Rationale and design of a study comparing two fixed-dose combination regimens to reduce albuminuria in patients with type II diabetes and hypertension

Bakris, George L.; Toto, Robert D.; McCullough, Peter A.

doi:10.1038/sj.jhh.1001789

Cited by 5 publications

(5 citation statements)

References 18 publications

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“…9 Tests for the superiority of the CCB/ACE inhibitor treatment regimen compared with the ACE inhibitor/diuretic treatment regimen were based on the null hypothesis, and a twosided test will be performed at the 5% significance level. 9 The sample size was determined based on 90% power, assuming no difference in the change from baseline to week 52 in the Ualb:Cr ratio between B þ A and B þ HCTZ treatment regimens. The power calculations allowed for a dropout rate of 20% after randomization.…”

Section: Methodsmentioning

confidence: 99%

“…9 For testing the hypothesis of noninferiority of the CCB/ACE inhibitor treatment regimen and the ACE inhibitor/diuretic treatment regimen, a one-sided test was performed at the 2.5% level of significance (or equivalently, a 97.5% one-sided confidence interval for the difference will be used). 9 Tests for the superiority of the CCB/ACE inhibitor treatment regimen compared with the ACE inhibitor/diuretic treatment regimen were based on the null hypothesis, and a twosided test will be performed at the 5% significance level. 9 The sample size was determined based on 90% power, assuming no difference in the change from baseline to week 52 in the Ualb:Cr ratio between B þ A and B þ HCTZ treatment regimens.…”

Section: Methodsmentioning

confidence: 99%

“…The rationale and design of the study are described elsewhere. 9 prematurely discontinued from the study primarily due to adverse events (AEs), being lost to follow-up, unsatisfactory therapeutic effect, or withdrawal of consent ( Figure 1). Among the patients who discontinued, 13 patients in the B þ A arm and 15 patients in the B þ HCTZ arm had one post-baseline assessment conducted and were included in the intent-to-treat population.…”

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confidence: 99%

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

Bakris

Toto

McCullough

et al. 2008

Kidney International

152

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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.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

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

Bakris

Toto

McCullough

et al. 2008

Kidney International

152

View full text Add to dashboard Cite

show abstract

“…Whether this combination also provides BP‐independent renoprotective effects remains to be determined. The Gauging Albuminuria Reduction With Lotrel in Diabetic Patients With Hypertension (GUARD) study, 27 an ongoing clinical trial comparing the effect of amlodipine‐besylate/benazepril‐HCl and benazepril‐HCl/hydrochlorothiazide on urinary albumin‐to‐creatinine ratio and progression to overt nephropathy in hypertensive microalbuminuric type 2 diabetic patients, may help to resolve this issue.…”

Section: Combination Of An Acei or Arb And A Ccbmentioning

confidence: 99%

Management Strategies for Patients With Hypertension and Diabetes: Why Combination Therapy Is Critical

Giunti

Cooper

2006

J of Clinical Hypertension

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Hypertension is commonly associated and acts synergistically with diabetes in increasing the risk of macrovascular and microvascular diabetic complications. Large-scale clinical trials have demonstrated that this risk is significantly reduced by intensive antihypertensive treatment, and accordingly, the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure guideline has further lowered the blood pressure goals for diabetic subjects to <130/80 mm Hg. This implies that most diabetic patients will require the combination of two or more antihypertensive agents to achieve this blood pressure target. Although the most effective combination strategy in diabetes has not yet been determined in large-scale randomized clinical trials, a combination that includes at least one agent that interrupts the renin-angiotensin system appears to not only have a good safety profile, but may also provide additional renal and cardiovascular protection. Other antihypertensive agents should be added based on the patients risk profile and overall treatment regimen to achieve blood pressure goal.

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“…76 However, few trials have been designed to test the effect of specific antihypertensive combinations on cardiovascular or renal end points. [77][78][79][80][81] Dual RAS/CCB blockade would seem a propitious combination, since these classes of antihypertensive agents target multiple mechanisms involved in hypertensive vascular disease progression. This hypothesis is supported by the recently reported results of the JIKEI Heart Study, 82 a prospective, randomized, open-label, blinded end point (PROBE) trial of more than 3000 patients with hypertension and cardiovascular disease treated to target BP of 130/80 mm Hg.…”

Section: Dual Calcium Channel/ras Blockadementioning

confidence: 99%

Targeting mechanisms of hypertensive vascular disease with dual calcium channel and renin–angiotensin system blockade

Weir

2007

J Hum Hypertens

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Patients with hypertension, particularly those with diabetes mellitus, are at heightened risk for cardiovascular and renal disease. Accumulated evidence indicates that the majority of hypertensive patients at high risk will require more than one antihypertensive agent to reach their blood pressure (BP) target. A reasonable strategy is to use agents with complementary mechanisms of action to enhance BP-lowering efficacy and prevent target organ damage. In experimental models, the combination of a calcium channel blocker (CCB) with an agent that blocks the renin-angiotensin system (RAS), an angiotensinconverting enzyme (ACE) inhibitor or angiotensin receptor blocker, improves measures of endothelial function, inflammation, ventricular remodelling and renal function to a greater degree than these classes given as monotherapy. In clinical trials, calcium channel/RAS blockade combination therapy has been shown to provide greater BP reductions and improve renal function in patients with diabetic and nondiabetic renal disease earlier and to a greater extent than monotherapy. In addition, dual calcium channel/RAS blockade increases arterial compliance, arterial distensibility and flow-mediated vasodilation. Expanding upon extensive research on the benefits of calcium channel blockade and RAS blockade for the prevention of vascular events and preclinical and clinical trial evidence suggests added effects of combination therapy by targeting the underlying mechanisms of hypertensive vascular disease.

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Rationale and design of a study comparing two fixed-dose combination regimens to reduce albuminuria in patients with type II diabetes and hypertension

Cited by 5 publications

References 18 publications

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

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

Management Strategies for Patients With Hypertension and Diabetes: Why Combination Therapy Is Critical

Targeting mechanisms of hypertensive vascular disease with dual calcium channel and renin–angiotensin system blockade

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