Download Guidelines for the secondary prevention of ischaemic heart disease

Guidelines for the secondary prevention of ischaemic heart disease.
Introduction:
Preventative care in general practice is haphazard. A recent significant event audit in the practice
identified less than optimal care of a patient following myocardial infarction. These guidelines have
been produced in response to a recommendation of that meeting.
In the six years after myocardial infarction:
 23% of men and 31% of women suffer a further MI.
 41% of men and 34% women develop angina.
 About 20% patients are disabled by heart failure.
 9% of men and 18% women have a stroke.
 13% of men and 6% women die suddenly.
(Petrie and McMurray, 1998)
There is much strong evidence for the effectiveness of interventions following myocardial infarction:
Aspirin:
(Antiplatelet Trialists’ Collaboration, 1994)
Early administration of aspirin reduces mortality during the acute phase.
Evidence for long term benefit is derived from meta-analysis:
 12% reduction in all cause mortality
 Reduction in vascular deaths from 9.4 to 8.1%.
 31% risk reduction in nonfatal reinfarction.
 Risk reduction of 39% in non-fatal stroke.
 Risk reduction of 25% in any serious vascular death.
The higher the absolute risk the greater the gains for giving aspirin, therefore greatest benefits for
patients with hypertension, diabetes and aged over 65.
18 patients with a 6% annual risk of coronary heart disease need to be treated for one year with
aspirin to prevent one event.
Potential problems:
Aspirin increases the risk of GI bleed 1.5 to 3 fold. Use of 75mg daily in preference to higher doses can
reduce the incidence of serious bleeding.
Conclusion:
Unless there are strong contraindications (allergy or GI bleeding) then aspirin should be prescribed to
patients with ischaemic heart disease in a dose of 75mg daily.
Remember that patients paying for prescriptions can buy aspirin cheaply. If they are not receiving
repeat prescriptions then for audit purposes it is important to record that they are taking the drug.
Beta-blockers:
Taking beta-blockers after myocardial infarction saves lives (reduction in all cause mortality and
sudden death by up to 20%) and reduces the likelihood of non-fatal reinfarction. (Yusuf et al, 1988)
Once again, those with highest absolute risk; the elderly, those with left ventricular dysfunction or
arrhythmias and diabetic patients benefit most from beta-blockers following myocardial infarction.
These patients are often denied these drugs for spurious reasons. (Petrie and McMurray, 1998.)
Potential problems:
Heart failure/left ventricular dysfunction.
Beta-blockers should not be prescribed for patients with acute decompensated heart failure, but those
with left ventricular dysfunction should not be denied beta-blockers. If necessary, a small dose of a
short acting preparation can be tried initially.
Hypoglycaemia:
Beta-blockers do not increase the incidence of hypoglycaemia in insulin dependant diabetics. The
particular benefit to diabetic patients requires that they should be given if at all possible following
myocardial infarction.
Intermittent claudication:
Beta-blockers rarely exacerbate intermittent claudication and therefore should be prescribed if at all
possible.
15 patients with a 6% annual risk of coronary heart disease need to be treated for one year with a
beta-blocker to prevent one event.
The practice uses atenolol as the first choice beta-blocker; there is little evidence on particular dosage
or type of drug. To prevent early morning re-infarction and sudden death a longer acting agent seems
sensible.
Verapamil may be an alternative to a beta-blocker as routine prophylaxis, its greatest benefit being in
patients without heart failure. (Petrie and McMurray, 1998)
Conclusion:
The majority of patients should be prescribed beta-blockers indefinitely following myocardial
infarction. Contraindications are asthma and acute decompensated heart failure (until corrected).
Consider verapamil if a beta-blocker cannot be prescribed.
ACE inhibitors:
(AIRE, 1993, Ambrosioni et al (SMILE), 1994, ISIS-4, 1995, Swedberg et al (CONSENSUS-II), 1992, GISSI3, 1994, Pfeffer et al.(SAVE),1992).
ACE inhibitors reduce all cause mortality, the development of heart failure, myocardial re-infarction,
sudden cardiac death and revascularisation procedures.
Short and long term trials have shown the largest benefits in patients with large infarcts, left
ventricular dysfunction and heart failure.
A considerable proportion of asymptomatic patients with ventricular dysfunction who otherwise
might be missed have much to gain from some form of post infarction screening. (The practice has
open access to echo-cardiography for assessment of left ventricular function.)
Elderly patients have been shown to have the same relative risk reduction and therefore greater
absolute risk reduction and should not be denied therapy.
Patients with a creatinine above 200mmols per litre or patients whose levels rise by 30-50% should
not be given ACE inhibitors. Target doses table 1:
Table 1: target doses of ACE inhibitors in large trials of patients post myocardial infarction.
SAVE / captopril
50mg 3 times daily
AIRE / ramipril
5mg twice daily
GISSI-3 / lisinopril
10mg once daily
ISIS-4 / captopril
50mg twice daily
The practice uses enalapril and lisinopril usually.
Conclusion:
Patients with large infarcts and those with left ventricular dysfunction should be treated with an ACE
inhibitor. Consideration should be given to echo-cardiography if it has not been done.
Cholesterol lowering drugs:
(4S, 1994, and Sacks et al (CARE),1996)
The first priority for lipid lowering therapy with a statin is patients who have had a myocardial
infarction. Treatment is indicated when the cholesterol level is as low as 4.8 mmol/l (or low density
Lipoprotein (LDL) as low as 3.2 mmol/l if measured.)
The second priority for lipid lowering therapy is patients with angina or other clinically overt
atherosclerotic disease who have total cholesterol of 5.5 mmol/l or more (or LDL 3.7 mmol/l or more).
(Includes peripheral vascular disease or symptomatic carotid disease or patients who have had a
bypass graft or angioplasty.) these patients have a risk of major coronary events which averages
approximately 3% per year.
Together these two priority groups encompass 4.8% of the population per year.
(Standing Medical Advisory Committee, 1997) – Their advice is summarised as:
1.
Consider other methods of reducing the risk of coronary heart before prescribing statins.
2.
Prescribe statins to those who have had a heart attack and have total cholesterol of 4.8 mmol/l or
more, or have angina and total cholesterol of 5.5 mmol/l or more.
3.
Treatment should be started at a low dose and increased as necessary to reduce total cholesterol
to 5.0 mmol/l or by 20-25% in those high risk patients (e.g. with a previous MI) who have serum
cholesterol below 6.3 mmol/l before starting treatment.
Statins reduce coronary heart disease mortality by 25%. Relative Risk for coronary heart disease
mortality = 0.74 (95%CI: 0.66-0.83).
The very long term safety of statins has not been established.
Fibrates reduce coronary heart disease mortality much less: Relative Risk = 0.93 (95%CI: 0.85-1.01)
(NHS Centre for Reviews and dissemination, 1998).
13 patients with an annual 6% risk of coronary heart disease would have to be treated with a statin to
prevent one event.
Use simvastatin or pravastatin usually.
Blood pressure:
(Sever et al, 1993)
Systematic reviews of RCTs show that for people with high blood pressure, anti-hypertensive
medication reduces the risk of all-cause mortality. The British Hypertensive Society advocates
aggressive treatment of hypertension in patients with coronary heart disease. Consensus is based on
attaining systolic BP below 160 and or diastolic below 90mmHg. Isolated systolic hypertension should
definitely be treated.
Lifestyle Advice:
Lifestyle interventions are as important as drug interventions. They may be shown to diminish the
need for drug intervention, (particularly lipid lowering).
Smoking:
Evidence for stopping smoking in both primary and secondary prevention is strong, (halving of
mortality), Daly, 1983.
Around 2% of patients given nonsmoking advice in a single consultation stop smoking and do not
relapse in one year. (Law and Tang, 1995). The use of nicotine gum increases the quit rate to 4%
(95%CI 2-6%).
The effect of advice to stop smoking is much greater among those who have had a myocardial
infarction with up to 36% stopping, resulting in a 30% reduction in mortality risk. (Burt et al, 1974)
10 patients with a 6% annual risk of coronary heart disease need to receive smoking advice to prevent
one event.
Diet:
Dietary advice following MI demonstrates a greater fall in cholesterol than in population based trials,
almost certainly due to patient motivation. This fall in blood cholesterol is not mirrored in metaanalysis by a significant coronary heart disease mortality reduction. (NHS Centre for Reviews and
dissemination, 1998).
The generally poor performance of some lipid lowering diets may be partly explained by the
substitution of complex carbohydrates for total fat, thus reducing both HDL and LDL cholesterol and
leaving the LDL/HDL ratio unaffected. (NHS Centre for Reviews and dissemination, 1998).
A) Garlic Oats and Soy protein diets:
Trials severely flawed. No clinical endpoints, NO evidence of decreased CDH risk. (NHS Centre for
Reviews and dissemination, 1998).
B) Oily Fish and Mediterranean diet:
1.
Oily fish (and Maxepa): Decreased CV morbidity WITHOUT reducing blood Cholesterol Relative
Risk = 0.65 (95%CI: 0.5-0.9)
2.
Mediterranean diet: No effect on blood cholesterol and again reduced CV morbidity. Relative Risk
= 0.25 (95% CI: 0.1-0.8). The most prominent change in the intervention group was an increase in
consumption of alpha-linolenic acid from rapeseed margarine as participants found it difficult to
consume high intakes of olive oil.
4 patients with 6% annual risk of coronary heart disease need to receive Mediterranean diet to
prevent one event. The number needed to treat for oily fish diet is 9.
Weight loss:
Weight loss in obese patients reduces coronary risk both independently and by improving lipid
concentrations, blood pressure and glucose tolerance. (Khatzel et al, 1995).
Exercise:
Exercise programmes have reduced death rates following myocardial infarction by 20%, (O’Connor et
al, 1989). Many patients with coronary heart disease are afraid of exercise. Advice to promote exercise
can improve survival.
Atrial fibrillation:
Non-rheumatic atrial fibrillation is an important risk factor for stroke, increasing the risk factor by five.
It is particularly important in the elderly. This risk is largely reversed by anticoagulation, (Atrial
Fibrillation Investigators,1994, European Atrial Fibrillation Trial Study Group, 1993). Patients should
have atrial fibrillation confirmed by ECG and should be anticoagulated with warfarin aiming for an INR
of 2.
Conclusions:
Virtually all patients in general practice with coronary heart disease have at least one aspect of
medical management which would benefit from change and at least half have two, Campbell et al,
1998.
References:
Ambrosioni E. Borghi C. Magnani B (1994). Survival of myocardial infarction long term evaluation
(SMILE) study; rationale, design, organisation and outcome definitions. Controlled Clinical Trials; 15:
201-10
Antiplatelet Trialists’ Collaboration, (1994) Collaborative overview of randomised trials of antiplatelet
therapy. 1. Prevention of death, myocardial infarction, and stroke by prolonged antiplatelet therapy in
various categories of patients. BMJ; 308: 81-106
Atrial Fibrillation Investigators (1994) Risk factors for stroke and efficacy of antithrombotic therapy in
atrial fibrillation. Analysis of pooled data from five randomised controlled trials. Arch Intern Med; 154:
1449-57
Burt A. Thornley P. Illingworth D. White P. Shaw TR. Turner R (1974) Stopping smoking after myocardial
infarction. Lancet; 1(7852):304-6, Feb 23.
Campbell N, Thain J, Deans H, Ritchie L, and Rawles J. (1998) Secondary prevention in coronary heart
disease: baseline survey of provision in general practice. BMJ; 316: 1430-4
European Atrial Fibrillation Trial Study Group, (1993) Secondary prevention in non-rheumatic atrial
fibrillation after transient ischaemic attack or minor stroke. Lancet; 342:1255-62
NHS Centre for Reviews and Dissemination, University of York. (1998) Cholesterol and Coronary heart
disease: screening and treatment. Effective Health care; 4(1): 1-15
Daly L, (1983) Long term effect on mortality of stopping smoking after unstable angina and myocardial
infarction. BMJ; 287: 324-6
ISIS-4 Collaborative Group,(1995) A randomised factorial trial assessing early captopril, oral
mononitrate, and intravenous magnesium sulphate in 58050 patients with suspected acute myocardial
infarction. Lancet; 345: 990-5
Khatzel L, Bleecker E, Colman E, Rogus E, Sorkin J, Goldberg A, (1995) Effects of weight loss vs aerobic
exercise training on risk factors for coronary disease in healthy obese, middle aged and older men. A
randomized controlled trial. JAMA; 274: 1915-21
Law M, Tang J, (1995) An analysis of the effectiveness of interventions intended to kelp people stop
smoking. Arch Int Med; 155:1933-41.
O’Connor G, Buring J, Yusuf S, Godhaber S, Olmstead E, (1989) An overview of randomised controlled
trials of rehabilitation with exercise after myocardial infarction. Circulation; 80: 234-44
Petrie M, McMurray J, (1998) Secondary prevention of myocardial infarction. Prescriber; Vol 9, issue
9:75-88
Pfeffer MA. Braunwald E. Moye LA. Basta L. Brown EJ Jr. Cuddy TE. Davis BR. Geltman EM. Goldman S.
Flaker GC. et al.(1992). Effect of captopril on mortality and morbidity in patients with left ventricular
dysfunction after myocardial infarction. Results of the survival and ventricular enlargement trial. The
SAVE Trial. NEJM; 327(10):669-77, Sep 3.
Sacks FM. Pfeffer MA. Moye LA. Rouleau JL. Rutherford JD. Cole TG. Brown L. Warnica JW. Arnold JM.
Wun CC. Davis BR. Braunwald E. (1996) The effect of pravastatin on coronary events after myocardial
infarction in patients with average cholesterol levels. Cholesterol and Recurrent Events Trial
investigators (CARE). NEJM; 335(14):1001-9, Oct 3.
Swedberg K, Held P, Kjekshus J, Rasmussen K, Ryden L and Wedel H, (1992) Effects of the early
administration of enalapril on mortality in patients with acute myocardial infarction. Results of the
Cooperative New Scadinavian Enalapril Survival Study II (CONSENSUS II). NEJM; 327(10): 678-84 Sep 3.
Scandinavian Simvastatin Study Group (1994) Randomised trial of cholesterol lowering in 4444
patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S). Lancet; 344:
1383-89
Sever P, Beevers G, Bulpitt C, Lever A, Ramsay L, Reid J, (1993) Management guidelines in essential
hypertension: report of the second working party of the British Hypertension Society. BMJ; 306: 983-7
Standing Medical Advisory Committee, (1997) The use of Statins. London: Department of Health,
(11061 HCD Aug97(04))
The Acute Infarction Ramipril Efficacy (AIRE) Investigators (1993). Effects of ramipril on mortality and
morbidity of survivors of acute myocardial infarction with clinical evidence of heart failure. Lancet;
342:821-8
Third Gruppo Italiano per lo Studio della Sopravvienza nell’infarcto Myocardio, (1994). GISSI-3: effects
of lisinopril and transdermal glyceryl trinitrate singularly and together on six week mortality and
ventricular function after acute myocardial infarction. Lancet; 343: 1115-22
Yusuf S, Wittes J, Friedman L, (1988) Overview of randomised clinical trials in heart disease. 1.
Treatments following myocardial infarction. JAMA; 260: 2088-93
Guidelines produced by:
John Potter
Steve Holmes
Adrian Dunbar
Sheena McMain
Shirley Brierley
Simon Towers
Alison Evans
Consultation with:
Keith Collett, General Practitioner
Julien Clark, General Practitioner
Barry Clarson, General Practitioner
Tony Salisbury, General Practitioner
Rob Bain, Cardiologist
Sian Burton, Dietician
Sheila Popplewell, Health Visitor
Sharman Burchell, Practice Nurse
Barbara Rafiuddin, Practice Nurse
To be reviewed after one year or before if new scientific evidence or professional consensus.