Abstract
This study was undertaken to compare the antihypertensive efficacy of zofenopril 30 mg + hydrochlorothiazide 12.5 mg fixed combination versus zofenopril alone in patients with essential hypertension with and without the metabolic syndrome, according to National Cholesterol Education Program-Adult Treatment Panel III criteria. After a 4-wk placebo washout period, 463 patients with mild to moderate essential hypertension (diastolic blood pressure [DBP] 95–115 mm Hg) aged 1 8 to 75 y were randomly assigned 2:1:1 to treatment with zofenopril + hydrochlorothiazide, zofenopril, or hydrochlorothiazide for 12 wk in an international, multicenter, double-blind, parallel-group study. DBP and systolic blood pressure changes with treatment were calculated. The first 12 wk of treatment were followed by a 24-wk open-label period during which only safety was assessed. Reported here is a subanalysis of the main study results, performed in patients with and without metabolic syndrome, limited to a zofenopril+hydrochlorothiazide versus zofenopril comparison. The antihypertensive effect of zofenopril+hydrochlorothiazide or zofenopril was similar in patients with (77%) and without metabolic syndrome. In patients with and without metabolic syndrome, however, DBP and systolic blood pressure reductions were significantly greater with zofenopril+hydrochlorothiazide (with metabolic syndrome: 14±8/21±14 mm Hg; without metabolic syndrome: 15±7/23±14 mm Hg) than with zofenopril alone (with metabolic syndrome: 10±9/11 ±15; without metabolic syndrome: 12±10/14±18 mm Hg). The safety of the 2 treatments was similar in patients with and without metabolic syndrome. The fixed combination of zofenopril+hydrochlorothiazide improved the efficacy of zofenopril alone. This effect was particularly evident in patients with metabolic syndrome, in whom blood pressure control is more difficult to achieve and who are at greater risk for cardiovascular events.
Similar content being viewed by others
References
Eckel RH, Grundy SM, Zimmet PZ. The metabolic syndrome.Lancet. 2005;365:1415–1428.
Hunt KJ, Resendez RG, Williams K, Haffner SM, Stern MP, for the San Antonio Heart Study. National Cholesterol Education Program versus World Health Organization metabolic syndrome in relation to all-cause and cardiovascular mortality in the San Antonio Heart Study.Circulation. 2004;110:1251–1257.
Lakka HM, Laaksonen DE, Lakka TA, et al. The metabolic syndrome and total and cardiovascular disease mortality in middle-aged men.JAMA. 2002;288:2709–2716.
Isomaa B, Almgren P, Tuomi T, et al. Cardiovascular morbidity and mortality associated with the metabolic syndrome.Diabetes Care. 2001;24:683–689.
Hu G, Qiao Q, Tuomilehto J, Balkau B, Borch-Johnsen K, Pyorala K, for the DECODE Study Group. Prevalence of the metabolic syndrome and its relation to all-cause and cardiovascular mortality in nondiabetic European men and women.Arch Intern Med. 2004;164:1066–1076.
Bonora E, Targher G, Formentini G, et al. The metabolic syndrome is an independent predictor of cardiovascular disease in type 2 diabetic subjects: prospective data from the Verona Diabetes Complications Study.Diabet Med. 2004;21:52–58.
Ford ES, Giles WH, Dietz WH. Prevalence of the metabolic syndrome among US adults: findings from the Third National Health and Nutrition Examination Survey.JAMA. 2002; 287:356–359.
Borghi C, Ambrosioni E, for the Survival of Myocardial Infarction Long-term Evaluation-2 Working Party. Double-blind comparison between zofenopril and lisinopril in patients with acute myocardial infarction: results of the Survival of Myocardial Infarction Long-term Evaluation-2 (SMILE-2) study.Am Heart J. 2003;145:80–87.
Borghi C, Bacchelli S, Esposti DD, Bignamini A, Magnani B, Ambrosioni E, for the SMILE (Survival of Myocardial Infarction Long-term Evaluation) Study Investigators. Effects of the administration of an angiotensin-converting enzyme inhibitor during the acute phase of myocardial infarction in patients with arterial hypertension.Am J Hypertens. 1999;12:665–672.
Borghi C, Bacchelli S, Esposti DD, Ambrosioni E, for the SMILE Study. Effects of the early ACE inhibition in diabetic nonthrombolyzed patients with anterior acute myocardial infarction.Diabetes Care. 2003;26:1862–1868.
Kelbaek H, Agner E, Wroblewski H, Vasehus Madsen P, Marving J. Angiotensin converting enzyme inhibition at rest and during exercise in congestive heart failure.Eur Heart J. 1993; 14:692–695.
Binkley PF, Haas GJ, Starling RC, et al. Sustained augmentation of parasympathetic tone with angiotensin-converting enzyme inhibition in patients with congestive heart failure.J Am Coll Cardiol. 1993;21:655–661.
Elijovich F, Laffer CL, Schiffrin EL. The effects of atenolol and zofenopril on plasma atrial natriuretic peptide are due to their interactions with target organ damage of essential hypertensive patients.J Hum Hypertens. 1997;11:313–319.
Lacourciere Y, Provencher P. Comparative effects of zofenopril and hydrochlorothiazide on office and ambulatory blood pressures in mild to moderate essential hypertension.Br J Clin Pharmacol. 1989;27:371–376.
Malacco E, Piazza S, Omboni S. Zofenopril versus lisinopril in the treatment of essential hypertension in elderly patients: a randomised, double-blind, multicentre study.Clin Drug Invest. 2005;25:175–182.
Leonetti G, Rappelli A, Omboni S, on behalf of the study group. A similar 24-h blood pressure control is obtained by zofenopril and candesartan in primary hypertensive patients.Blood Press. 2006;15(suppl 1):18–26.
Parati G, Omboni S, Malacco E, on behalf of the study group. Antihypertensive efficacy of zofenopril and hydrochlorothiazide combination on ambulatory blood pressure.Blood Press. 2006;15(suppl 1):7–17.
Zanchetti A, Parati G, Malacco E. Zofenopril plus hydrochlorothiazide: combination therapy for the treatment of mild to moderate hypertension.Drugs. 2006;66:1107–1115.
Grundy SM, Cleeman JI, Daniels SR, et al. Diagnosis and management of the metabolic syndrome: an American Heart Association/National Heart, Lung, and Blood Institute Scientific statement.Circulation. 2005;112:2735–2752.
Muller C, Reddert A, Wassmann S, Strehlow K, Bohm M, Nickenig G. Insulin-like growth factor induces up-regulation of AT(1)-receptor gene expression in vascular smooth muscle cells.J Renin Angiotensin Aldosterone Syst. 2000;l:273–277.
Unger T. The role of the renin-angiotensin system in the development of cardiovascular disease.Am J Cardiol. 2002;89:3A-9A.
Prasad A, Quyyumi AA. Renin-angiotensin system and angiotensin receptor blockers in the metabolic syndrome.Circulation. 2004;110:1507–1512.
Nickenig G, Bohm M. Interaction between insulin and AT1 receptor: relevance for hypertension and arteriosclerosis.Basic Res Cardiol. 1998;93(suppl 2):135–139.
Deedwania PC, Volkova N. Current treatment options for the metabolic syndrome.Curr Treat Options Cardiovasc Med. 2005;7:61–74.
Abuissa H, Jones PG, Marso SP, O’Keefe JH Jr. Angiotensin-converting enzyme inhibitors or angiotensin receptor blockers for prevention of type 2 diabetes: a meta-analysis of randomised clinical trials.J Am Coll Cardiol. 2005;46:821–826.
Sharma AM. Is there a rationale for angiotensin blockade in the management of obesity hypertension?Hypertension. 2004;44:12–19.
Singh BM, Mehta JL. Interactions between the renin-angiotensin system and dyslipidemia: relevance in the therapy of hypertension and coronary heart disease.Arch Intern Med. 2003; 163:1296–1304.
Tykarski A. Resistant hypertension.Blood Press. 2005;2(suppl):42–45.
Onat A, Avci GS, Barlan MM, Uyarel H, Uzunlar B, Sansoy V. Measures of abdominal obesity assessed for visceral adiposity and relation to coronary risk.Int J Obes Relat Metab Disord. 2004; 28:1018–1025.
Rexrode KM, Buring JE, Manson JE. Abdominal and total adiposity and risk of coronary heart disease in men.Int J Obes Relat Metab Disord. 2001;25:1047–1056.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Malacco, E., Omboni, S. Antihypertensive efficacy of zofenopril plus hydrochlorothiazide fixed combination for treatment in metabolic syndrome. Adv Therapy 24, 1006–1015 (2007). https://doi.org/10.1007/BF02877705
Issue Date:
DOI: https://doi.org/10.1007/BF02877705