Summary
A double-blind, parallel-group multicentre study has been done to compare the antihypertensive properties, effects on serum lipoproteins and adverse effect profiles of diltiazem and metoprolol given as monotherapy to primary hypertensive patients. 128 patients were included from 10 participating centers.
Following a placebo wash-out period of 5 weeks, patients were randomized either to diltiazem or metoprolol treatment according to a forced titration regimen. Each dose was given for a 4-week period in a stepwise regimen. A total of 119 patients, 59 and 60 in the two groups, completed the study.
Supine and standing BPs were reduced in a similar, dose-dependent fashion by diltiazem and metoprolol. In the former supine BP fell from 161/101 to 151/91 mm Hg at the highest dose level. In the latter patients, supine BP at the highest dose level was reduced from 161/102 to 155/94 mm Hg. Target pressures (DBP ≤ 90 mm Hg and/or DBP reduction of ≥ 10%) were reached in 63% and 48% of the patients, respectively.
HDL-cholesterol was increased in diltiazem-treated patients and decreased in those on metoprolol. Otherwise, serum lipoproteins did not differ significantly between treatments.
The incidence and severity of dose-dependent adverse effects did not differ significantly between treatments, although moderate to distressing side effects were reported more commonly by metoprolol-treated patients. Ankle oedema and breathlessness tended to be more common on diltiazem therapy, while tiredness, increased sweating and sleep disturbances appeared to be experienced more frequently by metoprolol-treated patients.
Thus, when given as monotherapy, the daily dose-ranges for a comperable reduction in BP were 120–360 mg diltiazem and 50–200 mg metoprolol. Within those dose-ranges, the antihypertensive efficacy and the overall incidence of adverse effects did not differ between the treatments. As monotherapies, diltiazem and metoprolol are both suitable for the management of mild to moderate hypertension.
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References
Godfraind T, Miller R, Wibo M (1986) Calcium antagonism and calcium entry blockade. Pharmacol Rev 38: 321–416
Kiowski W, Bolli P, Erne P, Hulthén UL, Müller FB, Bühler FR (1988) Hemodynamic and counterregulatory effects of calcium antagonists in hypertension. J Cardiovasc Pharmacol 12 [Suppl 6]: 539–543
Leonetti G, Rupoli L, Gradnik R, Zanchetti A (1987) Effects of a low sodium diet on antihypertensive and natriuretic responses to actue administration of nifedipine. J Hypertension 5 [Suppl 4]: S57-S60
Loutzenhiser RD, Epstein M (1988) Renal hemodynamic effects of calcium antagonists. J Cardiovasc Pharmacol 12 [Suppl 6]: S48-S52
Scriabine A (1987) Comparative pharmacology of 1.4 dihydropyridines and other Ca++ channel ligands. J Cardiovasc Pharmacol 9 [Suppl 1]: S3-S7
Chaffman M, Brogden RN (1985) Diltiazem a review of its pharmacological properties and therapeutic efficacy. Drugs 29: 387–454
Beaufield P, Clissold SP, Brogden RN (1986) Metoprolol. An updated review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy in hypertension, ischaemic heart disease and related cardiovascular disorders. Drugs 31: 376–429
Wikstrand J, Warnold I, Olsson G, Tuomilehto J, Elmfeldt D, Berglund G (1988) Primary prevention with metoprolol in patients with hypertension: mortality results from the MAPHY study. JAMA 259: 1976–1982
The 1988 Joint National Committée (1988) The 1988 report of the Joint National Committée on detection, evaluation and treatment of high blood pressure. Arch Intern Med 148: 1023–1038
Freestone S, Silas JH, Ramsay LE (1982) Sample size for short-term trials of antihypertensive drugs. Br J Clin Pharmacol 14 (2): 265–268
Altman DG (1980) Statistics and ethics in medical research. III How large a sample? Br Med J 281: 1336–1338
Danielsson B, Ekman R, Fex G, Johansson BG, Kristensson H, Nilsson-Ehle P, Wadstein J (1978) Changes in plasma high density lipoproteins in chronic male alcoholics during and after abuse. Scand J Clin Lab Invest 38: 113–119
Friedewald WT, Levy RI, Fredrickson DS (1972) Estimation of the concentration of LDL cholesterol in plasma without use of the preprative ultracentrifuge. Clin Chem 18: 499–502
Kiowski W, Bühler FR, Fadayomi MO, Erne P, Müller FB, Hulthén UL, Bolli P (1985) Age, race, blood pressure and renin: Predictors for antihypertensive treatment with calicum antagonists. Am J Cardiol 56: 81H-85H
Trimarco B, DeLuca N, Ricciardelli B, Volpe M, Veniero A, Cuocolo A, Cicala M (1984) Diltiazem in the treatment of mild to moderate essential hypertension: comparison with metoprolol in a cross-over double-blind trial. J Clin Pharmacol 24: 218–227
Weir MR, Josselson J, Giard MI, Warren JB, Posner JN, Lam YWF, Zaske DE, Saunders E (1987) Sustained-release diltiazem compared with atenolol monotherapy for mild to moderate systemic hypertension. Am J Cardiol 60: 361–411
Myburgh DP, Gordon NF (1987) Comparison of diltiazem and atenolol in young physically active men with essential hypertension. Am J Cardiol 60: 1092–1095
Pollare T, Lithell H, Ljunghall S, Mörlin C, Präntare H, Hvarfner A (1989) Metabolic effects of diltiazem and atenolol: Results from a randomzied, double-blind study with parallel groups. J Hypertension 7: 551–559
Luurila OJ, Gröhn P, Heikkilä J, Hämäläinen L, Härkönen R, Idänpään-Heikkulä U, Kohvakka A, Rytkönen U, Setälä M, Sundberg S (1987) Exercise capacity and hemodynamics in persons aged 20 to 50 years with systemic hypertension treated with diltiazem and atenolol. Am J Cardiol 60: 832–835
Massie B, MacCarthy EP, Ramanathan KB, Weiss RJ, Anderson M, Eidelson BA, Labreche DG, Tubau JF, Ulep D, Bartels D (1987) Diltiazem and propranolol in mild to moderate essential hypertension as monotherapy or with hydrochlorothiazide. Ann Intern Med 107: 150–157
Szlachcic J, Hirsch AT, Tubau JF, Vollmer C, Henderson S, Massie BM (1987) Diltiazem versus propranolol in essential hypertension: responses of rest and exercise blood pressure and effects on exercise capacity. Am J Cardiol 59: 393–399
Kawanishi DT, Leman RB, Pratt CM, O'Rourke RA (1987) Efficacy and safety of sustained-release diltiazem as replacement therapy for beta blockers and diuretics for stable angina pectoris and coexisting essential hypertension: a multicenter trial. Am J Cardiol 60: 29I-35I
Yamakado T, Oonishi N, Kondo S, Noziri A, Nakano T, Takezawa H (1983) Effects of diltiazem on cardiovascular responses during exercise in systemic hypertension and comparison with propranolol. Am J Cardiol 52: 1023–1027
Pool PE, Seagren SC, Salel AF (1985) Effects of diltiazem on serum lipid, exercise performance and blood pressure: randomized, double-blind placebo-controlled evaluation for systemic hypertension. Am J Cardiol 56: 86H-91H
Schulte K-L, Meyer-Sabellek WA, Haerttenberger A, Thiede H-M, Roecker L, Distler A, Gotzen R (1986) Antihypertensive and metabolic effects of diltiazem and nifedipine. Hypertension 8: 859–865
Schulte K-L, Meyer-Sabellek WA, Röcker L, Gotzen R, Distler A (1987) Effects of diltiazem alone and combined with mefruside on cardiovascular response at rest and during exercise, carbohydrate metabolism and serum lipoproteins in patients with systemic hypertension. Am J Cardiol 60: 826–831
Leren P (1984) Effect of alpha- and beta-blocker therapy on blood lipids: European experience. Am J Med 76 (2A): 67–71
Ames RP (1986) The effects of antihypertensive drugs on serum lipids and lipoproteins. II Non-diuretic drugs. Drugs 32: 335–357
Castelli WP (1984) Epidemiology of coronary heart disease: the Framingham study. Am J Med 76 (2A): 4–12
Weinberger MH (1986) Antihypertensive therapy and lipids. Pradoxical influences on cardiovascular disease risk. Am J Med 80 [Suppl 2A]: 64–70
Hedner T (1986) Calcium channel blockers: Spectrum of side effects and drug interactions. Acta Pharmacol Toxicol 58 [Suppl II]: 119–130
Trost BN, Weidmann P (1987) Effects of calcium antagonists on glucose homeostasis and serum lipids in non-diabetic and diabetic subjects. A review. J Hypertens 5 [Suppl 4]: S81-S104
Andrén L, Höglund P, Dotevall A, Eggertsen R, Svensson A, Olsson S-O, Wadenvik H (1988) Diltiazem in hypertensive patients with type II diabetes mellitus. Am J Cardiol 62: 114G-120G
Szlachcic J, Tubau J, Massie BM (1988) Diltiazem reduces left ventricular mass but does not change diastolic filling in mild hypertension. J Am Coll Cardiol 11: 82A
Weiss RJ, Bent R (1987) Diltiazem-induced left ventricular mass regression in hypertensive patients. J Clin Hypertension 3: 135–143
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For the Swedish Diltiazem-Metoprolol Multicentre Study Group
The Swedish Diltiazem-Metoprolol Multicentre Study Group: Thomas Hedner MD PhD, Jan Hedner MD PhD, Bengt Persson MD PhD (Gothenburg); Thomas Thulin MD PhD, Gunnar Persson MD PhD (Lund); Torbjörn Lundström MD (Skövde); Nels Henningsen MD PhD (Malmö); Erik Trell MD PhD, Sven Gustafsson MD (Sunne); Mats Danielson MD PhD (Stockholm); Peter Engfeldt MD PhD, Hans Wahrenberg MD PhD (Huddinge); Bo Hedbäck MD PhD (Oskarshamn); Anders Nilsson MD, Per Katzman MD PhD (Helsingborg); Lennart Andrén MD PhD, Karin Rennblad-Börner MD, Trausti Valdimarsson MD, Inger Wallin MD (Gothenburg); Peter Nilsson-Ehle MD PhD, Ulf Thilén MD, Göran Berglund MD PhD (Lund-Malmö); Carl Dahlöf MD PhD (Gothenburg)
Monitors: Sven-Olle Olsson PhD, Jan Johansson, Eje Berglund, Bo Dahlström (Malmö)
Statisticians: Jerker Ringström BSc, Liz Jergle BSc (Malmö)
Secretaries: Cristina Mardell, Ann-Christine Svensson, Majliz Olsson (Malmö)
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Hedner, T., Thulin, T., Gustafsson, S. et al. A comparison of diltiazem and metoprolol in hypertension. Eur J Clin Pharmacol 39, 427–433 (1990). https://doi.org/10.1007/BF00280931
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DOI: https://doi.org/10.1007/BF00280931