ISSN 0947 - 8736
European Journal of Clinical Research
Platelet Glycoprotein IIb/IIIa Inhibition and Management Strategies in Unstable Angina and Myocardial Infarction without ST Segment Elevation
Aaron Kugelmass, MD,
The acute coronary syndrome of unstable angina and myocardial infarction without ST segment elevation is a common cause for hospital admission. Initial therapy for this entity has included anti-ischemic and anti-thrombotic agents. On this backdrop, there has been significant debate as to the best diagnostic management strategy for these patients, routine cardiac catherization and revascularization versus stress testing, with angiography reserved only for those identified as high risk. Earlier studies, specifically the TIMI IIIb (1,2) and the Veterans Affairs Non-Q-Wave Infarction Strategies in Hospital (VANQWISH) (3) demonstrated no reduction, or an actual increase in recurrent ischemic events in patients assigned routine coronary angiography. Alternatively, the Fragmin and Fast Revascularization during Instability in Coronary Artery Disease II (FRISC II) (4) demonstrated improved patient outcomes for those assigned to a routine invasive strategy.
The decade during which these trials were conducted saw major mechanical
and pharmacologic advances in the management of coronary artery disease.
Coronary stenting has improved short and long term results of
percutaneous revascularization (5,6).
The contemporaneous introduction of platelet glycoprotein IIb/IIIa inhibitors has proven beneficial in the medical management of unstable angina and myocardial infarction without ST segment elevation when coronary angiography and revascularization are often employed (7,8). Earlier investigations of invasive or conservative management strategies predated these therapeutic advances. It is with the Treat Angina with Aggrastat and Determine Cost of Therapy with an Invasive or Conservative Strategy – Thrombolysis in Myocardial Infarction 18 (TACTICS – TIMI 18) trial (9) that we have a reconsideration of this diagnostic question on a platform that incorporates these contemporary therapies; broad platelet inhibition with a GP IIb/IIIa inhibitor and routine coronary artery stenting.
TACTICS-TIMI 18 demonstrates that with upfront GP IIb/IIIa inhibition (tirofiban, aspirin and heparin), a routine early invasive strategy, coronary angiography and physician directed revascularization reduces coronary events. This approach, as opposed to routine stress testing, reduced a primary composite endpoint of death, non-fatal myocardial infarction, and rehospitalization for coronary syndrome, as well as death and non-fatal infarction at both 30 and 180 days. In contradistinction to previous trials, these results likely reflect the combined benefits of profound platelet inhibition and coronary artery stenting, as the overall 30 day incidence of death or non-fatal myocardial infarction (4.7 percent) in this study is a historic low for this disease entity. Furthermore, earlier acute coronary syndrome trials demonstrated an early, (seven day) hazard with revascularization (10). This was not evident in TACTICS-TIM18, providing partial explanation for the advantage of an early invasive strategy.
While TACTICS-TIMI 18 demonstrates the benefit of an early invasive
strategy for the study population, it also establishes that this approach should
not be applied universally. Prespecified
risk stratification analysis in this study defines which patient groups will
benefit from an early invasive strategy. “High
risk” patients with unstable angina and myocardial infarction without ST
segment elevation; those with positive cardiac markers, troponin and CPK-MB, ST
segment depression, or clinical criteria of high or intermediate risk (11), are
those who benefit. Significantly,
the invasive strategy benefit was also restricted to those who undergo
revascularization, both percutaneous and surgical, but not those treated
medically. This latter finding
suggests a possible benefit of up front GPIIb/IIIa blockade in larger culprit
vessels, with revascularization itself a marker of vessel size and disease
extent, rather than the benefit being restricted to a reduction myocardial
infarction following percutaneous intervention.
Risk stratification is critical for selecting the optimal treatment
strategy for the diverse patient group with unstable angina and myocardial
infarction without ST segment elevation who are treated with upstream
anti-ischemic agents and GPIIb/IIIa inhibitors.
Our future challenge, as the authors of TACTICS-TIMI 18 identify, is to
prospectively investigate which patient groups require upstream GPIIb/IIIa
inhibition, potentially reserving this therapy to the catherization laboratory
following definition of coronary anatomy.
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Aaron Kugelmass, MD
Henry Ford Hospital
Detroit, Michigan, USA