Indapamide

Indapamide is a non-thiazide sulphonamide diuretic compound, generally used in the treatment of hypertension, as well as decompensated cardiac failure.

[Optimization of Control of Blood Pressure, Metabolic Disorders and Target Organs Protection With Fixed Perindopril and Indapamide Combination in Treated Patients With Arterial Hypertension].[Pubmed:28290783]

Kardiologiia. 2017 Feb;57(2):5-11.

PURPOSE: to assess the potential of fixed perindopril/Indapamide combination (FPIC) to improve angioprotection in patients with arterial hypertension (AP) with various efficacy of preceding therapy with combination of losartan and hydrochlorothiazide (HCTZ). MATERIAL AND METHODS: We included in this open study 50 patients with AP divided into two equal-sized groups in dependence on the achievement of target blood pressure (BP) less than 140/90 mm Hg on preceding therapy with losartan (100 mg) and HCTZ (12.5 mg). All patients underwent ambulatory BP monitoring (ABPM), applanation tonometry (assessment of augmentation index and central blood pressure), measurement of pulse wave velocity (PWV), laboratory tests (lipid profile, fasting glucose, HOMA index, homocysteine, leptin, adiponectin, high sensitivity C reactive protein [hsCRP]). Study duration was 12 weeks. RESULTS: Treatment with FPIC in patients not at target BP provided 14.5 and 6.6% reduction of systolic and diastolic BP (SBP and DBP), respectively (p<0.01), while in patients with target BP it was associated with additional reductions of SBP and DBP by 3.9 and 5.4%, respectively (p<0.01). According to ABPM data average day- and nighttime SBP decreased by 16.9 and 15.0%, average day- and nighttime DBP - by 10.6 and 13.6% (p<0.01) in the group of patients not at target BP. Reductions of PWV (by 15.2 and 2.2%), augmentation index (by 10.7 and 9.4%), central SBP (by 10.9 and 2.1%), central pulse BP vascular age (by 8.7 and 6.0%) were observed in groups of patients without and with target BP on preceding therapy, respectively (p<0.01). Leptin level decreased by 10.0 and 14.4%, hsCRP - by 17.7 and 11.0%; while level of adiponectin increased by 6.7 and 9.9% (p<0.01). CONCLUSION: Our results demonstrated advantages of FPIC over losartan+HCTZ combination relative to BP control, improvement of arterial elasticity, alleviation of insulin resistance and inflammation.

[Effect of Combined Antihypertensive Therapy With Perindopril and Indapamide on Morpho-Functional Parameters of The Heart, Blood Vessels of Small and Medium Caliber in Patients With Essential Hypertension].[Pubmed:28294884]

Kardiologiia. 2016 Mar;56(3):19-24.

AIM: to study effect of therapy with fixed combination of angiotensin-converting enzyme infibitor and diuretic on structural-functional parameters of the heart and vessels and cognitive function. MATERIAL AND METHODS: We included into this study 30 patients (20 women) with mean age 60.06+/-10.19 years, duration of hypertensive disease 14.7 (3; 32) years, body mass index 31.19+/-3.93 kg/m2, and without history of cerebrovascular diseases. Methods of investigation included clinical examination, measurement of parameters of hemodynamics, electro- and echocardiography. Vascular endothelial function and structural - functional state of finger skin capillary network was studied by photopletismography and video capillaroscopy, respectively. The state of cognitive sphere was evaluated with the help of the Montreal Cognitive Assessment (MoCA) test. RESULTS: We noted improvement of endothelial function of middle caliber arteries and microcirculatory vascular bed (MCVB) (increase of occlusion index at the level of MCVB from 1.4 to 1.8, p<0.00005; increase of density of skin capillary network at rest from 45 to 52 kap/2, p<0.00007); improvement of cognitive function according to changes of MoCA test results (from 23 to 27, p<0,0001). There were no changes of lipid and carbohydrate metabolism, and electrolyte balance. Conclision. The use of fixed of perindopril+indopamide is combination characterized by good tolerability and high results.

Blood pressure-lowering efficacy and safety of perindopril/indapamide/amlodipine single-pill combination in patients with uncontrolled essential hypertension: a multicenter, randomized, double-blind, controlled trial.[Pubmed:28306636]

J Hypertens. 2017 Jul;35(7):1481-1495.

OBJECTIVES: This 4-month, double-blind, randomized, controlled trial was designed to demonstrate the superiority of perindopril/Indapamide/amlodipine single pill over perindopril/Indapamide after 1 month and to determine further up-titration efficacy and safety in patients with mild-to-moderate hypertension. METHODS: After a 1-month run-in period on perindopril/Indapamide 5/1.25 mg, patients with SBP/DBP at least 150/95 mmHg and no diabetes or renal insufficiency received perindopril/Indapamide/amlodipine 5/1.25/5 mg single pill or continued on the same treatment. At 1, 2, and 3 months, patients with uncontrolled blood pressure (SBP/DBP >/= 140/90 mmHg) were gradually up-titrated with a higher dose of the triple therapy up to perindopril/Indapamide/amlodipine 10/2.5/10 mg in both groups. Efficacy was assessed on office supine SBP (main criterion) and DBP, blood pressure control, and response rates. Treatment effect on ambulatory blood pressure monitoring (ABPM) and home blood pressure monitoring (HBPM) parameters was also assessed in two subpopulations of 276 and 263 patients, respectively. RESULTS: A total of 454 hypertensive patients (diabetes and renal insufficiency excluded) were randomized, 227 to each group (56% were men, mean age was 55 years, blood pressure 162.3/101.1 mmHg). After 1 month, superior SBP (-3.1 mmHg, P = 0.02) and DBP (-2.8 mmHg, P < 0.001) reductions were observed with perindopril/Indapamide/amlodipine, which were even more pronounced after excluding white-coat effect in the sustained hypertension population (-5.3/-3.7 mmHg). Similar results were observed in terms of blood pressure response (72 vs. 53%, P < 0.0001) and control rates (32 vs. 25%, P = 0.005). Up-titration was effective at each visit in both treatment arms (P < 0.001). Both ABPM and HBPM results confirmed the superiority of the triple therapy at 1 month on ASBP/ADBP and HSBP/HDBP: -4.5/-2.0 mmHg for ABPM (P < 0.001/P = 0.04), and -4.9/-3.1 mmHg for HBPM (both, P < 0.001). Up-titration steps resulted in further significant decreases in both ABPM and HBPM. Both treatment regimens were well tolerated regarding adverse events or laboratory testing. In particular, peripheral edema known to be amlodipine dose dependent, appeared in only a few cases, none with the highest dose. Hypotension, orthostatic hypotension, and cough whatever the dose were infrequent. There were no treatment-related serious adverse events. CONCLUSION: Perindopril/Indapamide/amlodipine in a single pill produces superior reductions in blood pressure compared with dual therapy. Triple therapy up-titration was well tolerated and effective leading to BP control rates of over 80%. Analysis of 24-h ABPM and HBPM results corroborated these findings.

Single-Pill Combination of Perindopril/Indapamide/Amlodipine in Patients with Uncontrolled Hypertension: A Randomized Controlled Trial.[Pubmed:28181192]

Cardiol Ther. 2017 Jun;6(1):91-104.

INTRODUCTION: Patients with hypertension often require a combination of three antihypertensive agents to achieve blood pressure control, but very few single-pill triple combinations are available. The aim of this study was to determine whether a single-pill triple combination of perindopril, Indapamide, and amlodipine was as effective as a dual-pill combination of perindopril/Indapamide plus separate amlodipine at reducing blood pressure in patients with uncontrolled, essential hypertension. METHODS: This international, multicenter, open-label, randomized controlled trial was conducted in men or women aged >/=18 years old with confirmed essential hypertension (SBP >/=140 and <160 mmHg and DBP >/=90 and <100 mmHg), uncontrolled on maximal dose antihypertensive monotherapy or with a single dose of dual therapy. Patients were randomly assigned to: single-pill triple combination of perindopril 5 mg/Indapamide 1.25 mg/amlodipine 5 mg (Per/Ind/Aml) or dual-pill combination perindopril 5 mg/Indapamide 1.25 mg + amlodipine 5 mg (Per/Ind + Aml) once daily for 12 weeks. The primary endpoint was change in office supine SBP and DBP from baseline to week 12. The proportion of responders defined as those with normalized BP (SBP <140 mmHg and DBP <90 mmHg), and/or decrease of SBP >/=20 mmHg, and/or decrease of DBP >/=10 mmHg at week 12 (W12) compared with baseline was also assessed. Secondary efficacy endpoints included change in office supine SBP and DBP, response, and BP control at weeks 4 and 8. The tolerability of the treatments was also assessed. RESULTS: A total of 148 patients were randomized: 75 to Per/Ind/Aml and 73 to Per/Ind + Aml. Mean supine SBP and DBP were 149.1 +/- 4.7 and 94.1 +/- 3.1 mmHg, respectively, with no relevant between-group difference. At week 12, both triple-therapy regimens were associated with clinically significant reductions in SBP compared with baseline (-21.5 +/- 11.7 and -20.0 +/- 12.9 mmHg, respectively). Reductions in office supine DBP were also clinically significant (-15.3 +/- 7.8 and -14.8 +/- 9.0 mmHg, respectively). The proportion of treatment responders was high in both groups: 89.2 and 87.1%, respectively. The reduction in office supine SBP/DBP was already evident at week 4 and maintained for the duration of the study in both groups. The majority of patients were treatment responders at week 4 (89.2 and 82.9%, respectively) and had achieved BP control (87.8 vs. 78.6%, respectively), which was maintained until week 12 in both treatment groups. Both treatments were well tolerated with no between-group differences. CONCLUSIONS: In adult patients with uncontrolled essential hypertension on treatment, single-pill triple-combination therapy with Per/Ind/Aml is as effective as the same dose dual-pill combination of Per/Ind + Aml. Both treatments were associated with clinically significant BP reductions compared with baseline and were well tolerated. Clinical trials number: http://www.controlled-trials.com ISRCTN: 16442558. FUNDING: Les Laboratoires Servier.

Indapamide is a non-thiazide sulphonamide diuretic compound, generally used in the treatment of hypertension, as well as decompensated cardiac failure.

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