The Benefits of Indapamide

Since the 1970s, diuretics-especially hydrochlorothiazide (HCTZ)-have been frequently utilized as antihypertensive agents. Unfortunately, there have been many “chinks” in the HCTZ armor when it is evaluated as a pharmaceutical used to lower blood pressure. The antihypertensive action of HCTZ is only 8 hours in duration, but it is administered once a day.¹ In a large prospective trial (ACCOMPLISH), HCTZ did not reduce the occurrence of heart failure when it was compared to amlodipine.² Recent data suggest that 12.5 mg HCTZ may not have any impact on elevated blood pressures.³ Many combination anti-hypertensives contain only 12.5 mg. HCTZ. In another commentary, attention was focused on chlorthalidone as a potential substitute for HCTZ.⁴   Here, I would like to propose another diuretic choice, indapamide.

Indapamide, a non-thiazide diuretic, lowers systolic blood pressure 54% more than HCTZ.⁵ In addition to being more potent that HCTZ, indapamide has a number of other benefits.

A large segment of the population with hypertension is comprised of persons > 65 years of age who have diabetes. In this geriatric cohort, indapamide sustained release (SR) combined with amlodipine was compared to enalapril/amlodipine in a post-hoc analysis.⁶ At 52 weeks, mean systolic blood pressure reductions were significantly greater with the indapamide/amlodipine combination. Considering the well-earned antihypertensive reputation of enalapril, this favorable comparison with indapamide is impressive.

In another study pairing an ACEI (perindopril) with indapamide as the diuretic in hypertensive diabetic persons,⁷ the relative risks of diabetic micro- and macrovascular disease were reduced in the ACEI-indapamide combination by 9%, cardiovascular mortality by 18%, and all cause mortality by 14%.⁷

The RENAAL (Reduction of Endpoints in NIDDM with the Angiotensin II Antagonist Losartan) study⁸ demonstrated that microalbuminuria in diabetic patients is associated with greater cardiovascular risks and death.  In a cohort of patients with diabetes, hypertension, and microalbuminuria, systolic blood pressure below target was reached in 84% of persons taking perindopril/indapamide at the lower dose range and 90% at the higher dose range of both agents. In addition, microalbuminria decreased in 75% of those treated with the indapamide-ACEI combination.

Indapamide does not have more adverse metabolic effects than HCTZ. But, it clearly provides more “bang for the buck” when treating hypertension. Not only does it have a longer half-life, but it confers more antihypertensive potency and important pleiotropic effects that may include micro- and macrovascular benefits in patients with diabetes while it also reduced microalbuminuria.

Would any of your current patients benefit?

References

Pool PE, Applegate WB, Woehler T, et al. A randomized, controlled trial comparing diltiazem, hydrochlorthiazide, and their combination in the therapy of essential hypertension. Pharmacotherapy. 1993;13:487-493.

Roush GC, Ernst ME, Kostis JB, et al. Not just chlorthalidone: evidence-based, single tablet diuretic alternatives to hydrochlorothiazide for hypertension. Curr. Hypertens. Rep. 2015; 17:31.

Pareek AK, Messerli FH, Chandurkar NB, et al. Efficacy of low-dose chlorthalidone and hydrochlorothiazide as assessed by ambulatory blood pressure monitoring. J Am Coll Cardiol. 2016; 67:379-389.

Rutecki GW. Chlorthalidone: underappreciated, underutilized, and undervalued. Practical Cardiology. Accessed Feb 7, 2018.

Roush GC, Ernst ME, Kostis JB, et al. Head-to-head comparisons of hydrochlorthiazide with indapamide and chlorthalidone: antihypertensive and metabolic effects. Hypertension 2015; 65:1041-1046.

Hanon O, Caillard L, Chaussade E, et al. Blood pressure-lowering efficacy of indapamideSR/amlodipine combination in older patients with hypertension: A post hoc analysis of the NESTOR trial (Natrilix SR vs. Enalapril in Hypertensive Type 2 diabtecs with microalbuminuria. J Clin Hypertens. 2017; 10:965-972.

Levy BL, Taddei S. Vascular legacy beyond blood pressure control: benefits of perindopril/idapamide combination in hypertensive patients with diabetes. Curr. Med. Res. Opin. 2018; doi: 10.1080/03007995.2018.

Brenner BM, Cooper ME, de Zeeuw D, et al. Effects of losartan on renal and cardiovascular outcomes in patients with type 2 diabetes and nephropathy. N Engl J Med. 2001; 345:861-869.