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Managing hypertension in diabetic patients--focus on trandolapril/verapamil combination.

Sharma SK, Ruggenenti P, Remuzzi G - Vasc Health Risk Manag (2007)

Bottom Line: Hypertensive diabetes individuals are at higher risk for cardiovascular events and progression to end stage renal disease.There are physiological and clinical rationales for renin-angiotensin system blockade in hypertensive diabetics.Trandolapril/verapamil sustained released (SR) is a fixed-dose combination of trandolapril and a sustained release formulation of verapamil and indicated in treatment of hypertension in patients who require more than one drug to reach target blood pressure.

View Article: PubMed Central - PubMed

Affiliation: Clinical Research Centre for Rare Diseases Aldo e Cele Daccò, Mario Negri Institute for Pharmacological Research,Villa Camozzi, Ranica, Italy.

ABSTRACT
Hypertensive diabetes individuals are at higher risk for cardiovascular events and progression to end stage renal disease. Several well conducted clinical trials indicate that aggressive treatment of hypertension in individual with diabetes reduces these complications. Combinations of two or more antihypertensive drugs are frequently required to reach the target blood pressure and to improve the cardiovascular and renal outcomes in these patients. There are physiological and clinical rationales for renin-angiotensin system blockade in hypertensive diabetics. Trandolapril/verapamil sustained released (SR) is a fixed-dose combination of trandolapril and a sustained release formulation of verapamil and indicated in treatment of hypertension in patients who require more than one drug to reach target blood pressure. The antihypertensive efficacy of trandolapril/verapamil SR has been evaluated extensively in large trials. In the INVEST trial, a verapamil SR-based treatment strategy that included trandolapril in most patients was effective in reducing the primary outcome in hypertensive patients with coronary artery disease. The new onset of diabetes was also significantly lower in the verapamil SR/trandolapril treatment group in comparison with those on the atenolol/hydroclorothiazide treatment group. The BErgamo NEphrologic Diabetes Complications Trial (BENEDICT) documented that in hypertensive diabetes and normoalbuminuria, trandolapril plus verapamil or trandolapril alone delayed the onset of microalbuminuria independent of their blood pressure-reducing effect. Thus, trandolapril/verapamil is an effective option for treatment of hypertensive diabetes patients requiring more than one agent to achieve target blood pressure.

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Patients who developed microalbuminuria throughout the study period of the BENEDICT trial according to follow-up systolic blood pressure (SBP). These are patients with type 2 diabetes, arterial hypertension, and normoalbuminuria at baseline. Effective SBP reduction below the median (<139.16 mmHg) has specific and independent protective effects against the development of microalbuminuria. The risk reduction for microalbuminuria that was achieved by angiotensin converting enzyme inhibitor (ACEi) therapy in patients with follow-up SBP above the median (≥139.16 mmHg) was highly significant even after adjustment for baseline covariates and concomitant treatment with non-dihydropyridine calcium channel blockers. Thus ACEi therapy had a further protective effect, in particular when SBP was less effectively controlled (inset).
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fig3: Patients who developed microalbuminuria throughout the study period of the BENEDICT trial according to follow-up systolic blood pressure (SBP). These are patients with type 2 diabetes, arterial hypertension, and normoalbuminuria at baseline. Effective SBP reduction below the median (<139.16 mmHg) has specific and independent protective effects against the development of microalbuminuria. The risk reduction for microalbuminuria that was achieved by angiotensin converting enzyme inhibitor (ACEi) therapy in patients with follow-up SBP above the median (≥139.16 mmHg) was highly significant even after adjustment for baseline covariates and concomitant treatment with non-dihydropyridine calcium channel blockers. Thus ACEi therapy had a further protective effect, in particular when SBP was less effectively controlled (inset).

Mentions: Recently the post-hoc analysis of the BENEDICT trial was reported (Ruggenenti et al 2006). Of 1204 patients in the original study cohort, 1180 patients were included in the post-hoc analysis. Twenty-four patients were excluded because either they reached an endpoint, stopped regular study follow-up or blood pressure recording was inadequate for the analysis. Overall, the systolic blood pressure was decreased 6.5 ± 7.63% and diastolic blood pressure was decreased 6.4 ± 7.47% from baseline to follow-up. Baseline mean arterial pressure (MAP) and pulse pressure were 108.6 ± 8.33 mmHg and 63.3 ± 12.64 mmHg: they decreased by 6.5 ± 6.83% and 5.3 ± 14.70%, to 101.2 ± 6.47/58.9 ± 9.99 mmHg on follow-up. The findings from a post-hoc analysis suggest that in patients with type 2 diabetes and hypertension, effective blood pressure reduction has a specific and independent protective effect against the development of microalbuminuria. Nevertheless, trandolapril had a further protective effect, in particular when blood pressure was poorly controlled, whereas the ndCCB therapy was ineffective at any level of achieved blood pressure (Figure 3). The finding that the risk of developing microalbuminuria was not associated with baseline blood pressure provided consistent evidence that the lower incidence of microalbuminuria observed with more effective blood pressure reduction reflected a benefit of treatment and not simply less severe hypertension at study entry (Figure 4). Therefore, these results extend to the very early stages of diabetic renal disease previous evidence of a renoprotective effect of blood pressure control in people with diabetes and established nephropathy (Mogensen 1976; Dillon 1993; Bakris et al 2003; Pohl et al 2005; Remuzzi et al 2006). Of interest, patients with systolic, diastolic, mean blood pressure, and pulse pressure reduction above the medians compared with those with corresponding blood pressure reductions below the medians, were more frequently on ACE inhibitor therapy with trandolapril/verapamil or trandolapril alone and, on the contrary, were less frequently on treatment with concomitant antihypertensive medications such as diuretics, betablockers, ndCCBs, and sympatholytic agents (Table 3). The risk reduction achieved by ACE inhibitor therapy in patients with systolic, MAP, and pulse pressure below the median was significant even after adjustment for baseline covariates and concomitant treatment with ndCCBs. A similar trend was observed for diastolic blood pressure.


Managing hypertension in diabetic patients--focus on trandolapril/verapamil combination.

Sharma SK, Ruggenenti P, Remuzzi G - Vasc Health Risk Manag (2007)

Patients who developed microalbuminuria throughout the study period of the BENEDICT trial according to follow-up systolic blood pressure (SBP). These are patients with type 2 diabetes, arterial hypertension, and normoalbuminuria at baseline. Effective SBP reduction below the median (<139.16 mmHg) has specific and independent protective effects against the development of microalbuminuria. The risk reduction for microalbuminuria that was achieved by angiotensin converting enzyme inhibitor (ACEi) therapy in patients with follow-up SBP above the median (≥139.16 mmHg) was highly significant even after adjustment for baseline covariates and concomitant treatment with non-dihydropyridine calcium channel blockers. Thus ACEi therapy had a further protective effect, in particular when SBP was less effectively controlled (inset).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2291330&req=5

fig3: Patients who developed microalbuminuria throughout the study period of the BENEDICT trial according to follow-up systolic blood pressure (SBP). These are patients with type 2 diabetes, arterial hypertension, and normoalbuminuria at baseline. Effective SBP reduction below the median (<139.16 mmHg) has specific and independent protective effects against the development of microalbuminuria. The risk reduction for microalbuminuria that was achieved by angiotensin converting enzyme inhibitor (ACEi) therapy in patients with follow-up SBP above the median (≥139.16 mmHg) was highly significant even after adjustment for baseline covariates and concomitant treatment with non-dihydropyridine calcium channel blockers. Thus ACEi therapy had a further protective effect, in particular when SBP was less effectively controlled (inset).
Mentions: Recently the post-hoc analysis of the BENEDICT trial was reported (Ruggenenti et al 2006). Of 1204 patients in the original study cohort, 1180 patients were included in the post-hoc analysis. Twenty-four patients were excluded because either they reached an endpoint, stopped regular study follow-up or blood pressure recording was inadequate for the analysis. Overall, the systolic blood pressure was decreased 6.5 ± 7.63% and diastolic blood pressure was decreased 6.4 ± 7.47% from baseline to follow-up. Baseline mean arterial pressure (MAP) and pulse pressure were 108.6 ± 8.33 mmHg and 63.3 ± 12.64 mmHg: they decreased by 6.5 ± 6.83% and 5.3 ± 14.70%, to 101.2 ± 6.47/58.9 ± 9.99 mmHg on follow-up. The findings from a post-hoc analysis suggest that in patients with type 2 diabetes and hypertension, effective blood pressure reduction has a specific and independent protective effect against the development of microalbuminuria. Nevertheless, trandolapril had a further protective effect, in particular when blood pressure was poorly controlled, whereas the ndCCB therapy was ineffective at any level of achieved blood pressure (Figure 3). The finding that the risk of developing microalbuminuria was not associated with baseline blood pressure provided consistent evidence that the lower incidence of microalbuminuria observed with more effective blood pressure reduction reflected a benefit of treatment and not simply less severe hypertension at study entry (Figure 4). Therefore, these results extend to the very early stages of diabetic renal disease previous evidence of a renoprotective effect of blood pressure control in people with diabetes and established nephropathy (Mogensen 1976; Dillon 1993; Bakris et al 2003; Pohl et al 2005; Remuzzi et al 2006). Of interest, patients with systolic, diastolic, mean blood pressure, and pulse pressure reduction above the medians compared with those with corresponding blood pressure reductions below the medians, were more frequently on ACE inhibitor therapy with trandolapril/verapamil or trandolapril alone and, on the contrary, were less frequently on treatment with concomitant antihypertensive medications such as diuretics, betablockers, ndCCBs, and sympatholytic agents (Table 3). The risk reduction achieved by ACE inhibitor therapy in patients with systolic, MAP, and pulse pressure below the median was significant even after adjustment for baseline covariates and concomitant treatment with ndCCBs. A similar trend was observed for diastolic blood pressure.

Bottom Line: Hypertensive diabetes individuals are at higher risk for cardiovascular events and progression to end stage renal disease.There are physiological and clinical rationales for renin-angiotensin system blockade in hypertensive diabetics.Trandolapril/verapamil sustained released (SR) is a fixed-dose combination of trandolapril and a sustained release formulation of verapamil and indicated in treatment of hypertension in patients who require more than one drug to reach target blood pressure.

View Article: PubMed Central - PubMed

Affiliation: Clinical Research Centre for Rare Diseases Aldo e Cele Daccò, Mario Negri Institute for Pharmacological Research,Villa Camozzi, Ranica, Italy.

ABSTRACT
Hypertensive diabetes individuals are at higher risk for cardiovascular events and progression to end stage renal disease. Several well conducted clinical trials indicate that aggressive treatment of hypertension in individual with diabetes reduces these complications. Combinations of two or more antihypertensive drugs are frequently required to reach the target blood pressure and to improve the cardiovascular and renal outcomes in these patients. There are physiological and clinical rationales for renin-angiotensin system blockade in hypertensive diabetics. Trandolapril/verapamil sustained released (SR) is a fixed-dose combination of trandolapril and a sustained release formulation of verapamil and indicated in treatment of hypertension in patients who require more than one drug to reach target blood pressure. The antihypertensive efficacy of trandolapril/verapamil SR has been evaluated extensively in large trials. In the INVEST trial, a verapamil SR-based treatment strategy that included trandolapril in most patients was effective in reducing the primary outcome in hypertensive patients with coronary artery disease. The new onset of diabetes was also significantly lower in the verapamil SR/trandolapril treatment group in comparison with those on the atenolol/hydroclorothiazide treatment group. The BErgamo NEphrologic Diabetes Complications Trial (BENEDICT) documented that in hypertensive diabetes and normoalbuminuria, trandolapril plus verapamil or trandolapril alone delayed the onset of microalbuminuria independent of their blood pressure-reducing effect. Thus, trandolapril/verapamil is an effective option for treatment of hypertensive diabetes patients requiring more than one agent to achieve target blood pressure.

Show MeSH
Related in: MedlinePlus