BMJ  2004;328:693-697 (20 March), doi:10.1136/bmj.328.7441.693

Clinical review

Recent developments in secondary prevention and cardiac rehabilitation after acute myocardial infarction

¹ Lower Lemon Street Surgery, Truro TR1 2LZ, ² Peninsula Medical School, Barrack Road, Exeter EX2 5DW

Primary care has a key role in improving the health of patients who have had a myocardial infarction

Introduction

Acute myocardial infarction remains a common cause of death worldwide. Despite decreases in mortality from coronary heart disease in most developed countries, mortality is increasing in most eastern European countries and developing countries.¹ In the United Kingdom 1.2 million people are estimated to have survived heart attacks, yet few survivors are offered comprehensive cardiac rehabilitation.² Effective implementation of secondary prevention is a great challenge,^w1 and lack of implementation has been described as a collective failure of medical practice, as clear evidence shows that several interventions could reduce the risk of recurrent disease and death.³

Primary care's challenge is to make this happen. Two recent initiatives will change the face of secondary prevention in British primary care:

• The national service framework for coronary heart disease advocates the use of disease registers in primary care to provide long term follow up of patients with coronary heart disease and sets standards and milestones for secondary prevention^w2
  
• The imminent general medical services contract includes funding to encourage primary care teams to implement evidence based care.^w3
  

Growing evidence shows suboptimal application of secondary prevention, and examples show how evidence based practice can be applied in primary care to improve the quality of care for patients with coronary heart disease.^3-6 The number of patients in each practice, the benefits of continuity and the high frequency of comorbidity, and psychosocial problems have increased the role of the generalist. This puts primary care in the vanguard of saving lives.⁷ This review thus focuses on topics related to primary care.

Sources and selection criteria

We searched Medline for relevant reviews related to secondary prevention (after acute myocardial infarction) and papers published in the past three years; we also canvassed specialist and generalist colleagues. Recent large trials have included acute myocardial infarction with other cardiovascular diseases, as they share common risk factors^8-10; this review reflects this trend. We adopted the Scottish Intercollegiate Guidelines Network's definition of secondary prevention, which encompasses "identification and modification of risk factors by the introduction of lifestyle measures and pharmacological therapy and cardiac rehabilitation."^w4

Summary points Effective implementation of secondary prevention and cardiac rehabilitation after acute myocardial infarction remains suboptimal Coprescribing of antiplatelet drugs, statins, angiotensin converting enzyme inhibitors, and blockers should be considered in all patients after myocardial infarction Structured care for chronic cardiac disease management can improve the recording of risk factors Nurse led clinics for secondary prevention of coronary heart disease may improve clinical outcomes Exercise based cardiac rehabilitation after myocardial infarction has been shown to reduce all cause mortality Depression is common after myocardial infarction; the associated increased mortality seems to be refractory to psychological or drug treatment

Drugs and secondary prevention

Large randomised trials have confirmed the benefits of the four main prophylactic drug groups (box 1). Their routine use in secondary prevention is recommended in national guidelines^{w4 w5}; several recent trials have contributed new evidence for their use.

Antiplatelet drugs
A recent meta-analysis supported the long term use of low dose aspirin (75-150 mg daily) in secondary prevention: higher doses (500-1500 mg daily) are nomore effective and are associated with gastrotoxiticy.¹¹ Clopidogrel 75 mg daily is an effective but expensive alternative in patients with a genuine allergy or proved gastric intolerance to aspirin.^{11 12} Addition of clopidogrel to aspirin for up to nine months in patients with acute coronary syndromes (myocardial infarction without ST segment elevation) can prevent additional cardiovascular events or non-fatal myocardial infarction but carries a higher risk of bleeding (3.7% v 2.7%; relative risk 1.38, 95% confidence interval 1.13 to 1.67).^w6 Aspirin and clopidogrel should not be coprescribed routinely until the results of ongoing trials on their combined use are available (box 2).

Box 1: Four main prophylactic drug groups for secondary prevention of coronary heart disease Antiplatelet drugs blockers Statins Angiotensin converting enzyme inhibitors

Angiotensin converting enzyme inhibitors
Angiotensin converting enzyme inhibitors after acute myocardial infarction have been recommended in patients with signs of heart failure or confirmed left ventricular dysfunction.¹³ Two recent trials, however, reported reductions in cardiovascular death and events (myocardial infarction and stroke) and provide strong evidence for treating all patients after myocardial infarction with an angiotensin converting enzyme inhibitor regardless of left ventricular function (provided no contraindications exist).^{8 9} This view is endorsed by a recent editorial and is included in national guidelines.^{w5 w7} In a study in which 52% of participants were survivors of myocardial infarction, rates of readmission for heart failure were also reduced in patients who took ramipril.⁹ Angiotensin II antagonists have been advocated when patients are intolerant of angiotensin converting enzyme inhibitors (box 3).

Box 2: Key ongoing research studies Study of additional reductions in cholesterol and homocysteine (SEARCH): Study of patients after myocardial infarction randomised to receive 20 or 80 mg simvastatin daily, folic acid plus vitamin B-12, or placebo Primary outcome measures—total coronary heart disease events, including non-fatal myocardial infarction and coronary revascularisation Euro action: Project involving eight European countries that aims to show the effectiveness of multidisciplinary lifestyle measures in patients with coronary heart disease and their families (www.escardio.org/euroaction) Second Chinese cardiac study (CCS-2) to determine whether addition of oral clopidogrel to aspirin after suspected acute myocardial infarction can produce greater reductions in risk of major vascular events. J Cardiovasc Risk 2000;7: 435-41[ISI][Medline] Jolly K, Lip GYH, Sandercock J, Greenfield SM, Raftery JP, Mant J, et al. Home-based versus hospital-based cardiac rehabilitation after myocardial infarction or revascularisation: design and rationale of the Birmingham rehabilitation uptake maximisation study (BRUM): a randomised controlled trial. BMC Cardiovasc Disord 2003;3: 10[CrossRef][Medline] Home versus hospital based cardiac rehabilitation following myocardial infarction: a randomised trial to compare clinical outcomes and cost: Principal investigator: H M Dalal, Royal Cornwall Hospital, Truro, TR1 3LJ (hmdalal{at}doctors.net.uk)

Statins
Since the first landmark trial showed that statins decrease the risk of coronary events and total mortality in patients after myocardial infarction,^w10 these drugs have become the cornerstone of preventive therapy. Their benefits apply to women and to patients aged over 65 years, who had been under-represented in clinical trials.¹⁴ A recent large randomised trial with simvastatin showed that the benefits of statins apply irrespective of sex, age, or initial cholesterol concentrations.¹⁰ Thresholds for cholesterol lowering in secondary prevention have reduced with each successive secondary prevention study. Current British guidelines and the national service framework recommend treatment when total cholesterol concentrations are 5 mmol/l.^{w2 w11} Updated guidelines (due in 2004) are likely to recommend that survivors of myocardial infarction should be prescribed a statin irrespective of initial cholesterol concentrations. However, non-adherence to statin treatment may be a bigger problem than previously thought, with 60% non-adherence reported among elderly patients two years after an acute coronary event.¹⁵

Recent evidence has highlighted ageism in the prescribing of statins in primary care: patients aged 55-64 years with ischaemic heart disease were more likely to receive them than those aged 65-74 years or 75-84 years (odds ratios 0.63 and 0.15).^w12 This may be because of a perceived lack of evidence for use of statins in older patients or other factors, such as general practitioners' attitudes.^w13 However, the influence of these factors may change after the findings from the heart protection study, which included 5806 patients aged over 70 years and showed beneficial effects in this age group.¹⁰

Box 3: Comparison of angiotensin converting enzyme inhibitors and angiotensin II antagonists Two recent trials that compared losartan or valsartan with captopril in patients after myocardial infarction complicated by heart failure (left ventricular dysfunction) showed that angiotensin II antagonists were as effective as angiotensin converting enzyme inhibitorsw8 w9 Although losartan was better tolerated than angiotensin converting enzyme inhibitors, it resulted in significantly more cardiovascular deaths (n = 420, 15.3%) than did captopril (n = 363, 13.3%) (relative risk 1.17 (1.01 to 1.34))

blockers
blockers reduce the risk of death, non-fatal recurrent myocardial infarction, and sudden cardiac death and are recommended in national guidelines.^{w4 w5} Two studies confirmed that use of blockers remains suboptimal (22% and 63%).^{3 4} Anecdotally, primary care doctors report that the incidence of adverse events and side effects is higher than reported in trials. A recent major systematic review, however, showed no significant increased risk of depression and only small increases in the risks of fatigue and sexual dysfunction in patients who took blockers.¹⁶

The contraindication of blockers in patients with asthma or chronic obstructive pulmonary disease was questioned in a recent Cochrane review,^w14 which concluded that they do not produce adverse respiratory effects during short term treatment in patients with mild to moderate airway disease. The proved benefits of blockers in patients with heart failure, hypertension, and arrhythmias means that they should not be withheld. A study of 46 000 survivors of myocardial infarction with asthma and chronic obstructive pulmonary disease reported a 40% reduction in total mortality in patients treated with blockers and benefits for patients aged over 80 years and those with heart failure.^w15

An earlier review reported that blockers should be used with caution in patients with severe peripheral arterial disease but have little effect on the peripheral circulation in those with less severe forms of the disease.^w16 This view was shared by a recent clinical review.^w17

Organisation of care

Recent trials have provided evidence for the effectiveness of structured care in secondary prevention of coronary heart disease (table).^w18 Although a validated register of patients who survive acute myocardial infarction is the bedrock of any structured care system in primary care,¹⁷ good communication between hospital and primary care, with multidisciplinary working, is a common theme in successful schemes.⁶ Nurse led clinics for secondary prevention of coronary heart disease may produce improved clinical outcomes.

View this table: [in this window] [in a new window]   Evidence for structured systematic care in secondary prevention of coronary heart disease. Adapted from Begg 2003w18

 

Cardiac rehabilitation

The overall aims of cardiac rehabilitation are to optimise patients' functioning, enhance quality of life, and minimise the risk of recurrent cardiac events (box 4). Reviews of cardiac rehabilitation describe two types of cardiac rehabilitation—"exercise only" and "comprehensive cardiac rehabilitation" (see additional educational resources).

Comprehensive rehabilitation programmes include exercise training, behavioural changes, education, and psychological support.^w27 Long term maintenance of physical activity and lifestyle changes should be coupled with structured follow up to tackle secondary prevention risk factors (table). In some settings, this may include drugs to optimise risk factors such as hypertension, diabetes, and hyperlipidaemia. Overlap thus exists between the aims of cardiac rehabilitation programmes and secondary prevention clinics.

A recent Cochrane review confirmed a 27% reduction in all cause mortality (random effects model odds ratio 0.73 (0.54 to 0.98)) with exercise based cardiac rehabilitation (box 5).^w25 Participation in cardiac rehabilitation, however, has remained poor in the United States (10-20%) and the United Kingdom(14-23%).^{2 w28} Over the past decade, provision of rehabilitation services has increased steadily in the United Kingdom, from less than 100 programmes in 1989 to 300 in 1997.^w4 Historically, group based rehabilitation classes have been held in hospitals and have focused on exercise training, with variable multidisciplinary input on education, lifestyle advice, drugs, and risk factors. Some programmes also offer psychological support. Emerging evidence supports the safety and effectiveness of rehabilitation in other settings such as community centres and homes.^{18 19 w29 w30}

Box 4: Number needed to treat (NNT) An updated Canadian review of cardiac rehabilitation endorsed the findings of the Cochrane review and reported a relative risk reduction in all cause mortality of 24% (95% confidence interval 4% to 27%).w25 w26 This translates to a number needed to treat of 66 (35 to 273) over a mean of 28 months' follow up. The same review quoted number needed to treat for other accepted drug interventions after myocardial infarction, such as statin treatment (11-56), blocker treatment (84), and antiplatelet treatment (306). Care needs to be exercised in direct comparisons of numbers needed to treat, as many recent studies have included participants from non-comparable patient populations. Comprehensive cardiac rehabilitation that includes long term preventive drugs is a complex intervention, and attribution of benefits to each component by using numbers needed to treat may not be wholly appropriate. Cost effectiveness ratios for selected medical interventions are highlighted in a Canadian review.w26 Cardiac rehabilitation compared reasonably favourably with lipid lowering for secondary prevention (US$4950-15 000 (£2673-9000) per life year gained in 1995-6 v US$9630 (£5200) in 1996).

Box 5: A patient's perspective My experience of care after my heart attack was like being led through a fog by someone who knew the way. My first reaction was disbelief—there must be a mistake. I seemed as well as ever. The professionalism of the staff taking their work very seriously made the truth sink in. I had to do what I was told. I suddenly felt very fragile and feared a repeat attack. Slowly I was reassured by the care of the hospital staff. It was not going to happen again. I was eager for more information. How did I come to be in this situation? What was going to happen to me? I needed to know. After the first few days, you are not in the front line of care and medication becomes routine and predictable. In a way, you miss the attention and need to be reassured that care is continuing, albeit at a lower profile. There is a lot to learn to care for yourself. The rehabilitation nurse reassures you that your feelings of vulnerability are not unusual. There is a psychological aspect to recovering from a heart attack. At first you feel you'll never be able to do the things you enjoy again. Your family holds you back to shelter you, but this can be frustrating. The rehabilitation nurse reassures you about how much you should be able to do. This advice first received in hospital is worth covering again when you are at home. This continuity and the link between hospital and home definitely helps. 50 year old farmer, Cornwall

Additional educational resources Websites for health professionals Clinical Evidence (www.clinicalevidence.org)—sections on acute myocardial infarction and secondary prevention of ischaemic events provide a comprehensive review of all major evidence based interventions Scottish Intercollegiate Guidelines Network (www.sign.ac.uk)—guideline no 41: secondary prevention of CHD following myocardial infarction; guideline no 57: cardiac rehabilitation National Institute for Clinical Excellence (www.nice.org.uk)—clinical guideline A: prophylaxis for patients who have experienced a myocardial infarction (April 2001) British Heart Foundation (www.bhf.org.uk)—statistics on coronary heart disease National Service Framework for Coronary Heart Disease (www.dh.gov.uk/PolicyAndGuidance/HealthAndSocialCareTopics/CoronaryHeartDisease/fs/en) New general medical services contract (www.bma.org.uk/ap.nsf/Content/__Hub+GPC+contract) Cardiac rehabilitation. Effective Health Care Bulletin 1998;4(4). (www.york.ac.uk/inst/crd/ehc44.pdf) Brown A, Taylor R, Noorani H, Stone J, Skidmore B. Exercise-based cardiac rehabilitation programs for coronary artery disease: a systematic clinical and economic review. Ottawa: Canadian Coordinating Office for Health Technology Assessment, 2003 (www.ccohta.ca) Recent papers of interest Van der Elst ME, Buurma H, Bouvy ML, de Boer A. Drug therapy for prevention of recurrent myocardial infarction. Ann Pharmacother 2003;37: 1465-77[Abstract/Free Full Text] (comprehensive tables that list key randomised controlled trials and meta-analyses that give relative risk values for secondary prevention drug interventions and all cause mortality) Boersma E, Mercado N, Poldermans D, Gardien M, Vos J, Limoons ML. Acute myocardial infarction. Lancet 2003;361: 847-58[CrossRef][ISI][Medline] Ades PA. Cardiac rehabilitation and secondary prevention of coronary heart disease. N Engl J Med 2001;345: 892-902[Free Full Text] British Cardiac Society, British Hyperlipidaemia Association, British Hypertension Society, endorsed by the British Diabetic Association. Joint British recommendations on prevention of coronary heart disease in clinical practice. Heart 1998;80(suppl 2): S1-29

Home based cardiac rehabilitation programmes are increasingly popular and can increase uptake in rural areas where access to centre based classes can be difficult.⁶ Services near patients or home based programmes could increase participation by women, elderly people, and ethnic minorities, which is low with hospital based rehabilitation.¹⁹ Increasingly, patients prefer a choice of rehabilitation. The clinical and health economic outcomes of home based rehabilitation compared with hospital based rehabilitation are yet to be determined (box 2).

Psychosocial interventions

Smoking cessation
Although observational studies have estimated that mortality and subsequent cardiac events are reduced by 50% when patients with coronary heart disease stop smoking, the timing of benefits and amount of risk reduction have been debated. A recent systematic review of 20 high quality prospective cohort studies suggested that stopping smoking in patients with coronary heart disease (acute myocardial infarction and angina) reduced total all cause mortality (relative risk 0.64 (0.58 to 0.71)).²⁰

Smoking cessation clearly is a priority for all patients with coronary heart disease, including elderly patients.^w31 The challenge for primary care practitioners is how to achieve lifestyle changes, particularly smoking cessation. Nicotine replacement seems to be safe for patients with coronary heart disease.^w32

Psychological problems
Depression is common after myocardial infarction: 15-20% of patients have major depression, and a similar proportion have minor depression.^w33 This may be missed in primary care, and several commentators have suggested screening for depression.²¹

Depression and perception of lack of social support after myocardial infarction are associated with increased mortality, although the precise mechanism remains uncertain. A recent study of 2481 patients with coronary heart disease showed enhanced recovery after cognitive behaviour therapy or antidepressants (sertraline), as patients were less depressed and felt less isolated, but event free survival after 29 months' follow up did not increase.²²

Implementation

Implementation of the evidence is far from universal in primary and secondary care, as exemplified by variability in prescribing of statins in primary care and door to needle times in secondary care. This has been termed the "implementation gap."

Evidence produced after introduction of the national service framework confirmed the disappointing level of implementation of secondary prevention, most notably effective prescribing of statins, in British primary care and elsewhere.^{3 4 w34 w35} Lack of time, cost, and patient compliance are cited as underpinning the implementation gap across Europe.^w34 Recent decreases in mortality in patients with coronary heart disease bear witness to better secondary prevention,^w35 and other initiatives, such as the national primary care collaborative, show that treatment with statins is increasing in primary care.^w36

Summerskill and Pope explored this further in a qualitative study of general practitioners' attitudes to secondary prevention and implementation.²³ Themes emerged around the difficulties of prioritising secondary preventive measures within 10 minute consultations, especially for patients with comorbid disorders. General practitioners reported responding to immediate social or psychological needs rather than tackling longer term prevention and were more likely to implement interventions in consultations dedicated to reviews of coronary heart disease. Other studies showed that although general practitioners do not doubt the credibility of the evidence, they may find it difficult to apply in individual patients and are concerned about the resource implications of prescribing statins and monitoring patients who take them.^{w37 w38} Implementation is perhaps not as mechanistic as it first seems. Workload and costs can be barriers to implementing national guidelines.^{w2 w39}

The future

General practice seems to be responding to new evidence with increasing vigour. The revised definition of myocardial infarction diagnosed by troponin estimation, however, will probably result in increased reporting of myocardial infarction and further increased workloads in primary and secondary care.²⁴ The two sectors need to collaborate and communicate effectively to reduce treatment gaps and build on established models of integrated care with proved effectiveness. The impact of the national service framework, the new general medical services contract for general practitioners, and other initiatives (such as the national primary care collaborative) should improve quality of care after myocardial infarction for patients in the United Kingdom.

Sources of information for patients Hearts for Life (www.heartsforlife.co.uk)—provides patient friendly information on heart attacks, angina, heart failure, and prevention British Heart Foundation (www.bhf.org.uk)—printable information on heart attack and cardiac rehabilitation, with links to other sites DIPEx (www.dipex.org)—website about people's experiences of health and illness; the site links video, audio, and written interviews with evidence based information, patients' questions and answers, and links to other resources; information for patients who have had heart attacks will be available from August 2004 BBC Health (www.bbc.co.uk/health)—specific section on how to recover after a heart attack (www.bbc.co.uk/health/features/heart_attack_recovery.shtml)

---

Additional references and a second patient's perspective are on bmj.com>

We thank Joy Choules for her help with typing the manuscript and Alan Begg, Hugh Bethell, Denis Pereira Gray, Tony Mourant, Rod Taylor, and Jenny Wingham for their comments on earlier drafts of this paper.

Contributors: HD and PHE conducted the literature searches. All three authors contributed to the design of the review and writing the article.

Funding: HD is the lead researcher for Lower Lemon Street Surgery, Truro, which is an NHS research and development practice funded by the Department of Health. The Department of Health through SaNDNet (Somerset and North and East Devon Primary Care Research Network) funds PHE. JLC is the professor of general practice and primary care, funded by the Peninsula Medical School.

Competing interests: None declared.

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