Aspirin for ACS

What?

A 64-year-old male attends the Emergency Department (ED) following an episode of central crushing chest pain lasting 30 minutes. He was known to suffer from Ischaemic Heart Disease (IHD) and had taken his own glycerine trinitrate (GTN) with no effect.

An ambulance had been called and the paramedic crew administered intravenous (IV) morphine until he was pain free. The patients electrocardiogram (ECG) was suggestive of a non-ST elevation myocardial infarction (NSEMI) and he was therefore alerted into the resuscitation room of the ED.

On arrival the patient looked well, was haemodynamically stable and was now completely pain free. His ECG changes persisted, therefore blood samples were taken and the cardiology team was contacted.

Prior to leaving the paramedic crew explained they had not administered aspirin, as the patient was currently taking warfarin (lifelong following a pulmonary embolism 10 years earlier).

So What?

Chest pain and symptoms suggestive of myocardial ischaemia are one of the most common acute hospital presentations, accounting for 8-10% of all ED visits (Kontos et al 2010). Current guidance from the National Institute for Health and Care Excellence (NICE) recommends that all patients with suspected NSTEMI be given aspirin 300mgs as soon as possible to treat the potential thrombus (NICE 2014).

Thrombosis is the pathological formation of a clot (or thrombus) and can result in different clinical problems depending on whether they result in an arterial occlusion (e.g. MI, stroke) or venous occlusion (e.g. deep vein thrombosis or pulmonary embolism (Battista 2012).

NSEMI forms part of a group of clinical conditions often referred to as Acute Coronary Syndromes (ACS – shown in table 1) which usually present with chest pain or discomfort as a result of myocardial ischaemia (Nolan et al 2016). These syndromes essentially represent part of a spectrum of the same disease process, which is caused by a sudden and critical reduction of blood flow to the myocardium as a result of several mechanisms (Nolan et al 2016).

Table 1 – Acute Coronary Syndromes

Acute Coronary Syndromes
ST-elevation myocardial infarction (STEMI)
Non-ST-elevation myocardial infarction (NSTEMI)
Unstable angina

In ACS, arterial thrombi form due to endothelial wall damage caused by atherosclerotic plaque rupture, causing platelets to become activated and adhere to the damaged section forming a plug (Lymn et al 2010). This occurs through upregulation of glycoprotein IIa/IIIb receptors on the surface of the platelets which in turn bind to molecules e.g. von Willebrand factor (Lymn et al 2010). Once this has occurred the platelets produce arachidonic acid and subsequently thromboxane which is pro-aggregatory and further promote platelet aggregation (Lymn et al 2010). Other mechanisms including the contraction of smooth muscle within the artery wall also contribute, causing vasoconstriction which can further reduce the lumen of the vessel, which forms the rationale for concurrent administration of nitrates (Nolan et al 2016).

Aspirin is an effective drug in the treatment of ACS, as it irreversibly inhibits the enzyme cyclooxygenase (COX), therefore preventing the synthesis of thromboxane from arachidonic acid, which reduces platelet aggregation and the subsequent arterial thrombi which cause the coronary artery occlusion (Battista 2012).

Warfarin is a vitamin K antagonist and has a different mechanism of action compared to the antiplatelet drug aspirin. Vitamin K is an important co-factor involved in the hepatic synthesis of clotting factors II, VII, IX and X (Batchelder et al 2011). Whilst it is not an antagonist in the sense of acting on a specific receptor, warfarin competes with vitamin K for the reductase enzyme, therefore reducing the activity of vitamin K and the production of the relevant clotting factors (Lymn et al 2010). The primary function of warfarin is to prevent the formation of venous thrombi rather than the arterial thrombi seen in ACS (Lymn et al 2010).

The evidence supporting the use of aspirin in ACS stems from a seminal randomised controlled trial (RCT) in Europe and the United States, which contained over 17,000 patients (ISIS-2 1988). These patients were believed to be having an MI by the treating clinicians and were randomised to receive either aspirin, thrombolytic, both, or neither (ISIS-2 1998). The study demonstrated a mortality rate of 9.4% for those receiving aspirin versus 11.8% in the placebo group (ISIS-2 1998). This mortality improvement equated to a number needed to treat of 42 (meaning for every 42 patients receiving aspirin, one life was saved).

Concerns regarding the administration of aspirin in this case may have related to the accepted caution for the drug, whereby prescribers should be aware of increased bleeding risk for patients concomitantly receiving long term warfarin therapy (Joint Formulary Committee 2016). This caution was supported by a meta-analysis which demonstrated a nearly 3-fold increase in major bleeding rates when patients received both long term warfarin and aspirin following MI (Rothberg et al 2005). It is however worth noting that overall major bleeding rates were low (at around 1.5% per annum) and similar to the rates for patients with atrial fibrillation or pulmonary embolism (Rothberg et al 2005).

The consideration of long term treatment risk does not apply however to the one-off dose given in ACS and the only contra-indications listed currently, are active peptic ulceration or bleeding disorders (Joint Formulary Committee 2016).

Now what?

The administration of 300mgs oral aspirin for suspected ACS is a treatment recommended by national guidance and supported by a strong evidence base which demonstrates clear patient benefit. However, there remains some confusion about administration of aspirin when the patient currently takes warfarin regularly.

The antiplatelet action of aspirin has been demonstrated to exert an effect which predominantly reduces arterial thrombus formation, as opposed to the vitamin K antagonist warfarin, which predominantly prevents venous thrombus formation. This different mechanism of action means it is essential all patients without contraindications receive aspirin as soon as possible after presentation with symptoms suggestive of ACS.

 

Rob Fenwick

 

References

Batchelder, A., Rodrigues, C & Alrifai, Z. (2011) Rapid clinical pharmacology. Wiley-Blackwell. Chichester.

Battista, E. (2012) Pharmacology. Mosby Elsevier. Edinburgh.

Driscoll, J. (2007) Practicing clinical supervision: a reflective approach for healthcare professionals (2nd edition). Elsevier. Edinburgh.

ISIS-2 (Second International Study of Infarct Survival) Collaborative Group. (1988) Randomised trial of intravenous streptokinase, oral aspirin, both, or neither among 17,187 cases of suspected myocardial infarction: ISIS-2. The Lancet. Volume 332, number 8607, pp349-60.

Joint Formulary Committee. (2016) British National Formulary. 72nd Edition. London. BMJ Group and Pharmaceutical Press.

Kontos, M. C., Diercks, D. B & Kirk, J. D. (2010) Emergency department and office-based evaluation of patients with chest pain. Mayo Clinic Proceedings. Volume 85, number 3, pp284-99.

Lymn, J., Bowskill, D., Bath-Hextall, F & Knaggs, R. (2010) The new prescriber. Wiley-Blackwell. Chichester.

National Institute for Health and Care Excellence. (2014) Acute Coronary Syndromes in Adults. (Quality Standard 68). Available from: https://www.nice.org.uk/guidance/qs68 (last accessed 7th February 2017).

Nolan, J., Soar, J., Hampshire, S., Mitchell, S., Pitcher, D., Gabbott, D., Gwinnutt, C., Lockey, A & Perkins, G. (2016) Advanced Life Support Course Provider Manual (7th Edition). Resuscitation Council (UK). London.

Rothberg, M. B., Celestin, C., Fiore, L. D., Lawler, E & Cook, J. R. (2005) Warfarin plus aspirin after myocardial infarction or the acute coronary syndrome: meta-analysis with estimates of risk and benefit. Annals of internal Medicine. Volume 143, number 4, pp241-50.

One thought on “Aspirin for ACS

  1. Anonymous says:

    ECG was suggestive of NSTEMI? What does that mean?

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