Cardiovascular Drugs and Therapy

, Volume 5, Issue 3, pp 561–576 | Cite as

The applied pharmacology of beta-adrenoceptor antagonists (beta blockers) in relation to clinical outcomes

  • J. D. Fitzgerald
Focused Subsection on New Developments in Beta-Blockade


Despite the fact that beta blockers were introduced into clinical practice 25 years ago, new beta blockers with differing kinetic and dynamic profiles continue to be developed and marketed. This overview assesses some of the more extensively studied agents from the point of view of proof of utility and the validity of claims for therapeutic advances. The clinical data suggests that despite the expectations of improvements based on kinetic and dynamic consideration, none of the newer agents have been shownunequivocally, either in terms of efficiency or tolerability, to be an advance over the reference agents, the beta1 antagonists atenolol and metroprolol. This may be either because such improvements will not occur or because of shortcomings in the design and duration of comparative studies. There are trends to suggest that celiprolol has lesser effects on bronchial function and that it has a lesser impact on lipoprotein profiles. Approaches are suggested that might enable clinicians to appraise for themselves the validity of claims for the improved efficiency of new beta blockers.

Key Words

beta blockade atenolol metoprolol celiprolol 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Cruickshank JM, Prichard BNC.Beta blockers in clinical practice. London: Churchill Livingstone, 1987.Google Scholar
  2. 2.
    Riddell DA, Schull LG, Frist TH, et al. Experiences with pheochromocytoma in 21 patients: Use of dichloroisoproterenol hydrochloride for cardiac arrhythmias.Ann Surg 1963;157:980–988.PubMedCrossRefGoogle Scholar
  3. 3.
    Black JW, Stephenson JS. Pharmacology of anew adrenergic beta receptor blocking compound (Nethalide).Lancet 1962;2:311–313.PubMedCrossRefGoogle Scholar
  4. 4.
    Ablad B, Brogard M, Ek L. Pharmacological properties of H56/28 beta adrenergic receptor antagonist.Acta Pharmacol Toxicol 1967;25 (Suppl. 2):9–40.Google Scholar
  5. 5.
    Dunlop D, Shanks RG. Selective blockade of adrenoceptive beta receptors in the heart.Br J Pharmacol Chemother 1968;32:201–218.PubMedGoogle Scholar
  6. 6.
    Fitzgerald JD. Perspectives in adrenergic beta receptor blockade.Clin Pharmacol Therap 1969;10:292–306.Google Scholar
  7. 7.
    Vaughan Williams EM. Mode of action of beta receptor antagonists on cardiac muscle.Am J Cardiol 1966;18: 399–405.CrossRefGoogle Scholar
  8. 8.
    Rahn KH, Hawlina A, Kersting F, et al. Studies on the antihypertensive action of the optical isomers of propranolol in man.Naunyn-Schmiedebergs Arch Pharmacol 1974;286:319–323.PubMedCrossRefGoogle Scholar
  9. 9.
    Wilson AG, Brooke OG, Lloyd HJ, et al. Mechanism of action of beta adrenergic receptor blocking agents in angina pectoris: Comparison of action of propranolol with dexpropranolol and practolol.Br Med J 1969;4:399–401.PubMedGoogle Scholar
  10. 10.
    Fitzgerald JD, O’Donnell SR. The antagonism by propranolol and alpha methyl propranolol (ICI 77602) of vascular and cardiac responses to isoprenaline in anaesthetised dogs.Clin Exp Pharmacol Physiol 1978;5:585.CrossRefGoogle Scholar
  11. 11.
    Reidenberg M. The quality of clinical research.Clin Pharmacol Ther 1990;47:664–670.Google Scholar
  12. 12.
    Fitzgerald JD. By what means might beta blockers prolong life after acute myocardial infarction?Eur Heart J 1987;8:945–951.PubMedGoogle Scholar
  13. 13.
    Opie LH. Qualities of an ideal beta adrenoceptor antagonist in comparison of existing agents with a new cardioselective hydrophyllic vasodilator beta adrenoceptor antagonist, celiprolol.Am J Cardiol 1988;61:8c-13c.PubMedCrossRefGoogle Scholar
  14. 14.
    Prichard BNC, Tomlinson B. The additional properties of beta adrenoceptor blocking drugs.J Cardiovasc Pharmacol 1986;8(Suppl. 4):s1-s15.CrossRefGoogle Scholar
  15. 15.
    Lemoine H, Ehle, B, Kaumann AJ. On the participation of B1 and B2 adrenoceptors in the relaxation of calf trachea caused by (−) noradrenaline, (−) adrenaline and (+) fenoterol.Naunyn-Schmiedebergs Arch Pharmacol 1985;329:R81.Google Scholar
  16. 16.
    McDevitt DG. The assessment of beta adrenoceptor blocking drugs in man.Eur J Clin Pharmacol 1977;4: 413–425.Google Scholar
  17. 17.
    Wellstein A, Palm D, Beltz GG, et al. Reduction of exercise tachycardia in man after propranolol, atenolol and bisoprolol in comparison to beta adrenoceptor occupancy.Eur Heart J 1987;8(Suppl. M):3–8.PubMedGoogle Scholar
  18. 18.
    Lammers JWJ, Folgering HTM, an Herwaarden CLA. Respiratory tolerance of bisoprolol and metoprolol in asthmatic subjects.J Cardiovasc Pharmacol 1986;8(Suppl. 11):69–73.Google Scholar
  19. 19.
    Chatterjee SS. The cardioselective and hypotensive effects of bisoprolol in hypertensive asthmatics.J Cardiovasc Pharmacol 1986;8(Suppl. 11):74–77.Google Scholar
  20. 20.
    Lithell J, Selinus I, Hosie J, et al. Efficacy and safety of bisoprolol and atenolol in patients with mild to moderate hypertension: A double-blind parallel group international multicentre study.Eur Heart J 1987;8(Suppl. M):55–64.PubMedGoogle Scholar
  21. 21.
    Maltz MB, Dymond DS, Nathan AW, et al. A comparison of once daily bisoprolol (5 or 10 mg.) and atenolol 100mg. in the treatment of angina pectoris.Eur Heart J 1987;8(Suppl. M):37–42.PubMedGoogle Scholar
  22. 22.
    Bilski AJ, Haliday SE, Fitzgerald JD, et al. The pharmacology of a selective adrenoceptor antagonist (ICI 118551).J Cardiovasc Pharmacol 1983;5:430–439.PubMedCrossRefGoogle Scholar
  23. 23.
    O’Donnell SR, Wanstall JC. Evidence that ICI 118551 is a potent, highly selective B2 adrenoceptor antagonist and can be used to characterize beta adrenoceptor populations in tissues.Life Sci 1980;27:671–677.PubMedCrossRefGoogle Scholar
  24. 24.
    Dahlof B, Andren L, Spensson A, et al. Anti-hypertensive mechanism of beta adrenoceptor antagonists: The role of beta-2-blockade.J Hypertens 1983;1(Suppl. 2):112–115.Google Scholar
  25. 25.
    Robb OJ, Petrie JC, Webster J, et al. ICI 118551 does not reduce blood pressure in hypertensive patients responsive to atenolol and propranolol.Br J Clin Pharmacol 1985;19:541p-542p.Google Scholar
  26. 26.
    Vincent HH, Man in’T Veld A. Boomsa F, et al. Is B1 antagonism essential for the antihypertensive action of beta blockers?Hypertension 1987;9:198–203.PubMedGoogle Scholar
  27. 27.
    Moran NC, Perkins ME. Adrenergic blockade of the mammalian heart by a dichloro analogue of isoproteronol.J Pharmacol 1958;125:223–237.Google Scholar
  28. 28.
    Black JW. The predictive value of animal tests in relation to drugs affecting the cardiovascular system in man. In: Wolstenholm G, Porter R, eds.Drug responses in man. London: J. & A. Churchill Ltd., 1967:113, 121–122.Google Scholar
  29. 29.
    Giudicelli JF, Schmitt H, Boissier JR. Studies on D,L-4-(2-hydroxy-3-isopropylamino propoxy)-indole (LB 46). A new potent beta adrenergic blocking drug.J Pharmacol Exp Ther 1969;168:116–126.PubMedGoogle Scholar
  30. 30.
    Shanks RG. Review of a review: Partial agonist activity of beta adrenoceptor blocking drugs.Eur Heart J 1981;2:253–255.PubMedGoogle Scholar
  31. 31.
    Reale A, Motolese M. Partial agonist activity of beta adrenergic blocking agent and cardiac performance: A review.Eur Heart J 1981;2:245–251.PubMedGoogle Scholar
  32. 32.
    Gibson DG. Pharmacodynamic properties of beta adrenergic blocking drugs in man.Drugs 1974;7:8–38.PubMedCrossRefGoogle Scholar
  33. 33.
    Weinberger NH. Potential benefit of combination therapy with diuretics and beta blockers having intrinsic sympathomimetic activity.Eur Heart J 1990;11:560–565.PubMedGoogle Scholar
  34. 34.
    Taylor SH. Intrinsic sympathomimetic activity: Clinical fact or fiction?Am J Cardiol 1983;52:16d-26d.PubMedCrossRefGoogle Scholar
  35. 35.
    Cruickshank JM. Measurement and cardiovascular relevance of partial agonism activity (PAA) involving B1 and B2 adrenoceptors.Pharmac Ther 1990;46:199–242.CrossRefGoogle Scholar
  36. 36.
    Waller DG. Beta adrenoceptor partial agonists: A renaissance in cardiovascular therapy?Br J Clin Pharmacol 1990;30:157–171.PubMedGoogle Scholar
  37. 37.
    Ariens EJ. Intrinsic activity: Partial agonists and partial antagonists.J Cardiovasc Pharmacol 1983;5:S8-S15.PubMedGoogle Scholar
  38. 38.
    Kaumann AJ, Blinks JR. Stimulant and depressant effects of beta adrenoceptor blocking agents on isolated heart muscle: A positive inotropic effect not mediated through adrenoceptors.Naunyn-Schmiedebergs Arch Pharmacol 1980;311:205–218.PubMedCrossRefGoogle Scholar
  39. 39.
    Kaumann AJ, Lobnig BM. Mode of action of (−)-pindolol on feline and human myocardium.Br J Pharmacol 1986;89:207–218.PubMedGoogle Scholar
  40. 40.
    Kaumann AJ, Blinks JR. Adrenoceptor blocking agents as partial agonists in isolated heart muscle. Dissociation between blockade and stimulation.Naunyn-Schmiedebergs Archiv Pharmacol 1980;311:237–248.CrossRefGoogle Scholar
  41. 41.
    Bilski A, Wale J. Two types of intrinsic sympathomimetic activity with beta adrenoceptor blocking drugs.Br J Pharmacol 1976;56:362p.Google Scholar
  42. 42.
    Man in’T Velt AJ, Van den Neiracker AH, Schalekamp MA. Do beta blockers really increase peripheral vascular resistance? Review of the literature and new observations under basal conditions.Am J Hypertens 1988;1:91–96.Google Scholar
  43. 43.
    Leonetti G, Sampieri L, Cuspidi C, et al. Does B1 selective agonist activity interfere with the anti-hypertensive efficacy of B1 selective blocking agents?J Hypertens 1985;3(Suppl. 3):S243-S245.CrossRefGoogle Scholar
  44. 44.
    Conway J. Beta adrenergic blockade and hypertension. In: Oliver MF,Cardiology, 3. London: Butterworth 1975: 376–403.Google Scholar
  45. 45.
    Krupp P, Fanchamps A. Pindolol: Experience gained in ten years of safety monitoring.Am Heart J 1982;104:486–490.PubMedCrossRefGoogle Scholar
  46. 46.
    Committee on Safety of Medicines. Current problems. 1990;28:1–2.Google Scholar
  47. 47.
    Warren DJ, McSorey P, Niak RB. Effects of beta adrenergic blocking drugs on peripheral blood flow (abstr.) VIII Congress of Cardiology, Tokyo 1978.Google Scholar
  48. 48.
    Marshall AJ, Roberts CJC, Barrit DW. Raynaud’s phenomenon as a side effect of beta blockers in hypertension.Br Med J 1976;1:1489–1499.Google Scholar
  49. 49.
    Ohlsson O, Lindell SE. Effects of pindolol and prazozin on hand blood flow in patients with cold extremities and on treatment with beta blockers.Acta Med Scand 1981;201:217–219.Google Scholar
  50. 50.
    Feleke E, Lyngstan O, Rastam L, et al. Complaints of cold extremities among patients on anti-hypertensive treatment.Acta Med Scand 1983;213:381–385.PubMedGoogle Scholar
  51. 51.
    Jerm S. The effects of epanolol on quality of life.Drugs 1989;38(Suppl. 2):71–74.Google Scholar
  52. 52.
    Materson BJ, Lucas CP, Valchakis ND, et al. Dilevalol compared with metoprolol for treatment of hypertension: A multi-centre trial. Delivalol—the beta blocking vasodilator. Satellite Symposium to the Third European Meeting on Hypertension. 1987, Milan, Italy, abstract 18–19.Google Scholar
  53. 53.
    Schoenberger J, Frishman W, Gorwit J, et al. Comparison of the side effect profile of dilevalol with propranolol.J Cardiovasc Pharmacol 1988;11(Suppl. 2):S39.CrossRefGoogle Scholar
  54. 54.
    Coffman JD, Rasmussen HN. Effects of beta adrenoceptor blocking drugs in patients with Raynaud’s phenomenon.Circulation 1985;72:466–470.PubMedGoogle Scholar
  55. 55.
    Greminger P, Vetter H. Boerlin HJ. A comparative study between 100 mg. atenolol and 20 mg. pindolol slow release in essential hypertension.Drugs 1983;25(Suppl. 2):37–41.Google Scholar
  56. 56.
    Louis WJ, McNeil JJ. Beta adrenoceptor blocking drugs: The relevance of intrinsic sympathomimetic activity.Br J Clin Pharmacol 1982;13(Suppl. 2):317S-320S.PubMedGoogle Scholar
  57. 57.
    Tattersfield AE. Beta adrenoceptor antagonists and respiratory disease.J Cardiovasc Pharmacol 1986;8(Suppl. 4):S35-S39.PubMedCrossRefGoogle Scholar
  58. 58.
    Ruffin RE, Crockett AJ, Alpers JH. The effect of bucindolol on the airway function of asthmatics.Eur J Clin Pharmacol 1986;30:559–565.PubMedCrossRefGoogle Scholar
  59. 59.
    Hoffman W, Hoffmann H. Results of the Austrian celiprolol post-marketing surveillance study.J Cardiovasc Pharmacol 1986;8(Suppl. 4):S88-S90.CrossRefGoogle Scholar
  60. 60.
    Northcote RJ, Todd IC, Ballantine D. Beta blockers and lipoproteins: A review of current knowledge.Scot Med J 1986;31:220–228.PubMedGoogle Scholar
  61. 61.
    van Brummelen P. The relevance of intrinsic sympathomimetic activity for beta blocker induced changes in plasma lipids.J Cardiovasc Pharmacol 1983;5(Suppl. 1): S51-S55.PubMedGoogle Scholar
  62. 62.
    Roberts WC. Recent studies on the effects of beta blockers on blood lipid levels.Am Heart J 1990;112:709–714.Google Scholar
  63. 63.
    Byington RP, Worthy J, Craven T, et al. Propranolol induced lipid changes and their prognostic significance after myocardial infarction: The beta blocker heart attack trial experience.Am J Cardiol 1990;65:1287–1291.PubMedCrossRefGoogle Scholar
  64. 64.
    Zacest R. Gilimore E, Koch-Weser J. The treatment of essential hypertension with combined vasodilation and beta adrenergic blockade.N Engl J Med 1972;286:617–622.PubMedGoogle Scholar
  65. 65.
    Pedersen OL, Christensen CK, Mikelsen E. Relationship between the anti-hypertensive effect and steady state plasma concentration of nifedipine given alone or in combination with a beta adrenoceptor blocking agent.Eur J Clin Pharmacol 1980;18:287–293.CrossRefGoogle Scholar
  66. 66.
    Baum T, Sybertz EJ. Anti-hypertensive properties of an isomer of labetalol and other vasodilator beta adrenoceptor blockers.Fed Proc 1983;42:176–181.PubMedGoogle Scholar
  67. 67.
    Lund Johnsen P. Haemodynamic effects of beta blocking compounds possessing vasodilating activity: A review of labetalol, prizidilol and delivalol.J Cardiovasc Pharmacol 1988;11(Suppl. 2):512–517.Google Scholar
  68. 68.
    Louis WJ, McNeil JJ. Labetalol. In: Doyle AE, ed.Handbook of hypertension, Vol. 5. Amsterdam: Elsevier, 1984:225–245.Google Scholar
  69. 69.
    Hashimoto H, Asano M, Hayashi T, et al. Haemodynamic effects of arotinolol in anesthetised dogs and its affinity for adrenoceptorsin vitro.Arch Int Pharmacodyn 1984;267:23–34.PubMedGoogle Scholar
  70. 70.
    Takenaka T. Amosulalol. In: Scriabine A, ed.Cardiovascular drugs. New York: Raven Press, 1987:117–134.Google Scholar
  71. 71.
    Nichols AJ, Sulpizio AC, Ashton DJ, et al.In vitro pharmacologic profile of the novel beta adrenoceptor antagonist and vasodilator, carvedilol.Pharmacology 1989;39:327–336.PubMedCrossRefGoogle Scholar
  72. 72.
    Abshagen U. A new molecule with vasodilating and beta adrenoceptor blocking properties.J Cardiovasc Pharmacol 1987;10(Suppl. 11):S23-S32.PubMedCrossRefGoogle Scholar
  73. 73.
    Pruss TP, Khandwala A, Wolf PS, et al. Celiprolol: A new beta adrenoceptor antagonist with novel ancillary properties.J Cardiovasc Pharmacol 1986;8(Suppl. 4):S29-S32.PubMedCrossRefGoogle Scholar
  74. 74.
    Gordon RJ, Wolf PS, Pruss TP, et al. Further studies in the bronchodilator properties of celiprolol HCL, a cardio-selective beta blocker.Pharmacologist 1983;25:121–124.Google Scholar
  75. 75.
    Shirasawa Y, Fugaii M, Nakamura M. Venodilating action of nipradilol (K-351) in pithed rats pre-treated with dihydroergotamine.Jpn J Pharmacol 1985;39:77–82.PubMedCrossRefGoogle Scholar
  76. 76.
    Uchida Y, Nakamura M, Tsuruta T, et al. Nipradilol. In: Scriabine A, ed.New cardiovascular drugs. New York: Raven Press, 1987:95–115.Google Scholar
  77. 77.
    Van de Water A, Xhonneux R, Reneman RS, et al. Cardiovascular effects of DL-nebivolol and its enantiomers—a comparison with those of atenolol.Eur J Pharmacol 1988;156:95–103.PubMedCrossRefGoogle Scholar
  78. 78.
    Van de Water A, Janssens W, Van Neuten J, et al. Pharmacological and hemodynamic profile of nebivolol, a chemically novel, potent and selective B1 adrenergic antagonist.J Cardiovasc Pharmacol 1988;11:552–563.PubMedGoogle Scholar
  79. 79.
    DeCre J, Geukens H, Franken P, et al. Non-invasive cardiac haemodynamics of nebivolol in men.Acta Antwerpiensia 1989;6:2–21.Google Scholar
  80. 80.
    Hunyor SN, Bauer GE, Ross M, et al. Labetalol and propranolol in mild hypertensives: Comparison of blood pressure and plasma volume effects.Aust NZ J Med 1980, 10:162–166.Google Scholar
  81. 81.
    Kubik MM, Coote JH. Propranolol versus metoprolol versus labetalol: A comparative study in essential hypertension.Eur J Clin Pharmacol 1984;26:1–6.PubMedCrossRefGoogle Scholar
  82. 82.
    Taylor S, Beattie A, Silke B. Celiprolol in the treatment of hypertension: A comparison with propranolol.J Cardiovasc Pharmacol 1986;8(Suppl. 4):127–131.CrossRefGoogle Scholar
  83. 83.
    Stumpe K, Kolloch R, Mathieu M, et al. A comparison of celiprolol and atenolol in the treatment of hypertension: A placebo controlled double-blind study.Br J Clin Pract 1985;39(Suppl. 40):73–75.Google Scholar
  84. 84.
    DeCesaris, Ranieri G, Chiarappa R, et al. Comparison of the anti-hypertensive efficacy of carvedilol, a new vasodilating beta blocker, versus atenolol. A double-blind study.Drugs 1988;36(Suppl. 6):102–105.Google Scholar
  85. 85.
    Riddell JG, Shanks RG, Brogden RM. Celiprolol: A preliminary review of its pharmacodynamic and pharmacokinetic properties and its therapeutic use in hypertension and angina pectoris.Drugs 1987;34:438–458.PubMedCrossRefGoogle Scholar
  86. 86.
    Winniford MD, Huxley RL, Hillus LD. Randomized, double-blind comparison of propranolol alone and a propranolol-verapamil combination in patients with severe angina.J Am Coll Cardiol 1983;1:492–498.PubMedCrossRefGoogle Scholar
  87. 87.
    Dorow P. General discussion. A symposium: Hypertension into the nineties.Am J Cardiol 1988;61:57C.CrossRefGoogle Scholar
  88. 88.
    Norris RJ. Anti-hypertensive therapy with celiprolol: A new cardioselective beta blocker.Am J Cardiol 1988;61:23C-26C.CrossRefGoogle Scholar
  89. 89.
    Schnurr E, Widmann L, Glocke M. Efficacy and safety of carvedilol in the treatment of hypertension.J Cardiovasc Pharmacol (Suppl. 11):S101-S107.Google Scholar
  90. 90.
    Bulpitt CJ, Fletcher AE. The measurement of quality of life in hypertensive patients: A practical approach.Br J Clin Pharmacol 1990;30:353–364.PubMedGoogle Scholar
  91. 91.
    Fletcher AE, Bulpitt CJ, Hawkins CM, et al. Quality of life on anti-hypertensive therapy: A randomized double-blind controlled trial of captopril and atenolol.J Hypertens 1990;8:463–466.PubMedCrossRefGoogle Scholar
  92. 92.
    Croog SH, Levine S, Testa N, et al. The effects of antihypertensive therapy on the quality of life.N Engl J Med 1986;314:1657–1664.PubMedGoogle Scholar
  93. 93.
    Himms-Hagen J. Sympathetic regulation of metabolism.Pharmacol Rev 1967;19:367–461.PubMedGoogle Scholar
  94. 94.
    Harms HH, Gooren L, Spoelstera A, et al. Blockade of isoprenaline induced changes in plasma free fatty acids, immuno-reactive insulin levels and plasma renin activity in healthy human subjects by propranolol, pindolol, practolol, atenolol, metoprolol and asabutanol.Br J Clin Pharmacol 1978;5:19–26.PubMedGoogle Scholar
  95. 95.
    Lauridsen UB, Christensen NJ, Lyngsoe J. Effects of nonselective and beta-1-selective blockade on glucose metabolism and hormone responses during insulin induced hypoglycaemia in normal man.J Clin Endocrinol Metab 1983;56:876–882.PubMedCrossRefGoogle Scholar
  96. 96.
    Kolendorf K, Aerenlund Jensen H, Holst JJ, et al. Effect of acute selective beta-1-adrenoceptor blockade on humeral and cardiovascular responses to insulin induced hypoglycaemia in insulin dependent diabetic patients.Scand J Clin Lab Invest 1982;42:69–74.PubMedGoogle Scholar
  97. 97.
    Fuh MM, Sheuw HH, Shen DC, et al. Metabolic effects of diuretic and beta blocker treatment of hypertension in patients with non-insulin-dependent diabetes mellitus.J Hypertens 1990;3:387–390.Google Scholar
  98. 98.
    Houston MC. Treatment of hypertension in diabetes mellitus.Am Heart J 1989;115:820–829.Google Scholar
  99. 99.
    Kjekshus J, Gilpin E, Cali G, et al. Diabetic patients and beta blockers after acute myocardial infarction.Eur Heart J 1990;11:43–50.PubMedGoogle Scholar
  100. 100.
    Hitzenberger G. Effects of beta adrenoceptor blocking agent celiprolol on blood lipids.Br J Clin Pract 1985;39(Suppl. 40):85–87.Google Scholar
  101. 101.
    Pristautz H, Stradner F, Wirkung von celiprolol und metoprolol auf die serumlipide bei patienten mit verschiedenen formen von hyperlipoproteinamie.Weiner Medizin Woch 1986;136:443–450.Google Scholar
  102. 102.
    Fogari R, Soppi A, Pazotti C, et al. Plasma lipids during chronic anti-hypertensive therapy with different beta blockers.J Cardwvasc Pharmacol 1989;14(Suppl. 7): S28-S32.Google Scholar
  103. 103.
    Houston MC. New insights and new approaches for the treatment of essential hypertension: Selection of therapy based on coronary disease risk factors, haemodynamic profiles, quality of life and sub-sets of hypertension.Am Heart J 1989;117:911–951.PubMedCrossRefGoogle Scholar
  104. 104.
    Hjalmarson A, Gilpin EA, Kjekshus J, et al. Influence of heart rate on mortality after acute myocardial infarction.Am J Cardiol 1990;65:547–553.PubMedCrossRefGoogle Scholar
  105. 105.
    MacMahon S. The effects of anti-hypertensive drug treatment on the incidence of stroke and of coronary heart disease.Clin Exp Hyper-Theory and Pract 1989;A11 (5,6):807–823.CrossRefGoogle Scholar

Copyright information

© Kluwer Academic Publishers 1991

Authors and Affiliations

  • J. D. Fitzgerald
    • 1
  1. 1.Materia Medica, Mere CroftCheshireUK

Personalised recommendations