Skip to main content
CMAJ : Canadian Medical Association Journal logoLink to CMAJ : Canadian Medical Association Journal
. 1999 Aug 10;161(3):255–260.

Reference-based pricing of prescription drugs: exploring the equivalence of angiotensin-converting-enzyme inhibitors

C Bourgault 1, E Elstein 1, J Le Lorier 1, S Suissa 1
PMCID: PMC1230501  PMID: 10463046

Abstract

BACKGROUND: Reference-based pricing is a cost-containment policy applied to prescription drugs that are in the same class and deemed to be therapeutically equivalent. Recent reference-based pricing measures have targeted several drug classes, including angiotensin-converting-enzyme (ACE) inhibitors. The objective of this study was to assess whether patients treated for hypertension with various ACE inhibitors differed in their utilization of health care services and hence, whether the various ACE inhibitors should be considered therapeutically equivalent. METHODS: A retrospective cohort was formed from 4709 Saskatchewan residents aged 40-79 years who initiated treatment for hypertension with 1 of the 3 most frequently prescribed ACE inhibitors (captopril, enalapril or lisinopril) between Jan. 1, 1991, and Dec. 31, 1993. Information obtained from universal insurance databases included prescription drug use, the number of visits to a general practitioner (GP) or specialist and the number of hospital admissions during the year before treatment was initiated and during a follow-up period of up to 4 years. Rates were statistically adjusted for potential confounding variables and compared across treatment groups. RESULTS: Of the 4709 patients, 529 were prescribed captopril initially, 2939 enalapril and 1241 lisinopril. After treatment was initiated patients prescribed captopril were dispensed more medications on average, with an overall rate of 18.6 prescriptions per patient per year (v. 16.4 and 14.7 for enalapril and lisinopril users respectively); they were admitted to hospital more often, and they made more visits to GPs and specialists. The adjusted rate ratio of the number of visits to a GP for patients receiving enalapril, relative to captopril, was 0.84 (95% confidence interval [CI] 0.80-0.88), and for those receiving lisinopril it was 0.79 (95% CI 0.74-0.83). The adjusted rate ratios for the number of visits to a specialist were similar but lower, and for the number of hospital admissions they were 0.82 for patients prescribed enalapril initially (95% CI 0.73-0.93) and 0.65 (95% CI 0.56-0.75) for those prescribed lisinopril. INTERPRETATION: Patients with hypertension who are initially prescribed captopril used health care services more than those initially prescribed enalapril or lisinopril. This suggests that ACE inhibitors may not be therapeutically equivalent.

Full Text

The Full Text of this article is available as a PDF (135.8 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Boulet A. P., Tessier G. Reference-based pricing in British Columbia: implications for cardiologists--an analysis. Can J Cardiol. 1997 Jan;13(1):46–51. [PubMed] [Google Scholar]
  2. Briscoe T. A., Dearing C. J. Clinical and economic effects of replacing enalapril with benazepril in hypertensive patients. Am J Health Syst Pharm. 1996 Sep 15;53(18):2191–2193. doi: 10.1093/ajhp/53.18.2191. [DOI] [PubMed] [Google Scholar]
  3. Case D. B. Angiotensin-converting enzyme inhibitors: are they all alike? J Clin Hypertens. 1987 Sep;3(3):243–256. [PubMed] [Google Scholar]
  4. Conway J., Coats A. J., Bird R. Lisinopril and enalapril in hypertension: a comparative study using ambulatory monitoring. J Hum Hypertens. 1990 Jun;4(3):235–239. [PubMed] [Google Scholar]
  5. Edwards C. R., Padfield P. L. Angiotensin-converting enzyme inhibitors: past, present, and bright future. Lancet. 1985 Jan 5;1(8419):30–34. doi: 10.1016/s0140-6736(85)90975-4. [DOI] [PubMed] [Google Scholar]
  6. Espinel C. H., Williams J. L., Coughlin S. S. Enalapril and lisinopril in the treatment of mild to moderate essential hypertension. Clin Ther. 1990 Mar-Apr;12(2):181–190. [PubMed] [Google Scholar]
  7. Gavras H., Gavras I. Angiotensin converting enzyme inhibitors. Properties and side effects. Hypertension. 1988 Mar;11(3 Pt 2):II37–II41. doi: 10.1161/01.hyp.11.3_pt_2.ii37. [DOI] [PubMed] [Google Scholar]
  8. Gavras I., Gavras H. Captopril and enalapril. Ann Intern Med. 1983 Apr;98(4):556–557. doi: 10.7326/0003-4819-98-4-556_2. [DOI] [PubMed] [Google Scholar]
  9. Gerbrandt K. R., Yedinak K. C. Formulary management of ACE inhibitors. Pharmacoeconomics. 1996 Dec;10(6):594–613. doi: 10.2165/00019053-199610060-00006. [DOI] [PubMed] [Google Scholar]
  10. Gill T. H., Hauter F., Pelter M. A. Conversions from captopril to lisinopril at a dosage ratio of 5:1 result in comparable control of hypertension. Ann Pharmacother. 1996 Jan;30(1):7–11. doi: 10.1177/106002809603000101. [DOI] [PubMed] [Google Scholar]
  11. Gosse P., Dallocchio M., Gourgon R. ACE inhibitors in mild to moderate hypertension: comparison of lisinopril and captopril administered once daily. French Cooperative Study Group. J Hum Hypertens. 1989 Jun;3 (Suppl 1):23–28. [PubMed] [Google Scholar]
  12. Gourlay S., McNeil J., Forbes A., McGrath B. Differences in the acute and chronic antihypertensive effects of lisinopril and enalapril assessed by ambulatory blood pressure monitoring. Clin Exp Hypertens. 1993 Jan;15(1):71–89. doi: 10.3109/10641969309041612. [DOI] [PubMed] [Google Scholar]
  13. Herpin D., Conte D. Assessment of the antihypertensive effect of lisinopril using 24-hour ambulatory monitoring. J Hum Hypertens. 1989 Jun;3 (Suppl 1):11–15. [PubMed] [Google Scholar]
  14. Howes L. G. Critical assessment of ACE inhibitors. Part 2. Aust Fam Physician. 1995 Apr;24(4):639, 641-3. [PubMed] [Google Scholar]
  15. Inman W. H., Rawson N. S., Wilton L. V., Pearce G. L., Speirs C. J. Postmarketing surveillance of enalapril. I: Results of prescription-event monitoring. BMJ. 1988 Oct 1;297(6652):826–829. doi: 10.1136/bmj.297.6652.826. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Irvin J. D., Viau J. M. Safety profiles of the angiotensin converting enzyme inhibitors captopril and enalapril. Am J Med. 1986 Oct 31;81(4C):46–50. doi: 10.1016/0002-9343(86)90945-9. [DOI] [PubMed] [Google Scholar]
  17. Jenkins A. C., Dreslinski G. R., Tadros S. S., Groel J. T., Fand R., Herczeg S. A. Captopril in hypertension; seven years later. J Cardiovasc Pharmacol. 1985;7 (Suppl 1):S96–101. [PubMed] [Google Scholar]
  18. Kozma C. M., Schulz R. M., Dickson W. M., Dye J. T., Cox E. R., Holdford D. A., Michael L., Yates W. N., Jr, Young T. L. Economic impact of cost-containment strategies in third party programmes in the US. Part II. Pharmacoeconomics. 1993 Sep;4(3):187–202. doi: 10.2165/00019053-199304030-00004. [DOI] [PubMed] [Google Scholar]
  19. Lancaster S. G., Todd P. A. Lisinopril. A preliminary review of its pharmacodynamic and pharmacokinetic properties, and therapeutic use in hypertension and congestive heart failure. Drugs. 1988 Jun;35(6):646–669. doi: 10.2165/00003495-198835060-00003. [DOI] [PubMed] [Google Scholar]
  20. MacLeod S. M. Improving physician prescribing practices: bridge over troubled waters. CMAJ. 1996 Mar 1;154(5):675–677. [PMC free article] [PubMed] [Google Scholar]
  21. McAreavey D., Robertson J. I. Angiotensin converting enzyme inhibitors and moderate hypertension. Drugs. 1990 Sep;40(3):326–345. doi: 10.2165/00003495-199040030-00002. [DOI] [PubMed] [Google Scholar]
  22. McGregor M. Coverage of drug costs: reference-based pricing. Can J Cardiol. 1998 May;14(5):666–668. [PubMed] [Google Scholar]
  23. McLaughlin P. R. Reference-based pricing of prescription drugs. Can J Cardiol. 1997 Jan;13(1):31–32. [PubMed] [Google Scholar]
  24. Moyses C., Higgins T. J. Safety of long-term use of lisinopril for congestive heart failure. Am J Cardiol. 1992 Oct 8;70(10):91C–97C. doi: 10.1016/0002-9149(92)91364-a. [DOI] [PubMed] [Google Scholar]
  25. Murray N. H. Duration of angiotensin-converting enzyme inhibition: implications for tolerability. Cardiology. 1991;79 (Suppl 1):22–29. doi: 10.1159/000174903. [DOI] [PubMed] [Google Scholar]
  26. Olley P. M., McLaughlin P. R. The Canadian Cardiovascular Society and reference-based drug pricing. Can J Cardiol. 1998 May;14(5):669–670. [PubMed] [Google Scholar]
  27. Parish R. C., Miller L. J. Adverse effects of angiotensin converting enzyme (ACE) inhibitors. An update. Drug Saf. 1992 Jan-Feb;7(1):14–31. doi: 10.2165/00002018-199207010-00004. [DOI] [PubMed] [Google Scholar]
  28. Reeder C. E., Lingle E. W., Schulz R. M., Mauch R. P., Jr, Nightengale B. S., Pedersen C. A., Watrous M. L., Zetzl S. E. Economic impact of cost-containment strategies in third party programmes in the US (part I). Pharmacoeconomics. 1993 Aug;4(2):92–103. doi: 10.2165/00019053-199304020-00004. [DOI] [PubMed] [Google Scholar]
  29. Rigter H. Recent public policies in The Netherlands to control pharmaceutical pricing and reimbursement. Pharmacoeconomics. 1994;6 (Suppl 1):15–21. doi: 10.2165/00019053-199400061-00007. [DOI] [PubMed] [Google Scholar]
  30. Riley L. J., Jr, Vlasses P. H., Ferguson R. K. Clinical pharmacology and therapeutic applications of the new oral converting enzyme inhibitor, enalapril. Am Heart J. 1985 May;109(5 Pt 1):1085–1089. doi: 10.1016/0002-8703(85)90252-2. [DOI] [PubMed] [Google Scholar]
  31. Rotmensch H. H., Vlasses P. H., Ferguson R. K. Resolution of captopril-induced rash after substitution of enalapril. Pharmacotherapy. 1983 Mar-Apr;3(2 Pt 1):131–133. [PubMed] [Google Scholar]
  32. Rubin R. J., Mendelson D. N. A framework for cost-sharing policy analysis. Pharmacoeconomics. 1996;10 (Suppl 2):56–67. doi: 10.2165/00019053-199600102-00010. [DOI] [PubMed] [Google Scholar]
  33. Rush J. E., Lyle P. A. Safety and tolerability of lisinopril in older hypertensive patients. Am J Med. 1988 Sep 23;85(3B):55–59. doi: 10.1016/0002-9343(88)90352-x. [DOI] [PubMed] [Google Scholar]
  34. Rush J. E., Merrill D. D. The safety and tolerability of lisinopril in clinical trials. J Cardiovasc Pharmacol. 1987;9 (Suppl 3):S99–107. doi: 10.1097/00005344-198700003-00023. [DOI] [PubMed] [Google Scholar]
  35. Strom B. L. Generic drug substitution revisited. N Engl J Med. 1987 Jun 4;316(23):1456–1462. doi: 10.1056/NEJM198706043162306. [DOI] [PubMed] [Google Scholar]
  36. Strom B. L., Miettinen O. S., Melmon K. L. Postmarketing studies of drug efficacy: when must they be randomized? Clin Pharmacol Ther. 1983 Jul;34(1):1–7. doi: 10.1038/clpt.1983.119. [DOI] [PubMed] [Google Scholar]
  37. Waeber B., Gavras I., Brunner H. R., Gavras H. Safety and efficacy of chronic therapy with captopril in hypertensive patients: an update. J Clin Pharmacol. 1981 Nov-Dec;21(11-12):508–516. doi: 10.1002/j.1552-4604.1981.tb05658.x. [DOI] [PubMed] [Google Scholar]
  38. West R. Saskatchewan health data bases: a developing resource. Am J Prev Med. 1988;4(2 Suppl):25–27. [PubMed] [Google Scholar]
  39. Whelton A., Dunne B., Jr, Glazer N., Kostis J. B., Miller W. E., Rector D. J., Tresznewsky O. N. Twenty-four hour blood pressure effect of once-daily lisinopril, enalapril, and placebo in patients with mild to moderate hypertension. J Hum Hypertens. 1992 Aug;6(4):325–331. [PubMed] [Google Scholar]
  40. Whelton A., Miller W. E., Dunne B., Jr, Hait H. I., Tresznewsky O. N. Once-daily lisinopril compared with twice-daily captopril in the treatment of mild to moderate hypertension: assessment of office and ambulatory blood pressures. J Clin Pharmacol. 1990 Dec;30(12):1074–1080. doi: 10.1002/j.1552-4604.1990.tb01848.x. [DOI] [PubMed] [Google Scholar]
  41. Woollard R. F. Opportunity lost: a frontline view of reference-based pricing. CMAJ. 1996 Apr 15;154(8):1185–1188. [PMC free article] [PubMed] [Google Scholar]

Articles from CMAJ: Canadian Medical Association Journal are provided here courtesy of Canadian Medical Association

RESOURCES