Antihypertensive efficacy of metoprolol XL/Low dose chlorthalidone (6.25 mg) combination: a randomized, comparative study in Indian patients with mild-to-moderate essential hypertension

European Journal of Medical Research

ND Karnik²  NB Chandurkar¹  SB Salagre⁵  SD Zawar³  A Pareek⁴ 

[1] Clinical Research and Development, Ipca Laboratories Limited, Kandivli Industrial Estate, Kandivli (West), Mumbai, India;Department of Medicine, LTMM College and LTMG Hospital, Mumbai, India;Department of Medicine, Indira Gandhi Government Medical College and Mayo Hospital, Nagpur, India;Medical Affairs and Clinical Research, Ipca Laboratories Limited, Kandivli Industrial Estate, Kandivli (West), Mumbai, India;Department of Medicine, Seth GS Medical College and KEM Hospital, Mumbai, India

关键词: metoprolol;    essential hypertension;    diuretics;    chlorthalidone;    Beta-blocker;   

Others  :  1093671
DOI  :  10.1186/2047-783X-14-7-297

 received in 2009-04-13, accepted in 2009-05-05,  发布年份 2009

【 摘 要 】

Objective

High blood pressure is one of the most important risk factors, directly responsible for increasing the cardiovascular morbidity and mortality. The primary objective was to evaluate the efficacy of metoprolol XL/chlorthalidone against metoprolol XL/hydrochlorothiazide with respect to mean fall in systolic and diastolic blood pressure. The secondary objective was to compare the response rates and to evaluate the tolerability of study medications in patients with mild-tomoderate essential hypertension.

Methods

Total 130 eligible patients (65: metoprolol XL 25 mg/chlorthalidone 6.25 mg; 65: metoprolol XL 25 mg/HCTZ 12.5 mg) were enrolled in this randomized, comparative, multicentric, 12-weeks study. Sixty-two patients from each group completed the study. After 4-weeks of treatment, non-responders from chlorthalidone 6.25 mg combination group were shifted to metoprolol XL 50 mg/chlorthalidone 12.5 mg and non-responders from HCTZ 12.5 mg combination group were escalated to metoprolol XL 50 mg/HCTZ 12.5 mg.

Results

The study treatment groups were comparable with respect to demography and baseline disease characteristics. Both the starting therapies were comparable with respect to mean fall in SBP (p = 0.788) and DBP (p = 0.939), and response rates (p = 1.0) after 4-weeks of therapy. Also both the step-up therapies showed similar mean fall in SBP (p = 0.277) and DBP (p = 0.507) at the end of 12-weeks. However, significantly more number of patients from chlorthalidone 12.5 mg/metoprolol XL 50 mg group responded to therapy as compared to that from HCTZ 12.5 mg/metoprolol XL 50 mg group (p = 0.045). All the reported adverse events were of mild-to-moderate intensity. There were no clinically significant trends in electrolytes (Na⁺, K⁺, Cl^-)and fasting blood sugar, evident across the treatment groups.

Conclusion

Chlorthalidone in combination with metoprolol XL is as effective and well tolerated as widely used combination of metoprolol XL/HCTZ, thus providing an alternative therapeutic option.

【 授权许可】

   
2009 I. Holzapfel Publishers

【 图 表 】

【 参考文献 】

• [1]Kjeldsen SE, Julius S, Hedner T, Hanson L: Stroke is more common than myocardial infarction in hypertension: analysis based on 11 major randomized intervention trials. Blood Press 2001, 10:190-192.
• [2]Scholze J, Bida M, Hansen A, et al.: Initiation of hypertension treatment with a fixed-dose combination or its monocomponents - Does it really matter? Int J Clin Pract 2006, 60:265-274.
• [3]Mancia G: Blood pressure reduction and cardiovascular outcomes: past, present and future. Am J Cardiol 2007, 100:3J-9J. Epub 2007 May 25
• [4]The ALLHAT Officers and Coordinators for the ALLHAT Collaborative Research Group: Major outcomes in high risk hypertensive patients randomized to angiotensin-converting enzyme inhibitor or calcium channel blocker vs diuretic. The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). JAMA 2002, 288:2981-2997.
• [5]Wright JT, Dunn JK, Cutler JA, et al.: Outcomes in hypertensive black and nonblack patients treated with chlorthalidone, amlodipine, and lisinopril. JAMA 2005, 293:1595-1608.
• [6]Psaty BM, Lumley T, Furberg CD, et al.: Health outcomes associated with various antihypertensive therapies used as first-line agents: a network meta-analysis. JAMA 2003, 21(289):2534-2544.
• [7]Five-year findings of the hypertension detection and follow-up program. I: Reduction in mortality of persons with high blood pressure, including mild hypertension. Hypertension Detection and Follow-up Program Cooperative Group. JAMA 1979, 242:2562-2571.
• [8]The Multiple Risk Factor Intervention Trial Research Group (MRFIT): Mortality rates after 10.5 years for hypertensive participants in the Multiple Risk Factor Intervention Trial. Circulation 1990, 82:1616-1628.
• [9]SHEP Cooperative Research Group: Prevention of stroke by antihypertensive drug treatment in older persons with isolated systolic hypertension. Final results of the Systolic Hypertension in the Elderly Program (SHEP). JAMA 1991, 265:3255-3264.
• [10]Neaton JD, Grimm RH, Prineas RJ, et al.: Treatment of mild hypertension study. Final results. Treatment of Mild Hypertension Study Research Group. JAMA 1993, 270:713-724.
• [11]Chobanian AV, Bakris GL, Black HR, et al.: The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: the JNC 7 report. JAMA 2003, 289:2560-2572.
• [12]Carter BL, Ernst ME, Cohen JD: Hydrochlorothiazide versus chlorthalidone: evidence supporting their interchangeability. Hypertension 2004, 43:4-9. Epub 2003 Nov 24
• [13]Ernst ME, Carter BL, Goerdt CJ, et al.: Comparative antihypertensive effects of hydrochlorothiazide and chlor thalidone on ambulatory and office blood pressure. Hypertension 2006, 47:352-358. Epub 2006 Jan 23
• [14]Cushman WC, Ford CE, Cutler JA, et al.: Success and predictors of blood pressure control in diverse North American Settings: The Antihypertensive and Lipid - Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). J Clin Hypertens 2002, 4:393-404.
• [15]Hansson L, Zanchetti A, Carruthers SG, et al.: Effects of intensive blood - pressure lowering and low dose aspirin in patients with hypertension: Principal results of the Hypertension Optimal Treatment (HOT) randomized trial. HOT Study Group. Lancet 1998, 13(351):1755-1762.
• [16]Black HR, Elliot WJ, Grandits G, et al.: Principal results of the Controlled Onset Verapramil Investigation of Cardiovascular End Points (CONVINCE) trial. JAMA 2003, 289:2073-2082.
• [17]Dahlof B, Devereux RB, Kjeldsen SE, et al.: Cardiovascular morbidity and mortality in the Losartan Intervention for Endpoint reduction in Hypertensive Study. (LIFE): A randomized trial against atenolol. Lancet 2002, 359:995-1003.
• [18]Materson BJ, Reda DJ, Cushman WC, et al.: Single - drug therapy for hypertension in men. A comparison of six antihypertensive agents with placebo. The Department of Veterans Affairs Cooperative Study Group on Antihypertensive Agents. N Engl J Med 1993, 328:914-921.
• [19]European Society of Hypertension: European Society of Cardiology Guidelines for the management of arterial hypertension. J Hypertens 2003, 21:1011-1053.
• [20]Zidek W: Hochdruckleitlinien iiberabeitet. Was ist Praxis-relevant? MMW Fortschr Med 2004, (1-2):16/37-8/17.
• [21]Dabovisek J, Kanic V, Niegowska J, Rekic S, Soucek M, Spinar J: Efficacy and tolerability of losartan in patients with essential hypertension: a multicentre, double blind comparison of losartan with metoprolol. J Clin Basic Cardiol 2005, 8:43-46.
• [22]Bichisao E, Merlini L, Gambini O, Alberti D, Pollavini G: Chlorthalidone alone or in fixed combination with slow-release metoprolol in the management of arterial hypertension: a long-term study of 545 patients. J Int Med Res 1989, 17:339-349.
• [23]Jaattela A, Pyorala K: A controlled study on the antihypertensive effect of a new beta-adrenergic receptor blocking drug, metoprolol, in combination with chlorthalidone. Br J Clin Pharmacol 1976, 3:655-660.
• [24]Kieso HA, Gould BA, Mann S, Hornung RS, Altman DG, Raftrey EB: Effect on intra-arterial blood pressure of slow release metoprolol combined with placebo or chlorthalidone. Br Med J (Clin Res Ed.) 1983, 287:717-720.
• [25]Pareek A, Karnik N, Salagre S, Zawar S, Joglekar V, Chandurkar N, et al.: Clinical effectiveness of low-dose chlorthalidone (6.25 mg) + atenolol combination in stage I hypertensive patients: a multicentre, randomized, controlled study. Curr Med Res Opin 2008, 24:1771-1779.
• [26]Pareek A, Basavanagowdappa H, Zawar S, Kumar A, Chandurkar N: A randomized, comparative study evaluating the efficacy and safety of combination of losartan with low dose chlorthalidone (6.25 mg) versus losartan with hydrochlorothiazide combination in Indian patients with mild to moderate essential hypertension. In Jackson Cardiovascular-Renal Meeting. The university of Mississippi Medical Center; 2008.