A Comparison of Enalapril plus Hydrochlorothiazide with Standard Triple Therapy in Renovascular Hypertension

Abstract

This prospective, double-blind, multicenter study compared enalapril plus hydrochlorothiazide with standard triple therapy (STT; hydrochlorothiazide, timolol, and hydralazine) with regard to safety, tolerability, antihypertensive efficacy, and effect on renal function in 75 patients with documented renovascular hypertension. Both groups showed a significant mean decrease in systolic and diastolic blood pressure during the double-blind study, with the enalapril group showing a mean 12 mm greater decrease in systolic blood pressure as compared to STT ( < 0.05). Effective treatment of diastolic hypertension was noted in 96% of the enalapril group as compared to 82% on STT (p < 0.05). STT failure was seen exclusively in patients with bilateral renal artery stenosis of high grade and frequently in association with impaired renal function. ^CPAH, a measure of effective renal plasma flow, showed a significant increase in the enalapril group, as compared to the STT (p < 0.05). In contrast, there was a bimodal response of C_In (GFR): 80% of patients in the enalapril group showed no significant change while 20% (10 patients) showed a mean decrease of 28% along with a 12% increase in C_PAH (p < 0.01). No acute renal failure or toxic side effects were noted in the enalapril group. Enalapril plus hydrochlorothiazide is very effective in treating renovascular hypertension and is without significant toxic side effects. The self-limited increase in serum creatinine seen in 20% of renovascular hypertensive patients receiving enelapril and hydrochlorothiazide may identify a subset of patients with unilateral or bilateral high grade renal artery stenosis who should be treated with angioplasty or operative intervention.

Role of Renin-Angiotensin System Blockade in Atherosclerotic Renal Artery Stenosis and Renovascular Hypertension

“…33,34 Starting in the early 1980s, trials began to evaluate ACE inhibitors in patients with renovascular hypertension. [35][36][37][38][39] These studies showed that ACE inhibitors were more effective in controlling blood pressure than previously available therapy. For example, Franklin and Smith 35 compared combination therapy with enalapril plus hydrochlorothiazide against triple therapy based on hydrochlorothiazide, timolol, and hydralazine in 75 patients with renovascular hypertension.…”

Evaluation and management of bilateral renal artery stenosis in children: A case series and review

“…Similarly, blockade of the renin-angiotensinaldosterone mechanism may convert the hypertension from a predominantly renin-dependent state to a more volumedependent state [36]. Oral captopril, enalapril or lisinopril or intravenous enalaprilat are generally effective in reducing systemic blood pressure [42,43], but may occasionally result in renal ischemia without an appreciable change in serum creatinine levels or GFR [44,45]. These effects are often exacerbated in patients with RAS bilaterally or with a solitary kidney because they lack a compensatory mechanism for increasing GFR [44,46].…”

“…Reported rates of acute renal failure associated with ACEI are 17% and 23% for bilateral RAS [42,44], 38% for RAS in a solitary kidney [44] and 6% for unilateral or lowgrade RAS and hypertension [43]. The risk of ACEI-induced acute renal failure increases with depletion of circulatory volume by salt restriction, use of diuretic agents and with the severity of the stenosis [44,[46][47][48][49].…”

Renal injury from angiotensin I converting enzyme inhibitors

“…Since the fall in glomerular filtration rate after angiotensin I converting enzyme inhibition is reversible immediately after withdrawal of the drug [27,[30][31][32]36], some authors concluded that its use in patients with renal artery stenosis is relatively safe [37,38]. However, both animal data and human experience suggests that after continued treatment with an angiotensin I converting enzyme inhibitor, atrophy of the stenosed kidney (Fig.…”