Impressive Reduction Of Risk For Cvd In Diabetic Patients By Antihypertensive Treatment

There is strong evidence for a beneficial effect of BP reduction on CVD risk in T2DM, and these benefits have been demonstrated with all classes of antihypertensive drugs. In recent years many antihypertensive intervention studies (19-34), which have included a representative number of diabetic patients, have been published. All these intervention studies illustrate that BP lowering is very important for improving the poor prognosis of diabetic patients. Disagreements in the outcome of different clinical trials can easily be explained by heterogeneity of these studies. The included patients showed a wide variation concerning initial BP values and lowering of BP values. Most of the patients had long-standing diabetic disease, however the exact duration of diabetes and/or hypertension was not reported in most of the studies. The follow-up of the hypertensive patients ranged from 2 to 8 years and only newly diagnosed patients were only enrolled in the United Kingdom Prospective Diabetes Study (UKPDS).

In the Systolic Hypertension in Elderly Program (SHEP) the effect of low-dose diuretic-based antihypertensive treatment (19) on major CVD event rates was evaluated in older non-insulin-treated diabetic patients (n = 583) with isolated systolic hypertension (ISH) in comparison with nondiabetic patients. There were 4736 patients with ISH (SBP > 160 mm Hg; DBP < 90 mm Hg at baseline) who received either a low dose of chlorthalidone

(2.5-25.0 mm/day) with a step-up to atenolol, a beta-blocker (BB) at 25.0-50.0 mg/day or reserpine (0.05-0.10 mg/day) if needed. The major CVD rate was 34% lower for active treatment compared with placebo, both for diabetic patients and nondiabetic patients. Remarkably, the absolute risk reduction with active treatment compared with placebo was twice as great for diabetic versus nondiabetic patients (101/1000 vs. 51/1000) at the five year follow-up, reflecting the higher risk of diabetic patients. The authors concluded that a low-dose diuretic based treatment is effective in preventing major CVD events—cerebral and cardiac—in both non-insulin treated diabetic and nondiabetic patients with ISH.

In a substudy (20) of the UKPDS 1148 newly detected T2DM patients with a mean BP of 160/94 mm Hg were randomized to either "tight BP control" (n = 758) or "usual care" in the BP control (n = 390). The mean difference in the achieved BP level of 10/5 mm Hg between the two groups (144/82 vs.154/87mm Hg) resulted in a significant reduction in diabetes-related endpoints (-24%), diabetes-related death (-32%), stroke (-44%) and microvascular endpoints (-37%). Myocardial infarction or all-cause mortality, however, was not significantly reduced by BP lowering in the UKPDS. The beneficial effects of tight BP control were shown irrespective of whether captopril, an angiotensin-converting-enzyme inhibitor, (ACEi) or atenolol (a BB) was the basis of antihypertensive treatment (21). More patients needed additional antidiabetic drug treatment in the atenolol group compared with the captopril group, which may be explained by the more pronounced weight gain over 9 years in the atenolol group compared with the captopril group (3.4 vs. 1.6 kg).

The Hypertension Optimal Treatment (HOT) Study (22) included 1501 diabetic patients (total number: 18,790 patients) with hypertension who were randomly allocated to three different diastolic BP targets (< 90, < 85 and < 80 mm Hg). As basic treatment the calcium channel blocker (CCB) felodipine was used. The group of diabetic patients (n = 1501) with hypertension achieving a mean systolic BP of 139.7mm Hg and a mean diastolic BP of 81.1 mm Hg had a 51% reduction in major CV events and 67% reduction in CV mortality (Fig. 1) compared with the group with less tight control (143.7mm Hg, 85.2 mm Hg), although the absolute difference in the diastolic BP was only 4 mm Hg. Remarkably, the enormous risk reduction was seen only in the diabetic patients.

The Systolic Hypertension in Europe (Syst-Eur) trial was initiated to study the effect of the CCB dihydropyridine nitrendipine on the outcome of CV mortality and morbidity in 4695 patients with systolic BP of 160 to 219 mm Hg and diastolic BP below 95 mm Hg. Very positive results were reported for the subgroup of older T2DM patients (n = 492) with systolic

Diabetics Nondiabetics Diabetics Nondiabetics Diabetics Nondiabetics p < 0.005 p = NS p < 0.11 p = NS p < 0.01 p = NS

cardiovascular events myocardial infarction cardiovascular mortality

FIGURE 1 Significant relative risk reduction in diabetic patients (n = 1501) with target value for diastolic blood pressure < 80 mm Hg Abbreviations: NS, not significant. Source: From Ref. 22.

Diabetics Nondiabetics Diabetics Nondiabetics Diabetics Nondiabetics p < 0.005 p = NS p < 0.11 p = NS p < 0.01 p = NS

cardiovascular events myocardial infarction cardiovascular mortality

FIGURE 1 Significant relative risk reduction in diabetic patients (n = 1501) with target value for diastolic blood pressure < 80 mm Hg Abbreviations: NS, not significant. Source: From Ref. 22.

hypertension, randomized to treatment with either the CCB nitrendipine or placebo (23). In the diabetic patients, active treatment reduced overall mortality by 55%, CVevents by 76% and strokes by 73%, compared with placebo, although the median follow-up was only two years (Fig. 2). Active treatment with nitrendipine reduced the rate of all CV events by 69% in the diabetic patients but only by 26% in the patients without diabetes.

In the HOPE Study (Heart Outcomes Prevention Evaluation), which lasted 4.5 years, the role of the ACEi ramipril (10 mg per day) versus placebo was assessed in 9297 patients at high risk of CV events (25). In the Micro-HOPE study 3577 diabetic patients (mean age: 65 years; mean duration of diabetes: 11.6 years) were included, who had at least one other CVD risk factor or a history of a previous CV event. Ramipril treatment was associated with a risk reduction of myocardial infarction (22%), stroke (33%), CVD death (37%) and total mortality (24%) compared with placebo (25). Combined microvascular endpoints (overt nephropathy, dialysis or laser therapy for retinopathy) were also significantly reduced (16%). For the interpretation of the Micro-HOPE study, it is important to emphasize that 44% of the included diabetic patients did not have hypertension and that the initial mean BP values of 141.9 mm Hg systolic and 79.6 mm Hg diastolic were only reduced by 2.4 respectively 1.0 mm Hg in the ramipril group. Thus, the benefit could only partly be attributed to the modest mean reduction of blood pressure. In a small subgroup of patients with peripheral arterial disease (n = 38), 24-hour ambulatory blood pressure (ABP) measurements were performed before randomization and after one year (26). Although ramipril did not significantly reduce day ABP (6/2 mm Hg), it significantly reduced 24-hour ABP (10/4 mm Hg, p = 0.03), mainly because of a more pronounced blood pressure lowering effect during night-time (17/8 mm Hg, p < 0.001). Thus, the effects on CV morbidity and mortality seen with ramipril in the HOPE study may, to a larger extent than previously ascribed, relate to effects on blood pressure during nighttime (26).

In the Losartan Intervention For End Point Reduction in Hypertension Study (LIFE) 9153 patients with essential hypertension and left ventricular hypertrophy (LVH) were randomly assigned to either once daily losartan-based or atenolol-based antihypertensive treatment for 4 years (29). As a part of the LIFE study, 1195 patients with diabetes, hypertension and LVH with a mean age of 67 years and a mean blood pressure of 177/96 mm Hg were also included (30). Mean blood pressure fell to 146/79 mm Hg (17/11) in losartan patients and 148/69 mm Hg (19/11) in atenolol patients. Diabetic patients treated with losartan showed a significant reduction of CVD mortality (RR: 36.5%; p = 0.028) as well as total mortality (RR: 38.7%; p = 0.002) in comparison with patients under atenolol. In addition, myocardial infarction (RR: 17.1%) and stroke (RR: 21.2%) occurred less often in the losartan treated patients, however the difference to atenolol treatment did not reach levels of

Total mortality

Diabetes 2

Diabetes 2

Diabetes is a disease that affects the way your body uses food. Normally, your body converts sugars, starches and other foods into a form of sugar called glucose. Your body uses glucose for fuel. The cells receive the glucose through the bloodstream. They then use insulin a hormone made by the pancreas to absorb the glucose, convert it into energy, and either use it or store it for later use. Learn more...

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