Objective: To compare the efficacy and adverse drug reactions of monotherapy and combination therapy of antihypertensive drugs in diabetic hypertensive patients.

Methods: A prospective observational study of 18 months duration was conducted in the Department of Medicine of a tertiary care hospital in South India. A total of 200 patients were included in the study. Using a standard proforma, the details of patients such as demographic data and antihypertensive medications were collected and analyzed for efficacy and safety.

Results: Of 200 patients studied, 50% received monotherapy whereas the remaining 50% received combination therapy. There was male preponderance (54%) in the study population, with the mean age being 60.07±11.32 years. In monotherapy group, most commonly prescribed drug was amlodipine (38%), whereas in combination group, angiotensin receptor blocker (ARB) or calcium channel blocker (CCB) + beta blocker (18%) was commonly prescribed among 2-drug group and ARB+ thiazide+ CCB (25.6%) among 3-drug group. Monotherapy and combination therapy were analyzed to be equally efficacious in reducing systolic blood pressure and diastolic blood pressure. Based on the adverse effect profile, monotherapy comparatively produced more adverse effects than combination group. Amlodipine-induced pedal edema (56.7%) was the most common adverse effect observed, and it was predominantly managed by changing it to be a better tolerable CCB, namely cilnidipine.

Conclusion: The combination therapy may be a better treatment option in selected patient population.

Keywords: Systolic blood pressure, Diastolic blood pressure, Amlodipine, Cilnidipine, Pedal edema.

Author Biography

Laxminarayana Kurady Bairy, Department of Pharmacology, Kasturba Medical College, Manipal University, Manipal-576104, Karnataka
Department of Pharmacology, kasturba Medical College, Manipal University, Manipal.


1. Egan BM, Zhao Y. Different definitions of prevalent hypertension impact: The clinical epidemiology of hypertension and attainment of healthy people goals. J Clin Hypertens (Greenwich) 2013;15(3):154-61.
2. Anchala R, Kannuri NK, Pant H, Khan H, Franco OH, Di Angelantonio E, et al. Hypertension in India: A systematic review and meta-analysis of prevalence, awareness, and control of hypertension. J Hypertens
3. Srinath Reddy K, Shah B, Varghese C, Ramadoss A. Responding to the threat of chronic diseases in India. Lancet 2005;366(9498):1744-9.
4. Gupta R, Gupta VP. Hypertension epidemiology in India: Lessons from
Jaipur heart watch. Curr Sci 2009;97(3):349-55.
5. Mourad JJ. The evolution of systolic blood pressure as a strong predictor of cardiovascular risk and the effectiveness of fixed-dose ARB/CCB combinations in lowering levels of this preferential target. Vasc Health Risk Manag 2008;4(6):1315-25.
6. Bromfield S, Muntner P. High blood pressure: The leading global burden of disease risk factor and the need for worldwide prevention programs. Curr Hypertens Rep 2013;15:134-6.
7. Park JB, Kario K, Wang JG. Systolic hypertension: An increasing clinical challenge in Asia. Hypertens Res 2015;38(4):227-36.
8. Danaei G, Finucane MM, Lin JK, Singh GM, Paciorek CJ, Cowan MJ, et al. National, regional, and global trends in systolic blood pressure since 1980: Systematic analysis of health examination surveys and

epidemiological studies with 786 country-years and 5•4 million participants. Lancet 2011;377(9765):568-77.
9. Rossi GP, Seccia TM, Pessina AC. Secondary hypertension: The ways of management. Curr Vasc Pharmacol 2010;8(6):753-68.
10. Long AN, Dagogo-Jack S. Comorbidities of diabetes and hypertension: Mechanisms and approach to target organ protection. J Clin Hypertens (Greenwich) 2011;13(4):244-51.
11. Volpe M, Tocci G. Challenging hypertension: How to diagnose and treat resistant hypertension in daily clinical practice. Expert Rev Cardiovasc Ther 2010;8(6):811-20.
12. Hernandez-Vila E. A review of the JNC 8 blood pressure guideline. Tex
Heart Inst J 2015;42:226-8.
13. Alhawassi TM, Krass I, Pont LG. Hypertension in older persons: A systematic review of national and international treatment guidelines. J Clin Hypertens (Greenwich) 2015;17(6):486-92.
14. Ash GI, Eicher JD, Pescatello LS. The promises and challenges of the use of genomics in the prescription of exercise for hypertension: The
2013 update. Curr Hypertens Rev 2013;9(2):130-47.
15. Carty DM, Schiffer E, Delles C. Proteomics in hypertension. J Hum
Hypertens 2013;27(4):211-6.
16. The Use of the WHO-UMC System for Standardized Case Causality Assessment. Available from: pdf. [Last cited on 2015 Aug 26].
17. Everett BM, Glynn RJ, Danielson E, Ridker PM. Combination therapy versus monotherapy as initial treatment for stage 2 hypertension: A prespecified subgroup analysis of a community-based, randomized, open-label trial. Clin Ther 2008;30:661-72.
18. Lacourcière Y, Poirier L, Hebert D, Assouline L, Stolt P, Rehel B, et al. Antihypertensive efficacy and tolerability of two fixed-dose combinations of valsartan and hydrochlorothiazide compared with valsartan monotherapy in patients with stage 2 or 3 systolic hypertension: An 8-week, randomized, double-blind, parallel-group trial. Clin Ther 2005;27:1013-21.
19. Ruilope LM, Malacco E, Khder Y, Kandra A, Bönner G, Heintz D.
Efficacy and tolerability of combination therapy with valsartan plus hydrochlorothiazide compared with amlodipine monotherapy in hypertensive patients with other cardiovascular risk factors: The VAST study. Clin Ther 2005;27(5):578-87.
20. Yasmeen N, Varma RK, Siddiqua SS, Donepudi A. Efficacy and tolerability of different antihypertensive drugs in patients with mild to moderate hypertension in a tertiary care hospital - A prospective, comparative study. Arch Appl Sci Res 2011;3:436-43.
21. Pinto E. Blood pressure and ageing. Postgrad Med J
22. Janagan T, Kavitha R, Sridevi SA, Veerendra V. Prescription pattern of antihypertensive drugs used in hypertensive patients with associated type 2 diabetes mellitus in a tertiary care hospital. IJPRR 2014;3:1-5.
23. Pandaya S, Reyad-ul-ferdous M, Panthi VK, Pandey M, Maharjan L.
Effectiveness of antihypertensive agents among hypertensive patients of Nepal. Int Res J Pharm 2014;5:903-9.
24. White F, Wang L, Jelinek HF. Management of hypertension in patients with diabetes mellitus. Exp Clin Cardiol 2010;15(1):5-8.
25. Doumas M, Papademetriou V, Faselis C, Kokkinos P. Gender differences in hypertension: Myths and reality. Curr Hypertens Rep
26. Alavudeen SS, Alakhali KM, Ansari SMA, Khan NA. Prescribing pattern of antihypertensive drugs in diabetic patients of Southern province, Kingdom of Saudi Arabia. Ars Pharm 2015;56:109-14.
27. Kousalya K, Chirumamilla S, Manjunath S, Ramalakshmi S, Saranya P, Chamundeeswari D. Prescribing trend of antihypertensive drugs in hypertensive and diabetic hypertensive patients. Asian J Pharm Clin Res 2012;5:22-3.
28. Tamuno I, Fadare J. Drug treatment for hypertension in a tertiary care facility in Northern Nigeria. Int J Pharm Biomed Res 2011;2:104-9.
29. Etuk E, Isezuo SA, Chika A, Akuche J, Ali M. Prescription pattern of anti-hypertensive drugs in a tertiary health institution in Nigeria. Ann Afr Med 2008;7(3):128-32.
30. Whitworth JA; World Health Organization, International Society of Hypertension Writing Group 2003 World Health Organization (WHO)/ International Society of Hypertension (ISH) statement on management of hypertension. J Hypertens 2003;21(11):1983-92.
31. Sleight P. The HOPE study (Heart Outcomes Prevention Evaluation).

J Renin Angiotensin Aldosterone Syst 2000;1(1):18-20.
32. Bronsert MR, Henderson WG, Valuck R, Hosokawa P, Hammermeister K.
Comparative effectiveness of antihypertensive therapeutic classes and treatment strategies in the initiation of therapy in primary care patients: A Distributed Ambulatory Research in Therapeutics Network (DARTNet) study. J Am Board Fam Med 2013;26(5):529-38.
33. Kaur S, Gupta S, Kumar D, Lal M, Gilani Z. Prescribing pattern of antihypertensive drugs in a tertiary care hospital in Jammu-A descriptive study. JK Pract 2012;17:38-41.
34. Beulah S, Uma MR, Balaji S. Efficacy and tolerability of different antihypertensive drugs in diabetic patients with mild to moderate hypertension in a multi speciality hospital - A prospective comparative study. Indian J Pharm Pract 2012;5(1):21-7.
35. Panda BB, Pati MR, Sahu PK. Survey of prescription pattern of antihypertensive drugs in hypertensive in hypertensive and diabetic hypertensive patients. Asian J Pharm Clin Res 2015;8:250-2.
36. Bainbridge AD, Macfadyen RJ, Stark S, Lees KR, Reid JL. The antihypertensive efficacy and tolerability of a low dose combination of ramipril and felodipine ER in mild to moderate essential hypertension. Br J Clin Pharmacol 1993;36:323-30.
37. Naidu MU, Usha PR, Rao TR, Shobha JC. Evaluation of amlodipine, lisinopril, and a combination in the treatment of essential hypertension. Postgrad Med J 2000;76:350-3.
38. Miranda RD, Mion D Jr, Rocha JC, Koglmann O Jr, Gomes MA, Saraiva JF, 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;30:18-28.
39. Chrysant SG, Melino M, Karki S, Lee J, Heyrman R. The combination of olmesartan medoxomil and amlodipine besylate in controlling high blood pressure: COACH, a randomized, double-blind, placebo- controlled, 8-week factorial efficacy and safety study. Clin Ther
40. Bisognano JD, McLaughlin T, Roberts CS, Tang SS. Calcium channel blockers, angiotensin receptor blockers, and angiotensin-converting enzyme inhibitors: Effectiveness in combination with diuretics or beta-blockers for treating hypertension. Vasc Health Risk Manag
41. Maladkar M, Verma VK, Narsikar KA, Walinjkar DR, Patil WR, Saggu NJ, et al. Triple drug combination of telmisartan, amlodipine and hydrochlorothiazide in the treatment of essential hypertension. Open J Intern Med 2012;2:67-71.
42. Oparil S, Melino M, Lee J, Fernandez V, Heyrman R. Triple therapy with olmesartan medoxomil, amlodipine besylate, and hydrochlorothiazide in adult patients with hypertension: The TRINITY multicenter, randomized, double-blind, 12-week, parallel-group study. Clin Ther
43. 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
44. Hussain A, Aqil M, Alam MS, Khan MR, Kapur P, Pillai KK.
A pharmacovigilance study of antihypertensive medicines at a South
Delhi hospital. Indian J Pharm Sci 2009;71:338-41.
45. Severity Assessment of ADRs. Available from: http://www. adrs.html. [Last cited on 2015 Aug 28].
46. He J, Whelton PK, Appel LJ, Charleston J, Klag MJ. Long-term effects of weight loss and dietary sodium reduction on incidence of hypertension. Hypertension 2000;35:544-9.
47. Sacks FM, Svetkey LP, Vollmer WM, Appel LJ, Bray GA, Harsha D, et al. Effects on blood pressure of reduced dietary sodium and the Dietary Approaches to Stop Hypertension (DASH) diet. DASH-Sodium Collaborative Research Group. N Engl J Med 2001;344(1):3-10.
48. Vollmer WM, Sacks FM, Ard J, Appel LJ, Bray GA, Simons-Morton DG, et al. Effects of diet and sodium intake on blood pressure: Subgroup analysis of the DASH-sodium trial. Ann Intern Med
49. Kelley GA, Kelley KS. Progressive resistance exercise and resting blood pressure: A meta-analysis of randomized controlled trials. Hypertension 2000;35(3):838-43.
602 Views | 314 Downloads
How to Cite
Original Article(s)