Comparison of the effects of doxazosin and atenolol on target organ damage in adults with type 2 diabetes mellitus and hypertension in the CARDHIAC study: a 9-month, prospective, randomized, open-label, blinded-evaluation trial.

OBJECTIVE: The CARDHIAC (CARduran en pacientes Diabéticos con HIpertensi'on Arterial no Controlada) trial examined the effects of doxazosin gastrointestinal therapeutic system (GITS) and atenolol on 3 separate measures of target-organ damage--left ventricular mass index (LVMI), carotid intima media thickness (IMT), and urinary albumin excretion (UAE)--in patients with type 2 diabetes mellitus and hypertension. METHOD: This trial had a prospective, open-label, blinded-evaluation design and a duration of 9 months. Patients whose blood pressure (BP) was uncontrolled (systolic BP > or = 130 mm Hg and/or diastolic BP > or = 80 mm Hg) despite at least 1 month of treatment with a renin-angiotensin blocker and diuretic were randomly allocated to receive doxazosin GITS 4 mg or atenolol 50 mg once daily in addition to their existing treatment. Seated BP was measured at study visits at 1, 3, 6 and 9 months; if the BP goal was not achieved at any visit, the dose of doxazosin or atenolol was titrated upward to 8 or 100 mg, respectively. Treatment compliance (pill count) and adverse reactions were monitored at each visit. Each patient underwent echocardiography and Doppler ultrasonography at baseline and at the end of the study for evaluation of the change in LVMI. The change in carotid IMT was evaluated by carotid ultrasound examination at the same time points. UAE also was measured at baseline and the end of the study. RESULTS: Sixty patients (100% white; 51% female; mean [SD] age, 63.4 [7.5] years; body mass index, 28.2 [3.4] kg/m(2)) were randomized to receive doxazosin GITS (n=32) or atenolol (n=28). At baseline, mean BP was 150.2 (10.6)/90.1 (7.3) mm Hg in the doxazosin group and 153.1 (13.8)/92.3 (6.1) mm Hg in the atenolol group (P=NS). At the end of the study, BP had decreased by 10.1 (3.2)/5.2 (1.3) mm Hg in the doxazosin group and 12.2 (4.2)/6.3 (2.1) mm Hg in the atenolol group (both, P<0.001 vs baseline; P=NS between groups). Heart rate at the end of the study was 78(6) beats/min in the doxazosin group (P=NS vs baseline) and 66(7) beats/min in the atenolol group (P<0.01 vs baseline and between groups). LVMI decreased by 10.8 in the doxazosin group (P=0.001 vs baseline) and 4.2% in the atenolol group (P=NS vs baseline; P=0.03 between groups). The changes in carotid IMT and UAE were not statistically significant between groups. CONCLUSIONS: In this study in hypertensive patients with type 2 diabetes, LVMI was significantly decreased in doxazosin-treated patients relative to baseline and compared with atenolol-treated patients. The differences in carotid IMT and UAE were not statistically significant between groups.

Effect of candesartan on coronary flow reserve in patients with systemic hypertension.

BACKGROUND: Patients with hypertension have structural and functional changes in conductance and resistance vessels. In the absence of coronary stenosis the coronary microvascular function can be analysed by studying the coronary reserve. The aim of this study was to evaluate, non-invasively, the effect of candesartan on coronary microvascular function in hypertensive patients. METHODS: Twenty-two hypertensive patients (> 40 years) without clinical coronary disease (age 63.86 +/- 10.3 years; women, 59.1%) were studied. In addition to blood pressure (BP), measurement of carotid intima-medial thickness (IMT), left ventricle mass index (LVMI) and the coronary flow reserve (CFR) were evaluated with echography at the beginning, and after 3 months of treatment with 16 mg/day of candesartan. Twelve hypertensive controls (64.50 +/- 10.8 years; women, 58.4%) completed the same study without any change in treatment. RESULTS: A 15% improvement in CFR (3.10 +/- 1.02 to 3.56 +/- 1.06; P = 0.001) was observed simultaneously with the BP reduction. There was no change in CFR in the control group (2.9 +/- 1.1 to 3.01 +/- 0.9; P = 0.23). The IMT was not modified significantly at the end of the follow-up (0.86 +/- 0.1 to 0.83 +/- 0.1 mm; P = 0.103). CONCLUSION: Candesartan improves the CFR in hypertensive patients. The improvement was not related to BP control or LVMI regression. Patients with a lower CFR show a better response to candesartan. This fact can be demonstrated non-invasively with echography after 3 months of therapy.

Regression of left ventricular hypertrophy by a candesartan-based regimen in clinical practice. The VIPE study.

The VIPE study was a prospective, non-comparative, open-label clinical evaluation of 97 hypertensive patients (69.1% female; 68.9 +/- 9.5 years; mean blood pressure (BP) 160 +/- 12/90 +/- 9 mmHg) with echocardiographic evidence of left ventricular hypertrophy (LVH). Patients were treated for six months with a candesartan-based regimen (8 mg/16 mg + HCTZ 12.5 mg + additional drugs to lower BP < 140/90 mmHg). After six months, systolic/diastolic BP was decreased by 19.3 +/- 8/9.4 +/- 5 mmHg (p<0.001 for both), and left ventricular mass index (LVMI) decreased 17.01 g/m2 (95%CI: -13.2 to -20.99; p<0.001). During treatment with the candesartan-based regimen all echocardiographic parameters related to LVMI were significantly reduced and 28% achieved a target LVMI [< 134 g/m(2) (men) and < 110 g/m(2) (women)]. No significant changes were observed in ejection fraction, shortening fraction or LV diastolic function. Univariate analysis showed that both age (p=0.03) and diabetes (p=0.029) were predictive of LVH regression. Thus, a candesartan-based regimen for six months significantly reduced echocardiographic LVH in hypertensive patients in general practice. The drug was very well tolerated and no serious adverse events were reported.