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Published in: Cardiology and Therapy 1/2020

Open Access 01-06-2020 | Obesity | Original Research

Antihypertensive Effectiveness of Perindopril Arginine and Indapamide Single-Pill Combination According to Body Mass Index: Findings from the FORSAGE Study

Authors: M. G. Glezer, The FORSAGE Investigators

Published in: Cardiology and Therapy | Issue 1/2020

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Abstract

Introduction

Overweight and obesity are increasing worldwide and are associated with an increased risk for cardiovascular disease (CVD). The aim of this study was to examine the burden of CVD risk factors among normal weight, overweight, and obese subjects with hypertension, and to evaluate the effectiveness of switching to a single-pill combination (SPC) of perindopril arginine/indapamide for blood pressure (BP) control in overweight and obese subjects treated in routine clinical practice.

Methods

FORSAGE was a 3-month, multicenter, observational, open-label study conducted in Russian patients with uncontrolled arterial hypertension under previous antihypertensive therapy. Subjects were switched to the full-dose perindopril arginine 10 mg/indapamide 2.5 mg SPC. BP was assessed at 2 weeks, 1 month, and 3 months, and serum creatinine and general health status at 3 months. The present post hoc analysis of the FORSAGE study results explored the effectiveness of perindopril arginine/indapamide SPC in patients with arterial hypertension with regard to baseline body mass index (BMI): normal (< 25 kg/m2), overweight (25 ≤ BMI < 30 kg/m2), and obese (≥ 30 kg/m2).

Results

A total of 1969 patients were recruited, but BMI data were available for 1963 patients, two-thirds of whom were women. The distribution of BMI groups was as follows: < 25 kg/m2 (16.7%), overweight (48.7%), and obese (34.7%). Overweight or obese patients had more concomitant diseases such as diabetes mellitus or history of stroke, higher BP levels, serum cholesterol and creatinine, and lower glomerular filtration rates. Switching to perindopril arginine/indapamide SPC was associated with a statistically significant reduction in BP as early as the second week of treatment. At 3 months, systolic blood pressure (SBP)/diastolic blood pressure (DBP) had decreased significantly by 39.3/18.8 mmHg in the normal BMI group, 39.8/18.8 mmHg in overweight, and 39.4/18.7 mmHg in obese groups. The magnitude of the BP reduction was independent of BMI. Achievement of target BP (< 140/90 mmHg) was good in all groups, but lower in obese subjects (70.9%) than in overweight subjects (78.1%) or those with a normal BMI (81.8%) (P < 0.0001 for both comparisons).

Conclusions

In subjects with uncontrolled BP on existing antihypertensive therapy, switching to perindopril arginine 10 mg/indapamide 2.5 mg was associated with statistically significant decreases in BP and higher rates of target BP achievement in all BMI groups, including more than 70% of overweight and obese patients.

Trial Registration

ISRCTN ID, ISRCTN14315146 (retrospectively registered 18/11/2019).
Appendix
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Literature
1.
go back to reference Li YT, Wang HH, Liu KQ, Lee GK, Chan WM, Griffiths SM, et al. Medication adherence and blood pressure control among hypertensive patients with coexisting long-term conditions in primary care settings: a cross-sectional analysis. Medicine (Baltimore). 2016;95:e3572.CrossRef Li YT, Wang HH, Liu KQ, Lee GK, Chan WM, Griffiths SM, et al. Medication adherence and blood pressure control among hypertensive patients with coexisting long-term conditions in primary care settings: a cross-sectional analysis. Medicine (Baltimore). 2016;95:e3572.CrossRef
2.
go back to reference La Sierra A, Oliveras A, Armario P, Lucas S. Control de la presión arterial en pacientes en tratamiento con terapia combinada. Med Clin (Barc). 2015;144:145–50.CrossRef La Sierra A, Oliveras A, Armario P, Lucas S. Control de la presión arterial en pacientes en tratamiento con terapia combinada. Med Clin (Barc). 2015;144:145–50.CrossRef
3.
go back to reference Labeit AM, Klotsche J, Pieper L, Pittrow D, Einsle F, Stalla GK, et al. Changes in the prevalence, treatment and control of hypertension in Germany? A clinical-epidemiological study of 50.000 primary care patients. PLoS One. 2012;7:e52229.CrossRef Labeit AM, Klotsche J, Pieper L, Pittrow D, Einsle F, Stalla GK, et al. Changes in the prevalence, treatment and control of hypertension in Germany? A clinical-epidemiological study of 50.000 primary care patients. PLoS One. 2012;7:e52229.CrossRef
4.
go back to reference Chopra I, Kamal KM, Candrilli SD, Kanyongo G. Association between obesity and therapeutic goal attainment in patients with concomitant hypertension and dyslipidemia. Postgrad Med. 2014;126:66–77.CrossRef Chopra I, Kamal KM, Candrilli SD, Kanyongo G. Association between obesity and therapeutic goal attainment in patients with concomitant hypertension and dyslipidemia. Postgrad Med. 2014;126:66–77.CrossRef
5.
go back to reference Schmieder RE, Gitt AK, Koch C, Bramlage P, Ouarrak T, Tschöpe D. Achievement of individualized treatment targets in patients with comorbid type-2 diabetes and hypertension: 6 months results of the DIALOGUE registry. BMC Endocr Disord. 2015;15:23.CrossRef Schmieder RE, Gitt AK, Koch C, Bramlage P, Ouarrak T, Tschöpe D. Achievement of individualized treatment targets in patients with comorbid type-2 diabetes and hypertension: 6 months results of the DIALOGUE registry. BMC Endocr Disord. 2015;15:23.CrossRef
6.
go back to reference Reibis RK, Huber M, Karoff M, Kamke W, Kreutz R, Wegscheider K, et al. Target organ damage and control of cardiovascular risk factors in hypertensive patients. Evidence from the multicenter ESTher registry. Herz. 2015;40(Suppl 2):209–16.CrossRef Reibis RK, Huber M, Karoff M, Kamke W, Kreutz R, Wegscheider K, et al. Target organ damage and control of cardiovascular risk factors in hypertensive patients. Evidence from the multicenter ESTher registry. Herz. 2015;40(Suppl 2):209–16.CrossRef
7.
go back to reference Friedberg JP, Rodriguez MA, Watsula ME, Lin I, Wylie-Rosett J, Allegrante JP, et al. Effectiveness of a tailored behavioral intervention to improve hypertension control: primary outcomes of a randomized controlled trial. Hypertension. 2015;65:440–6.CrossRef Friedberg JP, Rodriguez MA, Watsula ME, Lin I, Wylie-Rosett J, Allegrante JP, et al. Effectiveness of a tailored behavioral intervention to improve hypertension control: primary outcomes of a randomized controlled trial. Hypertension. 2015;65:440–6.CrossRef
8.
go back to reference Glezer MG, Deev AD. How to increase the effectiveness of antihypertensive therapy in clinical practice: results of the Russian observational program FORSAZH. Kardiologiia. 2016;56:18–24.CrossRef Glezer MG, Deev AD. How to increase the effectiveness of antihypertensive therapy in clinical practice: results of the Russian observational program FORSAZH. Kardiologiia. 2016;56:18–24.CrossRef
9.
go back to reference Chooi YC, Ding C, Magkos F. The epidemiology of obesity. Metabolism. 2019;92:6–10.CrossRef Chooi YC, Ding C, Magkos F. The epidemiology of obesity. Metabolism. 2019;92:6–10.CrossRef
10.
go back to reference Zhernakova YV, Zheleznova EA, Chazova IE, Oshchepkova EV, Dolgusheva YA, Yarovaya EB, et al. The prevalence of abdominal obesity and the association with socioeconomic status in Regions of the Russian Federation, the results of the epidemiological study—ESSE-RF. Ter Arkh. 2018;90(10):14–22.PubMed Zhernakova YV, Zheleznova EA, Chazova IE, Oshchepkova EV, Dolgusheva YA, Yarovaya EB, et al. The prevalence of abdominal obesity and the association with socioeconomic status in Regions of the Russian Federation, the results of the epidemiological study—ESSE-RF. Ter Arkh. 2018;90(10):14–22.PubMed
11.
go back to reference Khan SS, Ning H, Wilkins JT, Allen N, Carnethon M, Berry JD, et al. Association of body mass index with lifetime risk of cardiovascular disease and compression of morbidity. JAMA Cardiol. 2018;3(4):280–7.CrossRef Khan SS, Ning H, Wilkins JT, Allen N, Carnethon M, Berry JD, et al. Association of body mass index with lifetime risk of cardiovascular disease and compression of morbidity. JAMA Cardiol. 2018;3(4):280–7.CrossRef
12.
go back to reference Kjeldsen SE, Naditch-Brule L, Perlini S, Zidek W, Farsang C. Increased prevalence of metabolic syndrome in uncontrolled hypertension across Europe: the Global Cardiometabolic Risk Profile in Patients with hypertension disease survey. J Hypertens. 2008;26:2064–70.CrossRef Kjeldsen SE, Naditch-Brule L, Perlini S, Zidek W, Farsang C. Increased prevalence of metabolic syndrome in uncontrolled hypertension across Europe: the Global Cardiometabolic Risk Profile in Patients with hypertension disease survey. J Hypertens. 2008;26:2064–70.CrossRef
13.
go back to reference Zidek W, Naditch-Brûlé L, Perlini S, Farsang C, Kjeldsen SE. Blood pressure control and components of the metabolic syndrome: the GOOD survey. Cardiovasc Diabetol. 2009;8:51.CrossRef Zidek W, Naditch-Brûlé L, Perlini S, Farsang C, Kjeldsen SE. Blood pressure control and components of the metabolic syndrome: the GOOD survey. Cardiovasc Diabetol. 2009;8:51.CrossRef
14.
go back to reference Astashkin EI, Glezer MG. Obesity and arterial hypertension [Russian]. Probl Women Health. 2008;4(3):23–33. Astashkin EI, Glezer MG. Obesity and arterial hypertension [Russian]. Probl Women Health. 2008;4(3):23–33.
15.
go back to reference Nedogoda SV, Chumachek EV, Ledyaeva AA, Tsoma VV, Salasyuk AS, Smirnova VO, et al. Optimization of control of blood pressure, metabolic disorders and target organ protection with fixed perindopril and indapamide combination in treated patients with arterial hypertension. Kardiologiia. 2017;57:5–11.PubMed Nedogoda SV, Chumachek EV, Ledyaeva AA, Tsoma VV, Salasyuk AS, Smirnova VO, et al. Optimization of control of blood pressure, metabolic disorders and target organ protection with fixed perindopril and indapamide combination in treated patients with arterial hypertension. Kardiologiia. 2017;57:5–11.PubMed
16.
go back to reference Roush GC, Ernst ME, Kostis JB, Tandon S, Sica DA. Head-to-head comparisons of hydrochlorothiazide with indapamide and chlorthalidone: antihypertensive and metabolic effects. Hypertension. 2015;65:1041–6.CrossRef Roush GC, Ernst ME, Kostis JB, Tandon S, Sica DA. Head-to-head comparisons of hydrochlorothiazide with indapamide and chlorthalidone: antihypertensive and metabolic effects. Hypertension. 2015;65:1041–6.CrossRef
17.
go back to reference Wang S, Li J, Zhou X, Liu K, Zhang X, Meng Q, et al. Comparison between the effects of hydrochlorothiazide and indapamide on the kidney in hypertensive patients inadequately controlled with losartan. J Hum Hypertens. 2017;31:848–54.CrossRef Wang S, Li J, Zhou X, Liu K, Zhang X, Meng Q, et al. Comparison between the effects of hydrochlorothiazide and indapamide on the kidney in hypertensive patients inadequately controlled with losartan. J Hum Hypertens. 2017;31:848–54.CrossRef
18.
go back to reference DiNicolantonio JJ, Bhutani J, Lavie CJ, O’Keefe JH. Evidence-based diuretics: focus on chlorthalidone and indapamide. Future Cardiol. 2015;11:203–17.CrossRef DiNicolantonio JJ, Bhutani J, Lavie CJ, O’Keefe JH. Evidence-based diuretics: focus on chlorthalidone and indapamide. Future Cardiol. 2015;11:203–17.CrossRef
19.
go back to reference Wan C, Su H, Zhang C. Role of NADPH oxidase in metabolic disease-related renal injury: an update. Oxid Med Cell Longev. 2016;2016:7813072.CrossRef Wan C, Su H, Zhang C. Role of NADPH oxidase in metabolic disease-related renal injury: an update. Oxid Med Cell Longev. 2016;2016:7813072.CrossRef
20.
go back to reference Zanoli L, Lentini P, Briet M, Castellino P, House AA, London GM, Malatino L, McCullough PA, Mikhailidis DP, Boutouyrie P. Arterial stiffness in the heart disease of CKD. J Am Soc Nephrol. 2019;30(6):918–28.CrossRef Zanoli L, Lentini P, Briet M, Castellino P, House AA, London GM, Malatino L, McCullough PA, Mikhailidis DP, Boutouyrie P. Arterial stiffness in the heart disease of CKD. J Am Soc Nephrol. 2019;30(6):918–28.CrossRef
21.
go back to reference Kambham N, Markowitz GS, Valeri AM, et al. Obesity-related glomerulopathy: an emerging epidemic. Kidney Int. 2001;59:1498–509.CrossRef Kambham N, Markowitz GS, Valeri AM, et al. Obesity-related glomerulopathy: an emerging epidemic. Kidney Int. 2001;59:1498–509.CrossRef
22.
go back to reference Kovesdy CP, Furth SL, Zoccali C. Obesity and kidney disease: hidden consequences of the epidemic. Blood Purif. 2017;43:346–54.CrossRef Kovesdy CP, Furth SL, Zoccali C. Obesity and kidney disease: hidden consequences of the epidemic. Blood Purif. 2017;43:346–54.CrossRef
23.
go back to reference Ionescu DD. Antihypertensive efficacy of perindopril 5-10 mg/day in primary health care: an open-label, prospective, observational study. Clin Drug Investig. 2009;29:767–76.CrossRef Ionescu DD. Antihypertensive efficacy of perindopril 5-10 mg/day in primary health care: an open-label, prospective, observational study. Clin Drug Investig. 2009;29:767–76.CrossRef
24.
go back to reference Kang S, Wu YF, An N, Ren M. A systematic review and meta-analysis of the efficacy and safety of a fixed, low-dose perindopril–indapamide combination as first-line treatment of hypertension. Clin Ther. 2004;26(2):257–70.CrossRef Kang S, Wu YF, An N, Ren M. A systematic review and meta-analysis of the efficacy and safety of a fixed, low-dose perindopril–indapamide combination as first-line treatment of hypertension. Clin Ther. 2004;26(2):257–70.CrossRef
26.
go back to reference Netchessova TA, Shepelkevich AP, Gorbat TV, NIKA Study Group. Efficacy of single-pill perindopril/indapamide in patients with hypertension and type 2 diabetes. High Blood Press Cardiovasc Prev. 2014;21(1):63–9.CrossRef Netchessova TA, Shepelkevich AP, Gorbat TV, NIKA Study Group. Efficacy of single-pill perindopril/indapamide in patients with hypertension and type 2 diabetes. High Blood Press Cardiovasc Prev. 2014;21(1):63–9.CrossRef
27.
go back to reference Carnagarin R, Matthews V, Gregory C, Schlaich MP. Pharmacotherapeutic strategies for treating hypertension in patients with obesity. Expert Opin Pharmacother. 2018;19:643–51.CrossRef Carnagarin R, Matthews V, Gregory C, Schlaich MP. Pharmacotherapeutic strategies for treating hypertension in patients with obesity. Expert Opin Pharmacother. 2018;19:643–51.CrossRef
28.
go back to reference Dahlöf B, Sever PS, Poulter NR, Wedel H, Beevers DG, Caulfield M, ASCOT Investigators, et al. Prevention of cardiovascular events with an antihypertensive regimen of amlodipine adding perindopril as required versus atenolol adding bendroflumethiazide as required, in the Anglo-Scandinavian Cardiac Outcomes Trial-Blood Pressure Lowering Arm (ASCOT-BPLA): a multicentre randomised controlled trial. Lancet. 2005;366(9489):895–906.CrossRef Dahlöf B, Sever PS, Poulter NR, Wedel H, Beevers DG, Caulfield M, ASCOT Investigators, et al. Prevention of cardiovascular events with an antihypertensive regimen of amlodipine adding perindopril as required versus atenolol adding bendroflumethiazide as required, in the Anglo-Scandinavian Cardiac Outcomes Trial-Blood Pressure Lowering Arm (ASCOT-BPLA): a multicentre randomised controlled trial. Lancet. 2005;366(9489):895–906.CrossRef
29.
go back to reference Wenzel UO, Benndorf R, Lange S. Treatment of arterial hypertension in obese patients. Semin Nephrol. 2013;33:66–74.CrossRef Wenzel UO, Benndorf R, Lange S. Treatment of arterial hypertension in obese patients. Semin Nephrol. 2013;33:66–74.CrossRef
30.
go back to reference Nedogoda SV, Ledyaeva AA, Chumachok EV, Tsoma VV, Mazina G, Salasyuk AS, et al. Randomized trial of perindopril, enalapril, losartan and telmisartan in overweight or obese patients with hypertension. Clin Drug Investig. 2013;33:553–61.CrossRef Nedogoda SV, Ledyaeva AA, Chumachok EV, Tsoma VV, Mazina G, Salasyuk AS, et al. Randomized trial of perindopril, enalapril, losartan and telmisartan in overweight or obese patients with hypertension. Clin Drug Investig. 2013;33:553–61.CrossRef
31.
go back to reference Ogilvie RI, Anand S, Roy P, Souza S. Perindopril for control of blood pressure in patients with hypertension and other cardiovascular risk factors. Clin Drug Investig. 2008;28:673–86.CrossRef Ogilvie RI, Anand S, Roy P, Souza S. Perindopril for control of blood pressure in patients with hypertension and other cardiovascular risk factors. Clin Drug Investig. 2008;28:673–86.CrossRef
32.
go back to reference Fogari R, Zoppi A, Lazzari P, Preti P, Mugellini A, Corradi L, et al. ACE inhibition but not angiotensin II antagonism reduces plasma fibrinogen and insulin resistance in overweight hypertensive patients. J Cardiovasc Pharmacol. 1998;32(4):616–20.CrossRef Fogari R, Zoppi A, Lazzari P, Preti P, Mugellini A, Corradi L, et al. ACE inhibition but not angiotensin II antagonism reduces plasma fibrinogen and insulin resistance in overweight hypertensive patients. J Cardiovasc Pharmacol. 1998;32(4):616–20.CrossRef
33.
go back to reference Semenkin AA, Zhenatov AB, Zhivilova LA, Nechaeva GI, Pritykina TV, Chindareva OI, et al. Direct comparison of endothelial and metabolic effects of perindopril combination with indapamide retard or hydrochlorothiazide. Kardiologiia. 2014;54(11):25–9.CrossRef Semenkin AA, Zhenatov AB, Zhivilova LA, Nechaeva GI, Pritykina TV, Chindareva OI, et al. Direct comparison of endothelial and metabolic effects of perindopril combination with indapamide retard or hydrochlorothiazide. Kardiologiia. 2014;54(11):25–9.CrossRef
Metadata
Title
Antihypertensive Effectiveness of Perindopril Arginine and Indapamide Single-Pill Combination According to Body Mass Index: Findings from the FORSAGE Study
Authors
M. G. Glezer
The FORSAGE Investigators
Publication date
01-06-2020
Publisher
Springer Healthcare
Published in
Cardiology and Therapy / Issue 1/2020
Print ISSN: 2193-8261
Electronic ISSN: 2193-6544
DOI
https://doi.org/10.1007/s40119-020-00162-x

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