gms | German Medical Science

The antihypertensive effect of a fixed combination (fc) of the ACE-inhibitor Spir with HCT in comparison to a continued monotherapy (mt) with Spir (6 mg) was to be investigated.

Period I: 347 out of 478 screened patients with moderate to severe hypertension (sitting diastolic blood pressure [siDBP] =100 mmHg and =115 mmHg and mean day-time diastolic blood pressure > 89 mmHg (ABPM) were included into a 6 week open-label mt with Spir 6 mg/d o.d.. Period II: 218 non-responders to the Spir mt (pre-dose siDBP =95 and =105 mmHg, and md-t DBP > 85 and = 92 mmHg) were randomised to a double-blind, parallel group, multicentre trial to continue the treatment with either a fc of Spir (6 mg/d) + HCT (25 mg/d) o.d. (= 107 pts.) or Spir mt (6 mg/d) + placebo (= 111 pts.) for 6 weeks. (Blood pressure measurements 24±2 h after last intake). Biometric analysis: Confirmatory ANCOVA.

From baseline to the final visit siDBP changed by -9.9 and by -6.5 mmHg (p < 0.0001) with the fc and continued mt, respectively. Md-t DBP decreased by -5.9 with the fc and by -2.4 (p < 0.001) with continued mt. The normalisation rates at final visit were calculated as (fc vs. continued mt) 53% vs. 35% for siDBP (< 90 mmHg), as 56% vs. 37% for siSBP (< 140 mmHg) and as 42% vs. 22% for normalisation of both siDBP and siSBP (all parameters at least p < 0.005). Normalisation rates assessed by ABPM were (fc vs. continued mt): 51% vs. 33% for md-t DBP (< 85 mmHg), 58% vs. 38% for md-t SBP (< 135 mmHg) and 44% vs. 21% for normalisation of both md-t DBP and md-t SBP (p < 0.005).

In patients who did not respond to a 6 week Spir mt (6 mg/d) the subsequent treatment with the fc of Spir (6 mg) + HCT (25 mg) o.d. resulted in a statistically significant and clinically relevant greater blood pressure reduction in comparison to continued Spir mt. Compared to continued mt the percentage of patients with normalisation of both systolic and diastolic BP was doubled with the fc.