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The Pharmaceutical Journal Vol 265 No 7108 p194-205
August 5, 2000 Special feature

Pharmaceutical care

(9) Coronary heart disease

By Steve McGlynn, MSc, MRPharmS, Fiona Reid, MSc, MRPharmS, John McAnaw, BSc, MRPharmS, Surarong Chinwong, MSc and Steve Hudson, MPharm, FRPharmS

Coronary heart disease affects 3.5 per cent of the UK adult population. This article examines the pharmaceutical care of coronary heart disease and covers primary and secondary prevention of the disease and the treatment of angina

Coronary heart disease (CHD) is a major public health problem. It is a contributor to mortality and morbidity in both westernised economies and in countries undergoing economic transition. CHD occurs because of narrowing and/or blockage of the coronary arteries. CHD may be sufficient to cause myocardial ischaemia (ischaemic heart disease, IHD) but may be present in the absence of symptoms. CHD may remain asymptomatic until it manifests as myocardial infarction (MI), sudden death or cardiac dysfunction (such as arrhythmias or cardiac failure). Some patients may therefore suffer consequences of myocardial ischaemia without any history of warning symptoms. Definitions of CHD are given in Panel 1.
About half of all patients known to have CHD complain of angina pectoris. Angina is a characteristic pain, variously described in the chest, jaw, shoulder, back or arm as a "crushing" or "heavy" feeling, although it may also be perceived by patients simply as "discomfort" or "indigestion". Typically, angina is precipitated by exercise, stress or emotion and is relieved by sublingual glyceryl trinitrate (GTN) or rest. In unstable angina, pain may occur at rest, particularly at night, with increasing frequency. Unstable angina is associated with increasing risk of myocardial infarction and it requires immediate medical referral. This paper focuses on the pharmaceutical care associated with the primary and secondary prevention of CHD and the treatment of angina symptoms. The acute hospital treatment of unstable angina and MI are outside the scope of this article.
Reductions in mortality and incidence of MI in those known to have CHD or to be at high risk of the disease are now major public health goals. The evidence base for secondary prevention with drug therapy has implications for pharmaceutical care to help ensure patients are treated appropriately once discharged after an MI. Clinical guidelines need active support through local teamwork in order to target patients most likely to derive benefit. Guidelines provide only a framework that must be carefully individualised to address such factors as the patient's co-morbidity and personal motivation. These factors go beyond the scientific base of the evidence and place emphasis on individualised pharmaceutical care. Table 1 provides examples of co-morbidity that exacerbate the symptoms of established IHD.

Panel 1: Definitions

  • Coronary heart disease - pathological definition:
    • "The narrowing or blockage of the coronary arteries by atheroma, leading to angina, coronary thrombosis or heart attack, heart failure and/or sudden death"1
  • Coronary heart disease - epidemiological definition:
    • Fatal or non-fatal myocardial infarction or incident angina
  • Cardiovascular disease
    • Coronary heart disease plus stroke, peripheral vascular disease and heart failure
Table 1: Conditions provoking or exacerbating ischaemia2
Increased oxygen demand Decreased oxygen supply
Cardiac Non-cardiac Cardiac Non-cardiac
Cardiomyopathy
Aortic stenosis
Tachyarrhythmias		 Hyperthermia
Hyperthyroidism
Sympathomimetic toxicity (eg, cocaine use)
Anxiety
Hypertension
Arteriovenous fistulae		 Aortic stenosis
Cardiomyopathy		 Anaemia
Hypoxaemia
Pneumonia
Asthma
Chronic obstructive pulmonary disease
Pulmonary hypertension
Interstitial pulmonary fibrosis
Obstructive sleep apnoea
Sympathomimetic toxicity (eg, cocaine use)
Hyperviscosity
Polycythaemia
Leukaemia
Thrombocytosis
Hypergammaglobulinaemia

Public health implications of CHD

The prevalence of angina in the UK adult population is estimated to be about 3.5 per cent. It increases with age from 2.5 per cent (in middle aged adults, aged 45-54 years) to 13 per cent (in the elderly, aged 65-74 years).7 CHD accounts for 128,500 UK deaths annually, representing 21 per cent of deaths in England/Wales and 24 per cent in Scotland in 1998.78,79 The trend throughout economically developed countries is towards lower mortality rates. In the UK, deaths from CHD have reduced by 4 per cent per year over the past 20 years. Nevertheless, the UK still has one of the worst CHD mortality rates for of all the populations monitored by the World Health Organisation.
While there appears to have been a decline in the incidence of CHD in the UK, the prevalence of the disease is rising as a result of the ageing population. There are well known inequalities in health attributed to CHD. Cardiovascular mortality in parts of England, Scotland and Northern Ireland are among the highest in the world. CHD is three times more common in unskilled male workers than in men in managerial or professional positions and it is twice as common in the wives of manual workers compared with the wives of non-manual workers.
IHD accounts for 9 per cent of all UK emergency hospital admissions. A recent study in Scotland, which included patients who were not admitted to hospital, has shown that 28-day mortality for MI patients approaches 50 per cent.3 A quarter of patients with an MI die before they are admitted to hospital.4 Survivors are at increased risk of further MI, stroke, cardiac failure and other major coronary events. There is a 10 per cent death rate in the year following discharge post-MI and a subsequent annual death rate of 5 per cent.4
The implementation of educational interventions, lifestyle modification and drug treatment to prevent the development of symptoms of CHD (angina or MI) in high-risk individuals is termed primary prevention. The use of similar measures in patients already presenting with angina or MI is referred to as secondary prevention.
Primary prevention includes a range of health promotion initiatives coupled with targeted pharmacological and non-pharmacological interventions. The identification of high-risk individuals and slowing of the progression of CHD is becoming increasingly important as a public health priority. However, resource implications constrain strategies for screening and primary prevention. A comprehensive screening programme would require almost all individuals over 45 years of age to be screened for lipid profile and blood pressure.6 The profile of CHD for a typical community pharmacy serving a population of 5,000 patients is given in Panel 2.

Evidence base and clinical guidelines in CHD

Panel 3: Modifiable risk factors in CHD

  • Smoking
  • Diet
  • Cholesterol
  • Exercise
  • Alcohol
  • Diabetes mellitus
  • Blood pressure
  • Obesity

Clinical guidelines relating to the management of CHD in the UK have recently addressed the management of hyperlipidaemia in primary prevention of CHD,8 aspirin/antithrombotic therapy in vascular disease,9,10 management of stable angina,11 revascularisation therapy in stable angina12 and secondary prevention of CHD post-MI.13
Drugs for which there is evidence of mortality benefit in CHD patients include statins, aspirin, b-blockers, verapamil and ACE inhibitors. Drugs used in the management of symptoms in angina include b-blockers, calcium channel blockers, nitrates (acute and prophylactic) and potassium channel openers.
The modifiable risk factors for CHD are generally accepted as smoking, poor diet, hypercholesterolaemia, obesity, excessive alcohol intake, lack of exercise, raised blood pressure and inadequate diabetes control (see Panel 3 and Table 2). The need to address such factors is increased in the presence of non-modifiable risk factors such as male gender, increasing age and family history of premature CHD. Other factors relevant to the development of CHD include diabetes and Asian ethnic origin. In practice, both the process of the identification of patients at risk and the interventions have major resource implications. Both primary and secondary prevention of CHD involve similar interventions.

Table 2: Evidence base for benefit of risk factor modification
Risk factor Primary prevention of coronary heart disease In patients with angina and in secondary prevention of myocardial infarction
Smoking Smoking cessation will reduce the risk of death by 50 per cent.32 Men who stop smoking have a reduced risk of MI33 and within two to three years the risk is similar to those who have never smoked34,35 Patients who continued to smoke after an MI had a 22-47 per cent increase in mortality risk.2 In patients followed up for 15 years, 82 per cent mortality was seen in those patients who continued to smoke after the first MI or unstable angina. In patients who had stopped smoking, the figure was 37 per cent.36
Diet Dietary changes (a reduction in saturated fat, cholesterol and an increase in polyunsaturated fat) can result in decreased mortality from CHD.33,37 The addition of stanol esters and plant sterols (which reduce cholesterol absorption) to food, for example margarine, has been shown to reduce plasma cholesterol concentrations by about 10 per cent. The effect equates with a mortality risk reduction of about 23 per cent; lack of control over intake results in variable effects38 There was a 29 per cent reduction in two-year all-cause mortality in post-MI patients who received advice on an increase in fatty fish intake.39 However, the incidence of re-infarction and CHD mortality was not significantly changed. A Mediterranean-type diet (replacing red meat with poultry and increasing fish, vegetables, fruit and use of olive oil) in MI patients demonstrated a 76 per cent reduction in the risk of mortality from CHD.13
Cholesterol Total serum cholesterol of >6mmol/L is associated with an increased incidence of CHD and risk of CHD mortality40  
Exercise Lack of physical fitness or physical activity are associated with an increased risk of death from all causes and from cardiovascular disease both in middle-aged40, 41 and older men42  
Alcohol Mortality from CHD is lowest in those who reported drinking eight to 14 units of alcohol. Drinking above 21 units a week increases total mortality.43 Differences between types and patterns of alcohol intake remain unclear44  
Diabetes mellitus Mortality from CHD increases about three to 10 fold and two to four fold in patients with type 1 and type 2 diabetes, respectively.2 The UKPDS study indicated that for each increment of 1 per cent in HbA1c there was a 1.11 fold increase in risk of CHD5  
Blood pressure Chronic hypertension is closely related to the risk of developing CHD.45 A decrease of 5mmHg in diastolic blood pressure is associated with a 21 per cent decrease in risk of developing CHD46  
Obesity Although increased body mass index is related to increased risk of CHD19, 20 there are no clinical trials of the effect of weight reduction on CHD morbidity or mortality8  

Lifestyle changes are able to address some of the modifiable risk factors, although drug therapy is usually required to control hypercholesterolaemia and hypertension as well as to reduce the likelihood of further vascular events and to control symptoms. Surgical intervention (angioplasty or coronary artery bypass surgery) is, however, the preferred option to treat established CHD in suitable patients.
Co-morbidity occurs with diabetes. Type 1 diabetes is associated with three to 10 times the mortality from CHD and type 2 diabetes with two to four times the mortality.2 In type 2 diabetes, each increment of 1 per cent in glycosylated haemoglobin (HbA1c) is associated with approximately a 10 per cent increase in the risk of CHD.5
Smoking intervention strategies have shown that nicotine replacement (NRT) can double success rates (from less than 5 per cent to 5-10 per cent). Best results (on average 17 per cent abstinence at 12 months14) are achieved when NRT is combined with intensive support (individual motivating advice and group smoking cessation reinforcement).15 NRT is most effective in those who smoke more than 10 cigarettes per day.14
Dietary modification lowers plasma cholesterol on average by only 5 per cent;16 therefore, in most patients drug therapy is necessary to reduce plasma cholesterol. Cardiac rehabilitation can reduce mortality in post-MI patients through a combination of exercise, education and psychological interventions.17
Recommended maximum alcohol intake for the general population is 21 units/week for men and 14 units/week for women.
For hypertension, the joint British recommendations on prevention of CHD in clinical practice suggest that blood pressure should be maintained below 140/85mmHg.18
Obesity (body mass index [BMI] greater than or equal to 30 kg/m2) and being overweight (BMI greater than or equal to 25 kg/m2) adversely affect many cardiovascular risk factors such as blood pressure and cholesterol.19,20

Panel 2: Profile of coronary heart disease in the population of a pharmacy serving 5,000 patients6-8

Risk factor prevalence
1,100 smokers (560 men, 540 women)
1,500 with hypertension (800 men, 700 women)
115 with diabetes (65 men, 50 women)
800 with cholesterol > 6.4 mmol/L (350 men and 450 women)

Candidates for primary prevention (aged 35-64)*
280 with CHD risk greater than or equal to 15 per cent over 10 years
50 with CHD risk greater than or equal to 30 per cent over 10 years

Ischaemic heart disease
120 adults report by questionnaire having had angina pectoris (aged 16 or over)
50 adults aged over 64 years (6 per cent of that age group)
115 adults self-report having had myocardial infarction (aged 16 or over)
65 adults aged over 64 years (9 per cent of that age group)
150 adults aged 35-64 eligible for secondary prevention of CHD

80 adults consult physicians for CHD at least once annually
25 will develop a diagnosis of angina annually
Eight will develop a diagnosis of myocardial infarction (first infarction) annually
11 will be admitted to hospital with acute myocardial infarction annually
11 will die because of CHD annually in England and Wales

14 people will die from CHD annually in Scotland (nine from an acute myocardial infarction)
18 people die from heart disease annually in Scotland (30 per cent of all deaths)

*Based on an analysis of Scottish data6 (other figures based on data for England and Wales unless specified)

Risk assessment in primary prevention

The thresholds for categorising patients at risk of developing CHD identify those at high risk (greater than or equal to 30 per cent risk over 10 years) and intermediate risk (greater than or equal to 15 per cent risk).
Methods to assess a patient's risk of developing CHD are based on estimates from a common source of epidemiological data (the Framingham study) but they vary in practical use. The methods only take into account the standard risk factors - gender, smoking, blood pressure, ratio of total cholesterol to high density lipoprotein (HDL) cholesterol and presence of diabetes. Other factors such as family history of premature CHD, ethnicity, obesity and lifestyle may need to be considered in clinical interpretation and decision making in individual patients. The most commonly used tools are the New Zealand Guidelines,21 the Sheffield Table6 and the Joint British Societies Coronary Prediction Chart.18
The Sheffield table has been used to identify those patients where measurements of total cholesterol and HDL cholesterol are indicated. The recently modified Sheffield table requires only a yes/no categorisation of the patient as hypertensive rather than a systolic blood pressure measurement.6 The Joint British Societies chart requires more information and is not intended for use in treated hypertensive patients. In treated hypertensive patients, the use of a current blood pressure measurement gives an underestimate of risk. None of the charts are used in patients who already have a diagnosis of CHD. The Joint British Societies recommendations have been summarised22 and are included in the Scottish Intercollegiate Guidelines Network (SIGN) recommendations.8
Cardiovascular risk is defined as the CHD risk plus the risk of stroke, vascular disease and heart failure. Cardiovascular risk can be estimated from the CHD risk since the two are correlated; a CHD risk of 15 per cent equates to a cardiovascular risk of 20 per cent.23
Risk assessment in primary prevention is facilitated by computer software to make the estimations. However, inbuilt assumptions and default values used by particular packages need to be recognised in order to avoid misinterpretation.24 Computer-based decision support has yet to be demonstrated to affect clinical decisions or clinical outcomes. The risk charts are accessible via websites (eg, http://cebm.jr2.ox.ac.uk/docs/prognosis.html). Panel 4 illustrates the estimation of coronary risk prediction.

Panel 4: Primary prevention of CHD

Measuring absolute coronary heart disease risk using: (1) the Sheffield tables;6 (2) the Joint British Recommendations coronary risk prediction chart;18 and (3) computer risk assessment18
Calculating absolute risk of developing CHD over 10 years in two patients
  Patient A Patient B
Gender Male Male
Age (years) 50 50
Smoker No Yes
Blood pressure (mmHg) 140/70 140/70
Total cholesterol (mmol/L) 8.2 6.2
HDL cholesterol (mmol/L) 1.3 0.7
Ratio of total cholesterol:HDL 6.3 8.85
Other risk factors None Diabetes mellitus
Sheffield categories for
Hypertension Yes Yes
Smoking No Yes
Diabetes No Yes
Calculated CHD risk (per 10 years):
(1) Sheffield table <15, >30 per cent >30 per cent
(2) Joint British Societies coronary risk prediction chart <15 per cent >30 per cent
(3) Joint British Societies cardiac risk assessor computer program using:
only systolic blood pressure 14 per cent 33 per cent
only diastolic blood pressure 10 per cent 28 per cent
Note: these risk prediction tools should not be used to assess patients with established CHD or other artherosclerotic disease, familial hypercholesterolaemia or malignant hypertension

Low dose aspirin In the absence of contra-indications, low dose aspirin is recommended as antiplatelet therapy by the Joint British recommendations in patients who have a CHD risk greater than or equal to 15 per cent and are aged greater than or equal to 50 years.18 Patients with hypertension should have their blood pressure controlled to minimise the risk of antiplatelet therapy contributing to risk of cerebrovascular bleeding. There is no compelling evidence to support the use of aspirin in lower risk subjects, such as middle-aged males with no other risk factors, eg, hypertension.80

Lipid lowering drugs Lipid lowering drugs are recommended in patients with hyper-cholesterolaemia and a greater than or equal to 30 per cent CHD risk. Since published studies comprise mainly male subjects under 65 years, it is not clear whether women (in whom the onset of CHD can be nearly 10 years later than that of men) or the elderly (in whom CHD is common) show similar benefits with these drugs.

Stable angina and secondary prevention of MI

Chest pain is likely to be due to angina if it is of the typical type and duration (see earlier), is provoked by exercise or stress, and is relieved by GTN or rest. Absence of any of these characteristics reduces the probability of the pain being due to angina. Chest pain may be due to unstable angina if it occurs at rest, is of new onset, is of increasing frequency/duration or occurs at a lower threshold of activity than previously. Some drugs can worsen angina (see Panel 5). Panel 6 shows the Canadian Cardiovascular Society grading system which describes four classes of angina, in a similar way to the four stage classification of heart failure.
Management of angina consists of prevention of serious cardiovascular events, principally fatal and non-fatal myocardial infarction, and symptom control.11 Table 3 contains a summary of the evidence base for secondary prevention in CHD. Drugs for which evidence of mortality benefit in angina patients exists include statins,25-27 aspirin,11,28-30 and ramipril.31 Drugs used in the management of symptoms in angina include b-blockers, calcium channel blockers, nitrates (short and long-acting) and potassium channel openers.11 Some patients may be candidates for surgical intervention - percutaneous transluminal coronary angioplasty (PTCA), usually with coronary stent insertion, or coronary artery bypass surgery.12
Unlike primary prevention, there is no need to assess risk in terms of multiple risk factors when considering lipid-lowering therapy. Total cholesterol concentration greater than or equal to 5mmol/L in a patient with angina is sufficient to warrant treatment, although local variations in the threshold for starting statin therapy may exist.11 Statin treatment can be monitored in secondary prevention to a target LDL cholesterol <3mmol/L.
Since clinical trial evidence supports the use of low-dose aspirin in patients with stable angina, the use of antiplatelet therapy should be considered in all patients with a diagnosis of angina. Provided there are no contraindications, aspirin at a dose of 75mg daily should be prescribed.11
The prescription of the ACE inhibitor ramipril may be considered for high-risk cardiovascular patients who have angina (see Table 3). Whether the benefit shown with this drug can be taken as a class effect awaits further trial evidence.

Panel 5: Drugs that may worsen angina symptoms

  • Short acting preparations of nifedipine
  • Sumatriptan
  • Sildenafil
  • Thyroxine
  • Sympathomimetics

Panel 6: Simplified grading system for angina*

  • Class I Ordinary physical activity does not cause angina
  • Class II Slight limitation of ordinary physical activity
  • Class III Marked limitation of ordinary physical activity
  • Class IV Inability to carry out any physical activity without discomfort
*Source: Canadian Cardiovascular Society2

Symptom control in angina

All patients with angina should be prescribed sublingual GTN to prevent chest pain before exercise and to treat acute attacks on exertion. If the pain is not relieved after three doses over 15 minutes, the situation should be treated as an emergency.
Long-term control of symptoms in angina requires comparison of the evidence base and consideration of additional effects that may make one drug preferable to another in a particular patient. b-blockers are considered the first choice because they have comparable efficacy to calcium channel blockers for angina symptom control. Unlike calcium channel blockers, b-blockers have clearly been shown to reduce mortality in patients with hypertension, left ventricular systolic dysfunction and post-MI.
A calcium channel blocker in the form of a "rate limiting" agent (one which depresses atrioventricular conduction - either verapamil or diltiazem) should be used where b-blockers are contraindicated or poorly tolerated.
Choice of second-line therapy is less clear. Panel 7 gives examples of useful combinations. However, when adding a calcium channel blocker to a b-blocker, verapamil should be avoided and diltiazem used only with caution because of the potential negative intropic effects of the combination. The place of nicorandil in the treatment of angina has still to be determined. The use of long-acting nitrates requires an asymmetric dosing regimen (eg, 8am and 2pm or 4pm and 10pm) to reduce the possibility of nitrate tolerance. In practice, a nitrate-free period can also be achieved using single daily dose oral controlled release preparations, or removing a transdermal patch at night. There is no evidence to support the addition of a third or fourth drug. However, in patients not suitable for either coronary artery bypass graft (CABG) surgery or PTCA, additional drugs are prescribed.

Surgical revascularisation These procedures include PTCA (usually with coronary stent insertion) and CABG surgery and they are indicated for symptom control in patients selected by coronary angiography.
Patients undergoing angioplasty with stent insertion also require combination antiplatelet therapy, such as clopidogrel 75mg daily for 28 days added to long-term low-dose aspirin. Patients need to be informed of the temporary nature of this treatment. Following bypass surgery or angioplasty it may be necessary to review the patient's drug treatment to allow the likely discontinuation of medication for angina symptoms. Intended changes to the medication need to be communicated to the patient and members of the primary care team. Panel 7 summarises recommendations on the management of stable angina.

Panel 7: Guidelines for the treatment of chronic stable angina pectoris2-11

Antiplatelet therapy to reduce risk of myocardial infarction
Aspirin 75mg daily in the absence of contraindications. Clopidogrel 75mg daily should be considered when aspirin is contraindicated

"When required" treatment
Short-acting nitrates as required in response to pain and before performing activities that are known to bring on pain

"Routine" treatment
Monotherapy
b-blockers as first-line agents in the absence of contraindications
Verapamil in patients who are intolerant of b-blockers
Diltiazem or long-acting dihydropyridine calcium channel blockers or long-acting nitrates in patients who are intolerant of b-blockers and verapamil
When nitrates are used, they should be used in a way that avoids nitrate tolerance

Combination therapy (useful additions)
Long-acting dihydropyridine calcium channel blockers or diltiazem in patients taking b-blockers
Isosorbide mononitrate in patients taking b-blockers who cannot tolerate diltiazem or long-acting dihydropyridine calcium channel blocker
Isosorbide mononitrate in patients taking verapamil or long-acting dihydropyridine calcium channel blocker
Long-acting calcium channel blocker in patients taking nitrate

Addition of a third drug
The effectiveness of adding a third anti-anginal drug is unclear. Patients who are not
adequately controlled on maximum therapeutic doses of two drugs should be referred to a cardiologist for further investigation

Secondary prevention post-MI

The evidence affecting pharmaceutical care post-MI is summarised in Table 3. Patients discharged from hospital after an infarct should receive aspirin, a b-blocker and, where indicated, a statin. An ACE inhibitor will also benefit all patients when given for four to six weeks post-MI. There is increasing evidence that patients with high cardiovascular risk (including those post-MI) will benefit from the continued use of ACE inhibitors as recommended by the SIGN guideline.13
Table 3: Evidence base for the benefit of pharmacological intervention
Drug Primary prevention Treatment of angina and secondary prevention
Antiplatelet agents The risk of MI was 44 per cent lower in patients taking aspirin 325mg every other day in a large randomised controlled trial.47 The effect on mortality is unclear Meta-analysis showed that aspirin given to high-risk patients with CHD led to a 25 per cent relative reduction in vascular events including MI, stroke or other vascular death and an absolute risk reduction of 1.2 per cent for all-cause mortality.29 ISIS-2 showed that aspirin 160mg daily in suspected acute MI patients starting within 24 hours, led to a 23 per cent reduction in five-week vascular mortality.48 SAPAT demonstrated that aspirin 75mg daily significantly reduced the risk of first MI or sudden death by 34 per cent and vascular events (non-fatal MI, non-fatal stroke and vascular death) by 32 per cent.28 Subgroup analysis of the US Physicians study demonstrated that patients with chronic stable angina (with no previous coronary bypass surgery or coronary angioplasty) given aspirin 325mg on alternate days showed an 86 per cent risk reduction for MI.30 The CAPRIE study demonstrated similar efficacy for clopidogrel 75mg daily and aspirin 300mg daily in post-MI patients49
Statins The WOSCOPS study showed men with raised cholesterol and no history of MI treated with pravastatin 40mg for five years had a 31 per cent reduction in mortality from coronary heart disease and non-fatal MI.50 The AFCAPS/TexCAPS study demonstrated that patients treated with lovastatin for 5.2 years showed a 37 per cent reduction in first acute major coronary events (unstable angina, fatal or non-fatal MI or sudden cardiac death)51 The 4S study demonstrated that treatment of patients with raised cholesterol with simvastatin for 5.4 years was associated with a 30 per cent reduction in total mortality (with a 42 per cent significant reduction in CHD mortality).25 The LIPID study in patients with raised cholesterol treated with pravastatin for six years showed a 22 per cent reduction in total mortality (with a 24 per cent significant reduction in CHD mortality).26 The CARE study demonstrated that in patients with a mean cholesterol level of 5.4 mmol/L, treatment with pravastatin for five years was associated with a 24 per cent lower incidence of coronary events27
ACE inhibitors   Meta-analysis showed that administration of ACE inhibitors within 36 hours of acute MI and continued for at least four weeks was associated with a 7 per cent reduction in 30-day mortality.52 The HOPE study assessed the effect of ramipril 10mg daily in patients with high cardiovascular risk who were not known to have a low ejection fraction or heart failure. After treatment for five years, there was a significant 22 per cent reduction in the risk of MI, stroke or cardiovascular death.31 Trials involving all post-MI patients with an ACE inhibitor include ISIS 4,53 GISSI 354 and SAVE,55 while AIRE56 and TRACE57 involved only those patients with evidence of left ventricular dysfunction. Although the former group of trials demonstrated benefit from ACE inhibitor therapy (with the exception of the CONSENSUS II58 study, which used intravenous enalaprilat early in the course of the infarct), the benefits were greater when patients with left ventricular dysfunction were targeted
b-blockers   A meta-analysis of studies where patients received a b-blocker long-term (six to 48 months minimum) post-MI showed a reduction in total mortality of 23 per cent, largely associated with reduction in sudden cardiac death.59 There is also evidence of benefit for the use of timolol up to six years post-MI in asymptomatic patients.60 An overview of 25 randomised trials of b-blocker therapy in patients following acute MI suggests that almost 25 per cent reduction in mortality can be achieved61
Calcium channel blockers   In the DAVIT II study, treatment with verapamil demonstrated a 20 per cent reduction in major events (death or re-infarction).62 Subgroup analysis of patients without heart failure showed a 36 per cent reduction in mortality rate and 30 per cent reduction in major event rate. Other trials in post-MI patients using verapamil or diltiazem have not demonstrated benefits in mortality or reinfarction rates13
Insulin   The DIGAMI study showed that when insulin was started in patients whose blood glucose was >11 mmol/L on admission, and continued for a minimum of three months, there was an absolute reduction in mortality of 11 per cent at three years12

Antiplatelet drugs Antiplatelet drugs reduce the risk of non-fatal re-infarction, non-fatal stroke, vascular death and all-cause mortality. If aspirin is to be prescribed, a dose of 75-150mg is recommended in post-MI patients. For those patients allergic to or intolerant of aspirin, clopidogrel is recommended.13
b-blockers are now considered to be contraindicated only in asthma, acute left ventricular failure or bradyarrhythmias. In particular, it is recommended that patients with diabetes receive these medicines since they are likely to derive greatest benefit.63 In patients with asthma, verapamil should be prescribed in place of a b-blocker provided there are no contraindications.13
The benefits of using ACE inhibitor therapy post-MI have been demonstrated in patients with or without evidence of left ventricular dysfunction. All MI patients should have their cholesterol concentration measured within 24 hours of an infarct and those patients with a plasma total cholesterol concentration greater than or equal to 5mmol/L should be considered for statin therapy although SIGN guidelines specify a treatment threshold of greater than or equal to 6mmol/L.13 #Plasma cholesterol must be checked three months post-MI to review the use of cholesterol lowering agents.
Modifiable risk factors must be addressed after an MI as part of a secondary preventive strategy. A meta-analysis of randomised clinical trials of cardiac rehabilitation programmes (involving education, exercise and risk factor modification) has demonstrated approximately 25 per cent reductions in both all-cause and cardiovascular mortality64 but without significant differences for non-fatal and recurrent MI.

Revascularisation procedures Revascularisation procedures are indicated in some patients during acute admission for MI as an alternative to thrombolytics or because of persistent chest pain. Exercise tolerance tests at three to six weeks post-discharge can identify other patients who might benefit from revascularisation.

Table 4: Drug therapy at stages of coronary heart disease
Disease progression Drug therapy indicated
Primary prevention of CHD (risk greater than or equal to 15 per cent in 10 years) Aspirin 75mg (if hypertensive, blood pressure must be controlled)   
Statin (if total cholesterol greater than or equal to 5.0mmol/L and if resources permit, otherwise if CHD risk greater than or equal to 30 per cent)
Treat blood pressure if systolic greater than or equal to 140mmHg or diastolic greater than or equal to 90 mmHg
Angina Further addition of:   
b-blocker   
Sublingual nitrate   
Ramipril31 to be considered
And where appropriate:   
Long-acting nitrate   
Calcium channel blocker   
Potassium-channel activator
Secondary prevention of MI Addition of:   
Aspirin 75-150mg   
Statin (if cholesterol raised)   
b-blocker (for at least three years)   
ACE inhibitor   
Sublingual nitrate   
BP control (systolic<140mmHg and diastolic <85 mmHg)

Individualised pharmaceutical care

Primary and secondary prevention of CHD are currently considered to be haphazard.65 Reported health screening and intervention initiatives with pharmacist participation have typically focused on lipid management, blood pressure monitoring, antiplatelet therapy and smoking cessation.66-72 Future development of strategies requires a multifaceted approach65 and pharmacists' contributions need to be integrated into local initiatives to improve the organisation of care in general practice. Nurse-led initiatives may depend on patients being motivated to attend clinics, whereas pharmacies may be able to target those individuals who are less motivated to access other services. Pharmacies may also be used to implement primary and secondary preventive strategies to a known catchment of patients in need.
The size of the problem of ensuring patients' needs are being met favours the targeting of groups of patients with specific co-morbidity, such as diabetes and hypertension, known to be associated with CHD risk. Pharmacists are in a position to reinforce the implementation of a variety of clinical guideline treatment goals (systolic BP <140 mmHg systolic and diastolic BP <90mmHg, total cholesterol <5mmol/L, and HbA1c <7 per cent). The use of pharmacy patient records to help identify and monitor patients who are candidates for primary and secondary CHD prevention has not been explored in health services research, and would seem worthy of investigation and development.
The implementation of risk assessment has major resource implications. The application of the lower threshold for primary prevention (CHD risk 15 per cent) includes over five times more candidates than the higher threshold (CHD risk 30 per cent)24 (see Panel 2). Primary preventive health checks and education programmes have had a limited impact on reducing CHD risk, and the findings to date question the value of cholesterol tests in motivating behavioural change.73
The prevention and management of CHD in primary care is constrained by inadequate documentation and management of risk factors (such as hypertension and hyperlipidaemia) and by inconsistent prescribing. Recent UK studies have indicated that adherence to guidelines for secondary prevention is not ideal. Adherence to recommendations for the use of aspirin post-MI has been around 80 per cent, but for the use of b-blockers has been less than 66 per cent and for the use of lipid lowering agents less than 20 per cent.74 The recently published National Service Framework for CHD recognises that adherence to guidelines for prescribing these drugs post-MI is inadequate. It sets a target for the prescribing of aspirin, b-blockers or ACE inhibitors, and statins post-MI of 80-90 per cent in patients discharged from hospital.1
Nurse-led clinics improve general practitioner (GP) follow up but have not been sufficient to address the problem of underprescribing or to affect overall outcomes.77 The impact of postal prompts on the prescribing of medication for secondary prevention, sent to both GPs and to patients who recently experienced an acute coronary event, has been disappointing.75 No published evaluated re-organisation of services has been designed to include the patient's community pharmacist in the information loop.
Table 5 summarises the range of pharmaceutical care issues that may arise in candidates for primary prevention of CHD, patients treated for angina, and patients receiving secondary prevention. There is an opportunity for pharmacists to extend their contribution within the primary care team by helping to implement clinical audits for assessing quality assurance of drug treatment interventions.76
Table 5: Pharmaceutical care in coronary heart disease
Stage of treatment Actions Points to consider at each stage

Treatment plan

  • Patient comprehension/active participation
  • Patient's characteristics
  • Indication (the need for each drug)
  • Drug history
  • Choice of medication
  • Contraindication/interaction
  • Conformity to guidelines
  • Continuity of care

Verify the plan in respect of:

  • Patient's characteristics
  • Medication suitability
  • Patient's needs for education
  • Concordance and agreed expectations

Modify the plan to address:

  • Specific educational needs
  • Need for individualisation of treatment plan
  • Patient's health beliefs, understanding of their condition, treatment goals, complications, the impact on their quality of life
  • Health messages, especially regarding smoking, diet, alcohol consumption and regular exercise/cardiac rehabilitation
  • Risk factors present, eg, hypertension, ethnicity. Identification of candidates for primary prevention
  • Modifiable risk factors. Motivation of patient with respect to lifestyle modification and treatment goal, eg, smoking cessation, achieving target cholesterol
  • Disease stage: primary prevention, angina treatment, secondary prevention
  • Other co-morbidities that influence treatment choice, eg, asthma, heart failure
  • Drugs known to worsen angina and potentially interacting drugs prescribed for concomitant conditions, eg, simvastatin and warfarin, ACE inhibitors and NSAIDs, GTN and anticholinergic drugs, b-blockers and b-agonists
  • Baseline renal and hepatic function assessment affecting the use of ACE inhibitors and statins
  • Drug choice against national or local guidelines
  • Education on use of "when required" treatment and when to seek help, eg, GTN
  • Transfer of information from secondary to primary care to assure continuity of care, especially post-MI

Implementation

  • Dose
  • Frequency
  • Timing
  • Compliance
  • Clinical signs
  • Laboratory markers

Monitor the patient for:

  • Continuing suitability of drug/dose regimen
  • Signs/symptoms of effectiveness and toxicity

Adjust the process by:

  • Further individualisation in response to monitoring
  • Patient compliance and the need to continue to reinforce health messages
  • Frequency and timing of doses to maximise effectiveness and compliance, eg, statins more effective at night as cholesterol production is higher
  • Monitoring of clinical markers such as blood pressure, heart rate, frequency of chest pain
  • Monitoring of laboratory markers and investigations, especially in the elderly and for initiation of ACE inhibitor therapy (eg, creatinine, potassium, urea, LDL and total cholesterol monitoring, ECG and exercise tolerance tests)
  • Dose/delivery mode adjustment to optimise response (especially sublingual and long acting nitrates)
  • Maximising ACE inhibitor dosage
  • Titration of statin dose to achieve target cholesterol reduction

Clinical outcome

  • Therapeutic benefit
  • Safety
  • Unwanted symptoms
  • Recorded adverse drug reaction

Confirm evidence of treatment success:

  • Reassure patient in relation to agreed expectations

Prompt a review from:

  • Identification of treatment failure
  • Newly identified patient's needs
  • Sharing information and discussion of implications with the prescriber and other team members
  • Attainment of treatment goals with good symptom control and maintenance of quality of life
  • Unwanted symptoms from medication (dyspepsia with aspirin, hypotension and cough with ACE inhibitors, fatigue with b-blockers)
  • Documentation of unexpected or serious adverse effects, eg, myositis with statins
  • Changes in a patient's needs in control of a condition, eg, post-CABG
  • Indications for treatment plan revisions such as persistent symptoms, hospitalisations and revascularisation

The follow-up of patients in the community post-MI requires more widespread communication between primary and secondary care services. Pharmacy services are well placed to enlist greater patient participation and to make specific contributions to safeguard the medication process during the transfer of care post-MI and in the continuing management of CHD once the patient is discharged. Panel 8 summarises a data set for post-MI patients that might be included in a pharmacy transfer record at hospital discharge for use by community pharmacists and GPs to confirm the required primary care follow up.
Table 6 summarises the predictable care issues in a pharmaceutical care plan relating to a post-MI patient. Continuity of care after MI offers an opportunity for local pharmacy initiatives to help address national goals for secondary prevention.
Co-operation with established nurse-led clinics and primary-secondary care liaison services are necessary if the complexities of the shared management and patient education in CHD are to be addressed.77 The implementation of guidelines relating to both primary and secondary prevention, and achievement of patient compliance with preventive medication, are the challenges for pharmacists in the provision of pharmaceutical care to this large section of the adult population.

Panel 8: Post-MI pharmacy discharge record

  • Patient identity and primary care contact details
  • Patient demographics (including body weight and BMI)
  • Clinical characteristics: site of MI, presence of heart failure, atrial fibrillation, diabetes, hypertension, hyperlipidaemia
  • Blood pressure and pulse
  • Plasma urea, creatinine and estimated creatinine clearance
  • Liver function tests and plasma cholesterol (baseline for statin treatment)
  • Plasma potassium
  • Drugs to be routinely checked against guidelines: digoxin, warfarin, loop diuretic, spironolactone
  • Patient counselling points that are outstanding for continued reinforcement
  • All patients to receive aspirin, plus b-blocker (unless specifically contraindicated), plus statin (when indicated), plus ACE inhibitor and sublingual GTN
Table 6: Example of a Post-MI pharmaceutical care plan
Care issue Action
1. Patient characteristics verified Minimum data set maintained
2. Accuracy of drug history verified Confirm drug history on hospital admission. Check that current prescribed medication does not include medication intended to be discontinued or which interacts
3. Contraindication/interaction, absence verified Screen for known drug and disease interactions/precautions
4. Conformity to secondary prevention prescribing guidelines verified Identify verified non-conformities and modify unverified non-conformities. Aspirin, b-blocker, ACE-inhibitor, GTN
5. Treatment of hyperlipidaemia verified Indication for statin and/or dietary modification based on lipid profile assessment
6. Patient comprehension of secondary prevention verified Check achievement of concordance with treatment plan. Identify patient counselling points for reinforcement
7. Patient comprehension of GTN verified Check achievement of concordance with use of GTN to treat chest pain or to diagnose cardiac chest pain. Care issues associated with correct GTN use
8. Patient comprehension of health messages verified Understanding and concordance with the concept of lifestyle modification
9. Monitor and adjust implementation of treatment plan Immediate follow-up of transfer of care to community. Plans to monitor statin response (lipid profile) and safety (liver function) at three months post discharge and then to address long-term goals
10. Confirm evidence of treatment success or prompt review where indicated Follow-up and document response to long-term goals. Assess symptomatic response (frequency and nature of chest pain) and other evidence of impact on quality of life. Seek evidence of modification of risk factors and prophylaxis of CHD

Case 1: Patient RW, female, 58 years, weight 70kg, height 1.6m, BMI 27

Case 2: Patient JS, male, 64 years, weight 74kg

Mr McGlynn is principal pharmacist and lecturer in clinical practice at Greater Glasgow pharmacy practice unit and University of Strathclyde;
Mrs Reid is principal pharmacist and lecturer in clinical practice at Lothian pharmacy practice unit and University of Strathclyde;
Mr McAnaw and Mr Chinwong are research pharmacists and Professor Hudson is Boots professor of pharmaceutical care and Scottish Office national specialist in pharmaceutical care. The authors are members of the pharmaceutical care health service unit, department of pharmaceutical sciences, University of Strathclyde, Glasgow

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