Anti hypertensive efficcacy of indapamide SR in hypertensive patients uncontrolled with a background therapy: the NATIVE study

Objectives: Antihypertensive monotherapy rarely achieves blood pressure (BP) control. NATIVE (NATrilix SR use in combination antihypertensive thErapy) evaluated indapamide sustained release (SR) in hypertensive patients receiving background therapy. Research design and methods: Patients remaining hypertensive (systolic BP [SBP], 145180 mmHg; diastolic BP [DBP], 95-105 mmHg) while receiving an angiotensin-converting enzyme (ACE) inhibitor (n = 709), beta-blocker (n= 629), calcium-channel blocker (CCB; n = 493), angiotensin 11 type 1 receptor blocker (ARB; n = 75), (x-blocker (n = 29) or other therapy (n = 6) were enrolled, recruited by physicians from 228 centres in Pakistan. Indapamide SR 1.5mg was administered daily for 3 months with background therapy. BP was assessed every 2 weeks, and blood glucose and total cholesterol were evaluated at baseline and study end in a patient subgroup. Adverse events were also recorded. Main outcome measures and results: Of 2073 enrolled patients (49% males; mean age 51 years), 1941 received indapamide SR and background therapy. SBP and DBP decreased significantly (SBP, 166 +/- 16 mmHg at baseline vs. 132 +/- 12 mmHg at 3 months; DBP, 102 +/- 8 mmHg vs. 83 6 mmHg; both p < 0.0001 vs. baseline). Patients uncontrolled with an ACE inhibitor, beta-blocker, CCB or ARB achieved an SBP/DBP decrease of 34 +/- 15/19 +/- 9, 33 +/- 17/19 +/- 10, 33 +/- 15/18 +/- 8 or 35 +/- 16/20 +/- 12 mmHg, respectively (all p < 0.0001). In all, 84% of patients achieved target SBP (<= 140 mmHg) and 61% achieved BP normalisation (SBP < 140, DBP <90 mmHg). The absence of placebo control may lead to an overestimation of the extent of the BP reduction achieved. Glucose and cholesterol levels were unaffected by indapamide SR. Four percent of patients experienced side-effects, which were mild-to-moderate in severity. Conclusions: In patients with hypertension despite antihypertensive therapy, indapamide SR significantly reduced BP with a good acceptability profile. Indapamide SR may represent an effective additional therapy for patients who do not achieve BP goals with other anti hypertensive agents.