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Impact of renin-angiotensin system inhibition on microalbuminuria in type 2 diabetes: a post hoc analysis of the Shiga Microalbuminuria Reduction Trial (SMART).

Hypertens Res. 2008 Jun;31(6):1171-6

Authors: , Uzu T, Sawaguchi M, Maegawa H, Kashiwagi A

The Shiga Microalbuminuria Reduction Trial (SMART) showed the advantage of ARB over CCB beyond the blood pressure (BP)-lowering effect in reducing microalbuminuria. To further assess the impact of BP control or renin-angiotensin system inhibition on microalbuminuria, the SMART patients were re-analyzed. Hypertensive patients with type 2 diabetes and microalbuminuria were randomly assigned to valsartan or amlodipine treatment groups for 24 weeks. Target blood pressure was set at <130/80 mmHg. Changes in the urinary albumin creatinine ratio (ACR) from baseline were assessed in the valsartan monotherapy (VM) group (n=33), the amlodipine monotherapy (AM) group (n=36), the concomitant valsartan and angiotensin-converting enzyme inhibitor group (VA) (n=33), and the concomitant amlodipine and angiotensin-converting enzyme inhibitor (AA) group (n=38). At the end of the study, mean BP was not different among the four treatment groups. The changes in ACR from baseline to the end of the treatment period in VM, AM, VA, and AA were -36%, +30%, -26%, and +8%, respectively. The dissociation between the anti-albuminuric and antihypertensive effects of valsartan or amlodipine was observed in the respective monotherapy groups. In the AA group, however, a significant positive relationship was found between the changes in ACR and those in systolic BP. In conclusion, RAS inhibitors may be necessary in order for calcium channel blockers to have an effect on microalbuminuria. Therefore, RAS inhibitors are first-line drugs for hypertensive patients with type 2 diabetes and microalbuminuria.

PMID: 18716365 [PubMed - indexed for MEDLINE]

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Add-on therapy with a nighttime dose of doxazosin in patients with uncontrolled hypertension: effects on autonomic modulation of the cardiovascular system.

Hypertens Res. 2008 Mar;31(3):443-53

Authors: Guzik P, Wykretowicz A, Krauze T, Piskorski J, Adamska K, Milewska A, Wesseling KH, Wysocki H

This study was designed to determine whether or not the addition of a single nighttime dose of doxazosin in extended-release form (GITS; gastrointestinal therapeutic system) would affect the autonomic modulation of the cardiovascular system in patients with uncontrolled hypertension treated with a multi-drug regimen. Resting 5-min noninvasive finger blood pressure and ECG signals, as well as 24-h Holter ECGs, were recorded in 30 patients with uncontrolled hypertension on multi-drug treatment before and after 16-week add-on therapy with doxazosin GITS. Cardiovascular autonomic modulation was evaluated by spectral analysis of heart rate variability (HRV) and a cross-correlation method for spontaneous baroreflex sensitivity (BRS) in 5-min resting recordings, and by the analysis of Poincaré plots and phase-rectified signal averaging of the duration of cardiac cycles in 24-h ECG recordings. This combined therapy significantly reduced systolic pressure (19.4+/-3.5 mmHg; p<0.0001), diastolic blood pressure (9.4+/-2.0 mmHg; p=0.0003), and pulse pressure (10.0+/-2.8 mmHg; p=0.0021). Concomitantly, there was a significant increase in resting spontaneous BRS (p=0.0191) and increases in 24-h short-term (p=0.0129) and total (p=0.0153) HRV, but with no significant change in heart rate or other measures of HRV. The improvements in HRV and BRS were observed mainly in patients already treated with thiazide diuretics. There was a significant association (r=0.49; p=0.0065) between the degree of change in diastolic blood pressure and short-term HRV caused by the combined treatment. The addition of 4 mg doxazosin GITS to multi-drug antihypertensive therapy is associated with an improvement in cardiovascular autonomic control.

PMID: 18497463 [PubMed - indexed for MEDLINE]

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Effect of renin-angiotensin-aldosterone system triple blockade on non-diabetic renal disease: addition of an aldosterone blocker, spironolactone, to combination treatment with an angiotensin-converting enzyme inhibitor and angiotensin II receptor blocker.

Hypertens Res. 2008 Jan;31(1):59-67

Authors: Furumatsu Y, Nagasawa Y, Tomida K, Mikami S, Kaneko T, Okada N, Tsubakihara Y, Imai E, Shoji T

Although dual blockade of the renin-angiotensin-aldosterone system (RAAS) with the combination of an angiotensin-converting enzyme inhibitor (ACE-I) and angiotensin II receptor blocker (ARB) is generally well-established as a treatment for nephropathy, this treatment is not fully effective in some patients. Based on the recent evidence implicating aldosterone in renal disease progression, this study was conducted to examine the efficacy of blockade with three different mechanisms by adding an aldosterone blocker in patients who do not respond adequately to the dual blockade. A 1-year randomized, open-label, multicenter, prospective controlled study was conducted, in which 32 non-diabetic nephropathy patients with proteinuria exceeding 0.5 g/day were enrolled after more than 12 weeks of ACE-I (5 mg enalapril) and ARB (50 mg losartan) combination treatment. These patients were allocated into two groups of 16 patients each: a triple blockade group in which 25 mg of spironolactone daily was added to the ACE-I and ARB combination treatment, and a control group in which 1 mg of trichlormethiazide or 20 mg of furosemide was added to the combination treatment instead of spironolactone depending upon the creatinine level. After 1 year of treatment, the urinary protein level decreased by 58% (p<0.05) with the triple blockade but was unchanged in the controls. Furthermore, urinary type IV collagen level decreased by 40% (p<0.05) with the triple blockade but was unchanged in the controls. The decreases in urinary protein and urinary type IV collagen were not accompanied by a decrease in blood pressure. Mean serum creatinine, potassium and blood pressure did not change significantly by either treatment. In conclusion, triple blockade of the RAAS was effective for the treatment of proteinuria in patients with non-diabetic nephropathy whose increased urinary protein had not responded sufficiently to a dual blockade.

PMID: 18360019 [PubMed - indexed for MEDLINE]

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