Drugs & Aging

, Volume 3, Issue 6, pp 525–531 | Cite as

A Double-Blind Randomised Comparison of Perindopril and Ketanserin in the Treatment of Hypertension in Elderly Diabetic Patients

  • J. Woo
  • K. S. Woo
  • K. H. Or
  • C. S. Cockram
  • M. G. Nicholls
Original Research Article
  • 9 Downloads

Summary

A double-blind, randomised study of the antihypertensive efficacy of perindopril and ketanserin in 44 elderly noninsulin-dependent diabetic patients aged ≥60 years was conducted. Blood pressure, blood biochemical and haematological parameters, plasma vasoactive hormones, urinary volume, electrolytes and microalbumin were measured at baseline, after a 4-week placebo period, and at intervals during 8 weeks of treatment with active drug. Electrocardiogram and echocardiogram data were also obtained. Dosages of perindopril used were 2mg once daily for 4 weeks doubling to 4mg once daily if a target blood pressure of ≤ 160/90mm Hg was not reached. Dosages of ketanserin were 40mg twice daily increasing to 80mg twice daily.

Both drugs caused a small but statistically insignificant reduction in blood pressure. Although the response rates (supine systolic blood pressure reduction of >10mm Hg) were 54% for perindopril and 45% for ketanserin, target blood pressure (supine blood pressure 160/90mm Hg) was reached in only 21% of perindopril and 20% of ketanserin recipients. Plasma creatinine and 24-hour urine sodium excretion increased in patients receiving ketanserin therapy. Glycaemic indices and the lipid profile did not change in either group, except for a reduction in plasma triglycerides in the ketanserin group. No changes in urinary microalbumin, electrocardiogram, or echocardiographic cardiac parameters were observed.

It is concluded that in the present study neither drug provoked a significant blood pressure lowering effect and that serum creatinine increased in the ketanserin group.

Keywords

Atrial Natriuretic Peptide Perindopril Ketanserin Antihypertensive Efficacy Glycaemic Index 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Amery A, Brixko P, Clement D, de Schaepdryver A, Fagard R, et al. Mortality and morbidity results from the European Working Party on high blood pressure in the elderly trial. Lancet 1: 1349–1354, 1985PubMedCrossRefGoogle Scholar
  2. Beretta-Piccoli C, Salvade G, Bachmann C, Riesen W, Zuppinger ketanserin. Antihypertensive and metabolic effects of ketanserin in diabetic patients with mild hypertension. Journal of Human Hypertension 2: 103–110, 1988PubMedGoogle Scholar
  3. Bielmann P, Leduc G, Gutkowska J, Davignon J. Effects of ketanserin on lipids, lipoproteins and plasma atrial natriuretic factor in patients with essential hypertension. Journal of Clinical Pharmacology 30: 438–443, 1990PubMedGoogle Scholar
  4. Bjorck S, Nyberg G, Mulec H, Granerus G, Herlitz H, et al. Beneficial effects of angiotensin converting enzyme inhibition on renal function in patients with diabetic nephropathy. British Medical Journal 293: 471–474, 1986PubMedCrossRefGoogle Scholar
  5. Brichard S, Ketelslegers JM, Lambert AE. Renal function, glycemic control and perindopril in diabetic patients. Clinical and Experimental Hypertension Part A 11 (Suppl. 2): 545–554, 1989Google Scholar
  6. Brogden RN, Sorkin EM. Ketanserin. Areview of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in hypertension and peripheral vascular disease. Drugs 40: 903–949, 1990PubMedCrossRefGoogle Scholar
  7. Chan JCN, Cockram CS, Nicholls MG, Cheung CK, Swaminathan R. Comparison of enalapril and nifedipine in treating non-insulin dependent diabetes associated with hypertension: one year analysis. British Medical Journal 305: 981–985, 1992PubMedCrossRefGoogle Scholar
  8. Cheung CK, Swaminathan R. Rapid, economical immuno-turbidimetric method for microalbuminuria. Clinical Chemistry 33: 204–205, 1987PubMedGoogle Scholar
  9. DeChatel R, Weidmann P, Flammer J, Ziegler WH, Beretta-Piccoli C, et al. Sodium, renin, aldosterone, catecholamines, and blood pressure in diabetes mellitus. Kidney International 12: 412–421, 1977CrossRefGoogle Scholar
  10. Dessi-Fulgheri P, Zanna C, Di Noto G, Baldinelli A, Paci MV, et al. Antihypertensive and metabolic effects of ketanserin in patients with hypertension and impaired glucose tolerance: A double-blind, randomized, placebo-controlled, crossover study. Current Therapeutic Research 49: 249–255, 1991Google Scholar
  11. Fagard R, Fiocchi, Lijnen P, Staessen J, Moerman E, et al. Haemodynamic and humoral responses to chronic ketanserin treatment in essential hypertension. British Heart Journal 51: 149–156, 1984PubMedCrossRefGoogle Scholar
  12. Feldberg W, Pyke DA, Stubbs WA. On the origin of non-insulin-dependent diabetes. Lancet 1: 1263–1264, 1985PubMedCrossRefGoogle Scholar
  13. Ferrannini E, Buzzigoli G, Bondonna R, Giorico MA, Oleggini M, et al. Insulin resistance in essential hypertension. New England Journal of Medicine 317: 350–357, 1987PubMedCrossRefGoogle Scholar
  14. Forette F, McClaran J, Delesalle MC, Hervy MP, Bouchacourt P, et al. Value of angiotensin converting enzyme inhibitors in the elderly: The example of perindopril. Clinical and Experimental Hypertension Part A 11 (Suppl. 2): 587–603, 1989Google Scholar
  15. Friedewald WT, Levy RI, Frederickson DS. Estimation of plasma low density lipoprotein cholesterol concentration without the use of the preparative ultracentrifuge. Clinical Chemistry 18: 499–512, 1972PubMedGoogle Scholar
  16. James MA, Potter JF. The effect of antihypertensive treatment on the quality of later years. Drugs & Aging 3: 26–39, 1993CrossRefGoogle Scholar
  17. Kosoglou T, Cressman MD, Vlasses PH, Rocci ML, Gabos C, et al. Antihypertensive response to ketanserin: Influence of race and weight. Journal of Clinical Pharmacology 28: 1017–1022, 1988PubMedGoogle Scholar
  18. Landsberg L. Diet, obesity and hypertension: An hypothesis involving insulin, the sympathetic nervous system, and adaptive thermogenesis. Quarterly Journal of Medicine 61: 1081–1090, 1986PubMedGoogle Scholar
  19. Lees KR, Reid JL, Scott MGB, Hosie J, Herpin D, et al. Captopril versus perindopril: a double blind study in essential hypertension. Journal of Human Hypertension 3: 17–22, 1989PubMedGoogle Scholar
  20. MacDonald D, Pang CP, Cockram CS, Swaminathan R. Fructosamine measurements in serum and plasma. Clinica Chimica Acta 168: 247–252, 1987CrossRefGoogle Scholar
  21. McCormack PME, Cox JP, Marron J, Mee F, Atkins N, et al. The antihypertensive efficacy of ketanserin in the elderly evaluated by ambulatory blood pressure measurement. Journal of Human Hypertension 4: 565–570, 1990PubMedGoogle Scholar
  22. Melbourne Diabetic Nephropathy Study Group. Comparison between perindopril and nifedipine in hypertensive and normotensive diabetic patients with microalbuminuria. British Medical Journal 302: 210–216, 1991CrossRefGoogle Scholar
  23. Mogensen CE. Management of diabetic renal involvement and disease. Lancet 1: 867–870, 1988PubMedCrossRefGoogle Scholar
  24. Ogihara T, Mikami H, Katahira K, Otsuka A. Comparative study of the effects of three angiotensin converting enzyme inhibitors on the cough reflex. American Journal of Hypertension 4: 46S–51S, 1991PubMedGoogle Scholar
  25. Pollare M, Lithell H, Berne C. A comparison of the effects of hydrochlorothiazide and captopril on glucose and lipid metabolism in patients with hypertension. New England Journal of Medicine 321: 868–873, 1989PubMedCrossRefGoogle Scholar
  26. Rosendorff C, Murray GD, for the International Study Group. Ketanserin versus metoprolol and hydrochlorothiazide in essential hypertension: only ketanserin’s hypotensive effect is age-related. Journal of Hypertension 4 (Suppl. 6): S109–S111, 1986Google Scholar
  27. Sebastian JL, McKinney WP, Kaufman J, Young MJ. Angiotensin-converting enzyme inhibitors and cough. Chest 99: 36–39, 1991PubMedCrossRefGoogle Scholar
  28. Talameh Y, Wei R, Naito H. Measurement of total HDL, HDL2, and HDL3 by dextran sulphate-MgC2 precipitation technique in human serum. Clinica Chimica Acta 158: 33–41, 1986CrossRefGoogle Scholar
  29. Thurston H, Mimran A, Zanchetti A, Creytens G, Rorive G, et al. A double blind comparison of perindopril and atenolol in essential hypertension. Journal of Human Hypertension 4: 547–552, 1990PubMedGoogle Scholar
  30. Vanhoutte P, Amery A, Birkenhager W, Breckenridge A, Biihler F, et al. Serotoninergic mechanisms in hypertension. Focus on the effects of ketanserin. Hypertension 11: 111–133, 1988PubMedCrossRefGoogle Scholar
  31. Weidmann P, Beretta-Piccoli C, Keusch G, Gluck T, Mujagic M, et al. Sodium-volume factor, cardiovascular reactivity and hypotensive mechanism of diuretic therapy in mild hypertension associated with diabetes mellitus. American Journal of Medicine 67: 779–784, 1979PubMedCrossRefGoogle Scholar
  32. Woo J, Chan TYK. A high incidence of cough associated with combination therapy of hypertension with isradipine and lisinopril in Chinese subjects. British Journal of Clinical Practice 45: 178–181, 1991PubMedGoogle Scholar
  33. Woo KS, Nicholls MG. Reappraisal of incidence of persistent cough in angiotensin converting enzyme inhibitors (CEI) therapy: A prospective double-blind controlled study. Circulation 82 (Suppl. III): 384, 1990Google Scholar
  34. Yandle TG, Espiner EA, Nicholls MG, Duff H. Radioimmunoassay and characterisation of atrial natriuretic peptide in human plasma. Journal of Clinical Endocrinology and Metabolism 63: 72–79, 1986PubMedCrossRefGoogle Scholar

Copyright information

© Adis International Limited 1993

Authors and Affiliations

  • J. Woo
    • 1
  • K. S. Woo
    • 1
  • K. H. Or
    • 1
  • C. S. Cockram
    • 1
  • M. G. Nicholls
    • 1
  1. 1.Department of Medicinethe Chinese University of Hong KongHong Kong

Personalised recommendations