Despite recommendations in guidelines, combinations containing a calcium channel blocker and diuretic are less commonly prescribed than combinations containing a renin angiotensin system (RAS) inhibitor in the management of hypertension. This randomized controlled trial assessed the systolic blood pressure (BP)-lowering efficacy and tolerability of the single-pill combinations (SPC) of indapamide sustained release (SR)/amlodipine vs valsartan/amlodipine over 3 monthsDesign and method:
Following a 4 week run-in with amlodipine 5 mg, 465 adult hypertensive patients (systolic BP > = 150 and <180 mmHg and/or diastolic BP <110 mmHg) were randomized to receive indapamide SR 1.5 mg/amlodipine 5 mg (n = 233) or valsartan 80 mg/amlodipine 5 mg (n = 232). Treatment was uptitrated to indapamide SR 1.5 mg/amlodipine 10 mg or valsartan 160 mg/amlodipine 5 mg at week 6 if office BP remained uncontrolled (systolic BP > = 140 and <180 mmHg and/or diastolic BP > = 90 and <110 mmHg). Office systolic BP was assessed at baseline, week 6, and week 12. Ambulatory BP monitoring (ABPM) was performed at baseline and week 12.Results:
At week 12, indapamide SR/amlodipine was as effective as valsartan/amlodipine at reducing office systolic BP (-21 mmHg vs -20 mmHg respectively, P<0.001 for non-inferiority). Amongst patients with BP uncontrolled on ABPM at baseline (BP >130/80 mmHg), indapamide SR/amlodipine (n = 104) was significantly more effective at week 12 at reducing office systolic BP vs valsartan/amlodipine (n = 112) (-23 mmHg vs -18 mmHg, respectively, P = 0.016). Treatment was well tolerated in both groups, in line with safety profiles, with very few patients reporting peripheral edema (n = 2) or orthostatic hypotension (n = 1) with the high dose indapamide SR 1.5 mg/amlodipine 10 mg.Conclusions:
These results confirm that in adult hypertensive patients, indapamide SR/amlodipine SPC effectively lowers office systolic BP at 3 months and is as effective as valsartan/amlodipine, a standard combination containing a RAS inhibitor. Amongst a subgroup of patients with sustained hypertension (uncontrolled BP on ABPM at baseline), indapamide SR/amlodipine was significantly more effective than valsartan/amlodipine at lowering office systolic BP. In addition, despite doubling the dose of amlodipine in the high- vs low-dose group, the indapamide SR/amlodipine combination was well tolerated with particularly low rates of edema and orthostatic hypotension.