Author(s): Diksha Sharma, Dinesh Kumar Mehta, Karun Bhatti, Rina Das, Ram Mohan Chidurala


DOI: 10.5958/0974-360X.2020.00532.6   

Address: Diksha Sharma1, Dinesh Kumar Mehta1, Karun Bhatti2, Rina Das1*, Ram Mohan Chidurala3
1M.M.College of Pharmacy, Maharishi Markandeshwar (Deemed to be) University, Mullana, Ambala, HR, India.
2Department of Medicine, M.M. Institute of Medical Sciences and Research, Maharishi Markandeshwar (Deemed to be) University, Mullana, Ambala, HR, India.
3Hospitalist medicine physicians of Ohio, Mount Carmel East Hospital, 6001 E.broad street, Columbus, Ohio, USA.
*Corresponding Author

Published In:   Volume - 13,      Issue - 6,     Year - 2020

Cardiovascular diseases are major public health challenge. Hypertension is among the most important modifiable risk-factors for cardiovascular diseases. Many placebo-controlled trials and meta-analysis study of antihypertensive medication have shown that such treatment can prevent and postpone myocardial infarction and stroke. Amlodipine and atenolol are widely used in the treatment of high blood pressure. Combining multiple classes of antihypertensive drugs together is one important practice for achieving blood pressure control in most hypertensive patients. Most of the benefits of combination therapy in comparison with monotherapy includes: a synergistic effect of each drug’s therapeutic effects and reduction of side effects due to lower dose of each drug. Amlodipine with atenolol might bestow a good option for combining these two classes of agents with proven cardiovascular benefits for better blood pressure control. In this study we have reviewed the effect of combination of atenolol and amlodipine over monotherapy of amlodipine and atenolol in patients with mild-to-moderate hypertension.

Cite this article:
Diksha Sharma, Dinesh Kumar Mehta, Karun Bhatti, Rina Das, Ram Mohan Chidurala. Amlodipine And Atenolol: Combination Therapy Versus Monotherapy In Reducing Blood Pressure - A Focus On Safety And Efficacy. Research J. Pharm. and Tech 2020; 13(6): 3007-3013. doi: 10.5958/0974-360X.2020.00532.6

Diksha Sharma, Dinesh Kumar Mehta, Karun Bhatti, Rina Das, Ram Mohan Chidurala. Amlodipine And Atenolol: Combination Therapy Versus Monotherapy In Reducing Blood Pressure - A Focus On Safety And Efficacy. Research J. Pharm. and Tech 2020; 13(6): 3007-3013. doi: 10.5958/0974-360X.2020.00532.6   Available on:

1.    Triggle DJ. Calcium channel antagonists: clinical uses-past, present and future. Biochem Pharmacol 2007; 74:1-9.
2.    Kjeldsen SE. Hypertension and cardiovascular risk: General aspects. Pharmacol Res 2018 Mar; 129: 95-99.
3.    Yoshihiro K. Prevention of Hypertension and Cardiovascular Diseases. Hypertension 2014; 63:655-660.
4.    Taylor SH. Usefulness of amlodipine for angina pectoris. Am J Cardiology 1994; 73:28A-33A.
5.    Tripathi KD. Essential of Medical pharmacology. 7th Ed. New Delhi: Jaypee; 2013.
6.    Fares H, DiNicolantonio JJ, O’Keefe JH, Lavie CJ. Amlodipine in hypertension: a first-line agent with efficacy for improving blood pressure and patient outcomes Open Heart 2016; 3: e000473.
7.    Guerrero-Garcia C, Rubio-Guerra AF. Combination therapy in the treatment of hypertension. Drugs in Context 2018; 7:212531.
8.    Mukherjee D, Fang J, Chetcuti S, Moscucci M, Kline-Rogers E, Eagle KA. Impact of combination evidence-based medical therapy on mortality in patients with acute coronary syndromes. Circulation 2004; 109:745-9.
9.    Saruta T, Kanno Y, Hayashi K, Suzuki H. Renal effects of amlodipine. J Human Hypertension 1995; 9 Suppl 1: S11-6.
10.    Saruta T, Ishii M, Abe K, Iimura I. Efficacy and safety of amlodipine in hypertensive patients with renal dysfunction. Clinical Cardiology 1994; 17:317-324.
11.    Mason RP. Mechanisms of atherosclerotic plaque stabilization for a lipophilic calcium antagonist amlodipine. Am J Cardiol 2001; 88: 7.
12.    Abernethy DR. Pharmacokinetics and pharmacodynamics of amlodipine. Cardio 1992;80 Suppl 1:31-6.
13.    Hermida RC, Ayala DE, Mojon A, Fernandez JR. Chronotherapy with nifedipine GITS in hypertensive patients: improved efficacy and safety with bedtime   dosing. Am J Hypertens 2008; 21:948-954.                                   
14.    Flynn JT, Smoyer WE, Timothy EB. Treatment of Hypertensive Children with Amlodipine. Am J Hypertens 2000; 13:1061-1066.
15.    Rabah F, El-Naggari M, Al-Nabhani D. Amlodipine: The double-edged sword. Jof Pediatrics and Child Health. 2017; 53: 540-542.
16.    Galappatthy P, CW Yasindu, IMS Mohomad, JW Thusitha, KSG Gamini . Leg edema with (S)-amlodipine vs conventional amlodipine given in triple therapy for hypertension: a randomized double blind controlled clinical trial. BMC Cardiovascular Disorders 2016; 16:168-78.
17.     Esin RA , Essien OE, Andy J. Amlodipine in the treatment of mild-to-moderate essential hypertension. Current Therapeutic Research 1994; 55:1112-16.
18.    Mehta JL, Lopez LM, Vlachakis ND, Gradman AH, Nash DT, O'Connell MT, Garland WT, Pickering BI. Conducted Double-blind evaluation of the dose-response relationship of amlodipine in essential hypertension. American Heart J 1993; 125:1704-1710.
19.    Burris JF, Allenby KS, Mroczek WJ. The effect of amlodipine on ambulatory blood pressure in hypertensive patients.  Am J of Cardiol 1994;73: A39-43.
20.    Valcarcel Y. Efficacy and Safety of Amlodipine-A Comparative Study of Hypertensive Patients Treated at Primary and Specialised-Care Centers. 2006; 26: 125-133.
21.    Wang JG, Yan P, Jeffers Wang JG, Yan P, Jeffers BW. Effects of amlodipine and other classes of antihypertensive drugs on long-term blood pressure variability: evidence from randomized controlled trials. J Am Soc Hypertens 2014; 8:340-9.
22.    Lee SA, Choi HM, Park HJ, Ko SK, Lee HY. Amlodipine and cardiovascular outcomes in hypertensive patients: meta-analysis comparing amlodipine-based versus other antihypertensive therapy. Korean J Intern Med 2014; 29:315-324.
23.    Hamada T, Watanabe M, Kaneda T, Ohtahara A, Kinugawa T, Hisatome I, Fujimoto Y, Yoshida A, Shigemasa C. Evaluation of changes in sympathetic nerve activity and heart rate in essential hypertensive patients induced by amlodipine and nifedipine. J Hypertens 1998 Jan; 16: 111-8.
24.    Mancia G, De Backer G, Dominiczak A, Cifkova R, Fagard R, Germano G, Grassi G, Heagerty AM, Kjeldsen SE, Laurent S, Narkiewicz K, Ruilope L, Rynkiewicz A, Schmieder RE, Boudier HA, Zanchetti A, Vahanian A, Camm J, De Caterina R, Dean V, Dickstein K, Filippatos G, Funck-Brentano C, Hellemans I, Kristensen SD, McGregor K, Sechtem U, Silber S, Tendera M, Widimsky P, Zamorano JL, Erdine S, Kiowski W, Agabiti-Rosei E, Ambrosioni E, Lindholm LH, Viigimaa M, Adamopoulos S, Agabiti-Rosei E, Ambrosioni E, Bertomeu V, Clement D, Erdine S, Farsang C, Gaita D, Lip G, Mallion JM, Manolis AJ, Nilsson PM, O'Brien E, Ponikowski P, Redon J, Ruschitzka F, Tamargo J, van Zwieten P, Waeber B, Williams B.Guidelines for the management of arterial hypertension, J Hypertension 2007;25:1105-1187.
25.    Julius S, Kjeldsen SE, Weber M, Brunner HR, Ekman S, Hansson L, Hua T, Laragh J, McInnes GT, Mitchell L, Plat F, Schork A. Outcomes in hypertensive patients at high cardiovascular risk treated with regimens based on valsartan or amlodipine: the value randomization. Lancet 2004; 363:2022-2031.
26.    Chrysant SG, Chrysant GS, Dimas B. Current and Future Status of Beta-blockers in the Treatment of Hypertension. Clinical Cardiology 2008; 31;249-252.
27.    Chobanian AV, Bakris GL, Black HR, Cushman WC, Green LA, Izzo JL Jr, Jones DW, Materson BJ, Oparil S, Wright JT Jr, Roccella EJ. The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC VII). JAMA 2003; 289: 2560-2572.
28.    European Society of Hypertension-European Society of Cardiology Guidelines Committee.European Society of Hypertension -European Society of Cardiology guidelines for the management of arterial hypertension. J Hypertension 2003; 21: 1011-1053.
29.    Webb AJ, Fischer U, Rothwell PM. Effects of β-blocker selectivity on blood pressure variability and stroke: a systematic review. Neurology 2011; 77:731-37.
30.    Kumar A, Joshi A, Starling S. β- Blockers: A systematic review. J. Chem. Pharm. Res 2011; 3:32-47.
31.    Cruickshank JM. The Role of Beta-Blockers in the Treatment of Hypertension. Adv Exp Med Biol 2017; 956:149-166.
32.    Larochelle P, Tobe SW, Lacourcière Y. β-Blockers in hypertension: studies and meta-analyses over the years. Can J Cardiol 2014;30: S16-22.
33.    Kotecha D, Holmes J, Krum H, Altman DG, Manzano L, Cleland JG, Lip GY, Coats AJ, Andersson B, Kirchhof P, von Lueder TG, Wedel H, Rosano G, Shibata MC, Rigby A, Flather . Efficacy of β blockers in patients with heart failure plus atrial fibrillation: an individual-patient data meta-analysis. Lancet 2014;384: 2235-43.
34.    Jackson JL, Cogbill E, Santana-Davila R, Eldredge C, Collier W ,  Gradall A , Sehgal N , Kuester J . A comparative effectiveness meta-analysis of drugs for the prophylaxis of migraine headache. PLoS One 2015;10: e0130733.
35.    Yun S, Vincelette ND, Abraham I. Cardioprotective role of β-blockers and angiotensin antagonists in early-onset anthracyclines-induced cardiotoxicity in adult patients: a systematic review and meta-analysis. Postgrad Med J 2015;91: 627-33.
36.    Peller M, Ozierański K, Balsam P, Grabowski M, Filipiak KJ, Opolski G. Influence of beta-blockers on endothelial function: a meta-analysis of randomized controlled trials. Cardiol J 2015; 22:70 8-16.
37.    Ibrahim MM. Clinical Evaluation of Atenolol in Hypertensive Patients. Circulation 1981; 64:368-374.
38.    Jeffers TA, Webster J, Petrie JC, Barker NP. Atenolol once-daily in hypertension. Br J Clin Pharmacology 1977 Oct; 4: 523-527.
39.    Hansson L, Aberg H, Karlberg BE, Westerlund A. Controlled Study of Atenolol in Treatment of Hypertension. British Medical J 1975; 2: 367-370.
40.    Douglas-Jones AP, Cruickshank JM. Once-daily dosing with atenolol in patients with mild or moderate hypertension. British Medical J 1976:1:990-991.
41.    Chen CH, Ting CT, Lin SJ, Hsu TL, Yin FC, Siu CO, Chou P, Wang SP, Chang MS. Different effects of fosinopril and atenolol on wave reflection in hypertensive patients.  Hypertension 1995; 25:1034-41.
42.    Nilsson OR, Karlberg BE, Ohlsson O, Thulin T, Tolagen K. Atenolol administered once daily in primary hypertension. Effects on blood pressure in relation to pre-treatment plasma renin activity. Acta Med Scand 1979; 206:303-8.
43.    Wilcox RG, Mitchell JR. Contribution of atenolol, bendrofluazide, and hydrallazine to management of severe hypertension. Br Med J 1977 ;27: 2:547-50.
44.    Jackson G, J Schwartz J, Kates RE, Winchester M, Harrison DC. Atenolol: once-daily cardio selective beta blockade for angina pectoris. Circulation 1 Mar 1980; 61:555-560.
45.    Carlberg B, Samuelsson O, Lindholm LH. Atenolol in hypertension: is it a wise choice? The lancet 2004; 364:1684-1689.
46.    Eriksson S, Olofsson B. Wester P. Atenolol in Secondary Prevention after Stroke. Cerebrovascular Diseases 1995; 5:21-25.
47.    Lindholm LH, Carlberg B, Samuelsson O. Should beta blockers remain first choice in the treatment of primary hypertension? A meta-analysis. Lancet 2005; 366:1545-53.
48.    Sarafidis P, Bogojevic Z, Basta E, Kirstner E, Bakris GL. Comparative efficacy of two different beta-blockers on 24-hour blood pressure control. The J of Clinical Hypertension. 2008; 10:112-118.
49.    Neutel JM, Smith DHG, Ram SCV, Kaplan NM, Papademetriou V, Fagan CT, Lefkowitz PM, Kazempour MK, Weber MA.  Application of ambulatory blood pressure monitoring in differentiating between antihypertensive agents. The American J of Medicine. 1993; 94:181-87.
50.    Wiysonge CS, Bradley H, Mayosi BM, Maroney R, Mbewu A, Opie LH, Volmink J. Beta-blockers for hypertension. Cochrane Database of Systematic Reviews. 2012;8:CD002003.
51.    Lindholm LH, Carlberg B, Samuelsson O. Should Beta blockers remain first choice in the treatment of primary hypertension? A meta-analysis. The Lancet. 2005; 366:1545-1553.
52.    Tiffany R.Richards, Sheldon W. Combining Other Antihypertensive Drugs with β-Blockers in Hypertension: A Focus on Safety and Tolerability. Canadian J of Cardio 2014; 30: S42-S46.
53.    Wald DS, Law M, Morris JK, Bestwick JP, Wald NJ. Combination Therapy Versus Monotherapy in Reducing Blood Pressure: Meta-analysis on 11,000 Participants from 42 Trials. Am J Med March 2009; 122:290-300.
54.    Barron AJ, Tapp RJ. Long-Term Differential Effects of Amlodipine and Atenolol based Antihypertensive Therapy on Left Ventricular Structure and Function: An ascot Sub-Study. Circulation. 2011;124: A16804.
55.    Tapp RJ, Sharp A, Stanton AV, O’Brien E, Chaturvedi N, Poulter NR, Sever PS, ThomSAM, Hughes AD, Mayet J and ASCOT Investigators. Differential Effects of Antihypertensive Treatment on Left Ventricular Diastolic Function.An ASCOT (Anglo-Scandinavian Cardiac Outcomes Trial) Substudy. J of the American College of Cardio 2010; 55: 1875-1881.
56.    Collier DJ, Poulter NR, Dahlöf B, Sever PS, Wedel H, Buch J, Caulfield MJ; Ascot Investigators. Impact of amlodipine-based therapy among older and younger patients in the anglo-scandinavian cardiac outcomes trial-blood pressure lowering arm (ascot-bpla). J hypertens 2011; 29:583-91.
57.    Schiffrin EL, Pu Q, Park JB. Effect of amlodipine compared to atenolol on small arteries of previously untreated essential hypertensive patients. Am J Hypertens 2002; 15:105-10.
58.    Chaswal M, Singh S. A study of pulmonary profile of hypertensive patients--comparison of atenolol vs amlodipine. Indian J Physiol Pharmacol 1998; 42:538-42.
59.    Rothwell PM, Howard SC, Dolan E, O'Brien E, Dobson JE, Dahlöf B, Poulter NR, Sever PS; ASCOT-BPLA and MRC Trial Investigators. Effects of beta blockers and calcium-channel blockers on within-individual variability in blood pressure and risk of stroke. Lancet Neurol 2010; 9:469-80.
60.    Manisty CH, Zambanini A, Parker KH, Davies JE, Francis DP, Mayet J, Simon AMT, Hughes AD. Differences in the magnitude of wave reflection account for differential effects of amlodipine- versus atenolol-based regimens on central blood pressure: An Anglo-Scandinavian Cardiac Outcome Trial sub study. Hypertension 2009; 54:724-30.  
61.    Sica DA. Drug Combinations in the Treatment of Hypertension Never-Ending Novelty Hypertension. Hypertension 2010; 56:22-23.
62.    Padilla MC, Armas-Hernández MJ, Hernández RH, Israili ZH, Valasco M. Update on diuretics in the treatment of hypertension. Am J Ther 2007; 14:154-160.
63.    Weir MR, Crikelair N, Levy D, Rocha R, Kuturu V, Glazer R. Evaluation of the dose response with valsartan and valsartan/hydrochlorothiazide in patients with essential hypertension. J Clin Hypertens (Greenwich) 2007; 9:103-112.
64.    Sowers JR, Neutel JM, Saunders E. Antihypertensive efficacy of Irbesartan/HCTZ in men and women with the metabolic syndrome and type 2 diabetes. J Clin Hypertens (Greenwich) 2006; 8:470-480.
65.    Jamerson KA, Nwose O, Jean-Louis L, Schofield L, Purkayastha D, Baron M. Initial angiotensin-converting 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; 17:495-501.
66.    Hair PI, Scott LJ, Perry CM. Fixed-dose combination lercanidipine/enalapril. Drugs 2007; 67:95-106.
67.    Nash DT. Systolic hypertension. Geriatrics 2006; 61:22-28.
68.    Julius S, Kjeldsen SE, Weber M, Outcomes in hypertensive patients at high cardiovascular risk treated with regimens based on valsartan or amlodipine: the value randomised trial. Lancet 2004; 363:2022-2031.
69.    T C Tham, N Herity. Haemodynamic comparison of amlodipine and atenolol in essential hypertension using the quantascope. Br J clin Pharmac 1993; 36: 555-560.
70.    Hill JA, Gonzalez JI, Kolb R, Pepine CJ. Effects of atenolol alone, nifedipine alone and their combination on ambulant myocardial ischemia. Am J Cardiol 1991; 67:671-5.
71.    Kostuk WJ, Pflugfelder P. Comparative effects of calcium entry-blocking drugs, beta-blocking drugs and their combination in patients with chronic stable angina. Circulation 1987;75 :114-21.
72.    Morse JR. Comparison of combination nifedipine-propranolol and dilti- azem-propranolol with high dose diltiazem monotherapy for stable angina pectoris. Am J Cardiol 1988; 62:1028-   32.
73.    Aberuethy DR. The pharmacokinetic profile of amlodipine. Am Heart J 1989; 118:1100-3.
74.    Burges RA, Dodd MG, Gardiner DG. Pharmacologic profile of amlodipine. Am J Cardiol 1989; 64:101-20I.
75.    DiBianco R, Schoomaker FW, Singh JB. Amlodipine combined with beta blockade for chronic angina: results of a multicenter, placebo- controlled, randomized double-blind study. Clin Cardiol 1992:15:519-24.
76.    Bonetti F, Margonato A, Mailhac A, Orazio Carandente, Alberto Cappelletti, CarloBallarotto , Sergio LC . Coronary collaterals reduce the duration of exercise-induced ischemia by allowing a faster recovery. Am Heart J 1992; 124:48-55.
77.    Johnson BF, Frishman WH, Brobyn R, Brown RD, Reeves RL, Wombolt DG. A randomized, placebo-controlled, double-blind comparison of amlodipine and atenolol in patients with essential hypertension. Am J Hypertension 1992; 5:727-32.
78.    Pehrsson SK, Ringqvist I, Ekdahl S, Karlson BW, Ulvenstam G, Persson S. Monotherapy with amlodipine or atenolol versus their combination instable angina pectoris. Clin Cardiol 2000; 23:763-70.
79.    Pareek A, Salkar H, Mulay P, Desai S, Chandurkar N, Redkar N. A randomized, comparative, multicentric evaluation of atenolol/amlodipine combination with atenolol alone in essential hypertensive patients. Am J Ther 2010; 17:46-52.
80.    Mettimano M, Pichetti F. Combination therapy with beta-adrenergic blockade and amlodipine as second line treatment in essential hypertension. Int J Clin Pract 2000; 54:424-8.
81.    Davies RF, Habibi H,  Klinke WP, Dessain P, Nadeau C, Phaneuf DC, Lepage S, Raman S. Effect of amlodipine, atenolol and their combination on myocardial ischemia during treadmill exercise and ambulatory monitoring. Canadian Amlodipine/Atenolol in Silent Ischemia Study (CASIS) Investigators. J Am Coll Cardiol 1995; 25:619-25.
82.    Saha L, Shekhar Gautam C. The effect of amlodipine in combination with atenolol on bowel habit patients with hypertension: An Observation International Scholarly Research Network ISRN Gastroenterology. Volume 2011.
83.    Sica DA. Rationale for Fixed-Dose Combinations in the Treatment of Hypertension. Drugs 2002; 62:443-462.  
84.    Burnier M. Antihypertensive combination treatment: state of the art. Curr Hypertens Rep 2015; 17:51.  
85.    Wald DS, Law M, Morris JK, Bestwick JP, Wald NJ. Combination therapy versus monotherapy in reducing blood pressure: meta-analysis on 11,000 participants from 42 trials. Am J Med 2009; 122:290-300.  
86.    Rubio-Guerra AF, Castro-Serna D, Elizalde-Barrera CI, Ramos-Brizuela LM. Current concepts in combination therapy for the treatment of hypertension: combined calcium channel blockers and raas inhibitors. Integr Blood Press Control 2009; 2:55-62.

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