Skip to main content
NCBI home page
British Heart Journal logoLink to British Heart Journal
. 1985 Sep;54(3):305–312. doi: 10.1136/hrt.54.3.305

Effects of enalapril in heart failure: a double blind study of effects on exercise performance, renal function, hormones, and metabolic state.

J G Cleland, H J Dargie, S G Ball, G Gillen, G P Hodsman, J J Morton, B W East, I Robertson, I Ford, J I Robertson
PMCID: PMC481900  PMID: 2994698

Abstract

Several studies have shown symptomatic and haemodynamic improvement after the introduction of angiotensin converting enzyme inhibitors in patients with heart failure treated with diuretics. The concomitant long term effects of the new orally effective long acting angiotensin converting enzyme inhibitor, enalapril, on symptoms, exercise performance, cardiac function, arrhythmias, hormones, electrolytes, body composition, and renal function have been further assessed in a placebo controlled double blind cross over trial with treatment periods of eight weeks. Twenty patients with New York Heart Association functional class II to IV heart failure who were clinically stable on digoxin and diuretic therapy were studied. Apart from the introduction of enalapril, regular treatment was not changed over the study period; no order or period effects were noted. Enalapril treatment significantly improved functional class, symptom score for breathlessness, and exercise tolerance. Systolic blood pressure was significantly lower on enalapril treatment. Echocardiographic assessment indicated a reduction in left ventricular dimensions and an improvement in systolic time intervals. In response to enalapril, the plasma concentration of angiotensin II was reduced and that of active renin rose; plasma concentrations of aldosterone, vasopressin, and noradrenaline fell. There were significant increases in serum potassium and serum magnesium on enalapril. Glomerular filtration rate measured both by isotopic techniques and by creatinine clearance declined on enalapril while serum urea and creatinine rose and effective renal plasma flow increased. Body weight and total body sodium were unchanged indicating that there was no overall diuresis. There was a statistically insignificant rise in total body potassium, though the increase was related directly to pretreatment plasma renin (r = 0.5). On enalapril the improvement in symptoms, exercise performance, fall in plasma noradrenaline, and rise in serum potassium coincided with a decline in the frequency of ventricular extrasystoles recorded during ambulatory monitoring. Adverse effects were few. In patients with heart failure, enalapril had a beneficial effect on symptoms and functional capacity. The decline in glomerular filtration rate on enalapril may not be beneficial in early heart failure.

Full text

PDF
305

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Ader R., Chatterjee K., Ports T., Brundage B., Hiramatsu B., Parmley W. Immediate and sustained hemodynamic and clinical improvement in chronic heart failure by an oral angiotensin-converting enzyme inhibitor. Circulation. 1980 May;61(5):931–937. doi: 10.1161/01.cir.61.5.931. [DOI] [PubMed] [Google Scholar]
  2. Arnold S. B., Byrd R. C., Meister W., Melmon K., Cheitlin M. D., Bristow J. D., Parmley W. W., Chatterjee K. Long-term digitalis therapy improves left ventricular function in heart failure. N Engl J Med. 1980 Dec 18;303(25):1443–1448. doi: 10.1056/NEJM198012183032503. [DOI] [PubMed] [Google Scholar]
  3. Aronow W. S., Lurie M., Turbow M., Whittaker K., Van Camp S., Hughes D. Effect of prazosin vs placebo on chronic left ventricular heart failure. Circulation. 1979 Feb;59(2):344–350. doi: 10.1161/01.cir.59.2.344. [DOI] [PubMed] [Google Scholar]
  4. Atkinson A. B., Morton J. J., Brown J. J., Davies D. L., Fraser R., Kelly P., Leckie B., Lever A. F., Robertson J. I. Captopril in clinical hypertension. Changes in components of renin-angiotensin system and in body composition in relation to fall in blood pressure with a note on measurement of angiotensin II during converting enzyme inhibition. Br Heart J. 1980 Sep;44(3):290–296. doi: 10.1136/hrt.44.3.290. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Atkinson A. B., Robertson J. I. Captopril in the treatment of clinical hypertension and cardiac failure. Lancet. 1979 Oct 20;2(8147):836–839. doi: 10.1016/s0140-6736(79)92186-x. [DOI] [PubMed] [Google Scholar]
  6. Ball S. G., Tree M., Morton J. J., Inglis G. C., Fraser R. Circulating dopamine: its effect on the plasma concentrations of catecholamines, renin, angiotensin, aldosterone and vasopressin in the conscious dog. Clin Sci (Lond) 1981 Oct;61(4):417–422. doi: 10.1042/cs0610417. [DOI] [PubMed] [Google Scholar]
  7. Biollaz J., Brunner H. R., Gavras I., Waeber B., Gavras H. Antihypertensive therapy with MK 421: angiotensin II--renin relationships to evaluate efficacy of converting enzyme blockade. J Cardiovasc Pharmacol. 1982 Nov-Dec;4(6):966–972. [PubMed] [Google Scholar]
  8. Boddy K., Brown J. J., Davies D. L., Elliott A., Harvey I., Haywood J. K., Holloway I., Lever A. F., Robertson J. I., Williams E. D. Concurrent estimation of total body and exchangeable body sodium in hypertension. Clin Sci Mol Med. 1978 Feb;54(2):187–191. doi: 10.1042/cs0540187. [DOI] [PubMed] [Google Scholar]
  9. Boddy K., King P. C., Hume R., Weyers E. The relation of total body potassium to height, weight, and age in normal adults. J Clin Pathol. 1972 Jun;25(6):512–517. doi: 10.1136/jcp.25.6.512. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Bravo E. L. Regulation of aldosterone secretion: current concepts and newer aspects. Adv Nephrol Necker Hosp. 1977;7:105–120. [PubMed] [Google Scholar]
  11. Britton K. E. Essential hypertension: a disorder of cortical nephron control. Lancet. 1981 Oct 24;2(8252):900–902. doi: 10.1016/s0140-6736(81)91393-3. [DOI] [PubMed] [Google Scholar]
  12. Brown J. J., Davies D. L., Johnson V. W., Lever A. F., Robertson J. I. Renin relationships in congestive cardiac failure, treated and untreated. Am Heart J. 1970 Sep;80(3):329–342. doi: 10.1016/0002-8703(70)90098-0. [DOI] [PubMed] [Google Scholar]
  13. Campbell B. C., Sturani A., Reid J. L. Evidence of parasympathetic activity of the angiotensin converting enzyme inhibitor, captopril, in normotensive man. Clin Sci (Lond) 1985 Jan;68(1):49–56. doi: 10.1042/cs0680049. [DOI] [PubMed] [Google Scholar]
  14. Cannon P. J. The kidney in heart failure. N Engl J Med. 1977 Jan 6;296(1):26–32. doi: 10.1056/NEJM197701062960108. [DOI] [PubMed] [Google Scholar]
  15. Chantler C., Garnett E. S., Parsons V., Veall N. Glomerular filtration rate measurement in man by the single injection methods using 51Cr-EDTA. Clin Sci. 1969 Aug;37(1):169–180. [PubMed] [Google Scholar]
  16. Cleland J. G., Dargie H. J., Hodsman G. P., Ball S. G., Robertson J. I., Morton J. J., East B. W., Robertson I., Murray G. D., Gillen G. Captopril in heart failure. A double blind controlled trial. Br Heart J. 1984 Nov;52(5):530–535. doi: 10.1136/hrt.52.5.530. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Cleland J., Semple P., Hodsman P., Ball S., Ford I., Dargie H. Angiotensin II levels, hemodynamics, and sympathoadrenal function after low-dose captopril in heart failure. Am J Med. 1984 Nov;77(5):880–886. doi: 10.1016/0002-9343(84)90530-8. [DOI] [PubMed] [Google Scholar]
  18. Cody R. J., Covit A. B., Schaer G. L., Laragh J. H. Evaluation of a long-acting converting enzyme inhibitor (enalapril) for the treatment of chronic congestive heart failure. J Am Coll Cardiol. 1983 Apr;1(4):1154–1159. doi: 10.1016/s0735-1097(83)80119-3. [DOI] [PubMed] [Google Scholar]
  19. Colucci W. S., Wynne J., Holman B. L., Braunwald E. Long-term therapy of heart failure with prazosin: a randomized double blind trial. Am J Cardiol. 1980 Feb;45(2):337–344. doi: 10.1016/0002-9149(80)90656-6. [DOI] [PubMed] [Google Scholar]
  20. Davidson C., Gibson D. Clinical significance of positive inotropic action of digoxin in patients with left ventricular disease. Br Heart J. 1973 Sep;35(9):970–976. doi: 10.1136/hrt.35.9.970. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. DiCarlo L., Chatterjee K., Parmley W. W., Swedberg K., Atherton B., Curran D., Cucci M. Enalapril: a new angiotensin-converting enzyme inhibitor in chronic heart failure: acute and chronic hemodynamic evaluations. J Am Coll Cardiol. 1983 Nov;2(5):865–871. doi: 10.1016/s0735-1097(83)80233-2. [DOI] [PubMed] [Google Scholar]
  22. Dyckner T., Wester P. O. Ventricular extrasystoles and intracellular electrolytes in hypokalemic patients before and after correction of the hypokalemia. Acta Med Scand. 1978;204(5):375–379. doi: 10.1111/j.0954-6820.1978.tb08458.x. [DOI] [PubMed] [Google Scholar]
  23. Ellis K. J., Vaswani A., Zanzi I., Cohn S. H. Total body sodium and chlorine in normal adults. Metabolism. 1976 Jun;25(6):645–654. doi: 10.1016/0026-0495(76)90061-5. [DOI] [PubMed] [Google Scholar]
  24. Franciosa J. A., Weber K. T., Levine T. B., Kinasewitz G. T., Janicki J. S., West J., Henis M. M., Cohn J. N. Hydralazine in the long-term treatment of chronic heart failure: lack of difference from placebo. Am Heart J. 1982 Sep;104(3):587–594. doi: 10.1016/0002-8703(82)90231-9. [DOI] [PubMed] [Google Scholar]
  25. Franciosa J. A., Wilen M. M., Jordan R. A. Effects of enalapril, a new angiotensin-converting enzyme inhibitor, in a controlled trial in heart failure. J Am Coll Cardiol. 1985 Jan;5(1):101–107. doi: 10.1016/s0735-1097(85)80090-5. [DOI] [PubMed] [Google Scholar]
  26. Franciosa J. A., Wilen M., Ziesche S., Cohn J. N. Survival in men with severe chronic left ventricular failure due to either coronary heart disease or idiopathic dilated cardiomyopathy. Am J Cardiol. 1983 Mar 1;51(5):831–836. doi: 10.1016/s0002-9149(83)80141-6. [DOI] [PubMed] [Google Scholar]
  27. Fraser R., Guest S., Young J. A comparison of double-isotope derivative and radioimmunological estimation of plasma aldosterone concentration in man. Clin Sci Mol Med. 1973 Sep;45(3):411–415. doi: 10.1042/cs0450411. [DOI] [PubMed] [Google Scholar]
  28. Glänzer K., Prüssing B., Düsing R., Kramer H. J. Hemodynamic and hormonal responses to 8-arginine-vasopressin in healthy man: effects of indomethacin. Klin Wochenschr. 1982 Oct 1;60(19):1234–1239. doi: 10.1007/BF01716729. [DOI] [PubMed] [Google Scholar]
  29. Hall J. E., Guyton A. C., Jackson T. E., Coleman T. G., Lohmeier T. E., Trippodo N. C. Control of glomerular filtration rate by renin-angiotensin system. Am J Physiol. 1977 Nov;233(5):F366–F372. doi: 10.1152/ajprenal.1977.233.5.F366. [DOI] [PubMed] [Google Scholar]
  30. Hodsman G. P., Isles C. G., Murray G. D., Usherwood T. P., Webb D. J., Robertson J. I. Factors related to first dose hypotensive effect of captopril: prediction and treatment. Br Med J (Clin Res Ed) 1983 Mar 12;286(6368):832–834. doi: 10.1136/bmj.286.6368.832. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Holland O. B., Nixon J. V., Kuhnert L. Diuretic-induced ventricular ectopic activity. Am J Med. 1981 Apr;70(4):762–768. doi: 10.1016/0002-9343(81)90530-1. [DOI] [PubMed] [Google Scholar]
  32. Holmes J., Kubo S. H., Cody R. J., Kligfield P. Arrhythmias in ischemic and nonischemic dilated cardiomyopathy: prediction of mortality by ambulatory electrocardiography. Am J Cardiol. 1985 Jan 1;55(1):146–151. doi: 10.1016/0002-9149(85)90317-0. [DOI] [PubMed] [Google Scholar]
  33. Kramer B. L., Massie B. M., Topic N. Controlled trial of captopril in chronic heart failure: a rest and exercise hemodynamic study. Circulation. 1983 Apr;67(4):807–816. doi: 10.1161/01.cir.67.4.807. [DOI] [PubMed] [Google Scholar]
  34. Miller R. R., Awan N. A., Maxwell K. S., Mason D. T. Sustained reduction of cardiac impedance and preload in congestive heart failure with the antihypertensive vasodilator prazosin. N Engl J Med. 1977 Aug 11;297(6):303–307. doi: 10.1056/NEJM197708112970604. [DOI] [PubMed] [Google Scholar]
  35. Mujais S. K., Fouad F. M., Textor S. C., Tarazi R. C., Bravo E. L., Hart N., Gifford R. W., Jr Transient renal dysfunction during initial inhibition of converting enzyme in congestive heart failure. Br Heart J. 1984 Jul;52(1):63–71. doi: 10.1136/hrt.52.1.63. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Myers B. D., Deen W. M., Brenner B. M. Effects of norepinephrine and angiotensin II on the determinants of glomerular ultrafiltration and proximal tubule fluid reabsorption in the rat. Circ Res. 1975 Jul;37(1):101–110. doi: 10.1161/01.res.37.1.101. [DOI] [PubMed] [Google Scholar]
  37. Nicholls M. G., Ikram H., Espiner E. A., Maslowski A. H., Scandrett M. S., Penman T. Hemodynamic and hormonal responses during captopril therapy for heart failure: acute, chronic and withdrawal studies. Am J Cardiol. 1982 Apr 21;49(6):1497–1501. doi: 10.1016/0002-9149(82)90367-8. [DOI] [PubMed] [Google Scholar]
  38. Padfield P. L., Morton J. J. Effects of angiotensin II on arginine-vasopressin in physiological and pathological situations in man. J Endocrinol. 1977 Aug;74(2):251–259. doi: 10.1677/joe.0.0740251. [DOI] [PubMed] [Google Scholar]
  39. Sahn D. J., DeMaria A., Kisslo J., Weyman A. Recommendations regarding quantitation in M-mode echocardiography: results of a survey of echocardiographic measurements. Circulation. 1978 Dec;58(6):1072–1083. doi: 10.1161/01.cir.58.6.1072. [DOI] [PubMed] [Google Scholar]
  40. Sharpe D. N., Murphy J., Coxon R., Hannan S. F. Enalapril in patients with chronic heart failure: a placebo-controlled, randomized, double-blind study. Circulation. 1984 Aug;70(2):271–278. doi: 10.1161/01.cir.70.2.271. [DOI] [PubMed] [Google Scholar]
  41. Spodick D. H., Doi Y. L., Bishop R. L., Hashimoto T. Systolic time intervals reconsidered. Reevaluation of the preejection period: absence of relation to heart rate. Am J Cardiol. 1984 Jun 1;53(11):1667–1670. doi: 10.1016/0002-9149(84)90599-x. [DOI] [PubMed] [Google Scholar]
  42. Staessen J., Lijnen P., Fagard R., Verschueren L. J., Amery A. Rise in plasma concentration of aldosterone during long-term angiotensin II suppression. J Endocrinol. 1981 Dec;91(3):457–465. doi: 10.1677/joe.0.0910457. [DOI] [PubMed] [Google Scholar]
  43. Tauxe W. N., Maher F. T., Taylor W. F. Effective renal plasma flow: estimation from theoretical volumes of distribution of intravenously injected 131-I orthoiodohippurate. Mayo Clin Proc. 1971 Aug;46(8):524–531. [PubMed] [Google Scholar]
  44. Unverferth D. V., Magorien R. D., Moeschberger M. L., Baker P. B., Fetters J. K., Leier C. V. Factors influencing the one-year mortality of dilated cardiomyopathy. Am J Cardiol. 1984 Jul 1;54(1):147–152. doi: 10.1016/0002-9149(84)90320-5. [DOI] [PubMed] [Google Scholar]
  45. Walsh W. F., Greenberg B. H. Results of long-term vasodilator therapy in patients with refractory congestive heart failure. Circulation. 1981 Sep;64(3):499–505. doi: 10.1161/01.cir.64.3.499. [DOI] [PubMed] [Google Scholar]
  46. Wenting G. J., Man in't veld A. J., Woittiez A. J., Boomsma F., Laird-Meeter K., Simoons M. L., Hugenholtz P. G., Schalekamp M. A. Effects of captopril in acute and chronic heart failure. Correlations with plasma levels of noradrenaline, renin, and aldosterone. Br Heart J. 1983 Jan;49(1):65–76. doi: 10.1136/hrt.49.1.65. [DOI] [PMC free article] [PubMed] [Google Scholar]
  47. Williams E. D., Boddy K., Harvey I., Haywood J. K. Calibration and evaluation of a system of total body in vivo activation analysis using 14 MeV neutrons. Phys Med Biol. 1978 May;23(3):405–415. doi: 10.1088/0031-9155/23/3/004. [DOI] [PubMed] [Google Scholar]
  48. Zimmerman B. G. Adrenergic facilitation by angiotensin: does it serve a physiological function? Clin Sci (Lond) 1981 Apr;60(4):343–348. doi: 10.1042/cs0600343. [DOI] [PubMed] [Google Scholar]

Articles from British Heart Journal are provided here courtesy of BMJ Publishing Group

RESOURCES