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Updated ACC/AHA Guidelines for the Management of Patients With Unstable Angina/Non–ST-Elevation Myocardial Infarction

An end in sight to the one-size-fits-all approach to anti-platelet therapy?

Myocardial Disease


The American College of Cardiology (ACC) and American Heart Association (AHA) have updated their 2007 joint guidelines for the management of patients with unstable angina and non-ST-elevation myocardial infarction (non-STEMI).(1) According to a press release issued by the two organisations the update aims to "keep pace with . . . the steady stream of new data on which previous diagnosis and care recommendations are based".

However, the update reflects "incremental" steps rather than a "paradigm shift", and anticipated outcome, said Dr R. Scott Wright, its lead author, will be seen in "incremental benefit as we learn to fine-tune the applications of therapies and revascularization".

Unstable angina and non-STEMI are overlapping conditions which represent a serious form of coronary artery disease characterised by "normal" or undetermined patterns on the ECG (non-ST segment elevation) and raised blood levels of a cardiac enzyme biomarker known as troponin. The most common cause - as in STEMI - is myocardial perfusion resulting from  a narrowing of the coronary arteries. Although MIs with ST segment elevation need more urgent treatment, hospital survival patterns for both are comparable, with a 7-10 per cent mortality at one year. A longer-term analysis from the Global Registry of Acute Coronary Events (GRACE) has also shown that non-STEMI patients have similar five-year morbidity and mortality rates as STEMI patients.(2) Presenting these data at last year's ESC Congress, the investigators said the incidence of MI, stroke, and hospital readmission in non-STEMI patients is high and later onset mortality "underrecognised".

The updated ACC/AHA guidelines primarily provide new information on the timing of acute intervention in non-STEMI patients, with the inclusion of evidence that "immediate intervention does not offer a benefit" over initial stabilisation and treatment in all but the highest risk populations.

There are also new recommendations on which patient groups should be treated with dual or triple anti-platelet therapy and on the effect of therapy in certain sub-populations treated with anti-platelet agents dependent on their gene profile (and whether genetic testing might improve outcome). A recently introduced anti-platelet treatment, prasugrel, is also included in the update.

Commenting on the practical implications of the guidelines for the ESC, Professor Marco Valgimigli from the Cardiovascular Institute, University of Ferrara, Italy, said: "The update is important because it clarifies new evidence on the best timing of intervention in non-STEMI patients, and very nicely outlines the two different diagnostic and therapeutic pathways to be taken - namely, the conservative or the invasive approach. Because different treatments are constantly being introduced and evaluated, the update now clarifies which treatment option best suits which management route.

"New recommendation have also been made for the use of anti-platelet agents - on the measurement of response to treatment or the necessity of genotyping patients for loss of functional alleles (gene variants) which reduce the effect of clopidogrel on platelet reactivity. Despite the negative results of some recent studies, it now seems clear that the one-size-fits-all approach to anti-platelet therapy will soon be over."

Last year the FDA issued a formal warning that poor metabolisers of clopidogrel may not receive its full benefits - and that a genetic test might best profile susceptible patients. The FDA alert was based on a growing concern that the antiplatelet effect of clopidogrel is dependent on the cytochrome P450 (CYP) system for its activation. According to the alert, patients with decreased CYP2C19 function because of genetic polymorphisms are poor metabolisers of clopidogrel and have higher rates of cardiovascular events after acute coronary syndrome and PCI than patients with normal CYP2C19 function. The updated guidelines note that "genotyping for a CYP2C19 loss of function variant in patients with UA/NSTEMI . . . on clopidogrel therapy might be considered if results of testing may alter management" (with grade C level of evidence).

The ESC published its Guidelines for the diagnosis and treatment of non-ST-segment elevation acute coronary syndromes in 2007, but considered non-STEMI separately in its (jointly produced with EACTS) Guidelines on myocardial revascularisation of 2010.

References

1. Anderson JL, Adams CD, Antman EM, et al. Jeffrey L. Anderson, Cynthia D. Adams, Elliott M. 2011 ACCF/AHA Focused Update Incorporated Into the ACC/AHA 2007 Practice Guidelines for the Management of Patients With Unstable Angina/Non ST-Elevation Myocardial Infarction: A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation 2011; DOI:10.1161/CIR.0b013e318212bb8b

2. Fox KAA, Carruthers KF, Dunbar DR, et al. Underestimated and underrecognized: the late consequences of acute coronary syndrome (GRACE UK-Belgian Study). Eur H Journal 2010; 31: 2755-2764.

Notes to editor

About the European Society of Cardiology
The European Society of Cardiology (ESC) represents more than 68,000 cardiology professionals across Europe and the Mediterranean. Its mission is to reduce the burden of cardiovascular disease in Europe.