Amlodipine and Angiotensin-Converting Enzyme Inhibitor Combination versus Amlodipine Monotherapy in Adult Primary Hypertension: A Meta-Analysis of Randomized Controlled Trials_Chinese Journal of Evidence-Based Medicine

Authors：

 LV Yan ¹ , ZOU Zui ² , JIA Huaixin ³ , ZHONG Jing ¹ , FANG WeiWu ¹

1. Department of Anesthesiology, 306 Military Hospital, Beijing 100101, China;2. Department of Anesthesiology, Changzheng Hospital, Second Military Medical University, Shanghai 20000, China;3. Department of Anesthesiology, 673 Hospital, Beijing 100000, China;

Corresponding author：

LV Yan, Email: lvyan1976@hotmail.com

Keywords：

Amlodipine; Angiotensin-converting enzyme inhibitors; Antihypertensive agent; Meta-analysis

DOI：

10.7507/1672-2531.20100452

Video：

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Objective 　To estimate the efficacy and tolerability of combination of Amlodipine and different angiotensin-converting enzyme inhibitors (ACEIs) in comparison with Amlodipine monotherapy in the treatment of hypertension.
Methods 　We searched the Cochrane Central Register of Controlled Trials (Issue 2, 2009), PubMed, MEDLINE, EMbase, CBM, and CNKI (from their inception to August 2009) for relevant studies. Two reviewers independently retrieved randomized controlled trials (RCTs) according to the inclusion and exclusion criteria, assessed the methodological quality of included trials, and extracted data. Meta-analysis was performed by Stata 10.0 soft.
Results 　Seventeen RCTs involving 3 291 patients were ultimately identified. The results of meta-analyses showed combination had a greater systolic blood pressure reduction (WMD=5.72, 95%CI 4.10 to 7.33, P=0.016) and diastolic blood pressure reduction (WMD=3.62, 95%CI 4.85 to 2.39, P=0.000) than monotherapy. Combination had fewer overall adverse events (RR=0.86, 95% CI 0.75 to 0.99) than that of monotherapy.
Conclusion 　The results of meta-analyses indicate that combination provides a superior blood pressure control to that of monotherapy and has fewer adverse events and better tolerability in hypertensive patients.

Citation： LV Yan,ZOU Zui,JIA Huaixin,ZHONG Jing,FANG WeiWu. Amlodipine and Angiotensin-Converting Enzyme Inhibitor Combination versus Amlodipine Monotherapy in Adult Primary Hypertension: A Meta-Analysis of Randomized Controlled Trials. Chinese Journal of Evidence-Based Medicine, 2010, 10(5): 578-584. doi: 10.7507/1672-2531.20100452 Copy

1.	陈少萍, 秦永文, 郑兴. 联合用药——高血压病人血压控制达标的基本策略. 药学服务与研究, 2006, 6(6): 401-405.
2.	Wu Y, Huxley R, Li L, et al. Prevalence, awareness, treatment, and control of hypertension in China: data from the China National Nutrition and Health Survey 2002. Circulation, 2008, 118(25): 2679-2686.
3.	Kostis JB, Lacy CR, Cosgrove NM, et al. Association of calcium channel blocker use with increased rate of acute myocardial infarction in patients with left ventricular dysfunction. Am Heart J, 1997, 133(5): 550-557.
4.	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(19): 2560-2572.
5.	Chalmers J, MacMahon S, Mancia G, et al. 1999 World Health Organization-International Society of Hypertension Guidelines for the management of hypertension. Guidelines sub-committee. J Hypertens, 1999, 17(2): 151-183.
6.	Jadad AR, Moore RA, Carroll D, et al. Assessing the quality of reports of randomized clinical trials: is blinding necessary? Control Clin Trials, 1996, 17(1): 1-12.
7.	DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials, 1986, 7(3): 177-188.
8.	Follmann D, Elliott P, Suh I, et al. Variance imputation for overviews of clinical trials with continuous response. J Clin Epidemiol, 1992, 45(7): 769-773.
9.	Begg CB, Mazumdar M. Operating characteristics of a rank correlation test for publication bias. Biometrics, 1994, 50(4): 1088-1101.
10.	Duval S, Tweedie R. Trim and fill: A simple funnel-plot-based method of testing and adjusting for publication bias in meta-analysis. Biometrics, 2000, 56(2): 455-463.
11.	Neutel JM, Smith DH, Weber MA. Effect of antihypertensive monotherapy and combination therapy on arterial distensibility and left ventricular mass. Am J Hypertens, 2004, 17(1): 37-42.
12.	Brown MJ, Dickerson JE. Alpha-blockade and calcium antagonism: an effective and well-tolerated combination for the treatment of resistant hypertension. J Hypertens, 1995, 13(6): 701-707.
13.	Cappuccio FP, Markandu ND, Singer DR, et al. Amlodipine and lisinopril in combination for the treatment of essential hypertension: efficacy and predictors of response. J Hypertens, 1993, 11(8): 839-847.
14.	Fogari R, Malamani GD, Zoppi A, et al. Effect of benazepril addition to amlodipine on ankle oedema and subcutaneous tissue pressure in hypertensive patients. J Hum Hypertens, 2003, 17(3): 207-212.
15.	Fogari R, Preti P, Zoppi A, et al. Effects of amlodipine fosinopril combination on microalbuminuria in hypertensive type 2 diabetic patients. Am J Hypertens, 2002, 15(12): 1042-1049.
16.	Fogari R, Preti P, Lazzari P, et al. Effect of benazepril amlodipine combination on fibrinolysis in hypertensive diabetic patients. Eur J Clin Pharmacol, 2003, 59(4): 271-275.
17.	Jamerson KA, Nwose O, Jean-Louis L, et al. Initial angiotensinconverting enzyme inhibitor/calcium channel blocker combination therapy achieves superior blood pressure control compared with calcium channel blocker monotherapy in patients with stage 2 hypertension. Am J Hypertens, 2004, 17(6): 495-501.
18.	Kuschnir E, Acuna E, Sevilla D, et al. Treatment of patients with essential hypertension: amlodipine 5 mg/benazepril 20 mg compared with amlodipine 5 mg, benazepril 20 mg, and placebo. Clin Ther, 1996, 18(6): 1213-1224.
19.	MacGregor MS, Deighan CJ, Rodger RS, et al. A prospective openlabel randomised trial of quinapril and/or amlodipine in progressive non-diabetic renal failure. Nephron, 2005, 101(3): c139-149.
20.	Messerli FH, Oparil S, Feng Z. Comparison of efficacy and side effects of combination therapy of angiotensin-converting enzyme inhibitor (benazepril) with calcium antagonist (either nifedipine or amlodipine) versus high-dose calcium antagonist monotherapy for systemic hypertension. Am J Cardiol, 2000, 86(11): 1182-1187.
21.	Miranda RD, Mion D, Rocha JC, et al. An 18-week, prospective, randomized, double-blind, multicenter study of amlodipine/ramipril combination versus amlodipine monotherapy in the treatment of hypertension: the assessment of combination therapy of amlodipine/ ramipril (ATAR) study. Clin Ther, 2008, 30(9): 1618-1628.
22.	Naidu MU, Usha PR, Rao TR, et al. Evaluation of amlodipine, lisinopril, and a combination in the treatment of essential hypertension. Postgrad Med J, 2000, 76(896): 350-353.
23.	Neutel JM, Smith DH, Weber MA, et al. Efficacy of combination therapy with amlodipine besylate/benazepril hydrochloride for lowering systolic blood pressure in stage 2 hypertension. Am J Geriatr Cardiol, 2006, 15(3): 142-150.
24.	Pool J, Kaihlanen P, Lewis G, et al. Once-daily treatment of patients with hypertension: a placebo-controlled study of amlodipine and benazepril vs amlodipine or benazepril alone. J Hum Hypertens, 2001, 15(7): 495-498.
25.	Chrysant SG, Sugimoto DH, Lefkowitz M, et al. The effects of high-dose amlodipine/benazepril combination therapies on blood pressure reduction in patients not adequately controlled with amlodipine monotherapy. Blood Pressure, 2007, 1: 10-17.
26.	Mohler ER, Herrington D, Ouyang P, et al. A randomized, doubleblind trial comparing the effects of amlodipine besylate/benazepril HCl vs amlodipine on endothelial function and blood pressure. J Clin Hypertens (Greenwich), 2006, 8(10): 692-698.
27.	Ueng KC, Lin LC, Voon WC, et al. An eight-week, multicenter, randomized, double-blind study to evaluate the efficacy and tolerability of fixed-dose amlodipine/benazepril combination in comparison with amlodipine as first-line therapy in chinese patients with mild to moderate hypertension. Blood pressure, 2008, 1: 24-31.

1. 陈少萍, 秦永文, 郑兴. 联合用药——高血压病人血压控制达标的基本策略. 药学服务与研究, 2006, 6(6): 401-405.
2. Wu Y, Huxley R, Li L, et al. Prevalence, awareness, treatment, and control of hypertension in China: data from the China National Nutrition and Health Survey 2002. Circulation, 2008, 118(25): 2679-2686.
3. Kostis JB, Lacy CR, Cosgrove NM, et al. Association of calcium channel blocker use with increased rate of acute myocardial infarction in patients with left ventricular dysfunction. Am Heart J, 1997, 133(5): 550-557.
4. 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(19): 2560-2572.
5. Chalmers J, MacMahon S, Mancia G, et al. 1999 World Health Organization-International Society of Hypertension Guidelines for the management of hypertension. Guidelines sub-committee. J Hypertens, 1999, 17(2): 151-183.
6. Jadad AR, Moore RA, Carroll D, et al. Assessing the quality of reports of randomized clinical trials: is blinding necessary? Control Clin Trials, 1996, 17(1): 1-12.
7. DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials, 1986, 7(3): 177-188.
8. Follmann D, Elliott P, Suh I, et al. Variance imputation for overviews of clinical trials with continuous response. J Clin Epidemiol, 1992, 45(7): 769-773.
9. Begg CB, Mazumdar M. Operating characteristics of a rank correlation test for publication bias. Biometrics, 1994, 50(4): 1088-1101.
10. Duval S, Tweedie R. Trim and fill: A simple funnel-plot-based method of testing and adjusting for publication bias in meta-analysis. Biometrics, 2000, 56(2): 455-463.
11. Neutel JM, Smith DH, Weber MA. Effect of antihypertensive monotherapy and combination therapy on arterial distensibility and left ventricular mass. Am J Hypertens, 2004, 17(1): 37-42.
12. Brown MJ, Dickerson JE. Alpha-blockade and calcium antagonism: an effective and well-tolerated combination for the treatment of resistant hypertension. J Hypertens, 1995, 13(6): 701-707.
13. Cappuccio FP, Markandu ND, Singer DR, et al. Amlodipine and lisinopril in combination for the treatment of essential hypertension: efficacy and predictors of response. J Hypertens, 1993, 11(8): 839-847.
14. Fogari R, Malamani GD, Zoppi A, et al. Effect of benazepril addition to amlodipine on ankle oedema and subcutaneous tissue pressure in hypertensive patients. J Hum Hypertens, 2003, 17(3): 207-212.
15. Fogari R, Preti P, Zoppi A, et al. Effects of amlodipine fosinopril combination on microalbuminuria in hypertensive type 2 diabetic patients. Am J Hypertens, 2002, 15(12): 1042-1049.
16. Fogari R, Preti P, Lazzari P, et al. Effect of benazepril amlodipine combination on fibrinolysis in hypertensive diabetic patients. Eur J Clin Pharmacol, 2003, 59(4): 271-275.
17. Jamerson KA, Nwose O, Jean-Louis L, et al. Initial angiotensinconverting enzyme inhibitor/calcium channel blocker combination therapy achieves superior blood pressure control compared with calcium channel blocker monotherapy in patients with stage 2 hypertension. Am J Hypertens, 2004, 17(6): 495-501.
18. Kuschnir E, Acuna E, Sevilla D, et al. Treatment of patients with essential hypertension: amlodipine 5 mg/benazepril 20 mg compared with amlodipine 5 mg, benazepril 20 mg, and placebo. Clin Ther, 1996, 18(6): 1213-1224.
19. MacGregor MS, Deighan CJ, Rodger RS, et al. A prospective openlabel randomised trial of quinapril and/or amlodipine in progressive non-diabetic renal failure. Nephron, 2005, 101(3): c139-149.
20. Messerli FH, Oparil S, Feng Z. Comparison of efficacy and side effects of combination therapy of angiotensin-converting enzyme inhibitor (benazepril) with calcium antagonist (either nifedipine or amlodipine) versus high-dose calcium antagonist monotherapy for systemic hypertension. Am J Cardiol, 2000, 86(11): 1182-1187.
21. Miranda RD, Mion D, Rocha JC, et al. An 18-week, prospective, randomized, double-blind, multicenter study of amlodipine/ramipril combination versus amlodipine monotherapy in the treatment of hypertension: the assessment of combination therapy of amlodipine/ ramipril (ATAR) study. Clin Ther, 2008, 30(9): 1618-1628.
22. Naidu MU, Usha PR, Rao TR, et al. Evaluation of amlodipine, lisinopril, and a combination in the treatment of essential hypertension. Postgrad Med J, 2000, 76(896): 350-353.
23. Neutel JM, Smith DH, Weber MA, et al. Efficacy of combination therapy with amlodipine besylate/benazepril hydrochloride for lowering systolic blood pressure in stage 2 hypertension. Am J Geriatr Cardiol, 2006, 15(3): 142-150.
24. Pool J, Kaihlanen P, Lewis G, et al. Once-daily treatment of patients with hypertension: a placebo-controlled study of amlodipine and benazepril vs amlodipine or benazepril alone. J Hum Hypertens, 2001, 15(7): 495-498.
25. Chrysant SG, Sugimoto DH, Lefkowitz M, et al. The effects of high-dose amlodipine/benazepril combination therapies on blood pressure reduction in patients not adequately controlled with amlodipine monotherapy. Blood Pressure, 2007, 1: 10-17.
26. Mohler ER, Herrington D, Ouyang P, et al. A randomized, doubleblind trial comparing the effects of amlodipine besylate/benazepril HCl vs amlodipine on endothelial function and blood pressure. J Clin Hypertens (Greenwich), 2006, 8(10): 692-698.
27. Ueng KC, Lin LC, Voon WC, et al. An eight-week, multicenter, randomized, double-blind study to evaluate the efficacy and tolerability of fixed-dose amlodipine/benazepril combination in comparison with amlodipine as first-line therapy in chinese patients with mild to moderate hypertension. Blood pressure, 2008, 1: 24-31.

Chinese Journal of Evidence-Based Medicine

Amlodipine and Angiotensin-Converting Enzyme Inhibitor Combination versus Amlodipine Monotherapy in Adult Primary Hypertension: A Meta-Analysis of Randomized Controlled Trials

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