1. Thiazide-Like/Calcium Channel Blocker (CCB) Agents: A Major Combination for Hypertension Management Safar M, Blacher J. Am J Cardiovasc Drugs. 2014; DOI 10.1007/s40256-014-0087-y.

2. Diuretic/CCB combinations: an alternative to inhibiting the renin- angiotensin-aldosterone system Approximately half of hypertensive patients achieve target blood pressure (BP), mostly due to difficulties in controlling systolic BP (SBP). However, SBP strongly correlates with cardiovascular (CV) risk and events. Therefore, it has become paramount that strategies that specifically lower SBP be developed. The guidelines recommend a diuretic/CCB combination as a new alternative. Indeed, blocking the renin-angiotensin system (RAS) is not always necessary. Combinations of diuretics with CCB already have proven CV benefits compared with other strategies, including those with RAS blockers. Indapamide SR and amlodipine are complementary molecules with well-proven CV benefits, especially on stroke.

3. SBP variability after 3 months of antihypertensive treatment was assessed by the standard deviation of 24h SBP readings or read-to-read ARV mode. Only indapamide and amlodipine significantly reduced 24h SBP variability, while candesartan did not. Only amlodipine and indapamide SR reduced 24h SBP variability *P<0.05 for treatment vs placebo. Abbreviations: ARV, average real variability; SBP, systolic blood pressure; SR, sustained release.

4. Strong efficacy for SBP DBP, diastolic blood pressure; SBP, systolic blood pressure; SR, sustained release. Blood pressure reduction in a hypertensive population receiving the single-pill combination of indapamide SR/amlodipine for 45 days. Office blood pressure control was reached by 85 % of patients. EFFICIENT trial

5. Conclusion Despite a wide range of combination therapies now available, SBP control remain a huge therapeutic challenge in hypertensive patients. Indapamide and amlodipine have solid evidence in reducing SBP, and are among the first antihypertensive agents to have been shown to reduce SBP variability. Combinations of thiazide diuretic/CCB are “preferred combinations” in the guidelines due to their strong evidence on CV risk reduction. The results of the first trial demonstrating strong SBP reduction with a single-pill formulation of indapamide SR/ amlodipine support the idea that there is a place in everyday practice for this new treatment.