatment of hypertension alone or in combination with another medication, left ventricular dysfunction after MI and reduce risk of stroke, MI and death
Ramiprilat 13-17 hrs
Onset: 1-2 hrs
Ramipril: 73%; Ramiprilat: 56%
Treatment of hypertension alone or in combination with another medication and left ventricular dysfunction after MI
Trandolapril / Mavik
Parent drug (trandolapril) 6 hrs
Onset: 1-2 hr
Parent: 1 hr
Comment: Multicenter, controlled trial of 285 normotensive patients with type 1 diabetes and normoalbuminuria randomly assigned to receive losartan (100 mg daily), enalapril (20 mg daily), or placebo for 5 years. Authors found that enalapril did not slow nephropathy progression but slowed the progression of retinopathy.
Comment: At the Steno Diabetes Center, 49 type 1 diabetic patients with diabetic nephropathy participated in double-masked randomised crossover trial with initial washout period followed by three treatment periods of 2 months each, receiving lisinopril 20, 40 and 60 mg once daily in randomised order in addition to slow-release furosemide. Compared with lisinopril 20 mg there was a further reduction in urinary albumin excretion rate of 23% with lisinopril 40 mg and 19% with 60 mg, p < 0.05.
Comment: Multicenter double-blind, randomized Bergamo Nephrologic Diabetes Complications Trial (BENEDICT) in subjects with hypertension, type 2 diabetes mellitus, and normal urinary albumin excretion. 1204 subjects randomly assigned to 3 years of trandolapril plus verapamil, trandolapril alone, verapamil alone or placebo. Trandolapril plus verapamil and trandolapril alone decreased the incidence of microalbuminuria to a similar extent.
Comment: American Diabetes Association recommendations for management of hypertension in diabetes.
Comment: Fifty-seven patients with diabetic nephropathy were divided equally into group A with treatment with losartan (50 mg) and fosinopril (10 mg) daily, group B with daily losartan treatment (50-100 mg), and group C with fosinopril treatment at the daily dose of 10-20 mg for 6-months. Combined use of losartan and fosinopril decreased blood pressure, 24-h urine protein excretion, serum creatinine and BUN to a greater extent than the use of either alone.
Comment: Meta-analysis concluding that ACE inhibitors improve microalbuminuria in normotensive patients with type 1 diabetes mellitus.
Comment: 235 normotensive IDDM patients with microalbuminuria participated in double-blind, randomised, placebo-controlled trials to assess the effects of captopril 50 mg twice daily on the progression to overt clinical albuminuria. The risk of progression over 24 months was significantly reduced by captopril (p = 0.004) with a risk reduction of 69.2% (31.7 - 86.1%).
Comment: Randomized, double-blind, placebo-controlled clinical trial of 2 years' duration including 92 patients with insulin-dependent diabetes mellitus and persistent microalbuminuria but no hypertension. Patients randomly allocated to receive either captopril, 50 mg, or placebo twice per day. Progression to clinical proteinuria was significantly reduced by captopril therapy (P = .03 by log-rank test).
Comment: Captopril protects against deterioration in renal function in insulin-dependent diabetic nephropathy as compared to other similarly effective treatments.
Comment: 94 normotensive, type II diabetic patients with microalbuminuria and normal renal function randomly assigned to receive enalapril, 10 mg per day, or placebo. Difference in rate of change in proteinuria between two groups favored enalapril [P < 0.05])
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