BACKGROUND: Arterial hypertension greatly increases the risk of cardiovascular disease, renal insufficiency, and retinopathy in patients with type 2 diabetes. Epidemiological studies all document a reduced risk for the aforementioned consequences at a blood pressure (BP) lower than 130/80 mmHg. For this reason, lower target BPs are recommended by recent guidelines committees. A lower threshold BP for treatment, also proposed in guidelines, could facilitate the attainment of the recommended target BP. However, little data exist on the efficacy and safety of starting pharmacological therapy in type 2 diabetic patients exhibiting high-normal BP (HNBP) or the first stage of isolated systolic hypertension previously considered as borderline isolated systolic hypertension (BISH). OBJECTIVE: To determine the antihypertensive efficacy and safety of the fixed-dose combination of the non-dihydropiridine calcium channel blocker (CCB) and ACE inhibitor verapamil SR/trandolapril 180/2 mg (V + T), versus trandolapril 2 mg (T), versus placebo (P) in previously untreated type 2 diabetic patients diagnosed as having HNBP or BISH. METHODS: Multicentric, double-blind, placebo-controlled study with a 16-week follow-up in three groups totalling 438 participants. The primary end-point was to attain the recommended guideline goal of a systolic BP (SBP) value lower than 130 mmHg in all patients and a diastolic BP (DBP) value lower than 85 mmHg in HNBP. Participants were randomized (2:2:1) to verapamil V + T, T, or P. Doses were doubled at week 8 if BP was not controlled. RESULTS: Both active groups were more effective than placebo to decrease SBP and DBP. The mean difference in SBP from placebo was 7.1 mmHg (3.3-10.9, 95% confidence interval (CI); P < 0.001) for T and 7.8 mmHg (3.9-11.6, 95% CI; P < 0.001) for V + T, with no statistical difference between both active groups. Combined treatment (V + T) decreased DBP by 4.6 mmHg (2.3-6.9, 95% CI; P < 0.001) more than placebo and 2.1 mmHg (0.3-4.0, 95% CI; P = 0.021) more than T. At the end of the study, 36.5% in the T group, 37.8% in the V + T group, and 14.9% (P = 0.009, P versus V + T and T) had attained the primary end-point. No significant difference was found between T and V + T with regard to the percentage of good control for SBP, but the control rate on the DBP (DBP < 85 mmHg) was significantly higher in the V + T group (88.8%), when compared with T (79.1%) or P (63.5%) (P = 0.002). Withdrawal rates due to adverse effects did not differ among trandolapril alone (9.4%), the combination (11.7%) and placebo (8.1%). CONCLUSION:Antihypertensive treatment is more effective than placebo for controlling SBP and DBP in previously untreated participants with type 2 diabetes exhibiting low threshold BP values. Combination therapy with verapamil SR/trandolapril was more effective than trandolapril alone for controlling DBP.
RCT Entities:
BACKGROUND: Arterial hypertension greatly increases the risk of cardiovascular disease, renal insufficiency, and retinopathy in patients with type 2 diabetes. Epidemiological studies all document a reduced risk for the aforementioned consequences at a blood pressure (BP) lower than 130/80 mmHg. For this reason, lower target BPs are recommended by recent guidelines committees. A lower threshold BP for treatment, also proposed in guidelines, could facilitate the attainment of the recommended target BP. However, little data exist on the efficacy and safety of starting pharmacological therapy in type 2 diabeticpatients exhibiting high-normal BP (HNBP) or the first stage of isolated systolic hypertension previously considered as borderline isolated systolic hypertension (BISH). OBJECTIVE: To determine the antihypertensive efficacy and safety of the fixed-dose combination of the non-dihydropiridine calcium channel blocker (CCB) and ACE inhibitor verapamil SR/trandolapril 180/2 mg (V + T), versus trandolapril 2 mg (T), versus placebo (P) in previously untreated type 2 diabeticpatients diagnosed as having HNBP or BISH. METHODS: Multicentric, double-blind, placebo-controlled study with a 16-week follow-up in three groups totalling 438 participants. The primary end-point was to attain the recommended guideline goal of a systolic BP (SBP) value lower than 130 mmHg in all patients and a diastolic BP (DBP) value lower than 85 mmHg in HNBP. Participants were randomized (2:2:1) to verapamil V + T, T, or P. Doses were doubled at week 8 if BP was not controlled. RESULTS: Both active groups were more effective than placebo to decrease SBP and DBP. The mean difference in SBP from placebo was 7.1 mmHg (3.3-10.9, 95% confidence interval (CI); P < 0.001) for T and 7.8 mmHg (3.9-11.6, 95% CI; P < 0.001) for V + T, with no statistical difference between both active groups. Combined treatment (V + T) decreased DBP by 4.6 mmHg (2.3-6.9, 95% CI; P < 0.001) more than placebo and 2.1 mmHg (0.3-4.0, 95% CI; P = 0.021) more than T. At the end of the study, 36.5% in the T group, 37.8% in the V + T group, and 14.9% (P = 0.009, P versus V + T and T) had attained the primary end-point. No significant difference was found between T and V + T with regard to the percentage of good control for SBP, but the control rate on the DBP (DBP < 85 mmHg) was significantly higher in the V + T group (88.8%), when compared with T (79.1%) or P (63.5%) (P = 0.002). Withdrawal rates due to adverse effects did not differ among trandolapril alone (9.4%), the combination (11.7%) and placebo (8.1%). CONCLUSION: Antihypertensive treatment is more effective than placebo for controlling SBP and DBP in previously untreated participants with type 2 diabetes exhibiting low threshold BP values. Combination therapy with verapamil SR/trandolapril was more effective than trandolapril alone for controlling DBP.