Skip to main content
Top
Published in: BMC Health Services Research 1/2013

Open Access 01-12-2013 | Research article

Economic impact of switching to fixed-dose combination therapy for Japanese hypertensive patients: a retrospective cost analysis

Authors: Manabu Akazawa, Katsushi Fukuoka

Published in: BMC Health Services Research | Issue 1/2013

Login to get access

Abstract

Background

The prescription of fixed-dose combinations (FDC) of antihypertensive drugs has increased rapidly since the relaxation of the prescription-term restriction.
In this study, we used the opportunity of this policy change in Japan as an instrument to assess the causal impact of switching to FDC on hypertensive treatment costs.

Methods

Claims data from 64 community pharmacies located in Tokyo were used to identify hypertensive patients under continuous treatment with angiotensin-receptor blockers (ARBs). Patients switching to FDC between December 2010 and April 2011 were compared to patients who did not receive FDC (control group). Changes in annual antihypertensive drug costs were compared using a difference-in-differences approach to adjust for patient characteristics and use of concomitant medication. Subpopulation analyses were also performed, taking into account pre-index treatment patterns and prescribers’ characteristics.

Results

There were 542 patients who switched to FDC and 9664 patients in the control group. No significant differences were observed between the 2 groups, except for antihypertensive drug use patterns before the policy change and prescribers’ characteristics. The switch to FDC was associated with an annual saving of 10,420 yen (US$112.0) in antihypertensive drug costs. Approximately 20% of the FDC patients, however, switched from ARB alone, and their drug costs increased by 2376 yen (US$25.5).

Conclusions

For hypertensive patients who required ARB-based combination therapy, switching to FDC drugs had a significant cost-saving effect. However, the policy change of relaxing the prescription-term restriction could encourage aggressive treatment, i.e., switching to a combination therapy from monotherapy, regardless of medical conditions. Further research is required to evaluate the possible negative aspects of FDC drugs.
Appendix
Available only for authorised users
Literature
1.
go back to reference Chobanian AV, Bakris GL, Black HR, Cushman WC, Green LA, Izzo JL, Jones DW, Materson BJ, Oparil S, Wright JT, Roccella EJ, Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. National Heart, Lung, and Blood Institute; National High Blood Pressure Education Program Coordinating Committee: Seventh report of the joint national committee on prevention, detection, evaluation, and treatment of high blood pressure. Hypertension. 2003, 42 (6): 1206-1252. 10.1161/01.HYP.0000107251.49515.c2.CrossRefPubMed Chobanian AV, Bakris GL, Black HR, Cushman WC, Green LA, Izzo JL, Jones DW, Materson BJ, Oparil S, Wright JT, Roccella EJ, Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. National Heart, Lung, and Blood Institute; National High Blood Pressure Education Program Coordinating Committee: Seventh report of the joint national committee on prevention, detection, evaluation, and treatment of high blood pressure. Hypertension. 2003, 42 (6): 1206-1252. 10.1161/01.HYP.0000107251.49515.c2.CrossRefPubMed
2.
go back to reference 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, Struijker 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, Kjeldsen SE, Erdine S, Narkiewicz K, Kiowski W, Agabiti-Rosei E, Ambrosioni E, Cifkova R, Dominiczak A, Fagard R, Heagerty AM, Laurent S, Lindholm LH, Mancia G, Manolis A, Nilsson PM, Redon J, Schmieder RE, Struijker-Boudier HA, Viigimaa M, Filippatos G, Adamopoulos S, Agabiti-Rosei E, Ambrosioni E, Bertomeu V, Clement D, Erdine S, Farsang C, Gaita D, Kiowski W, Lip G, Mallion JM, Manolis AJ, Nilsson PM, O'Brien E, Ponikowski P, Redon J, Ruschitzka F, Tamargo J, van Zwieten P, Viigimaa M, Waeber B, Williams B, Zamorano JL, The task force for the management of arterial hypertension of the European Society of Hypertension, The task force for the management of arterial hypertension of the European Society of Cardiology: 2007 Guidelines for the management of arterial hypertension: the task force for the management of arterial hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). Eur Heart J. 2007, 28 (12): 1462-1536.PubMed 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, Struijker 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, Kjeldsen SE, Erdine S, Narkiewicz K, Kiowski W, Agabiti-Rosei E, Ambrosioni E, Cifkova R, Dominiczak A, Fagard R, Heagerty AM, Laurent S, Lindholm LH, Mancia G, Manolis A, Nilsson PM, Redon J, Schmieder RE, Struijker-Boudier HA, Viigimaa M, Filippatos G, Adamopoulos S, Agabiti-Rosei E, Ambrosioni E, Bertomeu V, Clement D, Erdine S, Farsang C, Gaita D, Kiowski W, Lip G, Mallion JM, Manolis AJ, Nilsson PM, O'Brien E, Ponikowski P, Redon J, Ruschitzka F, Tamargo J, van Zwieten P, Viigimaa M, Waeber B, Williams B, Zamorano JL, The task force for the management of arterial hypertension of the European Society of Hypertension, The task force for the management of arterial hypertension of the European Society of Cardiology: 2007 Guidelines for the management of arterial hypertension: the task force for the management of arterial hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). Eur Heart J. 2007, 28 (12): 1462-1536.PubMed
3.
go back to reference Ogihara T, Kikuchi K, Matsuoka H, Fujita T, Higaki J, Horiuchi M, Imai Y, Imaizumi T, Ito S, Iwao H, Kario K, Kawano Y, Kim-Mitsuyama S, Kimura G, Matsubara H, Matsuura H, Naruse M, Saito I, Shimada K, Shimamoto K, Suzuki H, Takishita S, Tanahashi N, Tsuchihashi T, Uchiyama M, Ueda S, Ueshima H, Umemura S, Ishimitsu T, Rakugi H, Japanese Society of Hypertension Committee: The Japanese Society of Hypertension guidelines for the management of hypertension (JSH 2009). Hypertens Res. 2009, 32 (1): 3-107.PubMed Ogihara T, Kikuchi K, Matsuoka H, Fujita T, Higaki J, Horiuchi M, Imai Y, Imaizumi T, Ito S, Iwao H, Kario K, Kawano Y, Kim-Mitsuyama S, Kimura G, Matsubara H, Matsuura H, Naruse M, Saito I, Shimada K, Shimamoto K, Suzuki H, Takishita S, Tanahashi N, Tsuchihashi T, Uchiyama M, Ueda S, Ueshima H, Umemura S, Ishimitsu T, Rakugi H, Japanese Society of Hypertension Committee: The Japanese Society of Hypertension guidelines for the management of hypertension (JSH 2009). Hypertens Res. 2009, 32 (1): 3-107.PubMed
4.
go back to reference Kjeldsen SE, Jamerson KA, Bakris GL, Pitt B, Dahlöf B, Velazquez EJ, Gupte J, Staikos L, Hua TA, Shi V, Hester A, Tuomilehto J, Ostergren J, Ibsen H, Weber M, Avoiding Cardiovascular events through COMbination therapy in Patients LIving with Systolic Hypertension Investigators: Predictors of blood pressure response to intensified and fixed combination treatment of hypertension: the ACCOMPLISH study. Blood Press. 2008, 17 (1): 7-17. 10.1080/08037050801972857.CrossRefPubMed Kjeldsen SE, Jamerson KA, Bakris GL, Pitt B, Dahlöf B, Velazquez EJ, Gupte J, Staikos L, Hua TA, Shi V, Hester A, Tuomilehto J, Ostergren J, Ibsen H, Weber M, Avoiding Cardiovascular events through COMbination therapy in Patients LIving with Systolic Hypertension Investigators: Predictors of blood pressure response to intensified and fixed combination treatment of hypertension: the ACCOMPLISH study. Blood Press. 2008, 17 (1): 7-17. 10.1080/08037050801972857.CrossRefPubMed
5.
go back to reference Mori H, Ukai H, Yamamoto H, Saitou S, Hirao K, Yamauchi M, Umemura S: Current status of antihypertensive prescription and associated blood pressure control in Japan. Hypertens Res. 2006, 29 (3): 143-151. 10.1291/hypres.29.143.CrossRefPubMed Mori H, Ukai H, Yamamoto H, Saitou S, Hirao K, Yamauchi M, Umemura S: Current status of antihypertensive prescription and associated blood pressure control in Japan. Hypertens Res. 2006, 29 (3): 143-151. 10.1291/hypres.29.143.CrossRefPubMed
6.
go back to reference Kamijima Y, Ooba N, Yagame M, Samizo K, Shimodozono Y, Kageyama S, Horiguchi S, Nagai R, Kusunoki T, Kubota K: Hypertension management in diabetic patients: prescribing trends from 1999 to 2005 in three Japanese university hospitals. Pharmacoepidemiol Drug Saf. 2008, 17 (9): 904-911. 10.1002/pds.1609.CrossRefPubMed Kamijima Y, Ooba N, Yagame M, Samizo K, Shimodozono Y, Kageyama S, Horiguchi S, Nagai R, Kusunoki T, Kubota K: Hypertension management in diabetic patients: prescribing trends from 1999 to 2005 in three Japanese university hospitals. Pharmacoepidemiol Drug Saf. 2008, 17 (9): 904-911. 10.1002/pds.1609.CrossRefPubMed
7.
go back to reference Sakima A, Ohshiro K, Nakada S, Yamazato M, Kohagura K, Nakamoto M, Tana T, Ohya Y: Switching therapy from variable-dose multiple pill to fixed-dose single-pill combinations of angiotensin II receptor blockers and thiazides for hypertension. Clin Exp Hypertens. 2011, 33 (5): 309-315. 10.3109/10641963.2010.549260.CrossRefPubMed Sakima A, Ohshiro K, Nakada S, Yamazato M, Kohagura K, Nakamoto M, Tana T, Ohya Y: Switching therapy from variable-dose multiple pill to fixed-dose single-pill combinations of angiotensin II receptor blockers and thiazides for hypertension. Clin Exp Hypertens. 2011, 33 (5): 309-315. 10.3109/10641963.2010.549260.CrossRefPubMed
8.
go back to reference Taylor AA, Shoheiber O: Adherence to antihypertensive therapy with fixed-dose amlodipine besylate ⁄ benazepril HCl versus comparable component-based therapy. Congest Heart Fail. 2003, 9: 324-332. 10.1111/j.1527-5299.2003.03269.x.CrossRefPubMed Taylor AA, Shoheiber O: Adherence to antihypertensive therapy with fixed-dose amlodipine besylate ⁄ benazepril HCl versus comparable component-based therapy. Congest Heart Fail. 2003, 9: 324-332. 10.1111/j.1527-5299.2003.03269.x.CrossRefPubMed
9.
go back to reference Brixner DI, Jackson KC, Sheng X, Nelson RE, Keskinaslan A: Assessment of adherence, persistence, and costs among valsartan and hydrochlorothiazide retrospective cohorts in free-and fixed-dose combinations. Curr Med Res Opin. 2008, 24 (9): 2597-2607. 10.1185/03007990802319364.CrossRefPubMed Brixner DI, Jackson KC, Sheng X, Nelson RE, Keskinaslan A: Assessment of adherence, persistence, and costs among valsartan and hydrochlorothiazide retrospective cohorts in free-and fixed-dose combinations. Curr Med Res Opin. 2008, 24 (9): 2597-2607. 10.1185/03007990802319364.CrossRefPubMed
10.
go back to reference Neutel JM: Prescribing patterns in hypertension: the emerging role of fixed-dose combinations for attaining BP goals in hypertensive patients. Curr Med Res Opin. 2008, 24 (8): 2389-2401. 10.1185/03007990802262457.CrossRefPubMed Neutel JM: Prescribing patterns in hypertension: the emerging role of fixed-dose combinations for attaining BP goals in hypertensive patients. Curr Med Res Opin. 2008, 24 (8): 2389-2401. 10.1185/03007990802262457.CrossRefPubMed
11.
go back to reference Rabbani A, Alexander GC: Out-of-pocket and total costs of fixed dose combination antihypertensives and their components. Am J Hypertens. 2008, 21: 509-513. 10.1038/ajh.2008.31.CrossRefPubMed Rabbani A, Alexander GC: Out-of-pocket and total costs of fixed dose combination antihypertensives and their components. Am J Hypertens. 2008, 21: 509-513. 10.1038/ajh.2008.31.CrossRefPubMed
12.
go back to reference Gupta AK, Arshad S, Poulter NR: Compliance, safety, and effectiveness of fixed-dose combinations of antihypertensive agents: a meta-analysis. Hypertension. 2010, 55 (2): 399-407. 10.1161/HYPERTENSIONAHA.109.139816.CrossRefPubMed Gupta AK, Arshad S, Poulter NR: Compliance, safety, and effectiveness of fixed-dose combinations of antihypertensive agents: a meta-analysis. Hypertension. 2010, 55 (2): 399-407. 10.1161/HYPERTENSIONAHA.109.139816.CrossRefPubMed
13.
go back to reference Baser O, Andrews LM, Wang L, Xie L: Comparison of real-world adherence, healthcare resource utilization and costs for newly initiated valsartan/amlodipine single-pill combination versus angiotensin receptor blocker/calcium channel blocker free-combination therapy. J Med Econ. 2011, 14 (5): 576-583. 10.3111/13696998.2011.596873.CrossRefPubMed Baser O, Andrews LM, Wang L, Xie L: Comparison of real-world adherence, healthcare resource utilization and costs for newly initiated valsartan/amlodipine single-pill combination versus angiotensin receptor blocker/calcium channel blocker free-combination therapy. J Med Econ. 2011, 14 (5): 576-583. 10.3111/13696998.2011.596873.CrossRefPubMed
14.
go back to reference Sherrill B, Halpern M, Khan S, Zhang J, Panjabi S: Single-pill vs free-equivalent combination therapies for hypertension: a meta-analysis of health care costs and adherence. J Clin Hypertens (Greenwich). 2011, 13 (12): 898-909. 10.1111/j.1751-7176.2011.00550.x.CrossRef Sherrill B, Halpern M, Khan S, Zhang J, Panjabi S: Single-pill vs free-equivalent combination therapies for hypertension: a meta-analysis of health care costs and adherence. J Clin Hypertens (Greenwich). 2011, 13 (12): 898-909. 10.1111/j.1751-7176.2011.00550.x.CrossRef
15.
go back to reference Ferrario CM, Panjabi S, Buzinec P, Swindle JP: Clinical and economic outcomes associated with amlodipine/renin-angiotensin system blocker combinations. Ther Adv Cardiovasc Dis. 2013,  -Epub ahead of print Ferrario CM, Panjabi S, Buzinec P, Swindle JP: Clinical and economic outcomes associated with amlodipine/renin-angiotensin system blocker combinations. Ther Adv Cardiovasc Dis. 2013,  -Epub ahead of print
16.
go back to reference Stankus V, Hemmelgarn B, Campbell NR, Chen G, McAlister FA, Tsuyuki RT: Reducing costs and improving hypertension management. Can J Clin Pharmacol. 2009, 16 (1): e151-e155.PubMed Stankus V, Hemmelgarn B, Campbell NR, Chen G, McAlister FA, Tsuyuki RT: Reducing costs and improving hypertension management. Can J Clin Pharmacol. 2009, 16 (1): e151-e155.PubMed
17.
go back to reference Malesker MA, Hilleman DE: Comparison of amlodipine ⁄ valsartan fixed-dose combination therapy and conventional therapy. Manag Care. 2010, 19: 36-42.PubMed Malesker MA, Hilleman DE: Comparison of amlodipine ⁄ valsartan fixed-dose combination therapy and conventional therapy. Manag Care. 2010, 19: 36-42.PubMed
18.
go back to reference Arredondo A: Out-of-pocket costs to users: medicine options for hypertension. Am J Hypertens. 2008, 21: 492-10.1038/ajh.2008.150.CrossRefPubMed Arredondo A: Out-of-pocket costs to users: medicine options for hypertension. Am J Hypertens. 2008, 21: 492-10.1038/ajh.2008.150.CrossRefPubMed
20.
go back to reference John Wiley & Sons Ltd: Pharmaceutical Pricing and Reimbursement in Japan. Handbook of Current and Emerging Drug Therapies, Volume 5–8. 2007, Hoboken NJ: Wiley, 205-237. John Wiley & Sons Ltd: Pharmaceutical Pricing and Reimbursement in Japan. Handbook of Current and Emerging Drug Therapies, Volume 5–8. 2007, Hoboken NJ: Wiley, 205-237.
21.
22.
go back to reference Kawazoe H, Iihara N, Doi C, Morita S: Impact of prescription-term deregulation with revised medical service fees on drug therapy management. Yakugaku Zasshi. 2005, 125 (12): 959-969. 10.1248/yakushi.125.959.CrossRefPubMed Kawazoe H, Iihara N, Doi C, Morita S: Impact of prescription-term deregulation with revised medical service fees on drug therapy management. Yakugaku Zasshi. 2005, 125 (12): 959-969. 10.1248/yakushi.125.959.CrossRefPubMed
26.
go back to reference Wooldridge JM: Pooling cross sections across time, simple panel data method (Chapter 13). Introductory Econometrics: A Modern Approach. 2nd edition. 2003, Mason OH: South-Western, 426-460. Wooldridge JM: Pooling cross sections across time, simple panel data method (Chapter 13). Introductory Econometrics: A Modern Approach. 2nd edition. 2003, Mason OH: South-Western, 426-460.
28.
go back to reference Jackson KC, Sheng X, Nelson RE, Keskinaslan A, Brixner DI: Adherence with multiple-combination antihypertensive pharmacotherapies in a US managed care database. Clin Ther. 2008, 30 (8): 1558-1563. 10.1016/j.clinthera.2008.08.010.CrossRefPubMed Jackson KC, Sheng X, Nelson RE, Keskinaslan A, Brixner DI: Adherence with multiple-combination antihypertensive pharmacotherapies in a US managed care database. Clin Ther. 2008, 30 (8): 1558-1563. 10.1016/j.clinthera.2008.08.010.CrossRefPubMed
29.
go back to reference Patel BV, Remigio-Baker RA, Thiebaud P, Preblick R, Plauschinat C: Improved persistence and adherence to diuretic fixed-dose combination therapy compared to diuretic monotherapy. BMC Fam Pract. 2008, 9: 61-68. 10.1186/1471-2296-9-61.CrossRefPubMedPubMedCentral Patel BV, Remigio-Baker RA, Thiebaud P, Preblick R, Plauschinat C: Improved persistence and adherence to diuretic fixed-dose combination therapy compared to diuretic monotherapy. BMC Fam Pract. 2008, 9: 61-68. 10.1186/1471-2296-9-61.CrossRefPubMedPubMedCentral
30.
go back to reference Zeng F, Patel BV, Andrews L, Frech-Tamas F, Rudolph AE: Adherence and persistence of single-pill ARB/CCB combination therapy compared to multiple-pill ARB/CCB regimens. Curr Med Res Opin. 2010, 26 (12): 2877-2887. 10.1185/03007995.2010.534129.CrossRefPubMed Zeng F, Patel BV, Andrews L, Frech-Tamas F, Rudolph AE: Adherence and persistence of single-pill ARB/CCB combination therapy compared to multiple-pill ARB/CCB regimens. Curr Med Res Opin. 2010, 26 (12): 2877-2887. 10.1185/03007995.2010.534129.CrossRefPubMed
31.
go back to reference Peterson AM, Nau DP, Cramer JA, Benner J, Gwadry-Sridhar F, Nichol M: A checklist for medication compliance and persistence studies using retrospective databases. Value Health. 2007, 10 (1): 3-12. 10.1111/j.1524-4733.2006.00139.x.CrossRefPubMed Peterson AM, Nau DP, Cramer JA, Benner J, Gwadry-Sridhar F, Nichol M: A checklist for medication compliance and persistence studies using retrospective databases. Value Health. 2007, 10 (1): 3-12. 10.1111/j.1524-4733.2006.00139.x.CrossRefPubMed
32.
go back to reference Akazawa M, Nomura K, Kusama M, Igarashi A: Drug utilization reviews by community pharmacists in Japan: identification of potential safety concerns through the brown bag program. Value Health Regional Issues. 2012, 1: 98-104.CrossRef Akazawa M, Nomura K, Kusama M, Igarashi A: Drug utilization reviews by community pharmacists in Japan: identification of potential safety concerns through the brown bag program. Value Health Regional Issues. 2012, 1: 98-104.CrossRef
34.
go back to reference Zeng F, An JJ, Scully R, Barrington C, Patel BV, Nichol MB: The impact of value-based benefit design on adherence to diabetes medications: a propensity score-weighted difference in difference evaluation. Value Health. 2010, 13 (6): 846-852. 10.1111/j.1524-4733.2010.00730.x.CrossRefPubMed Zeng F, An JJ, Scully R, Barrington C, Patel BV, Nichol MB: The impact of value-based benefit design on adherence to diabetes medications: a propensity score-weighted difference in difference evaluation. Value Health. 2010, 13 (6): 846-852. 10.1111/j.1524-4733.2010.00730.x.CrossRefPubMed
35.
go back to reference Sun P, Chang J, Zhang J, Kahler KH: Evolutionary cost analysis of valsartan initiation among patients with hypertension: a time series approach. J Med Econ. 2012, 15 (1): 8-18. 10.3111/13696998.2011.626097.CrossRefPubMed Sun P, Chang J, Zhang J, Kahler KH: Evolutionary cost analysis of valsartan initiation among patients with hypertension: a time series approach. J Med Econ. 2012, 15 (1): 8-18. 10.3111/13696998.2011.626097.CrossRefPubMed
Metadata
Title
Economic impact of switching to fixed-dose combination therapy for Japanese hypertensive patients: a retrospective cost analysis
Authors
Manabu Akazawa
Katsushi Fukuoka
Publication date
01-12-2013
Publisher
BioMed Central
Published in
BMC Health Services Research / Issue 1/2013
Electronic ISSN: 1472-6963
DOI
https://doi.org/10.1186/1472-6963-13-124

Other articles of this Issue 1/2013

BMC Health Services Research 1/2013 Go to the issue