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Swiss Hypertension Treatment Programme with Verapamil and/or Enalapril in Diabetic Patients

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Summary

The purpose of the present study was to assess the efficacy and tolerability of diuretic-free antihypertensive therapy with a calcium antagonist and/or an angiotensin converting enzyme (ACE) inhibitor in patients with diabetes mellitus. 54 hypertensive [blood pressure (BP) above 140/90mm Hg] patients with diabetes mellitus type 1 (n = 7) or 2 (n = 47) and normal serum creatinine levels (mean 82 ± 6 μmol/L) received either verapamil or enalapril after a 2-week washout and a 4-week placebo phase. If BP remained elevated, both agents were combined.

Verapamil or enalapril alone normalised diastolic BP (to less than 90mm Hg) in 36 patients; verapamil decreased BP from 159/98 to 147/87mm Hg (n = 19, p < 0.001) and enalapril decreased BP from 166/99 to 146/88mm Hg (n = 17, p < 0.001). In 18 patients who remained hypertensive after 10 weeks of monotherapy, a combination of both drugs decreased BP from 169/104 to 151/90mm Hg (p < 0.001). Overall, 87% of patients achieved a target BP response at 30 weeks. Urinary albumin as related to creatinine excretion (UAE; μg albumin: mg creatinine) was on average not significantly changed after verapamil or enalapril treatment, alone or combined. Nevertheless, in patients with initial microalbuminuria, UAE decreased (p < 0.05) during enalapril treatment. Serum potassium, total lipids, high density lipoprotein cholesterol, low density lipoprotein cholesterol, glycosylated haemoglobin, serum C peptide and fructosamine levels were not significantly modified by treatment. Subjective tolerability of the drugs was also generally good.

Thus, in hypertensive patients with diabetes, a diuretic-free therapy based on the calcium antagonist verapamil or the ACE inhibitor enalapril, alone or combined, can effectively decrease BP without adversely affecting carbohydrate and lipid metabolism.

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References

  • Assmann G, Schulte H. The Prospective Cardiovascular Munster (PROCAM) study: prevalence of hyperlipidemia in persons with hypertension and/or diabetes mellitus and the relationship to coronary heart disease. American Heart Journal 116(Suppl. 2): 1713–1724, 1988

    Article  PubMed  CAS  Google Scholar 

  • Bakris GL. Effects of diltiazem or lisinopril on massive protein-uria associated with diabetes mellitus. Annals of Internal Medicine 112: 707–708, 1990

    PubMed  CAS  Google Scholar 

  • Beretta-Piccoli C, Weidmann P, Keusch G. Responsiveness of plasma renin and aldosterone in diabetes mellitus. Kidney International 20: 259–266, 1981

    Article  PubMed  CAS  Google Scholar 

  • Bilo HJG, Westerman RF, Nicolaas-Merkus AM, Donker AJM. Effects of enalapril with and without hydrochlorothiazide in hypertensive patients with non-insulin-dependent diabetes mellitus. Diabetes Research 9: 21–25, 1988

    PubMed  CAS  Google Scholar 

  • Björk 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, 1986

    Article  Google Scholar 

  • Burstein M, Scholnik HR, Morfin R. Rapid methods for the isolation of lipoproteins from human serum by precipitation with polyanions. Journal of Lipid Research 11: 583–595, 1970

    PubMed  CAS  Google Scholar 

  • Christensen CK, Mogensen CE. Effect of antihypertensive treatment on progression of incipient diabetic nephropathy. Hypertension 7(Suppl. II): 109–113, 1985

    Google Scholar 

  • Cole RA, Soeldner JS, Dunn PJ, Bunn HF. A rapid method for the determination of glycosylated hemoglobins using high pressure liquid chromatography. Metabolism 27: 289–301, 1978

    Article  PubMed  CAS  Google Scholar 

  • Cruickshank JK, Anderson NMcF, Wadsworth J, McHardy Young S, et al. Treating hypertension in black compared with white non-insulin dependent diabetics: a double blind trial of verapamil and metoprolol. British Medical Journal 297: 1155–1159, 1988

    Article  PubMed  CAS  Google Scholar 

  • Demarie BK, Bakris GL. Effects of different calcium antagonists on proteinuria associated with diabetes mellitus. Annals of Internal Medicine 113: 987–988, 1990

    PubMed  CAS  Google Scholar 

  • Ellis D, Conrod BA, Dorman JS, Kelsey SF, Becker DJ, et al. Choice of urine samples predictive of microalbuminuria in patients with insulin-dependent diabetes mellitus. American Journal of Kidney Disease 13: 321–328, 1989

    CAS  Google Scholar 

  • Feldt-Rasmussen B, Mathiesen ER, Deckert T, Giese J, Christensen NJ, et al. Central role for sodium in the pathogenesis of blood pressure changes independent of angiotensin, aldosterone and catecholamines in type 1 (insulin-dependent) diabetes mellitus. Diabetologia 30: 610–617, 1987

    PubMed  CAS  Google Scholar 

  • Ferrari P, Rosman JB, Weidmann P. Antihypertensive agents, serum lipoproteins and glucose metabolism. American Journal of Cardiology 67: 26B–35B, 1991

    Article  PubMed  CAS  Google Scholar 

  • Fouad-Tarazi FM, Liebson PR. Echocardiographic studies of regression of left ventricular hypertrophy in hypertension. Hypertension 9(Suppl. II): 65–68, 1987

    Google Scholar 

  • Gambaro G, Morbiato F, Cicerello E, Del Turco M, Sartori L, et al. Captopril in the treatment of hypertension in type I and type II diabetic patients. Journal of Hypertension 3(Suppl. II): 149–151, 1985

    Google Scholar 

  • Gill JS, Al-Hussary N, Zezulka AV, Pasi KJ, Atkin TW, et al. Effect of nifedipine on glucose tolerance, serum insulin, and serum fructosamine in diabetic and nondiabetic patients. Clinical Therapeutics 9(Suppl. III): 304–310, 1987

    PubMed  CAS  Google Scholar 

  • Hawthorne VM. Preventing the kidney disease of diabetes mellitus: public health perspectives. Consensus Statement American Journal of Kidney Disease 13: 1–6, 1989

    CAS  Google Scholar 

  • Hommel E, Parving HH, Mathiesen E, Edsberg B, Nielsen MD, et al. Effect of captopril on kidney function in insulin-dependent diabetic patients with nephropathy. British Medical Journal 293: 467–470, 1986

    Article  PubMed  CAS  Google Scholar 

  • Kannel WB, McGee DL. Epidemiology of sudden death: insights from the Framingham study. Cardiovascular Clinics 15: 93–105, 1985

    PubMed  CAS  Google Scholar 

  • Kaplan NM. Our appropriate concern about hypokalemia. American Journal of Medicine 77: 1–14, 1984

    Article  PubMed  CAS  Google Scholar 

  • Krämer BK, Risler T. Sustained-release verapamil in the treatment of hypertensive patients with impaired renal function. Current Therapeutic Research–Clinical and Experimental 44: 986–993, 1988

    Google Scholar 

  • Kroc Collaborative Study Group. Blood glucose control and the evolution of diabetic retinopathy and albuminuria. New England Journal of Medicine 311: 365–372, 1984

    Article  Google Scholar 

  • Laragh JH, Case DB, Atlas SA, Sealey JE. Captopril compared with other antirenin system agents in hypertensive patients: its tri phasic effects on blood prssure and its use to identify and test the renin factor. Hypertension 2: 586–593, 1980

    Article  PubMed  CAS  Google Scholar 

  • Lipid Research Clinics Program. Manual of Laboratory Operations. Lipid and lipoprotein analysis (publication NIH) 75-628 US Department of Health, Education and Welfare, 1974

  • MacMahon SW, Cutler JA, Neater JD, Furberg CD, Cohen JD, et al. for the Multiple Risk Factor Intervention Trial Research Group. Relationship of blood pressure to coronary and stroke morbidity and mortality in clinical trial and epidemiological studies. Journal of Hypertension 4(Suppl IV): 14–17, 1986

    Google Scholar 

  • Marre M, Chatellier G, LeBlanc H, Guyenne TT, Menard J, et al. Prevention of diabetic nephropathy with enalapril in normotensive diabetics with microalbuminuria. British Medical Journal 297: 1092–1095, 1988

    Article  PubMed  CAS  Google Scholar 

  • McLenechan JM, Henderson E, Morris KI, Dargie HJ. Ventricular arrhythmias in patients with hypertensive left ventricular hypertrophy. New England Journal of Medicine 317: 787–792, 1987

    Article  Google Scholar 

  • Melbourne Diabetic Nephropathy Study Group. Comparison between perindopril and nifedipine in hypertensive and normotensive diabetic patients with microalbuminuria. British Medical Journal 302: 210–216, 1991

    Article  Google Scholar 

  • Midtbo K, Lauve O, Hals O. No metabolic side effects of long-term treatment with verapamil in hypertension. Angiology 39: 1025–1029, 1988

    Article  PubMed  CAS  Google Scholar 

  • Mimran A, Insua A, Ribstein J, Monnier L, Bringer J, et al. Contrasting effects of captopril and nifedipine in normotensive patients with incipient diabetic nephropathy. Journal of Hypertension 6: 919–923, 1988

    Article  PubMed  CAS  Google Scholar 

  • Mogensen CE. Long-term of antihypertensive treatment inhibiting progression of diabetic nephropathy. British Medical Journal 285: 685–688, 1982

    Article  PubMed  CAS  Google Scholar 

  • Mogensen CE. Microalbuminuria as a predictor or clinical diabetic nephropathy. Kidney International 31: 673–689, 1987

    Article  PubMed  CAS  Google Scholar 

  • Moore PM, Elliot TW, Gary Nicholls M. Hormonal and metabolic effects of enalapril treatment in hypertensive subjects with NIDDM. Diabetes Care 11: 397–401, 1988

    Article  PubMed  CAS  Google Scholar 

  • Murphy MB, Lewis PJ, Kohner E, Schumer B, Dollery CT. Glucose intolerance in hypertensive patients treated with diuretics: a fourteen-year follow-up. Lancet 2: 1293–1295, 1982

    Article  PubMed  CAS  Google Scholar 

  • Odigwe C, McCulloch AJ, Williams DO, Tunbridge WMG. A trial of the calcium antagonist nisoldipine in hypertensive non-insulin-dependent diabetic patients. Diabetic Medicine 3: 463–467, 1987

    Article  Google Scholar 

  • Parving HH, Andersen AR, Smidt UM, Hommel E, Mathiesen ER, et al. Effect of antihypertensive treatment on kidney function in diabetic nephropathy. British Medical Journal 294: 1443–1447, 1987

    Article  PubMed  CAS  Google Scholar 

  • Parving HH, Hommel E, Smidt UM. Protection of kidney function and decrease in albuminuria by captopril in insulin-dependent diabetics with nephropathy. British Medical Journal 297: 1086–1091, 1988

    Article  PubMed  CAS  Google Scholar 

  • Passa P, Le Blanc H, Marre M. Effects of enalapril in insulin-dependent diabetic subjects with mild to moderate uncomplicated hypertension. Diabetes Care 10: 200–204, 1987

    Article  PubMed  CAS  Google Scholar 

  • Peer G, Korzets A, Levtov O. Plasma lipid profile in verapamil-treated hypertensive patients. International Journal of Clinical Pharmacology, Therapy and Toxicology 25: 489–492, 1987

    CAS  Google Scholar 

  • Pollare T, 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, 1989a

    Article  PubMed  CAS  Google Scholar 

  • Pollare T, Lithell H, Mörlin C, Präntare H, Hvarfner A, et al. Metabolic effects of diltiazem and atenolol: results from a randomized, double-blind study with parallel groups. Journal of Hypertension 7: 551–559, 1989b

    Article  PubMed  CAS  Google Scholar 

  • Pyörälä K, Savolainen E, Kaukola S, Haapakoski J. Plasma insulin as coronary heart disease factor: relationship to other risk factors and predictive value during 9.5-year follow-up of the Helsinki Policemen Study Population. Acta Medica Scandinavica 701 (Suppl.): 38–52, 1985

    PubMed  Google Scholar 

  • Riesen WF, Sturzenegger E, Imhof C, Mordasini R. Quantitation of apolipoprotein E by polyclonal and monoclonal antibodies. Clinica Chimica Acta 154: 29–40, 1986

    Article  CAS  Google Scholar 

  • Sullivan PA, Kelleher M, Twomey M, Dieneen M. Effects of converting enzyme inhibition on blood pressure, plasma renin activity (PRA) and plasma aldosterone in hypertensive diabetics compared to patients with essential hypertension. Journal of Hypertension 3(Suppl. IV): 359–363, 1985

    Article  PubMed  CAS  Google Scholar 

  • Taguma Y, Kitamoto Y, Futaki G, Ueda H, Monma H, et al. Effect of capropril on heavy proetinuria in azotemic diabetics. New England Journal of Medicine 313: 1617–1620, 1985

    Article  PubMed  CAS  Google Scholar 

  • Trost BN, Weidmann P. Antihypertensive therapy in diabetic patients. Hypertension 7(Suppl. II): 102–108, 1985

    Google Scholar 

  • Trost BN, Weidmann P. Metabolic effects of calcium antagonists in humans, with emphasis on carbohydrate, lipid, potassium and uric acid homeostases. Journal of Cardiovascular Pharmacology 12(Suppl. 6): 86–92, 1988

    Article  Google Scholar 

  • Vardan S, Mehrotra KG, Mookherjee S, Willsey GA, Gens JD, et al. Efficacy and reduced metabolic side effects of a 15-mg chlorthalidone formulation in the treatment of mild hypertension. A multicenter study. Journal of the American Medical Association 258: 484–488, 1987

    Article  PubMed  CAS  Google Scholar 

  • Wada S, Nakayama M, Masaki K. Effects of diltiazem on serum lipids: comparison with beta-blockers. Clinical Therapeutics 5: 163–173, 1982

    PubMed  CAS  Google Scholar 

  • Warram JH, Laffel LMB, Valsania P, Christlieb R, Krolewsky AS. Excess mortality associated with diuretic therapy in diabetes mellitus. Archives of Internal Medicine 151: 1350–1356, 1991

    Article  PubMed  CAS  Google Scholar 

  • World Health Organization Multinational Study of Vascular Disease in Diabetes. Prevalence of small vessel and large vessel disease in diabetic patients from 14 centers. Diabetologia 28: 615–640, 1985

    Article  Google Scholar 

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Authors and Affiliations

  1. Medizinische Poliklinik, University of Berne, Berne, Switzerland

    Claudia Fevrier, Paolo Ferrari,  Peter Weidmann & Carlo Beretta-Piccoli

  2. Stoffwechsellabor, University of Basle, Basle, Switzerland

    Ulrich Keller

  3. Lipid Laboratory, University of Berne, Berne, Switzerland

    Walter F. Riesen

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  1. Claudia Fevrier
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  2. Paolo Ferrari
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  3. Peter Weidmann
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  4. Ulrich Keller
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  5. Carlo Beretta-Piccoli
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  6. Walter F. Riesen
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Fevrier, C., Ferrari, P., Weidmann, P. et al. Swiss Hypertension Treatment Programme with Verapamil and/or Enalapril in Diabetic Patients. Drugs 44 (Suppl 1), 74–84 (1992). https://doi.org/10.2165/00003495-199200441-00014

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  • DOI: https://doi.org/10.2165/00003495-199200441-00014

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