Success in ACS: From research to reality

Cathy Allen, Jordan Carroll, Bakir Al-Dulaimy, Ana Gavrila

Introduction Treatment for ACS

Acute coronary syndromes (ACS) include ST-elevation myocardial infarction (STEMI), non-ST-elevation Clopidogrel Aspirin
myocardial infarction (NSTEMI) and unstable angina (UA). These syndromes arise from thrombus Aspirin is one of the world’s most
Evidence from the Clopidogrel
formation on a ruptured atheromatous plaque. Thrombus formation and the vasoconstriction commonly used drugs. As a non-
versus Aspirin in Patients at
produced by platelet release of serotonin and thromboxane A2, results in myocardial ischaemia due steroidal anti-inflammatory drug
Risk of Ischaemic Events
to reduction of coronary blood flow. Myocardial infarction(MI) occurs when cardiac myocytes die due (NSAID), it reduces thromboxane A2
(CAPRIE) trial suggests that
to myocardial ischaemia. [1] production. This causes an inhibitory
Clopidogrel may be a slightly
more effective antiplatelet drug effect on platelet aggregation which can
How ACS presents than aspirin. [5] control thrombus formation. [12]
The PCI-CURE trial showed that A 1988 study provided evidence of the
Patients presenting with ACS, dependant on the sub-diagnosis, may complain of new onset chest
Clopidogrel reduces vascular benefit of aspirin for treatment
pain, chest pain at rest, or an exacerbation of pre-existing angina. However, some patients present
events by 27% compared to following MI in over 17000 patients.
with atypical features e.g. a feeling of indigestion, pleuritic chest pain, nausea, dyspnoea or referred
placebo and by 10% compared The study, ISIS II, randomly assigned
pain. [1]
with aspirin. patients presenting within 24 hours of
onset of acute MI to streptokinase and
Platelet activation & aggregation Thienopyridines used in
conjunction with aspirin reduce aspirin.  Significant survival benefits of
death or MI by 77% compared aspirin were seen at the end of 5 weeks
Mechanism[2] and remained evident after 10 years[13].
to aspirin alone. [6]
Rupture of the atheromatous plaque reveals collagen and von Willebrand factor.
GP IIb/IIIa receptor antagonists PCI  CABG 
Platelet receptors bind to the collagen and VWF, stimulating an influx of Ca2+ ions into GP IIb/IIIa receptor antagonists have therefore been Percutaneous intervention is Coronary artery bypass grafting uses arteries or veins
the platelet.
developed to prevent clotting in thrombophillic recommended for all patients (commonly the right internal mammary artery or
The platelet is now said to be activated and undergoes conformational change, individuals. [7,8] (respective of personal choice and if inverted long saphenous vein) to bypass occluded
characterised by three events: It was thought that drugs developed such as clinically indicated) within 96 hours of sections of coronary vessels, most commonly the left
abciximab, tirofiban and eptifibatide could increase admission.[14] A coronary angiogram is anterior descending. [15] Venous grafts, not being
risk of catastrophic haemorrhage especially in those performed to visualise the area of specifically suited to this purpose, have a limited
GP IIb/IIIa exposure –
Change of shape –
membrane structure
Degranulation – release undergoing PCI, however this theory has now been vessel stenosis and a balloon catheter lifespan, however
pseudopodia form from of vasoconstrictor and revised and according to the most recent NICE inserted and inflated in the area to arterial grafts are
changes lead to a
the previously smooth platelet-activating factors
revealing of membrane guidelines abciximab should be used. [9] widen vessels and allow for blood flow not always
platelet membrane, that cause to artery
glycoproteins, which
increasing its surface area
when ‘revealed’ can bind
vasoconstriction and In the PRISM study the substitution of tirofiban for to ischemic tissues. 30% of patients go available. The
assisting in platelet aggregation of platelet unfractioned heparin reduced mortality rate by 1.3%. on to have stenosis in the same area, process of the
to fibrinogen stabilising
aggregation. cells.
the platelet plug.[3] [10] And in the PURSUIT study repeat MI or death in however outcomes can be improved by operation itself,
a placebo-controlled 10,948 strong study showed a the placement of a stent- a metallic most notably
1.5% decrease at day 4. [11] scaffold sometimes coated with anti- cardiac bypass, has
How is ACS diagnosed? GP IIb/IIIa receptor antagonists are now mostly proliferative agents- to prevent re- been shown to
recommended for use in troponin-positive diabetics stenosis. [15] affect other systems,
Patients who have symptoms of ACS and are given an scheduled for PCI. [1] even IQ. [16,17]
electrocardiogram (ECG) which may or may not show
ST segment elevation. Patients who have ischemic
discomfort without an ST-segment elevation are Cost effectiveness of Conclusion
suffering from unstable angina, or a NSTEMI.
The ST segment of the cardiac cycle represents the anti-platelet therapy As we have explored throughout the poster, the results of research has paved
period between the depolarisation and repolarisation the way forward for many kinds of treatments available for managing ACS.
of the left ventricle. In normal state, the ST segment is A study on aspirin (antiplatelet drug) was conducted in 2007. They randomly Furthermore, these success rates have also affected the way ACS is managed
isoelectric relative to the PR segment. In an acute MI assigned a cohort of UA patients with two different interventions. The amount in modern medical practice.
the ST segment can be variable in shape. of patients included in the study isn’t clear. With intervention 1 there was no
As with everything in medicine, treatment of ACS still remains an imperfect
aspirin used, though with intervention 2 aspirin 150mg/day was given though science, although this advancement has saved countless lives.
There are also biochemical markers that can indicate the duration is unclear. They found out that in total, people that underwent
the intervention with the aspirin lived longer. The cost of aspirin per life year Researchers are currently on the lookout of ways of preventing the onset of
the onset of ACS. Measurement of creatinine-kinase-MB level was until recently as the standard
symptoms. Targeting arthrosclerosis from the start is complicated, as it
marker for myocyte death; however, presence of low levels of CK-MB in the serum of normal gained was £58 on average.
involves modifying lifestyle through weight management, diet, exercise,
individuals and patients with muscle damage, has limited its accuracy. Another study on Clopidogrel was conducted in 2007 as well. The cohort of controlling hypertension and smoking cessation.
Cardiac troponins are more commonly used as markers as they are cardiac-specific. Monoclonal patients they used in the study were ones admitted to hospital with UA or Research has also highlighted that there are other factors such as systemic
antibody tests to troponin I and T are highly sensitive markers of myocyte necrosis. If the initial NSTEMI. The amount of patients included in the study is unclear. Intervention inflammation may contribute to our ability to predict future risk of
troponin assay is negative, it should be repeated 9–12 hours after admission. The troponin assay has A was the standard therapy and intervention B was the standard therapy cardiovascular disease. Kaplan et al commented that research into this area
prognostic information that can determine mortality risk in ACS and define which patients may including Clopidogrel 75mg/day with a 300mg loading dose. On average, can lead to the identification of new targets for preventive or therapeutic
benefit from aggressive medical therapy and early coronary revascularization. people that underwent the second intervention with the Clopidogrel lived 7 interventions. In addition, markers of inflammation may be useful as a means