Clinical features and contemporary management of patients with low and preserved ejection fraction heart failure: baseline characteristics of patients in the Candesartan in Heart failure--Assessment of Reduction in Mortality and morbidity (CHARM) programme

doi:10.1016/S1388-9842(03)00052-7

European Journal of Heart Failure 2003 5(3):261-270; doi:10.1016/S1388-9842(03)00052-7

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Clinical features and contemporary management of patients with low and preserved ejection fraction heart failure: baseline characteristics of patients in the Candesartan in Heart failure—Assessment of Reduction in Mortality and morbidity (CHARM) programme

J. McMurray^a^,*, J. Östergren^b, M. Pfeffer^c, K. Swedberg^d, C. Granger^e, S. Yusuf^f, P. Held^g, E. Michelson^h, B. Olofsson^g and On behalf of the CHARM committees and investigators

^a Department of Cardiology, Western Infirmary, University of Glasgow Glasgow G11 6NT, Scotland, UK
^b Karolinska Hospital Stockholm, Sweden
^c Brigham and Women's Hospital Boston, MA, USA
^d Department of Medicine, Sahlgrenska University Hospital/Östra Goteborg, Sweden
^e Duke University Medical Center Durham, NC, USA
^f HGM-McMaster Clinic Hamilton, Ont., Canada
^g AstraZeneca, R&D, Moindal Sweden
^h AstraZeneca LP Wayne, PA, USA

^* Corresponding author. Tel.: +44-141-211-1838; fax: +44-141-211-2252. E-mail address: j.mcmurray{at}bio.gla.ac.uk

Abstract

Aims: To describe the clinical characteristics and contemporary treatmentof a broad spectrum of patients with chronic heart failure (CHF)randomised in the Candesartan in Heart failure—Assessmentof Reduction in Mortality and morbidity (CHARM) programme, consistingof three component studies comparing placebo to candesartan.

Methods and results: CHARM Alternative, CHARM Added and CHARM Preserved enrolled2028 low left ventricular ejection fraction (LVEF) ACE inhibitorintolerant patients, 2548 low LVEF ACE inhibitor treated patientsand 3025 preserved LVEF patients, respectively. Patients inCHARM Preserved were more often female. The proportion of womenin CHARM Preserved was 40% compared to 32% in CHARM Alternativeand 21% in CHARM Added. Patients in CHARM Preserved were alsomore often hypertensive than in the other two trials (64% vs.50% and 48%, respectively). Symptoms and signs (with the exceptionof a third heart sound) were similar in all three patient groups.Beta-blockers were used in over half of patients in all threegroups. Digoxin and spironolactone were used less frequentlyand calcium antagonists more frequently in CHARM Preserved.Spironolactone was used most frequently in CHARM Alternative,i.e. in ACE inhibitor intolerant patients.

Conclusions: The CHARM Programme provides the largest and most detailed comparisonto date of patients low- and preserved-LVEF CHF. It also describesthe causes of ACE-inhibitor intolerance in a large cohort ofpatients and the other treatment which these patients receive.

Key Words: Chronic heart failure • Beta-blockers • Spironolactone • Angiotensin II receptor antagonists • Ejection fraction • Diastolic dysfunction

Received December 6, 2002; Revised March 19, 2003; Accepted March 27, 2003

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				R.A.P. Weir, J. J.V. McMurray, M. Puu, S. D. Solomon, B. Olofsson, C. B. Granger, S. Yusuf, E. L. Michelson, K. Swedberg, M. A. Pfeffer, et al. Efficacy and tolerability of adding an angiotensin receptor blocker in patients with heart failure already receiving an angiotensin-converting inhibitor plus aldosterone antagonist, with or without a beta blocker. Findings from the Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity (CHARM)-Added trial Eur J Heart Fail, February 1, 2008; 10(2): 157 - 163. [Abstract] [Full Text] [PDF]

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				K. O. Akosah, A. M. Schaper, L. M. Haus, M. A. Mathiason, S. I. Barnhart, and V. L. McHugh Improving Outcomes in Heart Failure in the Community: Long-term Survival Benefit of a Disease-Management Program Chest, June 1, 2005; 127(6): 2042 - 2048. [Abstract] [Full Text] [PDF]

				Authors/Task Force Members, K. Swedberg, Writing Committee:, J. Cleland, H. Dargie, H. Drexler, F. Follath, M. Komajda, L. Tavazzi, O. A. Smiseth, et al. Guidelines for the diagnosis and treatment of chronic heart failure: executive summary (update 2005): The Task Force for the Diagnosis and Treatment of Chronic Heart Failure of the European Society of Cardiology Eur. Heart J., June 1, 2005; 26(11): 1115 - 1140. [Full Text] [PDF]

				E. O'Meara, E. Lewis, C. Granger, M. E. Dunlap, R. S. McKelvie, J. L. Probstfield, J. B. Young, E. L. Michelson, J. Ostergren, J. Carlsson, et al. Patient perception of the effect of treatment with candesartan in heart failure. Results of the Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity (CHARM) programme Eur J Heart Fail, June 1, 2005; 7(4): 650 - 656. [Abstract] [Full Text] [PDF]

				A Varela-Roman, L Grigorian, E Barge, P Bassante, M G de la Pena, and J R Gonzalez-Juanatey Heart failure in patients with preserved and deteriorated left ventricular ejection fraction Heart, April 1, 2005; 91(4): 489 - 494. [Abstract] [Full Text] [PDF]

				S. Kasama, T. Toyama, H. Kumakura, Y. Takayama, S. Ichikawa, T. Suzuki, and M. Kurabayashi Effects of candesartan on cardiac sympathetic nerve activity in patients with congestive heart failure and preserved left ventricular ejection fraction J. Am. Coll. Cardiol., March 1, 2005; 45(5): 661 - 667. [Abstract] [Full Text] [PDF]

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				J. B. Young, M. E. Dunlap, M. A. Pfeffer, J. L. Probstfield, A. Cohen-Solal, R. Dietz, C. B. Granger, J. Hradec, J. Kuch, R. S. McKelvie, et al. Mortality and Morbidity Reduction With Candesartan in Patients With Chronic Heart Failure and Left Ventricular Systolic Dysfunction: Results of the CHARM Low-Left Ventricular Ejection Fraction Trials Circulation, October 26, 2004; 110(17): 2618 - 2626. [Abstract] [Full Text] [PDF]

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				M.J Lenzen, W.J.M Scholte op Reimer, E Boersma, P.J.M.J Vantrimpont, F Follath, K Swedberg, J Cleland, and M Komajda Differences between patients with a preserved and a depressed left ventricular function: a report from the EuroHeart Failure Survey Eur. Heart J., July 2, 2004; 25(14): 1214 - 1220. [Abstract] [Full Text] [PDF]

				V. Franco, S. Oparil, and O. A. Carretero Hypertensive Therapy: Part II Circulation, June 29, 2004; 109(25): 3081 - 3088. [Full Text] [PDF]

				J. J. McMurray Angiotensin inhibition in heart failure Journal of Renin-Angiotensin-Aldosterone System, March 1, 2004; 5(1_suppl): S17 - S22. [Abstract] [PDF]

				K. Hogg, K. Swedberg, and J. McMurray Heart failure with preserved left ventricular systolic function: epidemiology, clinical characteristics, and prognosis J. Am. Coll. Cardiol., February 4, 2004; 43(3): 317 - 327. [Abstract] [Full Text] [PDF]

				I. L. Pina A better survival for women with heart failure? it's not so simple... J. Am. Coll. Cardiol., December 17, 2003; 42(12): 2135 - 2138. [Full Text] [PDF]

				A. V. Chobanian, G. L. Bakris, H. R. Black, W. C. Cushman, L. A. Green, J. L. Izzo Jr, D. W. Jones, B. J. Materson, S. Oparil, J. T. Wright Jr, et al. Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure Hypertension, December 1, 2003; 42(6): 1206 - 1252. [Abstract] [Full Text] [PDF]

				S. Orn and K. Dickstein Neurohormonal inhibition in heart failure, is there no limit? Eur. Heart J., October 1, 2003; 24(19): 1705 - 1706. [Full Text] [PDF]

				A. P. Coletta, J. G.F. Cleland, N. Freemantle, H. Loh, A. Memon, and A. L. Clark Clinical trials update from the European Society of Cardiology: CHARM, BASEL, EUROPA and ESTEEM Eur J Heart Fail, October 1, 2003; 5(5): 697 - 704. [Abstract] [Full Text] [PDF]

				J. Ostergren and J. J. McMurray Angiotensin receptor blockers in heart failure Journal of Renin-Angiotensin-Aldosterone System, September 1, 2003; 4(3): 171 - 175. [Abstract] [PDF]