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Aspirin is an antiplatelet drug currently recommended for use in the management and secondary prevention of cardiovascular events such as myocardial infarctions and strokes.
Current guidelines are published in the UK through The National Institute for Health and Clinical Excellence, www.nice.org.uk1; and Scottish Inter Collegiates Network (www.sign.ac.uk).2, Both of which hold very similar opinions on the indication for and use of aspirin within cardiovascular disease.
It has been used clinically for the for the primary and secondary prevention of cardiovascular disease for over 25 years with its cost effectiveness making it a wide spread commonly used drug3.
Many patients experience events which initially are believed to be of a cardiovascular nature and are started on long term aspirin therapy which is never reviewed. These are the patients who are on aspirin for no clinical reason and need a medications review in light of this.
This review aims to clarify the guidelines for prescribing aspirin for management and secondary prevention of cardiovascular events and aims to help identify patients in clinical practice who are able to stop taking it due to the risks that come with the taking of the drug.
Aspirin is an antiplatelet agent that works by irreversibly inhibiting the enzyme cyclooxygenase (COX) which results in the prevention of thromboxane (TXA2) which is a powerful inducer of platelet aggregation. Platelets cannot synthesize COX but endothelial cells can and lose doses of 75mg daily can produce selective inhibition of COX over the time period of the dose therefore preventing platelet aggregation and assisting in prevention of thrombus formation.
The risks associated with taking aspirin are gastrointestinal irritation and possible bleeds both GI and intracranial which are limiting factors to take into account when prescribing it. Due to the risks patient preference is an important factor to consider when looking at concordance and adherence.
Due to its effect on platelet aggregation there is a reduced thrombo-embolic potential and therefore a prolonged bleeding time.
The risk of bleeding with aspirin is however the lowest of all the antiplatelet therapies available.
The risk of suffering an intracranial haemorrhage is higher than if not taking it but is independent of the severity of cardiovascular disease, therefore the risk of bleeding is the same for all taking it but the risk of suffering an ischaemic stroke is reduced3.
Gastrointestinal irritation is thought to be caused by aspirin due to damage to the gastric mucosa and research has shown that enteric coated tablets are of no benefit and do not reduce the risk of irritation. Combining aspirin with other drugs in particular non steroidal anti inflammatory drugs (NSAIDS) can further increase this risk and combinations should be avoided6.
Patients who have experienced a stroke or Transient ischaemic attack, TIA, are initially placed on aspirin therapy for 2 week before continuing on definitive antiplatelet treatments such as clopidogrel.
A study in the Lancet, published in 1993, The European Atrial Fibrilation Trial Study Group. Secondary prevention in non-rheumatic atrial fibrillation after transient ischaemic attack or minor stroke7, showed that aspirin reduced the number of vascular events by 40 per 1000 patient years of treatment in patients in which intracranial haemorrhage had been ruled out.
Aspirin in the secondary prevention of myocardial infarction has been tested widely as can be seen in the ISIS-2, ISIS3 and GISSI 2 trials8-10
A meta analysis of randomised trials carried out in 2009, looking at primary and secondary prevention of vascular disease using aspirin showed that in the primary prevention trials aspirin reduced the occurrence of vascular events by 12%. This was primarily due to the reduction in number of non-fatal MIs. The effect on stroke was insignificant. The overall vascular mortality did not differ but aspirin use was shown to produce an increase in major gastrointestinal and extra cranial bleeds showing that the potential risks were far greater than the potential benefits deeming aspirin of no use in the primary prevention of vascular events.
In the secondary prevention component of the meta analysis it showed that aspirin had an overall absolute reduction in serious vascular events. This was with a non-significant increase in haemorrhagic stroke but with approximately a reduction of a fifth in the total number of strokes and coronary events. These figure all being similar for both men and women. Therefore it can be seen that aspirin in primary prevention of cardiovascular events in asymptomatic patients is of little benefit with greater risks and that its use needs to be weighed up against the risk of potential bleeds yet its secondary prevention effects being of significance11.
Results of the Physicians' Health Study12, did show in men aged over 55 years that aspirin may prevent myocardial infarctions in those with risk factors but in primary prevention there was seen to be an increase in the rate of intra cranial bleeds, which therefore concludes that in the primary prevention of strokes aspirin should be avoided.
A more recent meta analysis conducted by Hart et al13, in the use of aspirin for the prevention of vascular events showed similar results in that aspirin is not of benefit in the primary prevention of stroke in people without vascular disease and that it may actually increase the risk of stroke, although this finding was not significant.
CURRENT NATIONAL GUIDELINES
Current guidelines have been developed in accordance with trails and study findings and are continuously being updated in review of new and up to date findings.
Current guidelines that recommend antiplatelet theapy with asprin include; secondary prevention of cardiovascular events in stable angina, patients in heart failure with atherosclerotic arterial disease (including coronary heart disease); patients presenting with chest pain of recent onset (Acute coronary syndrome) and patients who have had an NSTEMI or have unstable angina14-16 It is also recommended for patient in atrial fibrilation with a CHA2 DS2-VASc score of >1, (see below).
SIGN guidelines stating aspirin therapy are included in SIGN 129, Antithrombotics: indications and management Quick reference guide and include the same conditions and situations as NICE guidance.
SIGN guidelines state that aspirin is not to be used in the primary prevention of cardiovascular disease when the risk of haemorrhage is greater than the potential benefits.
Clinical guidelines and individual clinician judgement all play their role in deciding on treatment and whether to prescribe aspirin or not and some clinicians will treat in a way they always have regardless of the evidence and new guidelines produced.
Scoring systems in place for clinicians to use to help with the decision as to prescribe aspirin, an alternative or nothing in patients with atrial fibrillation include the CHA2 DS2-VASc score for the risk of stroke in AF.
This scoring system gives the patient a score which then relates to the treatment the patient receives.
Congestive heart failure (or Left ventricular systolic dysfunction)
Hypertension: blood pressure consistently above 140/90 mmHg (or treated hypertension on medication)
Age ≥75 years
Prior Stroke or TIA or thromboembolism
Vascular disease (e.g. peripheral artery disease, myocardial infarction, aortic plaque)
Age 65-74 years
Sex category -female gender
Annual Stroke risk
Stroke Risk %
Based on the CHA2 DS2-VASc score oral anticoagulation is recommended or preferred for patients with one or more stroke risk factors (i.e. a CHA2DS2-VASc score of 1 and above). For scores of 1 which is classed as moderate risk the choice of therapy is either aspirin 75mg per day or an alternative anticoagulant such as Warfarin. This is patient and clinician choice but when the score is >1 the risk is high and the choice of therapy is that of Warfarin or a suitable alternative but not aspirin.
This is based on Eckman et al17 findings when analyzing the scoring system and risk factors associated with atrial fibrillation.
Other means of scoring patients and categorising them is the estimated 10 year risk of a cardiovascular event. This takes into account many modifiable and non modifiable risk factors and certain parameters that need to be measured in order to calculate the risk, they include; blood pressure, weight and waist measurements, lipids, glucose to rule out diabetes, and renal function.
The Framingham Risk score is a common system used and requires age, gender,
Smoking status, systolic blood pressure, cholesterol and HDL values. The values can be put into an online calculator which then gives the 10 year cardiovascular risk.
Other scoring systems are based around the Framingham system
There are now official cardiovascular risk charts published in the British National Formulary (BNF) which are based on the Joint British Societies, JBS guidelines.These carts do not include LVH and diabetes as these conditions are already classed as high risk so therefore are not required for assessing the risk score.
From this risk the clinician is able to decide on whether preventative therapy is required.
Patients with a 10 year cardiovascular risk of >20% are recommended to undertake primary prevention with aspirin even without having had a cardiovascular event. This is the recommendation of the British Hypertension Society but only if the balance of benefit outweighs the risk of harm (usually from gastrointestinal bleeding).Other studies and trials question the risk of benefit in patients at a lower 10 year cardiovascular risk and in those with diabetes18.
In the light of all the evidence and studies continuously being carried out in cardiovascular medicine the current standing on aspirin therapy is now for mainly use in secondary prevention of cardiovascular event and not in primary prevention.
In May 2009 a meta-analysis, published in the Lancet by the Oxford Antithrombotic Treatment Trialists (ATT) showed that aspirin should not be used in primary prevention. This was the same group who 7 years previously published a meta-analysis 19that proved that aspirin should be used in primary prevention which was one of the main grounds for using it as such. This shows how continuous evaluation and research can change in light of new developments and shows the importance of continuous research even in areas that have had endless time and resources spent on them as new discoveries are constantly been made as more and more evidence is gathered.
In the light of changes in opinions and new evidence, guidelines change and adapt to represent the new findings.
Clinician however still use their own judgement when prescribing aspirin and specialists in cardiovascular medicine may differ in their opinions so guidelines need to be clearer to enable primary care physicians, who are the principle physicians who initiate treatment with aspirin for primary prevention, to evaluate the evidence and therefore put the evidence into practice.
The use of aspirin in primary prevention in diabetic patients still remains unclear and further analysis of studies is required to come to a conclusion but . Therefore clinician's individual judgement will be required. Diabetic patients have a two to four fold increased risk of dying from a complications of cardiovascular disease. Currently there is very little research but what research there is comes to the conclusion that aspirin is of benefit. For primary prevention the US Physicians' Health Study12 showed that aspirin showed a risk reduction for myocardial infarction. This study is old and further studies are required to prove its efficacy in asymptomatic diabetic patients.
Current guidelines recommend aspirin for secondary prevention of cardiac events in patients who have already experienced such an event and this should be in the form of 75mg per day indefinitely.
The use of aspirin in primary prevention is still inconclusive and the risk of such is thought to outweigh the benefit so should be considered on a case by case basis at the physicians digression. With many specialists in cardiology removing the prescription form patients when seen in secondary care if the deem the risks to be greater than the benefits.