Effects of different ACE inhibitor combinations on albuminuria: results of the GUARD study

Abstract

Clinical practice guidelines recommend blockers of the renin-angiotensin system alone or in combination with other agents to reduce blood pressure and albuminuria in patients with type 2 diabetes. Dihydropyridine calcium channel blockers, however, may lower blood pressure but not albuminuria in these patients. Here we tested the hypothesis that combining an ACE inhibitor with either a thiazide diuretic or a calcium channel blocker will cause similar reductions in blood pressure and albuminuria in hypertensive type 2 diabetics. We conducted a double blind randomized controlled trial on 332 hypertensive, albuminuric type 2 diabetic patients treated with benazepril with either amlodipine or hydrochlorothiazide for 1 year. The trial employed a non-inferiority design. Both combinations significantly reduced the urinary albumin to creatinine ratio and sitting blood pressure of the entire cohort. The percentage of patients progressing to overt proteinuria was similar for both groups. When we examined patients who had only microalbuminuria and hypertension we found that a larger percentage of the diuretic and ACE inhibitor normalized their albuminuria. We conclude that initial treatment using benzaepril with a diuretic resulted in a greater reduction in albuminuria compared to the group of ACE inhibitor and calcium channel blocker. In contrast, blood pressure reduction, particularly the diastolic component, favored the combination with amilodipine. The dissociation between reductions in blood pressure and albuminuria may be related to factors other than blood pressure.

Angiotensin-II receptor antagonist combined with calcium channel blocker or diuretic for essential hypertension

“…First, the dose of trichlormethiazide was increased to achieve further blood pressure reduction, although the use of highdose diuretics is not recommended in terms of preventing coronary heart disease. 41,42 Second, olmesartan was used in a single dose; however, the increase in the dose of ARB may be a choice of treatment to intensify the antihypertensive effect.…”

Angiotensin II receptor blocker and long-acting calcium channel blocker combination therapy decreases urinary albumin excretion while maintaining glomerular filtration rate

“…Recently, the GUARD study in the United States 10 showed treatment with an ACEI (benazepril) plus a diuretic (hydrochlorothiazide) in patients with diabetic nephropathy reduced albuminuria to a greater extent than an ACEI plus CCB (amlodipine). These results called into question whether a diuretic or CCB is more suitable as a second-line agent with a renin-angiotensin system inhibitor.…”

Comparison of medium-dose losartan/hydrochlorothiazide and maximal-dose angiotensin II receptor blockers in the treatment of Japanese patients with uncontrolled hypertension: the Kobe-CONNECT Study

“…The Gauging Albuminuria Reduction With Lotrel in Diabetic Patients With Hypertension trial has also demonstrated that the concomitant use of ACEIs and diuretics reduces microalbuminuria. 7 However, secondary analysis of the Avoiding Cardiovascular Events Through Combination Therapy in Patients Living With Systolic Hypertension (ACCOMPLISH) trial revealed the progression of chronic kidney disease in patients treated with a combination of ACEIs/diuretics. 8 In our study, the reduction in the urine albumin-to-creatinine ratio values was significantly larger in the losartan/HCTZ group than in the maximal-ARB group.…”

“…2 However, the rate of diuretic prescription in Japan is still low because of the associated adverse metabolic effects, including hypokalemia, hyperuricemia, and the harmful influences on glucose and lipid metabolism. 6 Furthermore, it is still controversial whether a combination of rennin-angiotensin system (RAS) inhibitors and diuretics confers beneficial effects with regard to renal 7,8 and cardiovascular outcomes. 9 However, complete blockade of the RAS through increased doses of ARBs is recommended, based on the clinical benefits observed in patients with cardiovascular disease.…”