Single pill combinations present a proven fast track in practice to reach the target blood pressure

Abstract Objective To assess the efficacy of ambulatory blood pressure (BP) lowering with perindopril/amlodipine (dual SPC arm) and perindopril/amlodipine/indapamide (triple SPC arm) in newly diagnosed and uncontrolled hypertensive patients. Design and method: 450 adults with essential hypertension were assessed in the interventional, open-label, prospective, international, multicentre PRECIOUS trial. Treatment duration was 16 weeks, divided into four treatment periods. ABPM was performed at the baseline and end of the study (prior to the visit 1 and 5), with a validated automated portable BP-measuring device (Mobil-O-Graph PWA) worn on the non-dominant arm for a 24-hour period, measuring BP in 20 minutes interval during the day and 30 minutes interval during the night. At inclusion, naïve or patients uncontrolled on previous mono or dual therapy (other than perindopril/amlodipine (P/A)) were assigned to dual SPC arm with initial dose of 4/5 mg P/A. Those uncontrolled on previous dual or triple therapy were assigned to triple SPC arm with initial dose of 4/5/1.25 mg perindopril/amlodipine/indapamide (P/A/I). If office BP control was not reached, the initial dose was up titrated in 4-week intervals to 8/5 mg, 8/10 mg P/A or 8/10/2.5 mg P/A/I in dual SPC arm and to 8/5/2.5 mg, or 8/10/2.5 mg P/A/I in triple SPC arm. Results After 16 weeks of treatment the decrease in average ambulatory BP was −16.1/−10.8 mmHg (from 142.8/92.6 mmHg to 125.1/80.8 mmHg) in dual SPC arm and −21.8/−13.5 mmHg (from 147.3/93.3 mmHg to 124.2/79.0 mmHg) in triple SPC arm. The relative reductions in ambulatory BP were −11.1%/−11.3% in dual and −14.5%/−14.2% in triple SPC arm. The absolute as well as relative ABPM reductions were higher for the awake-time BP. All ambulatory BP reductions were statistically significant in both arms (p<0.001). 71% of patients reached the normal 24h SBP levels and 45.6% the normal 24h DBP levels. At the end of the trial, the mean dose of perindopril was 6.4±2.0 mg and of amlodipine 6.5±2.3 mg in dual SPC arm. In triple SPC arm, the mean dose of perindopril was 6.66±1.89 mg, of amlodipine 6.51±2.30 mg, and of indapamide 2.08±0.59 mg. Treatment tolerability was good. 85% of patients experienced no adverse events; the recorded ones were clinically irrelevant. Conclusions Applying dual (perindopril/amlodipine) and triple (perindopril/amlodipine/indapamide) SPC treatment strategy resulted in a significant and fast BP reduction, measured by ABPM, in naïve and in patients uncontrolled on previous therapy. In even 71% of patients normal 24h SBP was reached. It seems that adding long acting diuretic in triple SPC enhanced drug efficacy even though the patients in the triple SPC arm had a more resistant hypertension. Funding Acknowledgement Type of funding sources: None.