|
| Team Leader: Dr David Fone |
Date of completion: 30.9.98 |
|
This bulletin is a supplement to, not a substitute for, professional skills and experience. Users are advised to consult the supporting evidence for a consideration of all the implications of a recommendation. | |
| The Statements | The Evidence |
| 4.1 Clinical guidelines | |
| 4.1a. Acute myocardial infarction characteristically
presents with an acute onset of severe chest pain at resti.
Clinical guidelines and audit standards for the management of acute
myocardial infarction are available from the British Cardiac
Societyi, the American Heart Associationii and
European Society of Cardiologyiii. (Health gain notation - 1 "beneficial")
|
i. de
Bono DP, Hopkins A, for a working party of the joint audit committee of
the British Cardiac Society and the Royal College of Physicians of London.
The management of acute myocardial infarction. British Cardiac
Society, 1996. http://www.cardiac.org.uk/ (Type V evidence - expert opinion) ii. Ryan TJ, Anderson JL, Antman EM, et al. ACC/AHA guidelines for management of patients with acute myocardial infarction: a report of the American College of Cardiology/American Heart Association task force on practice guidelines (committee on management of acute myocardial infarction). Circulation 1996;94:2341-50 http://www.americanheart.org/Scientific/statements/1996/ acmi-toc.htm (Type V evidence - expert opinion) iii. Julian DG, Boissel JP, de Bono DP, et al. Acute Myocardial Infarction: pre-hospital and in-hospital management. European Heart Journal 1996;17:43-63. http://www.escardio.org/guidelines/96acute.pdf [Adobe Acrobat reader required] (Type V evidence - expert opinion) |
| 4.2 Out of hospital cardiac arrest | |
| 4.2a. Bystander cardio-pulmonary resuscitation (CPR) is
associated with improved survival to discharge from hospital to home (2.9%
vs. 0.8%, odds ratio for survival 3.7; 95% CI: 1.7, 8.8; p<0.001). CPR
judged to be performed effectively has greater benefit (survival 4.6% vs.
2.0%, odds ratio for CPR effectively compared to ineffectively performed
3.9; 95% CI: 1.1, 14.0; p<0.04)i. (Health gain notation - 1 "beneficial") |
i. Gallagher E, Lombardi G,
Gennis P. Effectiveness of bystander cardiopulmonary resuscitation and
survival following out-of hospital cardiac arrest. Journal of the
American Medical Association 1995;274:1922-25 |
| 4.2b. Defibrillation and Basic Life Support (BLS) of
patients with out-of-hospital cardiac arrest is associated with a
9.2% increase in survival compared to BLS and no defibrillationi
(odds ratio 0.92; 95% CI: 0.88, 0.96; p=0.0003)ii.
(Health gain notation - 1 "beneficial") Caveat: Meta-analysis based on USA case series, limited by exclusion of unpublished studies and the complexity of confounding variables.
|
i.
Watts DD. Defibrillation by basic emergency medical technicians: effect on
survival. Annals of Emergency Medicine 1995;26:635-39. In:
Database of Reviews of Effectiveness. The Cochrane Library,
Issue 4. Oxford: Update Software, 1998 (Type IV evidence - systematic review and meta-analysis of 1827 patients in seven prospective case series) ii. Auble TE, Menegazzi JJ, Paris PM. Effect of out-of-hospital defibrillation by basic life support providers on cardiac arrest mortality: a meta-analysis. Annals of Emergency Medicine 1995;25:642-48. In: Database of Reviews of Effectiveness. The Cochrane Library, Issue 4. Oxford: Update Software, 1998 (Type IV evidence - systematic review and meta-analysis of 4017 patients in ten case series) |
| 4.2c. Compared to Basic Life Support (BLS) &
defibrillation, a two-tier system including Advanced Life Support
(ALS) for out-of-hospital cardiac arrest is associated with increased
survival (ALS survival to discharge 10.5% vs. BLS & defibrillation
5.2%). A one-minute decrease in the mean response time of ALS was
associated with an absolute increase in survival of
0.7%i. (Health gain notation - 1 "beneficial") Caveat: Meta-analysis based on USA case services in limited geographical areas. Further studies are required to examine the effectiveness of out-of-hospital life support systems. |
i.
Nichol G, Detsky AS, Stiell IG, O’Rourke K, Wells G, Laupacis A.
Effectiveness of emergency medical services for victims of out-of-hospital
cardiac arrest: a meta-analysis. Annals of Emergency Medicine
1996;27:700-10. In: Database of Reviews of Effectiveness.
The Cochrane Library, Issue 4. Oxford: Update Software,
1998 (Type IV evidence - systematic review and meta-analysis of 23,313 cardiac arrests in 36 case series)
|
| 4.2d. Evidence-based guidelines for the pre-hospital
management of acute myocardial infarction (MI) are
availablei. (Health gain notation - 1 "beneficial") |
i.
Arntz H, Bossaert L, Carli P, et al. The pre-hospital management
of acute heart attacks. Recommendations of a Task Force of the European
Society of Cardiology and the European Resuscitation Council. European
Heart Journal 1998;19:1140-64 http://www.escardio.org/guidelines/98prehosp.pdf [Adobe Acrobat reader required] (Type V evidence - expert opinion) |
| 4.3 Thrombolytic therapy | |
| 4.3a. Thrombolytic therapy improves survival in acute
MI, with greatest benefit in patients treated within one hour of
symptom onseti: proportional mortality reduction at 35 days
48%; 95% CI: 31%, 61%; and significantly higher in patients treated within
two hours, 44% (32%, 53%) than in those treated later, 20% (15%, 25%).
Pre-hospital thrombolysis is associated with significantly reduced risk of
cardiac deathii,iii. Survival benefits apply to all age-groups
and cost-effectiveness has been demonstrated in the elderlyiv.
Overall benefits of thrombolytic therapy are 65 (95% CI: 38, 93)
lives saved per 1000 treated patients at 0-1 hours following symptom
onset, 37 (20, 55), 26 (14, 37), 29 (19, 40) and 18 (7, 29) in the 1-2,
2-3, 3-6 and 6-12 hour intervals, respectively. No benefit was found for
thrombolysis at 12-24 hours, 9 (-5, 22)i. (Health gain notation - 1 "beneficial") Caveat: Thrombolytic therapy is associated with several major adverse effectsv: five extra deaths (SD 1)/1000 patients treated and 4 extra strokes (2 fatal)/1000 on day of randomisation, and 7/1000 excess of major non-cerebral bleeds (requiring transfusion or life-threatening) at 35 days. |
i.
Boersma E, Maas AC, Deckers JW, Simoons ML. Early thrombolytic
treatment in acute myocardial infarction: reappraisal of the golden hour.
Lancet 1996;348:771-75 (Type I evidence - systematic review and meta-analysis of 50,246 patients in 22 randomised controlled trials) ii. Rawles J. Magnitude of benefit from earlier thrombolytic treatment in acute myocardial infarction: new evidence from Grampian Region Early Anistreplase Trial. (GREAT). British Medical Journal 1996;312:212-26 (Type II evidence - randomised controlled trial of 311 patients (mean age 63 years, 70% men) with suspected acute MI randomised to anistreplase or placebo at home within four hours of symptom onset) iii. The European Myocardial Infarction Project (EMIP) Group. Prehospital thrombolytic therapy in patients with suspected acute myocardial infarction. New England Journal of Medicine 1993;329:383-89. (Type II evidence - randomised controlled trial of 2750 patients with suspected acute MI home within six hours of symptom onset randomised to anistreplase prehospital with placebo in hospital, or placebo prehospital followed by anistreplase in hospital) iv. Krumholtz HM, Pastemak RC, Weinstein MC, et al. Cost effectiveness of thrombolytic therapy with streptokinase in elderly patients with suspected acute myocardial infarction. New England Journal of Medicine 1992; 327:7-13 (Type IV evidence - decision analytical model based on randomised controlled trial data) v. Fibrinolytic Therapy Trialists’ (FTT) Collaborative Group. Indications for fibrinolytic therapy in suspected acute myocardial infarction: collaborative overview of early mortality and major morbidity results from all randomised trials of more than 1000 patients. Lancet 1994;343:311-22 (Type I evidence - systematic review and meta-analysis of nine trials randomising >1000 patients with suspected acute MI to fibrinolytic therapy or control) |
| 4.3b. Immediate percutaneous transluminal coronary
angioplasty (PTCA) is more effective than thrombolytic therapy in
acute MI: odds ratio of death at 30 days 0.66; 95% CI: 0.46, 0.94;
p=0.02i. No convincing reduction in mortality in patients
receiving both thrombolysis and PTCA compared to thrombolysis alone has
been demonstatedii. (Health gain notation - 2 "likely to be beneficial") Caveat: Studies were performed in hospitals with the experience and facilities to provide primary PTCA. Further trials evaluating longer-term outcomes, operator experience, time to treatment and optimal thrombolytic regimes are required.
|
i.
Weaver WD, Simes RJ, Betriu A, et al. Comparison of primary coronary
angioplasty and intravenous thrombolytic therapy for acute myocardial
infarction: a quantitative review. Journal of the American Medical
Association 1997;278:2093-98. In: Database of Reviews of
Effectiveness. The Cochrane Library, Issue 4. Oxford: Update
Software, 1998 (Type I evidence - systematic review and meta-analysis of 2606 patients in ten trials comparing primary PTCA vs. thrombolysis) ii. Michels KB, Yusuf S. Does PTCA in acute myocardial infarction affect mortality and reinfarction rates? A quantitative overview (meta-analysis) of the randomised clinical trials. Circulation 1995;91(2):476-85 (Type I evidence - systematic review and meta-analysis of seven trials evaluating primary PTCA and 16 trials evaluating PTCA following thrombolysis) |
| 4.4 Drug therapy | |
| 4.4a. Treatment of patients with suspected or definite
acute MI with antiplatelet therapy is associated with
reduced MI, stroke and vascular mortality at one month (% odds reduction
29% (SD 4%), risk reduction 38/1000 patients, p<0.000, NNT=26) and a
significant reduction in non-fatal MI (% odds reduction 54%, SD 8%,
12/1000; p<0.000, NNT=83) and non-fatal stroke (% odds reduction 40%,
SD 17%, 2/1000; p<0.02, NNT=50)i. Benefits of aspirin
therapy are independent of, and additive to, thrombolytic
therapyii and early survival benefits are maintained for at
least ten yearsiii. (Health gain notation - 1 "beneficial") |
i.
Antiplatelet Trialist's Collaboration. Collaborative overview of
randomised trials of antiplatelet therapy - I: Prevention of death,
myocardial infarction and stroke by prolonged antiplatelet therapy in
various categories of patients. British Medical Journal
1994;308:81-106. In: Database of Reviews of Effectiveness.
The Cochrane Library, Issue 4. Oxford: Update Software,
1998 (Type I evidence - systematic review and sub-group meta-analysis of 20,000 patients in nine trials of antiplatelet therapy in patients with acute MI) ii. ISIS-2 (Second International Study of Infarct Survival) Collaborative Group. Randomised trial of intravenous streptokinase, oral aspirin, both, or neither among 17,187 cases of suspected acute myocardial infarction: ISIS-2. Lancet 1988;2:349-60 (Type II evidence - randomised controlled trial) iii. ISIS-2 (Second International Study of Infarct Survival) Collaborative Group: 10 year survival among patients with suspected acute myocardial infarction in randomised comparison of intravenous streptokinase, oral aspirin, both, or neither. British Medical Journal 1998;316:1337-43 (Type II evidence - randomised controlled trial) |
| 4.4b. Early or late post-MI therapy with
beta-blockers reduces one year mortalityi,ii (odds ratio
0.81; 95% CI: 0.75, 0.87, p<0.0001)ii. High risk patients
(previous MI or angina) receive greater benefit than low
riski. (Health gain notation - 1 "beneficial") Caveat: Trial data mainly pre-dates the thrombolytic era |
i. The
Beta-Blocker Pooling Project (BBPP): subgroup findings from randomised
trials in post infarction patients. European Heart Journal
1988;9:8-16 (Type I evidence - systematic review and meta-analysis of 13,679 patients in nine trials) ii. Teo KK, Yusuf S, Furberg CD. Effects of prophylactic antiarrhythmic drug therapy in acute myocardial infarction. An overview of results from randomised controlled trials. Journal of the American Medical Association 1993;270:1589-95 (Type I evidence - systematic review and meta-analysis of 53,268 patients in 55 trials) |
| 4.4c. Heparin therapy without aspirin reduces ten day
mortality by 25% (95% CI: 10%, 38%; p=0.002) representing 35 (SD 11) fewer deaths/1000. There is little benefit from the addition of heparin therapy to aspirin: reduction in ten day mortality 6% (95% CI: 0%, 10%; p=0.03) representing 5 fewer deaths/1000. Both regimes are associated with adverse effects of excess major bleeds of between 3 and 13/1000, p<0.000i. (Health gain notation - 3 "trade-off between beneficial and adverse effects") Caveat: Outcome measures were poorly defined and not assessed blind to treatment group in the primary studies. |
i.
Collins R, Mac Mahon S, Flather M, et al. Clinical effects of
anticoagulant therapy in suspected therapy in suspected acute myocardial
infarction: a systematic overview of randomised trials. British Medical
Journal 1996;313:652-59. In: Database of Reviews of
Effectiveness. The Cochrane Library, Issue 4. Oxford: Update
Software, 1998 (Type I evidence - systematic review and meta-analysis of 5000 patients in 21 trials without routine use of aspirin and 68,000 patients in six trials with routine use of aspirin that assessed the addition of iv or sc heparin) |
| 4.4d.
Hirudin has not been shown to be more effective than heparin
as adjunctive therapy to thrombolysis in preventing unsatisfactory
outcome at 30 days (death, recurrent infarction, congestive failure or
cardiogenic shock) in patients with acute MI, with no difference in the
rate of major haemorrhagei,ii. (Health gain notation - 4 "unknown") Caveat: Further trials to assess the most effective dose and duration of hirudin therapy are required. |
i.
Antman E, for the TIMI 9B Investigators. Thrombolysis and Thrombin
Inhibition in Myocardial Infarction (TIMI) 9B Trial. Circulation
1996;94(5):911-21 (Type II evidence - randomised controlled trial of 3002 patients with unstable angina or acute MI randomised to heparin or hirudin together with thrombolytic therapy) ii. The Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO) IIb Investigators. A comparison of recombinant hirudin with heparin for the treatment of acute coronary syndromes. New England Journal of Medicine 1996;335:775-82 (Type II evidence - randomised controlled trial of 12,142 patients with unstable angina or acute MI randomised to 72 hours therapy with heparin or hirudin following treatment with aspirin and thrombolytic therapy) |
| 4.4e. The most robust evidence available suggests that
magnesium sulphate following thrombolysis in acute MI is not
associated with a reduction in mortality at short-term (five week)
follow-upi. (Health gain notation - 5 "unlikely to be beneficial")
|
i.
ISIS-4: A randomised factorial trial assessing early oral captopril, oral
mononitrate, and intravenous magnesium sulphate in 58 050 patients with
suspected acute myocardial infarction. Lancet
1995;345:669-85 (Type I evidence - meta-analysis of nine small trials, and two larger trials: one randomising 2316 patients with acute MI to iv magnesium sulphate or placebo and ISIS-4, a randomised controlled trial of 58,050 patients in a 2´ 2´ 2 factorial design comparing captopril, mononitrate and iv magnesium sulphate with placebo) |
| 4.4f. An overview of early trials suggests
amiodarone reduces the risk of arrhythmic cardiac death post-MI (odds
ratio 0.71; 95% CI: 0.51, 0.97; p=0.03)i. Patients at high risk
of arrhythmic death are likely to
benefitii,iii. (Health gain notation - 2 "likely to be beneficial") Caveat: Poor validity of some primary studies in the meta-analysisi. Due to serious adverse effects of amiodarone, use is reserved for patients at high risk of arrhythmic death.
|
i. Teo
KK, Yusuf S, Furberg CD. Effects of prophylactic antiarrhythmic drug
therapy in acute myocardial infarction. An overview of results from
randomised controlled trials. Journal of the American Medical
Association 1993;270:1589-95 (Type I evidence - systematic review and meta-analysis of 1557 patients in eight trials, 191 patients in heart failure in three trials and 1366 patients within one month post-MI) ii. Julian DG, Camm AJ, Frangin G, et al, for the European Myocardial Infarct Amiodarone Trial Investigators. Randomised trial of effect of amiodarone on mortality in patients with left ventricular dysfunction after myocardial infarction: EMIAT. Lancet 1997;349:667-74 (Type II evidence - randomised controlled trial of 1486 patients with acute MI and ejection fraction <40% randomised to amiodarone or placebo with median 21 month follow-up) iii. Cairns JA, Connolly SJ, Roberts R, Gent M, for the Canadian Amiodarone Myocardial Infarction Arrhythmia Trial Investigators. Randomised trial of outcome after myocardial infarction in patients with frequent or repetitive ventricular premature depolarisations. CAMIAT. Lancet 1997;349:675-82 (Type II evidence - randomised controlled trial of 1202 patients with acute MI and frequent ventricular premature depolarisations randomised to amiodarone or placebo with two year follow-up) |
| 4.4g. Angiotensinogen converting enzyme (ACE) inhibitor
therapy started early in acute MI is associated with a
one-month odds reduction in mortality of 7%; 95% CI: 2%, 11%; p=<0.004,
equivalent to 5 (SD 2) fewer deaths/1000 treated. Survival benefit seems
to persist for at least one yeari. (Health gain notation - 2 "likely to be beneficial) Caveat: ACE inhibitors have significant adverse effects of hypotension and renal dysfunction. |
i. ACE
inhibitor Myocardial Infarction Collaborative Group. Indications for ACE
inhibitors in the early treatment of acute myocardial infarction.
Circulation 1998;97:2202-12 (Type I evidence - systematic review and meta-analysis of 98,496 patients in four randomised controlled trials ACE inhibitor treatment in acute phase MI) |
| 4.4h. Oral mononitrate therapy started early in
acute MI is not associated with a significant reduction in five-week
mortalityi. Meta-analysis of trials of oral and iv nitrates
found a non-significant 3% odds reduction in short-term
mortalityi. (Health gain notation - 4 "unknown") Caveat: There was significant heterogeneity between the trials - effectiveness of nitrates remains unproven. |
i.
ISIS-4: A randomised factorial trial assessing early oral captopril, oral
mononitrate, and intravenous magnesium sulphate in 58 050 patients with
suspected acute myocardial infarction. Lancet
1995;345:669-85 (Type I evidence - randomised controlled trial of58,050 patients in a 2´ 2´ 2 factorial design comparing captopril, mononitrate and iv magnesium sulphate with placebo, and meta-analysis of 23 randomised controlled trials of oral and iv nitrates in early MI) |
| 4.4i. Nifedipine therapy may be associated with an
increased risk in total mortality in patients with coronary heart disease
(CHD); overall risk ratio 1.16; 95% CI: 1.01, 1.33. The risk increases
with increasing doses so that only daily doses of 80mg or more are
associated with excess mortality; risk ratio 2.83; 95% CI: 1.35,
5.93i. (Health gain notation - 6 "likely to be harmful") Caveat: The validity of the primary studies was not assessed and the search strategy not stated. Further larger trials comparing with other therapies such as beta-blockers are necessary for more robust clinical implications to be drawn. |
i.
Furberg CD, Psaty BM, Meyer JV. Nifedipine: dose-related increase in
mortality in patients with coronary heart disease. Circulation
1995;92:1326-31. In: Database of Reviews of Effectiveness.
The Cochrane Library, Issue 4. Oxford: Update Software,
1998 (Type I evidence - systematic review and meta-analysis of 8354 patients in 16 trials of secondary prevention with nifedipine: 12 MI, three unstable and one stable angina) |
| 4.5 Implantable cardioverter defibrillators and pacemakers | |
| 4.5a. There is preliminary evidence that implantable
cardioverter defibrillators may prove an efficaciousi - iii
and cost-effectiveii treatment for malignant ventricular
tachyarrhythmias: % relative reduction in total mortality 39% (95% CI:
19%, 59%) at one year, 27% (6%, 48%) at two years and 31% (10%, 52%) at
three yearsiii. No benefit was found in a trial of prophylactic
implantation of defibrillators in patients undergoing elective coronary
artery bypass surgeryiv. (Health gain notation - 2 "likely to be beneficial") Caveat: Restrictive entry criteria to these trials limit the generalisability of the findings. Further trials are in progress to ascertain the precise sub-groups of high risk patients likely to benefitv and further evidence of cost-effectiveness is required. |
i. Moss
AJ, Hall J, Cannom DS, et al, for the Multicenter Automatic Defibrillator
Implantation Trial (MADIT) Investigators. Improved survival with an
implanted defibrillator in patients with coronary disease at high risk for
ventricular arrhythmia. New England Journal of Medicine
1996;335:1933-40 (Type II evidence - randomised controlled trial of 196 high-risk patients aged 25 to 80 years with CHD and asymptomatic unsustained ventricular tachycardia, randomised to antiarrhythmic therapy or defibrillator) ii.Wever EFD, Hauer RNW,
Schrijvers G, et al. Cost-effectiveness of implantable defibrillator as
first-choice therapy versus electrophysiologically guided, tiered strategy
in post-infarct sudden death survivors. A randomised study.
Circulation 1996;93:489-96 |
| 4.5b. Guidelines for the management of arrhythmias with
cardiac pacemakers and implantable cardioverter
defibrillators are availablei. (Health gain notation - 1 "beneficial")
|
i.
Gregoratos G, Cheitlin MD, Conill A, et al. ACC/AHA guidelines for
implantation of cardiac pacemakers and antiarrhythmia devices: a report of
the American College of Cardiology/American Heart Association task force
on practice guidelines (committee on pacemaker implementation). Journal
of the American College of Cardiology 1998;31:1175-1209 http://www.americanheart.org/Scientific/statements/1998/ 049802.html (Type V evidence - expert opinion) |
| 4.6 Secondary prevention | |
| 4.6a. CHD and total mortality risk is proportional to
net reduction in total cholesterol (10% reduction in total
cholesterol associated with an expected 15% risk reduction in CHD and 11%
total mortality)i. (Health gain notation - 1 "beneficial") |
i.
Gould AL, Rossouw JE, Santanello NC, Heyse JF, Furberg CD. Cholesterol
reduction yields clinical benefit - impact of statin trials.
Circulation 1998;97:946-52 (Type I evidence - systematic review and meta-analysis of 38 observational primary and secondary prevention studies and randomised controlled trials of lipid lowering agents including eight statin trials) |
| 4.6b. Simvastatin therapy in men and post-menopausal
women aged 35 to 70 years, with a history of MI more than six
months previously and/or stable angina, and a trial entry total
cholesterol of 5.5 to 8.0 mmol/l and serum triglyceride = 2.5 mmol/l,
reduced the risk of death from any cause (primary endpoint) by 30% (95%
CI: 15%, 42%; p=0.0003), from CHD by 42% (95% CI: 27%, 54%), of a major
coronary event (secondary endpoint - CHD death, non-fatal MI or
resuscitated cardiac arrest) by 34% (95% CI: 25%, 41%; p<0.00001), and
revascularisation (one of four tertiary endpoints) by 37% (95% CI: 26%,
46%; p<0.00001). Post-hoc analysis found a reduction in fatal or
non-fatal stroke of 30% (95% CI: 4%, 48%; p=0.024)i. No
interactions between therapy, gender or age were found; benefits apply to
both males and females aged under or over 60 years. (Health gain notation - 1 "beneficial") Caveat: The many exclusion criteria used in this study, including unstable angina, MI in previous six months, planned revascularisation, arrhythmia, heart failure and previous stroke, limits the generalisability of the results. In addition only 37% of subjects were taking aspirin. |
i.
Scandinavian Simvastatin Survival Study Group. Randomised trial of
cholesterol lowering in 4444 patients with coronary heart disease: the
Scandinavian Simvastatin Survival Study (4S). Lancet
1994;344:1383-89 (Type II evidence - randomised controlled secondary prevention trial of 3617 men and 827 post-menopausal women aged 35-70 with stable angina or previous MI (79%), randomised to double blind treatment with simvastatin 20-40mg or placebo, median 5.4 year follow-up) |
| 4.6c. Pravastatin therapy in men and post-menopausal
women aged 21-75 years, with a history of MI in the last three to
20 months, a trial entry total cholesterol < 6.2 mmol/l, LDL
cholesterol of 3.0 to 4.5 mmol/l, and fasting triglyceride <4.0 mmol/l,
reduced the overall risk of the study primary endpoint of non-fatal MI or
death from CHD by 24% (95% CI: 9%, 36%; p=0.003). The risk reduction of a
major coronary event (primary endpoint or revascularisation) was minus 3%
(95% CI: -38%, 23%) for those with an LDL cholesterol <3.2 mmol/l, 26% (95% CI: 13%, 38%) with an LDL cholesterol 3.2 to 3.9 mg/dl, and 35% (95% CI: 17%, 50%) with an LDL cholesterol >3.9 to 4.5 mmol/l. These effects were not substantially altered by factors such as age, smoking status co-morbidity or previous revascularisationi. Risk reduction for stroke was 31% (95% CI: 3%, 52%; p=0.03). (Health gain notation - 1 "beneficial") Caveat: Patients with poorly controlled diabetes or symptomatic congestive heart failure (ejection fraction <25%) were excluded from the trial; the results may not be generalisable to these sub-groups. |
i.
Sacks FM, Pfeffer MA, Moye LA, et al, for the Cholesterol and Recurrent
Events (CARE) Trial Investigators. The effect of pravastatin on coronary
events after myocardial infarction in patients with average cholesterol
levels. New England Journal of Medicine
1996;335:1001-09 (Type II evidence - randomised controlled secondary prevention trial of 3583 men and 576 post menopausal women aged 21-75 years, with previous MI, and total cholesterol levels <6.2mmol/l and LDL cholesterol 3.0 to 4.5 mmol/l, randomised to double blind treatment with pravastatin 40mg daily or placebo, median five year follow-up)
|
| 4.6d. A further analysisi of a systematic
review and meta-analysis of ten secondary prevention trialsii
found that to prevent one combined endpoint of death, non-fatal
stroke or non-fatal myocardial infarction, 11 people (95% CI: 10, 13) with
a history of MI and/or stable angina would have to be treated with a
statin for 2.9 years. (Health gain notation - 1 "beneficial")
|
i.
Statins. Bandolier 1997, Number 47. Volume 5, Issue 1 http://www.jr2.ox.ac.uk/bandolier/band47/b47-2.html (Type I evidence - NNT calculations using data from ten randomised controlled secondary prevention trials of 20,589 patients, mean 2.9 year follow-up) ii. Hebert PR, Gaziano JM, Chan KS, Hennekens CH. Cholesterol lowering with statin drugs, risk of stroke, and total mortality. An overview of randomised trials. Journal of the American Medical Association 1997;278:313-21 (Type I evidence - systematic review and meta-analysis of ten randomised controlled secondary prevention trials of 20,589 patients, mean 2.9 year follow-up) |
| 4.6e. The evidence for the cost-effectiveness of
simvastatin and pravastatin in the secondary prevention of MI is strong
after other cost-effective interventions, including aspirin, smoking
cessation, dietary change and exercise, and antihypertensive therapy have
been implementedi. (Health gain notation - 3 "balance of risk and cost-benefit") Caveat: The cost-effectiveness of statin therapy improves when treatment is targeted at high risk individuals. Further research is needed to determine whether a previous MI or an elevated LDL cholesterol is the best risk factor to identify those patients likely to benefit most. |
i.
Cholesterol and coronary heart disease: screening and treatment.
Effective Health Care. Volume 4 Number 1. University of York: NHS
Centre for Reviews and Dissemination 1998 http://www.york.ac.uk/inst/crd/ehc41.htm (Type II evidence - systematic literature review of cost-effectiveness studies based on randomised controlled trial data) |
| 4.6f. Antiplatelet therapy for patients with previous
MI reduces MI, stroke and vascular mortality at 27 month follow-up (%
odds reduction 25%, SD 4%; risk reduction 36/1000 patients, NNT=28) and
significantly reduces non-fatal MI (% odds reduction 31%, SD 6%, 18/1000;
p<0.000, NNT=56) and non-fatal stroke (% odds reduction 39%, SD 11%,
6/1000; p=0.0005, NNT=200)i. Most patients received aspirin -
where comparison between regimens and antiplatelet agents were possible no
significant differences were notedi. (Health gain notation - 1 "beneficial") |
i.
Antiplatelet Trialist's Collaboration. Collaborative overview of
randomised trials of antiplatelet therapy - I: Prevention of death,
myocardial infarction and stroke by prolonged antiplatelet therapy in
various categories of patients. British Medical Journal
1994;308:81-106. In: Database of Reviews of Effectiveness.
The Cochrane Library, Issue 4. Oxford: Update Software,
1998 (Type I evidence - systematic review and sub-group meta-analysis of 20,000 patients in 11 trials of antiplatelet therapy in patients with previous MI)
|
| 4.6g. Clopidogrel may be more effective than aspirin in
the secondary prevention of non-fatal ischaemic stroke, non-fatal MI, or
vascular death (the CAPRIE composite primary outcome) in patients with
recent ischaemic stroke, MI, or symptomatic peripheral vascular disease:
5.32% vs. 5.83%; relative risk reduction 8.7%; 95% CI: 0.3, 16.5; p=0.043.
No benefit was found for the secondary outcomes of vascular death alone or
death from any cause. No major differences in safety were
showni. (Health gain notation - 2 "likely to be beneficial") Caveat: Significant benefit of clopidogrel was only found for the protocol specified primary outcome. No benefit was shown for clopidogrel over aspirin in the four protocol specified secondary outcomes, including vascular and all-cause mortality. Sub-group analysis found significant heterogeneity between the three patient sub-groups, with significant benefit shown only in patients with previous history of peripheral vascular disease. Further trials and evidence of greater cost-effectiveness is required before the use of clopidogrel is justified over aspirin. |
i.
CAPRIE steering committee. A randomised, blinded trial of clopidogrel
versus aspirin in patients at risk of ischaemic events (CAPRIE). Lancet
1996;348:1329-39 (Type II evidence - randomised controlled trial of 19,185 patients, mean 1.9 year follow-up) |
| 4.6h. A Cochrane Review to determine the relative
effectiveness and safety of ticlopidine and clopidogrel compared to
aspirin in the secondary prevention of important vascular outcomes in
patients at high risk (previous TIA, ischaemic stroke, MI and peripheral
vascular disease) is due for publication in
1999i. (Health gain notation - 2 "likely to be beneficial") |
i. Hankey GJ, Dunbabin
DW, Sudlow CLM. Thienopyridine derivatives (ticlopidine, clopidogrel)
versus aspirin in the secondary prevention of stroke and other important
vascular events among high risk patients. Protocol for a Cochrane Review.
In: The Cochrane Library, Issue 4. Oxford: Update Software,
1998 (Type I evidence - systematic review and meta-analysis) |
| 4.6i.
UK multi-factorial evidence-based guidelines for the
prevention of coronary heart disease are due for publication in
1998i. Updated Joint European guidelines are now
availableii. (Health gain notation - 1 "beneficial")
|
i.
British Cardiac Society, British Hypertension Society, British
Hyperlipidaemia Association http://www.cardiac.org.uk/ (Type V evidence - expert opinion) ii. Wood D, De Backer G, le Faergeman O, Graham I, Mancia G, Pyorala K. Prevention of coronary heart disease in clinical practice. Recommendations of the Second Joint Task Force of European and other Societies on coronary prevention. European Heart Journal 1998;19:1434-1503 http://www.escardio.org/guidelines/98prevention.pdf [Adobe Acrobat reader required] (Type V evidence - expert opinion) |
| 4.7 Cardiac rehabilitation | |
| 4.7a. Cardiac rehabilitation exercise training leads to
improvement in exercise tolerance in patients with CHD and heart failure.
Improvement occurs without significant cardiovascular complications or
adverse outcomesi. (Health gain notation - 1 "beneficial")
|
i.
Wenger NK, Froelicher ES, Smith LK, et al. Cardiac
Rehabilitation. Clinical Practice Guideline Number 17 AHCPR.
Rockville MD: Agency for Health Care Policy and Research and the National
Heart, Lung and Blood Institute, Public Health Service, US Department of
Health and Human Services, 1995. In: Database of Reviews of Effectiveness.
The Cochrane Library, Issue 4. Oxford: Update Software,
1998 http://text.nlm.nih.gov/ftrs/pick?dbName=crpq&ftrsK=33572&cp=1&t=924603855&collect=ahcpr (Type I evidence - systematic review of 46 randomised controlled trials, 25 non-randomised controlled trials and 43 observational studies) |
| 4.7b. Cardiac rehabilitation exercise training reduces
symptoms of angina pectoris in patients with CHD and reduces symptoms of
heart failure in patients with left ventricular systolic
dysfunctioni. (Health gain notation - 1 "beneficial") |
i.
Wenger NK, Froelicher ES, Smith LK, et al. Cardiac
Rehabilitation. Clinical Practice Guideline Number 17 AHCPR.
Rockville MD: Agency for Health Care Policy and Research and the National
Heart, Lung and Blood Institute, Public Health Service, US Department of
Health and Human Services, 1995. In: Database of Reviews of Effectiveness.
The Cochrane Library, Issue 4. Oxford: Update Software,
1998 http://text.nlm.nih.gov/ftrs/pick?dbName=crpq&ftrsK=33572&cp=1&t=924603855&collect=ahcpr (Type I evidence - systematic review of 12 randomised controlled trials, seven non-randomised controlled trials and seven observational studies) |
| 4.7c. Improved lipid and lipoprotein levels are
achieved in patients with CHD who have undergone multifactorial cardiac
rehabilitationi. (Health gain notation - 1 "beneficial")
|
i. Wenger NK, Froelicher
ES, Smith LK, et al. Cardiac Rehabilitation. Clinical Practice
Guideline Number 17 AHCPR. Rockville MD: Agency for Health Care Policy
and Research and the National Heart, Lung and Blood Institute, Public
Health Service, US Department of Health and Human Services, 1995. In:
Database of Reviews of Effectiveness. The Cochrane Library,
Issue 4. Oxford: Update Software, 1998 http://text.nlm.nih.gov/ftrs/pick?dbName=crpq&ftrsK=33572&cp=1&t=924603855&collect=ahcpr (Type I evidence - systematic review of 18 randomised controlled trials, six non-randomised controlled trials and 13 observational studies) |
| 4.7d. Cigarette smoking is reduced in patients who
undergo multifactorial cardiac rehabilitation with well designed
educational and behavioural componentsi. (Health gain notation - 1 "beneficial")
|
i.
Wenger NK, Froelicher ES, Smith LK, et al. Cardiac
Rehabilitation. Clinical Practice Guideline Number 17 AHCPR.
Rockville MD: Agency for Health Care Policy and Research and the National
Heart, Lung and Blood Institute, Public Health Service, US Department of
Health and Human Services, 1995. In: Database of Reviews of Effectiveness.
The Cochrane Library, Issue 4. Oxford: Update Software,
1998 http://text.nlm.nih.gov/ftrs/pick?dbName=crpq&ftrsK=33572&cp=1&t=924603855&collect=ahcpr (Type I evidence - systematic review of five randomised controlled trials, one non-randomised controlled trial and one observational study) |
| 4.7e. Psychological and social functioning are enhanced
through exercise training, particularly as a component of multifactorial
cardiac rehabilitationi. (Health gain notation - 1 "beneficial")
|
i.
Wenger NK, Froelicher ES, Smith LK, et al. Cardiac
Rehabilitation. Clinical Practice Guideline Number 17 AHCPR.
Rockville MD: Agency for Health Care Policy and Research and the National
Heart, Lung and Blood Institute, Public Health Service, US Department of
Health and Human Services, 1995. In: Database of Reviews of Effectiveness.
The Cochrane Library, Issue 4. Oxford: Update Software,
1998 http://text.nlm.nih.gov/ftrs/pick?dbName=crpq&ftrsK=33572&cp=1&t=924603855&collect=ahcpr (Type I evidence - systematic review of nine randomised controlled trials, eight non-randomised controlled trials and two observational studies) |
| 4.7f. Total and cardiovascular mortality are reduced in
patients following MI who participate in cardiac rehabilitation exercise
training as a component of multifactorial rehabilitation. Based on
meta-analysis, at three year follow up, there is a 25% relative reduction
in total mortality in patients undergoing rehabilitation including
exercise trainingi. (Health gain notation - 1 "beneficial") Caveat: Low risk patients were studied. Benefits are likely to apply to high risk patients, but caution in generalising the results is required. |
i. Wenger NK, Froelicher
ES, Smith LK, et al. Cardiac Rehabilitation. Clinical Practice
Guideline Number 17 AHCPR. Rockville MD: Agency for Health Care Policy
and Research and the National Heart, Lung and Blood Institute, Public
Health Service, US Department of Health and Human Services, 1995. In:
Database of Reviews of Effectiveness. The Cochrane Library,
Issue 4. Oxford: Update Software, 1998 http://text.nlm.nih.gov/ftrs/pick?dbName=crpq&ftrsK=33572&cp=1&t=924603855&collect=ahcpr (Type I evidence - two meta-analyses of 7063 patients in 21 randomised controlled trials) |
| 4.7g. Based on aggregate data from the USA (1980-1984),
the very low rates of occurrence of MI (one non-fatal MI per 293,900
patient-hours with one cardiac mortality per 783,976 patient-hours) and
few cardiovascular complications (one cardiac arrest per 111,996
patient-hours) associated with exercise training as part of cardiac
rehabilitation, suggest that cardiac rehabilitation exercise training
is relatively safei. (Health gain notation - 1 "beneficial")
|
i.
Wenger NK, Froelicher ES, Smith LK, et al. Cardiac
Rehabilitation. Clinical Practice Guideline Number 17 AHCPR.
Rockville MD: Agency for Health Care Policy and Research and the National
Heart, Lung and Blood Institute, Public Health Service, US Department of
Health and Human Services, 1995. In: Database of Reviews of Effectiveness.
The Cochrane Library, Issue 4. Oxford: Update Software,
1998 http://text.nlm.nih.gov/ftrs/pick?dbName=crpq&ftrsK=33572&cp=1&t=924603855&collect=ahcpr (Type IV evidence - questionnaire survey of 167 randomly selected cardiac rehabilitation programmes in the USA covering 51,303 patients) |
| 4.7h. Post-MI exercise stress tests are recommended for
determining functional capacity before prescription of exercise intensity
as a component of cardiac rehabilitationi,ii. (Health gain notation - 2 "likely to be beneficial")
|
i.
Thompson DR, Bowman GS, de Bono D P, Hopkins A. Cardiac
rehabilitation: guidelines and audit standards. London: Royal College
of Physicians of London, 1997 (Type V evidence - expert opinion) ii. American College of Sports Medicine. Guidelines for exercise testing and prescription, 4th ed. Philadelphia: Lea and Febiger, 1991 (Type V evidence - expert opinion) |
| 4.7i. Guidelines and audit standards for cardiac
rehabilitation in the UK are availablei. (Health gain notation - 1 " beneficial") |
i.
Thompson DR, Bowman GS, de Bono D P, Hopkins A. Cardiac rehabilitation:
guidelines and audit standards. London: Royal College of Physicians of
London, 1997 (Type V evidence - expert opinion) |
| 4.7j.
Psychosocial interventions in patients with CHD in cardiac
rehabilitation schemes are associated with greater reductions in
physiological distress, systolic blood pressure, heart rate, cholesterol
level, a 41% reduction in mortality at two year follow-up (log-adjusted
odds ratio for mortality in patients not receiving psychosocial
interventions 1.70; 95% CI: 1.09, 2.99) and a 46% reduction in cardiac
recurrence (log-adjusted odds ratio for mortality in patients not
receiving psychosocial interventions 1.84; 95% CI: 1.12,
2.99)i. (Health gain notation - 2 "likely to be beneficial") Caveat: Poor quality meta-analysis with limited literature search did not assess the validity of the primary studies. Further research to identify the specific most effective types of psychosocial interventions is necessary. |
i.
Linden W, Stossel C, Maurice J. Psychosocial interventions for
patients with coronary artery disease: a meta-analysis. Archives of
Internal Medicine 1996; 156:745-52. In: Database of Reviews of
Effectiveness. The Cochrane Library, Issue 4. Oxford: Update
Software, 1998 (Type I evidence - systematic review and meta-analysis of 23 randomised controlled trials covering 3180 patients) |
| 4.7k. There is no valid evidence that patient
education in patients with CHD improves mortality, morbidity and
lifestyle factorsi. (Health gain notation - 4 "unknown") Caveat: Methodological problems include the validity of the primary studies, the diversity of interventions and follow-up, the imprecise inclusion criteria and systematic exclusion of studies in multiple sub-group analyses. |
i. Mullen PD, Mains DA,
Velez R. A meta-analysis of controlled trials of cardiac patient
education. Patient Education and Counselling 1992;19:143-62.
In: Database of Reviews of Effectiveness. The Cochrane
Library, Issue 4. Oxford: Update Software, 1998 (Type I evidence - systematic review and meta-analysis of 28 studies: 14 randomised controlled trials and 14 quasi-experimental studies) |
| 4.7l. There has been no comprehensive
economic evaluation of cardiac rehabilitation. The available
economic evaluations, while limited in scope, suggest that there may be
favourable economic outcomesi. (Health gain notation - 4 "unknown") |
i.
Wenger NK, Froelicher ES, Smith LK, et al. Cardiac
Rehabilitation. Clinical Practice Guideline Number 17 AHCPR.
Rockville MD: Agency for Health Care Policy and Research and the National
Heart, Lung and Blood Institute, Public Health Service, US Department of
Health and Human Services, 1995. In: Database of Reviews of Effectiveness.
The Cochrane Library, Issue 4. Oxford: Update Software,
1998 http://text.nlm.nih.gov/ftrs/pick?dbName=crpq&ftrsK=33572&cp=1&t=924603855&collect=ahcpr (Type II evidence - two randomised controlled trials and two non-randomised controlled studies) |
Dr Alison Weightman, Protocol Enhancement Project, Duthie Library, UWCM, Cardiff CF4 4XN. e-mail: weightmanal@cardiff.ac.uk