Larger Blood Pressure Reduction by Fixed-Dose Compared to Free Dose Combination Therapy of ACE Inhibitor and Calcium Antagonist in Hypertensive Patients

Abstract

The introduction of fixed combination of ACEi+CCB (Fixed) has significantly increased patients compliance and adherence to therapy. At the moment, however, there are no data suggesting the better control of once-daily fixed (Fixed) over free doses in separate administrations combination therapy in hypertensives. In a population of 39 consecutive outpatient patients referred to the departmental Hypertension clinic of the University Hospital of Salerno Medical School with the first diagnosis of arterial hypertension, we tested the hypothesis that the Fixed achieve a better control of blood pressure than the Free combination. Patients were randomized to either strategy and after 3 months patients underwent a clinical assessment to evaluate the antihypertensive effect. The two groups, matched for anthropometric and clinical parameters, received Amlodipine (5-10 mg/daily) and Perindopril (5-10 mg/daily). Perindopril and Amlodipine doses did not significantly differ between the two groups. After 3 months BP control was improved in both groups and BP targets were similarly reached in both groups (SBP; Fixed: 61.54%; Free 69.23%; n.s. DPB; Fixed: 80.77%; Free 84.62%; n.s.). The reduction in systolic blood pressure was similar in both groups (Fixed:7.64±2.49%; Free: 7.81±4.00%, n.s.), while the reduction of diastolic blood pressure was greater in the Fixed group (Fixed: 14.22±2.03%; Free: 4.92±5.00%, p<0.05). Although both strategies are effective in reducing BP, the use of Fixed dose has an advantage in the reduction of BP. The present study does not allow to identify the mechanisms of this difference, which can be assumed to be due to the pharmacokinetics of the drugs administered in once-daily fixed combination.

Keywords: ACE Inhibitors; Blood pressure control; Calcium Antagonist; Hypertension; combination therapy.

Figure 1

Effects of once-daily fixed dose vs free dose combination therapy on systolic blood pressure (SBP). Fixed group (Left graph) showed a statistically significant reduction of SBP, while the reduction of Free group (Right graph) was not significant. Statistic significance was assessed by T-test (*= p<0.05; FU= follow-up).

Figure 2

Effects of once-daily fixed dose vs free dose combination therapy on diastolic blood pressure (DBP). Fixed group (Left graph) showed a statistically significant reduction of DBP, while the reduction of Free group (Right graph) was not significant. Statistic significance was assessed by T-test (*= p<0.05; FU= follow-up).

Figure 3

Differences between fixed dose vs free dose combination therapy on blood pressure reduction. The reduction in systolic blood pressure (SBP) (Left graph) showed no major differences between the two groups, while the reduction of diastolic blood pressure (DBP) (Right graph) was significantly higher. Statistic significance was assessed by T-test (*= p<0.05).