The authority responsible for issuing advice on the use of recently licensed medicines in Scotland has recommended a fixed-dose combination of the ACE inhibitor, perindopril (4 mg), and the thiazide-like diuretic, indapamide (1.25 mg), for general use in hypertensive patients.

A statement released this month by the Scottish Medicines Consortium (SMC)1 confirms that the perindopril/indapamide combination, Coversyl Plus(r) (Servier), reduces blood pressure in patients with essential hypertension uncontrolled by perindopril alone. It adds that a daily dose of Coversyl Plus costs 'virtually the same as the individual drug preparations'.

The advice follows a comprehensive assessment by the SMC's New Drugs Committee (NDC), a working group of health professionals, of the cost-benefits and clinical evidence supporting the use of Coversyl Plus. It is the first antihypertensive combination agent to receive SMC endorsement. Coversyl Plus brings together the long-term efficacy of perindopril (Coversyl(r), Servier )2 and the metabolic neutrality of indapamide (Natrilix SR(r), Servier)3 in a once-daily fixed dose. Previous studies have shown that the two agents act synergistically in reducing blood pressure4.

It is widely recognised that reducing blood pressure to target levels in the majority of hypertensive patients is likely to require more than one agent, and combining drugs is seen as a rational way to ensure maximum antihypertensive efficacy with minimum side effects. The combination of an ACE inhibitor with a diuretic is recommended by guidelines5,6 and has been supported by studies. Concern, however, has been raised about the number of tablets patients are required to take and the effect that may have on compliance6. Appropriate fixed-dose combinations are therefore likely to find increasing use in general practice.

Perindopril and indapamide are both well tolerated, providing lipid and glucose neutrality3,7. Perindopril provides superior 24-hour blood pressure control compared with other ACE inhibitors 2,8, while indapamide displays benefits not shown by other diuretics, including LVH regression9 and reduction in microalbuminuria10.

Notes 

The Scottish Medicines Consortium advises NHS Boards and Area Drug and Therapeutic Committees (ADTCs) in Scotland about the use of all newly licensed medicines, all new formulations of existing medicines and any major new indications for established products. The SMC has formed a New Drugs Committee (NDC) to advise it and make recommendations on the issues surrounding newly licensed products.

References

1. Scottish Medicines Consortium. Advice on use of perindopril/indapamide (Coversyl Plus) for hypertension. Recommendation 64/03. September 2003. http://www.scottishmedicines.org.uk/press/detail.asp?id=237

2. Myers MG.A dose-response study of perindopril in hypertension: effects on blood pressure 6 and 24-hours after dosing. Can J Cardiol1996;12(11):1191-1196

3. Weidmann P. Metabolic profile of indapamide sustained-release in patients with hypertension: data from three randomised double-blind studies. Drug Saf 2001;24(15):1155-65.

4. Randomised trial of a perindopril-based blood-pressure-lowering regimen among 6105 individuals with previous stroke or transient ischaemic attack. PROGRESS Collaborative Group. Lancet 2001; 358:1033-1041.

5. Ramsay L, Williams B, Johnston G, et al. Guidelines for management of hypertension: report of the third working party of the British Hypertension Society. J Hum Hypertens 1999;13(9):569-592.

6. Brown M, Cruickshank K, Dominiczak A, et al. Better blood control: how to combine drugs. J Hum Hypertens 2003;17:81-86.

7. Jandrain B, Herbaut C, Depoorter J-C et al. Long-term (1 year) acceptability of perindopril in type II diabetic patients with hypertension. Am J Med 1992;92(4B):91S-94S

8. Yusoff K, Rasak TA, Yusof N, et al. Comparative efficacy of perindopril and enalapril once daily using 24-hour ambulatory blood pressure monitoring.IJCP 1999;53:4.

9. Gosse P, Sheridan DJ, Zannad F, et al. Regression of left ventricular hypertrophy in hypertensive patients treated with indapamide SR 1.5 mg versus enalapril 20 mg: the LIVE study. J Hypertens 2000;18(10):1465-1475.

10. Marre M. [Treatment of hypertensive type 2 diabetes patients with microalbuminuria]. Presse Med 2002;31(Spec No 2):S21-23.