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Effect of Cardiac Rehabilitation Dose on Mortality and Morbidity: A Systematic Review and Meta-regression Analysis

      Abstract

      Objective

      To ascertain the effect of cardiac rehabilitation (CR) dose (ie, duration × frequency/wk; categorized as low [<12 sessions], medium [12-35 sessions], or high [≥36 sessions]) on mortality and morbidity.

      Methods

      The Cochrane, CINAHL, EMBASE, PsycINFO, and MEDLINE databases were systematically searched from inception through November 30, 2015. Inclusion criteria included randomized or nonrandomized studies with a minimum CR dose of 4 or higher and presence of a control/comparison group. Citations were considered for inclusion, and data were extracted in included studies independently by 2 investigators. Studies were pooled using random-effects meta-analysis and meta-regression where warranted (covariates included study quality, country, publication year, and diagnosis).

      Results

      Of 4630 unique citations, 33 trials were included comparing CR to usual care (ie, no dose). In meta-regression, greater dose was significantly related to lower all-cause mortality (high: −0.77; SE, 0.22; P<.001; medium: −0.80; SE, 0.21; P<.001) when compared with low dose. With regard to morbidity, meta-analysis revealed that dose was significantly associated with fewer percutaneous coronary interventions (high: relative risk, 0.65; 95% CI, 0.50-0.84; medium/low: relative risk, 1.04; 95% CI, 0.74-1.48; between subgroup difference P=.03). This reduction was also significant in meta-regression (high vs medium/low: −0.73; SE, 0.20; P<.001). Publication bias was not evident. No dose-response association was found for cardiovascular mortality, all-cause hospitalization, coronary artery bypass graft surgery, or myocardial infarction.

      Conclusion

      A minimum of 36 CR sessions may be needed to reduce percutaneous coronary interventions. Future studies should examine the effect of actual dose of CR, and trials are needed comparing different doses.

      PROSPERO Registration

      Abbreviations and Acronyms:

      CABG (coronary artery bypass graft), CCR (comprehensive cardiac rehabilitation), CR (cardiac rehabilitation), CV (cardiovascular), CVD (cardiovascular disease), HF (heart failure), MI (myocardial infarction), PCI (percutaneous coronary intervention)
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      References

        • World Health Organization
        Cardiovascular diseases (CVDs).
        (Fact sheet No. 317) (Updated May 2017. Accessed September 1, 2015)
        • Mozaffarian D.
        • Benjamin E.J.
        • Go A.S.
        • et al.
        • American Heart Association Statistics Committee
        • Stroke Statistics Subcommittee
        Heart Disease and Stroke Statistics—2016 Update a report from the American Heart Association.
        Circulation. 2016; 133 ([published correction appears in Circulation. 2016;133(15):e599]): e38-e360
        • Stone J.
        • Arthur H.M.
        • Suskin N.
        • et al.
        Canadian Guidelines for Cardiac Rehabilitation and Cardiovascular Disease Prevention: Translating Knowledge into Action.
        3rd ed. Canadian Association of Cardiac Rehabilitation, Winnipeg, Manitoba, Canada2009
        • Ades P.A.
        • Keteyian S.J.
        • Wright J.S.
        • et al.
        Increasing cardiac rehabilitation participation from 20% to 70%: a road map from the Million Hearts Cardiac Rehabilitation Collaborative.
        Mayo Clin Proc. 2017; 92: 234-242
        • Forman D.E.
        Cardiac rehabilitation: the mandate grows.
        Mayo Clin Proc. 2016; 91 ([editorial]): 125-128
        • Wong W.P.
        • Feng J.
        • Pwee K.H.
        • Lim J.
        A systematic review of economic evaluations of cardiac rehabilitation.
        BMC Health Serv Res. 2012; 12: 243
        • Leggett L.E.
        • Hauer T.
        • Martin B.J.
        • et al.
        Optimizing value from cardiac rehabilitation: a cost-utility analysis comparing age, sex, and clinical subgroups.
        Mayo Clin Proc. 2015; 90: 1011-1020
        • Anderson L.
        • Oldridge N.
        • Thompson D.R.
        • et al.
        Exercise-based cardiac rehabilitation for coronary heart disease: Cochrane systematic review and meta-analysis.
        J Am Coll Cardiol. 2016; 67: 1-12
        • Shanmugasegaram S.
        • Perez-Terzic C.
        • Jiang X.
        • Grace S.L.
        Cardiac rehabilitation services in low- and middle-income countries: a scoping review.
        J Cardiovasc Nurs. 2014; 29: 454-463
        • Price K.J.
        • Gordon B.A.
        • Bird S.R.
        • Benson A.C.
        A review of guidelines for cardiac rehabilitation exercise programmes: is there an international consensus?.
        Eur J Prev Cardiol. 2016; 23: 1715-1733
        • Colbert J.D.
        • Martin B.-J.
        • Haykowsky M.J.
        • et al.
        Cardiac rehabilitation referral, attendance and mortality in women.
        Eur J Prev Cardiol. 2015; 22: 979-986
        • Whellan D.J.
        • Shaw L.K.
        • Bart B.A.
        • Kraus W.E.
        • Califf R.M.
        • O'Connor C.M.
        Cardiac rehabilitation and survival in patients with left ventricular systolic dysfunction.
        Am Heart J. 2001; 142: 160-166
        • Suaya J.A.
        • Stason W.B.
        • Ades P.A.
        • Normand S.-L.T.
        • Shepard D.S.
        Cardiac rehabilitation and survival in older coronary patients.
        J Am Coll Cardiol. 2009; 54: 25-33
        • Hammill B.G.
        • Curtis L.H.
        • Schulman K.A.
        • Whellan D.J.
        Relationship between cardiac rehabilitation and long-term risks of death and myocardial infarction among elderly Medicare beneficiaries.
        Circulation. 2010; 121: 63-70
        • Doll J.A.
        • Hellkamp A.
        • Thomas L.
        • et al.
        Effectiveness of cardiac rehabilitation among older patients after acute myocardial infarction.
        Am Heart J. 2015; 170: 855-864
        • Grace S.L.
        • Turk-Adawi K.I.
        • Contractor A.
        • et al.
        Cardiac rehabilitation delivery model for low-resource settings: an International Council of Cardiovascular Prevention and Rehabilitation consensus statement.
        Prog Cardiovasc Dis. 2016; 59: 303-322
        • Taylor R.S.
        • Brown A.
        • Ebrahim S.
        • et al.
        Exercise-based rehabilitation for patients with coronary heart disease: systematic review and meta-analysis of randomized controlled trials.
        Am J Med. 2004; 116: 682-692
        • Heran B.S.
        • Chen J.M.
        • Ebrahim S.
        • et al.
        Exercise-based cardiac rehabilitation for coronary heart disease.
        Cochrane Database Syst Rev. 2011; : CD001800
        • Lawler P.R.
        • Filion K.B.
        • Eisenberg M.J.
        Efficacy of exercise-based cardiac rehabilitation post-myocardial infarction: a systematic review and meta-analysis of randomized controlled trials.
        Am Heart J. 2011; 162: 571-584.e2
        • Kuo L.-Y.
        • Shen S.-L.
        • Hsu C.-L.
        • et al.
        Effect of cardiac rehabilitation on cardiovascular events after coronary artery bypass grafting in a 6-year follow-up study.
        Health Sci J. 2016; 10: 1-6
        • National Institute for Health Research
        PROSPERO - International prospective register of systematic reviews.
        (Published 2015. Accessed March 6, 2016)
        • Higgins J.
        • Green S.
        Cochrane Handbook for Systematic Reviews of Interventions.
        (Version 5.1.0. Cochrane website) (Published 2011. Accessed April 22, 2016)
        • American Association of Cardiovascular and Pulmonary Rehabilitation
        Guidelines for Cardiovascular and Secondary Prevention Programs.
        5th ed. Human Kinetics, Champaign, IL2013
        • Grace S.L.
        • Turk-Adawi K.I.
        • Contractor A.
        • et al.
        Cardiac rehabilitation delivery model for low-resource settings.
        Heart. 2016; 102: 1449-1455
        • Downs S.H.
        • Black N.
        The feasibility of creating a checklist for the assessment of the methodological quality both of randomised and non-randomised studies of health care interventions.
        J Epidemiol Community Health. 1998; 52: 377-384
        • Dalal H.M.
        • Evans P.H.
        • Campbell J.L.
        • et al.
        Home-based versus hospital-based rehabilitation after myocardial infarction: a randomized trial with preference arms—Cornwall Heart Attack Rehabilitation Management Study (CHARMS).
        Int J Cardiol. 2007; 119: 202-211
        • Jolly K.
        • Lip G.Y.H.
        • Taylor R.S.
        • et al.
        The Birmingham Rehabilitation Uptake Maximisation study (BRUM): a randomised controlled trial comparing home-based with centre-based cardiac rehabilitation.
        Heart. 2009; 95: 36-42
        • Reid R.D.
        • Dafoe W.A.
        • Morrin L.
        • et al.
        Impact of program duration and contact frequency on efficacy and cost of cardiac rehabilitation: results of a randomized trial.
        Am Heart J. 2005; 149: 862-868
        • Papadakis S.
        • Reid R.D.
        • Coyle D.
        • Beaton L.
        • Angus D.
        • Oldridge N.
        Cost-effectiveness of cardiac rehabilitation program delivery models in patients at varying cardiac risk, reason for referral, and sex.
        Eur J Cardiovasc Prev Rehabil. 2008; 15: 347-353
        • Plüss C.E.
        • Billing E.
        • Held C.
        • et al.
        Long-term effects of an expanded cardiac rehabilitation programme after myocardial infarction or coronary artery bypass surgery: a five-year follow-up of a randomized controlled study.
        Clin Rehabil. 2011; 25: 79-87
        • West R.R.
        • Jones D.A.
        • Henderson A.H.
        Rehabilitation After Myocardial Infarction Trial (RAMIT): multi-centre randomised controlled trial of comprehensive cardiac rehabilitation in patients following acute myocardial infarction.
        Heart. 2012; 98: 637-644
        • DerSimonian R.
        • Laird N.
        Meta-analysis in clinical trials.
        Control Clin Trials. 1986; 7: 177-188
        • Higgins J.P.
        • Thompson S.G.
        Quantifying heterogeneity in a meta-analysis.
        Stat Med. 2002; 21: 1539-1558
        • Oxman A.D.
        • Guyatt G.H.
        A consumer's guide to subgroup analyses.
        Ann Intern Med. 1992; 116: 78-84
        • Morton S.C.
        • Adams J.L.
        • Suttorp M.J.
        • Shekelle P.J.
        Meta-regression Approaches: What, Why, When, and How?.
        Agency for Healthcare Research and Quality, Rockville, MD2004 (AHRQ Technical Reviews, No. 8. Report No. 04-0043)
        • Egger M.
        • Davey Smith G.
        • Schneider M.
        • Minder C.
        Bias in meta-analysis detected by a simple, graphical test.
        BMJ. 1997; 315: 629-634
        • Alter D.A.
        • Oh P.I.
        • Chong A.
        Relationship between cardiac rehabilitation and survival after acute cardiac hospitalization within a universal health care system.
        Eur J Cardiovasc Prev Rehabil. 2009; 16: 102-113
        • Austin J.
        • Williams W.R.
        • Ross L.
        • Hutchison S.
        Five-year follow-up findings from a randomized controlled trial of cardiac rehabilitation for heart failure.
        Eur J Cardiovasc Prev Rehabil. 2008; 15: 162-167
        • Beauchamp A.
        • Worcester M.
        • Ng A.
        • et al.
        Attendance at cardiac rehabilitation is associated with lower all-cause mortality after 14 years of follow-up.
        Heart. 2013; 99: 620-625
        • Bengtsson K.
        Rehabilitation after myocardial infarction: a controlled study.
        Scand J Rehabil Med. 1983; 15: 1-9
        • Bondestam E.
        • Breikss A.
        • Hartford M.
        Effects of early rehabilitation on consumption of medical care during the first year after acute myocardial infarction in patients ≥65 years of age.
        Am J Cardiol. 1995; 75: 767-771
        • Briffa T.G.
        • Eckermann S.D.
        • Griffiths A.D.
        • et al.
        Cost-effectiveness of rehabilitation after an acute coronary event: a randomised controlled trial.
        Med J Aust. 2005; 183: 450-455
        • Carlsson R.
        Serum cholesterol, lifestyle, working capacity and quality of life in patients with coronary artery disease: experiences from a hospital-based secondary prevention programme.
        Scand Cardiovasc J Suppl. 1998; 50: 1-20
        • Chung C.C.
        • Huang W.C.
        • Chiou K.R.
        • et al.
        Ratio of early mitral inflow peak velocity to flow propagation velocity predicts training effects of cardiac rehabilitation in patients after acute myocardial infarction.
        J Rehabil Med. 2010; 42: 232-238
        • Davidson P.M.
        • Cockburn J.
        • Newton P.J.
        • et al.
        Can a heart failure-specific cardiac rehabilitation program decrease hospitalizations and improve outcomes in high-risk patients?.
        Eur J Cardiovasc Prev Rehabil. 2010; 17: 393-402
        • Dendale P.
        • Berger J.
        • Hansen D.
        • Vaes J.
        • Benit E.
        • Weymans M.
        Cardiac rehabilitation reduces the rate of major adverse cardiac events after percutaneous coronary intervention.
        Eur J Cardiovasc Nurs. 2005; 4: 113-116
        • Dendale P.
        • Hansen D.
        • Berger J.
        • Lamotte M.
        Long-term cost-benefit ratio of cardiac rehabilitation after percutaneous coronary intervention.
        Acta Cardiol. 2008; 63: 451-456
        • Denollet J.
        • Brutsaert D.L.
        Reducing emotional distress improves prognosis in coronary heart disease: 9-year mortality in a clinical trial of rehabilitation.
        Circulation. 2001; 104: 2018-2023
        • Erdman R.
        • Duivenvoorden H.
        • Verhage F.
        • Kazemier M.
        • Hugenholtz P.G.
        Predictability of beneficial effects in cardiac rehabilitation: a randomized clinical trial of psychosocial variables.
        J Cardiopulm Rehabil. 1986; 6: 206-213
        • Fridlund B.
        • Högstedt B.
        • Lidell E.
        • Larsson P.A.
        Recovery after myocardial infarction: effects of a caring rehabilitation programme.
        Scand J Caring Sci. 1991; 5: 23-32
        • Hansen D.
        • Dendale P.
        • Leenders M.
        • et al.
        Reduction of cardiovascular event rate: different effects of cardiac rehabilitation in CABG and PCI patients.
        Acta Cardiol. 2009; 64: 639-644
        • Hedbäck B.
        • Perk J.
        • Hörnblad M.
        • Ohlsson U.
        Cardiac rehabilitation after coronary artery bypass surgery: 10-year results on mortality, morbidity and readmissions to hospital.
        J Cardiovasc Risk. 2001; 8: 153-158
        • Kentala E.
        Physical fitness and feasibility of physical rehabilitation after myocardial infarction in men of working age.
        Ann Clin Res. 1972; 4: 1-84
        • Kovoor P.
        • Lee A.K.Y.
        • Carrozzi F.
        • et al.
        Return to full normal activities including work at two weeks after acute myocardial infarction.
        Am J Cardiol. 2006; 97: 952-958
        • La Rovere M.T.
        • Bersano C.
        • Gnemmi M.
        • Specchia G.
        • Schwartz P.J.
        Exercise-induced increase in baroreflex sensitivity predicts improved prognosis after myocardial infarction.
        Circulation. 2002; 106: 945-949
        • Leizorovicz A.
        • Saint-Pierre A.
        • Vasselon P.
        • Boissel J.P.
        • P.RE.COR. Group
        Comparison of a rehabilitation programme, a counselling programme and usual care after an acute myocardial-infarction: results of a long-term randomized trial.
        Eur Heart J. 1991; 12: 612-616
        • Lidell E.
        • Fridlund B.
        Long-term effects of a comprehensive rehabilitation programme after myocardial infarction.
        Scand J Caring Sci. 1996; 10: 67-74
        • Maroto Montero J.M.
        • Artigao Ramírez R.
        • Morales Durán M.D.
        • de Pablo Zarzosa C.
        • Abraira V.
        Cardiac rehabilitation in patients with myocardial infarction: a 10-year follow-up study.
        Rev Esp Cardiol. 2005; 58 ([in Spanish]): 1181-1187
        • Mehani S.H.M.
        Correlation between changes in diastolic dysfunction and health-related quality of life after cardiac rehabilitation program in dilated cardiomyopathy.
        J Adv Res. 2013; 4: 189-200
        • Nielsen K.M.
        • Faergeman O.
        • Foldspang A.
        • Larsen M.L.
        Cardiac rehabilitation: health characteristics and socio-economic status among those who do not attend.
        Eur J Public Health. 2008; 18: 479-483
        • O'Connor C.M.
        • Whellan D.J.
        • Lee K.L.
        • et al.
        • HF-ACTION Investigators
        Efficacy and safety of exercise training in patients with chronic heart failure: HF-ACTION randomized controlled trial.
        JAMA. 2009; 301: 1439-1450
        • Oldridge N.
        • Guyatt G.
        • Jones N.
        • et al.
        Effects on quality of life with comprehensive rehabilitation after acute myocardial infarction.
        Am J Cardiol. 1991; 67: 1084-1089
        • Schuler G.
        • Hambrecht R.
        • Schlierf G.
        • et al.
        Regular physical exercise and low-fat diet: effects on progression of coronary artery disease.
        Circulation. 1992; 86: 1-11
        • Sivarajan E.S.
        • Bruce R.A.
        • Lindskog B.D.
        • Almes M.J.
        • Belanger L.
        • Green B.
        Treadmill test responses to an early exercise program after myocardial infarction: a randomized study.
        Circulation. 1982; 65: 1420-1428
        • Vestfold Heartcare Study Group
        Influence on lifestyle measures and five-year coronary risk by a comprehensive lifestyle intervention programme in patients with coronary heart disease.
        Eur J Cardiovasc Prev Rehabil. 2003; 10: 429-437
        • Yu C.-M.
        • Lau C.-P.
        • Chau J.
        • et al.
        A short course of cardiac rehabilitation program is highly cost effective in improving long-term quality of life in patients with recent myocardial infarction or percutaneous coronary intervention.
        Arch Phys Med Rehabil. 2004; 85: 1915-1922
        • Zeng W.
        • Stason W.B.
        • Fournier S.
        • et al.
        Benefits and costs of intensive lifestyle modification programs for symptomatic coronary disease in Medicare beneficiaries.
        Am Heart J. 2013; 165: 785-792
        • Zwisler A.-D.O.
        • Soja A.M.B.
        • Rasmussen S.
        • et al.
        • DANREHAB Group
        Hospital-based comprehensive cardiac rehabilitation versus usual care among patients with congestive heart failure, ischemic heart disease, or high risk of ischemic heart disease: 12-month results of a randomized clinical trial.
        Am Heart J. 2008; 155: 1106-1113
      1. Santiago de Araujo Pio C, Marzolini S, Pakosh M, Grace SL. Dose of cardiac rehabilitation across the globe [poster presentation]. In: Toronto General Research Institute Research Day. Toronto, Canada; 2016.

        • Babu A.S.
        • Lopez-Jimenez F.
        • Thomas R.J.
        • et al.
        • International Council of Cardiovascular Prevention and Rehabilitation (ICCPR)
        Advocacy for outpatient cardiac rehabilitation globally.
        BMC Health Serv Res. 2016; 16: 471
        • Menezes A.R.
        • Lavie C.J.
        • Milani R.V.
        • Forman D.E.
        • King M.
        • Williams M.A.
        Cardiac rehabilitation in the United States.
        Prog Cardiovasc Dis. 2014; 56: 522-529
        • Polyzotis P.A.
        • Tan Y.
        • Prior P.L.
        • Oh P.
        • Fair T.
        • Grace S.L.
        Cardiac rehabilitation services in Ontario: components, models and underserved groups.
        J Cardiovasc Med (Hagerstown). 2012; 13: 727-734
        • British Heart Foundation
        The National Audit of Cardiac Rehabilitation: Annual Report 2015.
        British Heart Foundation, London, EnglandDecember 2015
        • Doherty P.
        • Salman A.
        • Furze G.
        • Dalal H.M.
        • Harrison A.
        Does cardiac rehabilitation meet minimum standards: an observational study using UK national audit?.
        Open Heart. 2017; 4: e000519
        • Oosenbrug E.
        • Marinho R.P.
        • Zhang J.
        • et al.
        Sex differences in cardiac rehabilitation adherence: a meta-analysis.
        Can J Cardiol. 2016; 32: 1316-1324
        • Shanmugasegaram S.
        • Gagliese L.
        • Oh P.
        • et al.
        Psychometric validation of the cardiac rehabilitation barriers scale.
        Clin Rehabil. 2012; 26: 152-164
        • Grace S.L.
        • Midence L.
        • Oh P.
        • et al.
        Cardiac rehabilitation program adherence and functional capacity among women: a randomized controlled trial.
        Mayo Clin Proc. 2016; 91: 140-148
        • Javaid A.
        • Steinberg D.H.
        • Buch A.N.
        • et al.
        Outcomes of coronary artery bypass grafting versus percutaneous coronary intervention with drug-eluting stents for patients with multivessel coronary artery disease.
        Circulation. 2007; 116: I200-I207