Cost Effectiveness Analysis Study between Atenolol and Amlodipine in Essential Hypertension

 

Dr. Dhananjay Sangle¹*, Dr.Amit Naik¹, Dr. Amol Ghorpade², Dr. Vikram Ghatkar²,

Dr. Suvarna Ghuge², Dr. Dipti Ingle², Dr. Rishikesh Ingle²

¹Assistant Professor, University Department of Interpathy Research and Technology (UDIRT), Maharashtra University of Health Sciences (MUHS), Nashik.

²M.Sc. Pharmaceutical Medicine, University Department of Interpathy Research and Technology (UDIRT), Maharashtra University of Health Sciences (MUHS), Nashik.

*Corresponding Author E-mail: sangle_dhananjay@rediffmail.com

Objective: The primary objective of study was to perform a cost effectiveness analysis study between Tab. Atenolol (50mg OD) and Tab. Amlodipine (5mg OD) in treatment of essential hypertension as a mono-therapy.  The secondary objective was to evaluate and compare the   tolerability of study medications.

 

Method: This observational, prospective, comparative, parallel group, phase IV study was conducted at District Civil Hospital over a period of 8 weeks. Total 300 patients fulfilling the inclusion criteria i.e. having essential hypertension and receiving monotherapy of either Amlodipine or Atenolol were selected for the study after written informed consent.  There were 150 patients each in Atenolol group (50mg OD) and Amlodipine group (5mg OD). Unit costs of atenolol and amlodipine were applied to the daily dosages of individual patients to calculate the total costs and average costs per patient in each treatment group on an intent-to-treat basis. Efficacy rates were used to calculate the average treatment cost per unit (10 mm of Hg) reduction in Mean Arterial Pressure (MAP). The MAP was calculated at baseline visit and at final visit (at the end of 8 weeks).

 

Result: Tab. Amlodipine (5mg) OD required less cost i.e. Rs.3.43/pt. as compared to Tab.Atenolol (50mg) OD i.e Rs.5.05/pt. for the reduction of MAP by one unit (i.e.10 mm Hg). There was no statistically significant difference between average MAP reduction in Amlodipine monotherapy (17.49 mm Hg) Vs Atenolol monotherapy (16.61 mm Hg) .Although not statistically significant, Amlodipine treatment resulted in a higher ADRs   (23.33%) vs. Atenolol (18.66%)

 

Conclusion: This study concludes that Amlodipine monotherapy is more cost effective compared with an Atenolol monotherapy.

 

 

INTRODUCTION:

Hypertension is an important public health challenge worldwide because of its high prevalence and the concomitant increase in risk of cardiovascular and renal disease. Hypertension is the most important modifiable risk factor for coronary heart disease, stroke, congestive heart failure, and end-stage renal disease ¹.

 

It has been identified as the leading cause of global burden of disease and has been ranked third in terms of disability adjusted life years ². In developed countries, most patients with hypertension do not have adequate treatment and control of their BP ^{3, 4}.

                

Over all, according to recent estimates, the worldwide prevalence of hypertension in 2000 was approx. 26%, totaling approx. 1 billion people. The number of adults with hypertension in 2025 was predicted to increase by about 60% to a total of 1.56 billion ^5. Amlodipine and Atenolol are the prodrugs of Calcium Channel blocker and Beta Blocker groups respectively and is used extensively for treatment of essential hypertension as a monotherapy.

A cross sectional population based study of cost effectiveness of hypertension treatment was conducted in Brazil in 2002. It was concluded that the control of hypertension using mono-therapy was better in patients taking CCB (80%) and BB (71%), in comparison with those taking diuretics (54.9%) and ACE inhibitors (52%). The cost of antihypertensive treatment was lower for Diuretics and Beta blockers in mono-therapy or combination than for calcium channel blocker and ACE inhibitors⁶.

 

A prospective, randomized study to compare cost effectiveness of Amlodipine and Atenolol based regimen in treatment of hypertension was conducted with a Markov model in patients with modrate hypertension in UK and Sweden in 2007. The regimens used were Amlodipine5-10mg with Perindopril 4-8mg or Atenolol 50-100mg with Bendroflumethiazide 1.25-2.5mg. It was concluded that the Amlodipine based regimen is cost effective as compared with Atenolol based regimen in treatment of hypertension ⁷.

     

In another randomized and cross-sectional population study in 738 hypertensive adults approximately half of the participants received antihypertensive treatment as mono-therapy and the best percentage of control with mono-therapy was obtained with beta blocker but the Diuretics was the most cost effective ⁸.

 

 This was an observational study to determine the cost of treatment for essential hypertension and cost effectiveness analysis between Tab. Atenolol (50mg) and Amlodipine (5mg) for the treatment of essential hypertension as mono-therapy. This study will help physicians to prescribe the cost effective treatment in essential hypertension.

 

OBJECTIVES:

The primary objective of study was to perform cost effectiveness analysis study between Atenolol and Amlodipine in treatment of essential hypertension as a mono-therapy.

                

The secondary objective was to evaluate and compare the   tolerability of study medications Atenolol and Amlodipine.  

 

 METHODOLOGY:

This observational, prospective, comparative, parallel group, phase IV study was conducted at District Civil hospital over a period of 8 weeks. The study was conducted in compliance with ICH-GCP and all applicable regulatory requirements including Declaration of Helsinki, Schedule Y and ICMR guidelines. Total 300 patients fulfilling inclusion criteria i.e. having essential hypertension and receiving monotherapy of either Amlodipine or Atenolol were selected for the study after written informed consent. There were 150 patients each in Atenolol group (50mg OD) and Amlodipine group (5mg OD). Unit costs of Atenolol and Amlodipine were applied to the daily dosages of individual patients to calculate the total costs and average costs per patient in each treatment group on an intent-to-treat basis.

                 

The efficacy of treatment was evaluated as   reduction in Mean Arterial Pressure (MAP) by 10 mm of Hg (1unit). MAP was taken as an efficacy measure variable because it includes both systolic and diastolic BP andwas calculated by formula MAP = 2 DBP+SBP/3. The MAP was calculated at baseline visit and at final visit (at the end of 8 weeks).The cost of medication required to reduce one unit of MAP was calculated and compared for both groups.

                  

The incidence of ADRs in both treatment groups was assessed and compared during study and reported in ADR form and the study questionnaire.

 

 

 

 

Table 1: Comparison of Avg. MAP reduction and Cost required between Amlodipine and Atenolol group

Table 1 hows that Amlodipine group resulted in mean MAP reduction by 17.49 mm Hg and cost required for one unit reduction in MAP was 3.43 Rs. while Atenolol group resulted in mean MAP reduction by 16.61 mm Hg and cost required for one unit reduction in MAP was 5.05 Rs.

 

RESULT:

Data analysis of Atenolol) group  and Amlodipine group was done by measuring difference between Mean Arterial Pressure  (MAP )of screening and final visit blood pressure and then change in average MAP of both treatment groups was calculated.

 

The total reduction in MAP of Atenolol group was 2492.46 mm Hg and Mean MAP was 16.61 mm Hg.The cost required to treat essential hypertension within Atenolol group was Rs. 0.14/dose/day/pt. i.e Rs. 8.40 for 8 weeks. So the cost required to reduce MAP by 1 unit (10mmhg) in Atenolol group was Rs 5.05.

                       

The total reduction in MAP of Amlodipine group was 2623.55 mm Hg and Mean MAP was 17.49 mm Hg.

The cost required to treat essential hypertension within Amlodipine was Rs. 0.10/dose/day/pt. i.e Rs. 6.00 for 8 weeks.

 

The cost required to reduce MAP by 1 unit (10mmhg) in Amlodipine group was Rs.3.43.

 

So this study reveals that Tab.Amlodipine (5mg) OD requires less cost i.e Rs.3.43/pt. as compared to Tab.Atenolol (50mg) OD i.e Rs.5.05/pt. for the reduction of MAP by one unit (i.e.10 mm Hg). However Avg. MAP reduction in Amlodipine monotherapy (17.49 mm Hg) Vs Atenolol monotherapy (16.61 mm Hg) was not clinically significant.

 

Total number of ADR cases found in Atenolol group were 28 (18.66%) comprising Palpitations (08), Syncope (06), Dry mouth (04), Sweating (03), Headache (03), Flushing (02), Ankle edema (02).

 

The total number of ADRs in Amlodipine group was 35      (23.33%) with distribution as follows:  Headache (08), Ankle edema (07), Syncope (06), Dry Mouth (06), Palpitation (02), Weakness (02), Sweating (01), Constipation (01), GI Disturbances (01).

 

So this study shows that, although not statistically significant, the treatment with Tab. Amlodipine (5mg) OD presents more ADRs as compared to treatment with Tab. Atenolol (50mg) OD. 

 

DISCUSSION:

This cost effectiveness analysis study suggests that Tab. Amlodipine (5mg) OD requires less cost i.e. Rs.3.43 per patient  as compared to Tab. Atenolol (50mg) OD i.e. Rs.5.05 per patient  to reduce MAP by 1 unit (10mm Hg) for the treatment of essential hypertension. Thus lesser cost with equal efficacy makes Amlodipine an attractive choice. Previous studies have shown that Amlodipine based regimen were more cost effective than Atenolol based regimen ⁷ .This cost effectiveness  has been brought out in our study as well even though it was comparison between monotherapy of Amlodipine Vs. Atenolol.

 

The Avg. MAP reduction in Amlodipine monotherapy and Atenolol monotherapy was similar and not clinically significant. Study conducted by de Bruijn B et al. concluded that once-daily dosing with either Amlodipine or Atenolol significantly reduces blood pressures and both Amlodipine and Atenolol are well tolerated⁹.

 

Our study revealed that the treatment with Tab. Amlodipine (5mg) OD resulted in more ADRs as compared to treatment with Tab. Atenolol (50mg) OD. The difference between tolerability was not statistically significant. This can be attributed to short study period and small sample size. Study conducted by Pehrsson SK et al also observed that the incidence of adverse events was significantly lower in the Atenolol group than in the other treatment groups including Amlodipine group.

 

CONCLUSION:

This study for cost effectiveness analysis between Atenolol and Amlodipine group for the treatment of essential hypertension as mono-therapy concludes that Amlodipine monotherapy is more cost effective compared with an Atenolol monotherapy.

 

REFERENCES:

1.        He J, Whelton Pk. Epidemiology and prevention of hypertension, Med Clin North Am. 1997 Sep; 81(5):1077-97.

2.        Ezzati M, lopezAD, Rodgers A, Hoom SV, Murray CJ. Comparative Risk Assessment Collaborating Group. Selected major risk factors and global and regional burden of  disease. Lancet. 2002 Nov 2; 360(9343):1347-60.

3.        Bhatt DL, Steg PG, Ohman EM, Hirsch AT, Ikeda Y, Mas JL, Goto S, Liau CS, Richard AJ, Röther J, Wilson PW.  Investigators .International prevalence, recognition, and treatment of cardiovascular risk factors in out patients with atherothrombosis. JAMA. 2006 Jan 11;295(2):180-9

4.        Wolf-Maier K, Cooper RS, Kramer H, Banegas JR, Giampaoli S, Joffres MR, Poulter N, Primatesta P, Stegmayr B, Thamm M. Hypertension treatment and control in five European countries, Canada and the United States. Hypertension. 2004  Jan;43(1):10-7. Epub 2003 Nov 24

5.        Kearney PM, Whelton M, Reynolds K, Muntner P, Whelton PK, He J. Global burden of hypertension: analysis of worldwide data. Lancet 2005 Jan 15-21;365(9455):217-23.Dias da Costa JS, Fuchs SC, Olinto MT, Gigante DP, Menezes AM, Macedo S, Gehrke S..Cost effectiveness of hypertension treatment: a population based study. Sao Paulo Med J. 2002 Jul 4;120(4):100-4.

6.        P Lindgren, M Buxton, T Kahan, N R Poulter, B Dahlof, P S Sever, H Wedel Jönsson B; ASCOT trial investigators. Economic Evaluation of   ASCOT-BPLA: Antihypertensive treatment with an Amlodipine based regimen is cost effective compared with an atenolol   based regimen. Heart. 2008 Feb;94(2):e4. Epub 2007 Oct 4.

7.        Moreira GC, Cipullo JP, Martin JF, Ciorlia LA, Godoy MR, Cesarino CB, Cordeiro JA, Lupino PL, Ciorlia G, Burdmann  EA. Evaluation of awareness, control and cost effectiveness of hypertensive treatment in Brazilian city. J Hypertens. 2009 Sep;27(9):1900-7.

8.        De Bruijn B, Cocco G, Tyler HM. Multicenter placebo-controlled comparison of amlodipine and atenolol in mild to moderate hypertension. J Cardiovasc Pharmacol. 1988;12 Suppl 7:S107-9.  

 

 

Received on 25.05.2013          Modified on 22.06.2013

Accepted on 06.07.2013         © RJPT All right reserved