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01-08-2013 | Original Research Article

Randomized Trial of Perindopril, Enalapril, Losartan and Telmisartan in Overweight or Obese Patients with Hypertension

Authors: Sergey V. Nedogoda, Alla A. Ledyaeva, Elena V. Chumachok, Vera V. Tsoma, Galina Mazina, Alla S. Salasyuk, Irina N. Barykina

Published in: Clinical Drug Investigation | Issue 8/2013

Abstract

Background and Objectives

Obesity exacerbates hypertension and stimulates the renin–angiotensin–aldosterone system (RAAS). Full-dose RAAS inhibition could be a therapeutic option in overweight or obese patients with hypertension. This study compared four RAAS inhibitors at full therapeutic doses to determine their effect on blood pressure (BP) and cardiovascular risk factors in these patients.

Methods

We conducted a 24-week, single-blind, randomized, parallel-group study in 120 overweight or obese patients (body mass index ≥27 kg/m²) with hypertension, aged 18–60 years. The primary endpoint was the change in mean 24-h systolic BP and diastolic BP from baseline to study end. Central BP, arterial stiffness, and metabolic and cardiac indices were also investigated. Patients were randomly allocated to perindopril 10 mg/day, enalapril 20 mg/day, losartan 100 mg/day or telmisartan 80 mg/day. Nonpharmacological interventions were also recommended.

Results

Reductions in mean 24-h systolic BP (and diastolic BP) were all significant (p < 0.05 versus baseline) for perindopril, enalapril, losartan and telmisartan: systolic BP −22, −11, −12 and −15 mmHg, respectively; (and diastolic BP −13, −6, −13 and −12 mmHg, respectively). Aortic elasticity improved with perindopril and telmisartan. Perindopril was associated with the greatest reductions in central aortic BP and leptin levels [30 % versus 2 %, 7 % and 14 % with enalapril, losartan and telmisartan, respectively (all p < 0.05 versus perindopril)]. Reductions in other BP, echocardiographic, metabolic and anthropometric parameters occurred with all treatments.

Conclusion

Full-dose RAAS inhibition, particularly with perindopril, effectively reduces BP, improves arterial structure and regulates cardiovascular risk factors in overweight or obese patients with hypertension.

Mancia G, De Backer G, Dominiczak A, et al. 2007 Guidelines for the management of arterial hypertension: the Task Force for the Management of Arterial Hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). Eur Heart J. 2007;28(12):1462–536.PubMed

Mancia G, Laurent S, Agabiti-Rosei E, et al. Reappraisal of European guidelines on hypertension management: a European Society of Hypertension Task Force document. J Hypertens. 2009;27(11):2121–58.PubMedCrossRef

Schmieder RE, Gatzka C, Schachinger H, et al. Obesity as a determinant for response to antihypertensive treatment. BMJ. 1993;307(6903):537–40.PubMedCrossRef

Jordan J, Engeli S. Obesity, hypertension, and cardiovascular health: is there anything poor Cassandra tries to tell us? J Hypertens. 2012;30(6):1103–5.PubMedCrossRef

Schmieder RE, Rockstroh JK. Obesity and hypertension. Curr Opin Nephrol Hypertens. 1994;3(5):546–9.PubMedCrossRef

Gortmaker SL, Swinburn BA, Levy D, et al. Changing the future of obesity: science, policy, and action. Lancet. 2011;378(9793):838–47.PubMedCrossRef

Ludwig DS. Childhood obesity—the shape of things to come. N Engl J Med. 2007;357(23):2325–7.PubMedCrossRef

MacMahon SW, Blacket RB, Macdonald GJ, et al. Obesity, alcohol consumption and blood pressure in Australian men and women. The National Heart Foundation of Australia Risk Factor Prevalence Study. J Hypertens. 1984;2(1):85–91.PubMedCrossRef

Bramlage P, Pittrow D, Wittchen HU, et al. Hypertension in overweight and obese primary care patients is highly prevalent and poorly controlled. Am J Hypertens. 2004;17(10):904–10.PubMedCrossRef

10.

Dorresteijn JA, Visseren FL, Spiering W. Mechanisms linking obesity to hypertension. Obes Rev. 2012;13(1):17–26.PubMedCrossRef

11.

Kurukulasuriya LR, Stas S, Lastra G, et al. Hypertension in obesity. Med Clin North Am. 2011;95(5):903–17.PubMedCrossRef

12.

Whitworth JA. 2003 World Health Organization (WHO)/International Society of Hypertension (ISH) statement on management of hypertension. J Hypertens. 2003;21(11):1983–92.PubMedCrossRef

13.

Jordan J, Yumuk V, Schlaich M, et al. Joint statement of the European Association for the Study of Obesity and the European Society of Hypertension: obesity and difficult to treat arterial hypertension. J Hypertens. 2012;30(6):1047–55.PubMedCrossRef

14.

Fox KM. Efficacy of perindopril in reduction of cardiovascular events among patients with stable coronary artery disease: randomised, double-blind, placebo-controlled, multicentre trial (the EUROPA study). Lancet. 2003;362(9386):782–8.PubMedCrossRef

15.

Tropeano AI, Boutouyrie P, Pannier B, et al. Brachial pressure-independent reduction in carotid stiffness after long-term angiotensin-converting enzyme inhibition in diabetic hypertensives. Hypertension. 2006;48(1):80–6.PubMedCrossRef

16.

Yusuf S, Sleight P, Pogue J, et al. Effects of an angiotensin-converting-enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients. The Heart Outcomes Prevention Evaluation Study Investigators. N Engl J Med. 2000;342(3):145–53.PubMedCrossRef

17.

Kalil GZ, Haynes WG. Sympathetic nervous system in obesity-related hypertension: mechanisms and clinical implications. Hypertens Res. 2012;35(1):4–16.PubMedCrossRef

18.

Nakamura T, Kawachi K, Saito Y, et al. Effects of ARB or ACE-inhibitor administration on plasma levels of aldosterone and adiponectin in hypertension. Int Heart J. 2009;50(4):501–12.PubMedCrossRef

19.

Sharma AM, Pischon T, Engeli S, et al. Choice of drug treatment for obesity-related hypertension: where is the evidence? J Hypertens. 2001;19(4):667–74.PubMedCrossRef

20.

Asmar R, Topouchian J, Pannier B, et al. Pulse wave velocity as endpoint in large-scale intervention trial. The Complior study. Scientific, Quality Control, Coordination and Investigation Committees of the Complior Study. J Hypertens. 2001;19(4):813–8.PubMedCrossRef

21.

Manrique C, Lastra G, Gardner M, et al. The renin angiotensin aldosterone system in hypertension: roles of insulin resistance and oxidative stress. Med Clin North Am. 2009;93(3):569–82.PubMedCrossRef

22.

Dzau VJ, Bernstein K, Celermajer D, et al. The relevance of tissue angiotensin-converting enzyme: manifestations in mechanistic and endpoint data. Am J Cardiol. 2001;88(9 suppl):1L–20L.PubMedCrossRef

23.

Ceconi C, Francolini G, Olivares A, et al. Angiotensin-converting enzyme (ACE) inhibitors have different selectivity for bradykinin binding sites of human somatic ACE. Eur J Pharmacol. 2007;577:1–6.PubMedCrossRef

24.

Morishita T, Tsutsui M, Shimokawa H, et al. Long-term treatment with perindopril ameliorates dobutamine-induced myocardial ischemia in patients with coronary artery disease. Jpn J Pharmacol. 2002;88(1):100–7.PubMedCrossRef

25.

van Vark LC, Bertrand M, Akkerhuis KM, et al. Angiotensin-converting enzyme (ACE) inhibitors reduce mortality in hypertension—a meta-analysis of randomized clinical trials of renin-angiotensin-aldosterone-system (RAAS) inhibitors involving 158,998 patients. Eur Heart J. 2012;33(16):2088–97.PubMedCrossRef

26.

Krysiak R, Sierant M, Marek B, et al. The effect of perindopril and enalapril on plasma resistin levels in normotensive patients with coronary heart disease. Endokrynol Pol. 2010;61(6):683–90.PubMed

27.

Krysiak R, Sierant M, Marek B, et al. The effect of angiotensin-converting enzyme inhibitors on plasma adipokine levels in normotensive patients with coronary artery disease. Endokrynol Pol. 2010;61(3):280–7.PubMed

28.

Ferrari R. Angiotensin-converting enzyme inhibition in cardiovascular disease: evidence with perindopril. Expert Rev Cardiovasc Ther. 2005;3(1):15–29.PubMedCrossRef

29.

Ferrari R, Fox K. Insight into the mode of action of ACE inhibition in coronary artery disease: the ultimate ‘EUROPA’ story. Drugs. 2009;69(3):265–77.PubMedCrossRef

30.

Fox KM. Management of coronary artery disease: implications of the EUROPA trial. Br J Cardiol. 2004;11(3):195–204.

31.

Physicians’ desk reference. 58th ed. Montvale: PDR Network LLC, 2004.

32.

Morgan T, Anderson A. Duration of antihypertensive effect of perindopril (P), enalapril (E) and captopril (C). Hypertension. 1993;21(4):568.

33.

Devissaguet JP, Ammoury N, Devissaguet M, et al. Pharmacokinetics of perindopril and its metabolites in healthy volunteers. Fundam Clin Pharmacol. 1990;4(2):175–89.PubMedCrossRef

34.

Guo W, Turlapaty P, Shen Y, et al. Clinical experience with perindopril in patients nonresponsive to previous antihypertensive therapy: a large US community trial. Am J Ther. 2004;11(3):199–205.PubMedCrossRef

35.

Stolarz-Skrzypek K, Thijs L, Richart T, et al. Blood pressure variability in relation to outcome in the International Database of Ambulatory Blood Pressure in Relation to Cardiovascular Outcome. Hypertens Res. 2010;33(8):757–66.PubMedCrossRef

36.

Blacher J, Asmar R, Djane S, et al. Aortic pulse wave velocity as a marker of cardiovascular risk in hypertensive patients. Hypertension. 1999;33(5):1111–7.PubMedCrossRef

37.

Nedogoda S. Efficiency of perindopril in patients with arterial hypertension and obesity [in Russian]. Kardiologiia. 2011;51(11):38–44.PubMed

38.

Cordonnier DJ, Pinel N, Barro C, et al. Expansion of cortical interstitium is limited by converting enzyme inhibition in type 2 diabetic patients with glomerulosclerosis. The Diabiopsies Group. J Am Soc Nephrol. 1999;10(6):1253–63.PubMed

39.

Hermans MP, Brichard SM, Colin I, et al. Long-term reduction of microalbuminuria after 3 years of angiotensin-converting enzyme inhibition by perindopril in hypertensive insulin-treated diabetic patients. Am J Med. 1992;92(4B):102S–7S.PubMedCrossRef

40.

Rodriguez-Granillo GA, Vos J, Bruining N, et al. Long-term effect of perindopril on coronary atherosclerosis progression (from the PERindopril’s Prospective Effect on Coronary aTherosclerosis by Angiography and IntraVascular Ultrasound Evaluation [PERSPECTIVE] Study). Am J Cardiol. 2007;100(2):159–63.PubMedCrossRef

41.

Dahlof B, Sever PS, Poulter NR, 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.PubMedCrossRef

42.

Ceconi C, Fox KM, Remme WJ, et al. ACE inhibition with perindopril and endothelial dysfunction. Results of a substudy of the EUROPA study: PERTINENT. Cardiovasc Res. 2007;73:237–46.PubMedCrossRef

43.

Myers MG. A dose-response study of perindopril in hypertension: effects on blood pressure 6 and 24 h after dosing. Perindopril Multicentre Dose-Response Study Group. Can J Cardiol. 1996;12(11):1191–6.PubMed

44.

Tsoukas G, Anand S, Yang K. Dose-dependent antihypertensive efficacy and tolerability of perindopril in a large, observational, 12-week, general practice-based study. Am J Cardiovasc Drugs. 2011;11(1):45–55.PubMedCrossRef

45.

Ficek J, Kokot F, Chudek J, et al. Influence of antihypertensive treatment with perindopril, pindolol or felodipinon plasma leptin concentration in patients with essential hypertension. Horm Metab Res. 2002;34(11–12):703–8.PubMedCrossRef

46.

Harwood HJ Jr. The adipocyte as an endocrine organ in the regulation of metabolic homeostasis. Neuropharmacology. 2012;63:57–75.PubMedCrossRef

47.

Poggi L, Renucci JF, Denolle T. Treatment of essential hypertension in general practice: an open-label study of 47,351 French hypertensive patients treated for one year with perindopril. Can J Cardiol. 1994;10(Suppl):D21D–4D.

48.

Jandrain B, Herbaut C, Depoorter JC, et al. Long-term (1 year) acceptability of perindopril in type II diabetic patients with hypertension. Am J Med. 1992;92(4B):91S–4S.PubMedCrossRef

49.

Andrejak M, Santoni JP, Carre A, et al. A double-blind comparison of perindopril and hydrochlorothiazide-amiloride in mild to moderate essential hypertension. Fundam Clin Pharmacol. 1991;5(3):185–92.PubMedCrossRef

50.

Marre M, Leye A. Effects of perindopril in hypertensive patients with or without type 2 diabetes mellitus, and with altered insulin sensitivity. Diabetes Vasc Dis Res. 2007;4(3):163–73.CrossRef

51.

Bohlen L, Bienz R, Doser M, et al. Metabolic neutrality of perindopril: focus on insulin sensitivity in overweight patients with essential hypertension. J Cardiovasc Pharmacol. 1996;27(6):770–6.PubMedCrossRef

52.

Fogari R, Mugellini A, Zoppi A, et al. Losartan and perindopril effects on plasma plasminogen activator inhibitor-1 and fibrinogen in hypertensive type 2 diabetic patients. Am J Hypertens. 2002;15(4):316–20.PubMedCrossRef

Title: Randomized Trial of Perindopril, Enalapril, Losartan and Telmisartan in Overweight or Obese Patients with Hypertension
Authors: Sergey V. Nedogoda
Alla A. Ledyaeva
Elena V. Chumachok
Vera V. Tsoma
Galina Mazina
Alla S. Salasyuk
Irina N. Barykina
Publication date: 01-08-2013
Publisher: Springer International Publishing
Published in: Clinical Drug Investigation / Issue 8/2013
Print ISSN: 1173-2563
Electronic ISSN: 1179-1918
DOI: https://doi.org/10.1007/s40261-013-0094-9

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Randomized Trial of Perindopril, Enalapril, Losartan and Telmisartan in Overweight or Obese Patients with Hypertension

Abstract

Background and Objectives

Methods

Results

Conclusion

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background and Objectives

Methods

Results

Conclusion

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