Nathan.qxp 29/7/08 10:06 Page 20
Acute Coronary Syndromes
Figure 3: Association Between Adherence with Nine Individual
reduction in diabetic ACS patients, and 27% 30-day mortality reduction in
ACC/AHA Class 1 Recommended Therapies (Represented as
high-risk patients undergoing PCI.
45–47
Contemporary registries also support
Quartiles of Guideline Adherence) and In-hospital Mortality in the
these findings, and data continue to accrue linking the use of this drug class
CRUSADE Registry
and other evidence-based pharmacotherapies with improved survival after
7
6.33
hospital discharge (see Figure 3). Accordingly, early use of intravenous
5.95
6
GPIIb/IIIa inhibitors in high-risk NSTE-ACS has been endorsed in the
5.16
5.07 4.97
4.63
published practice guidelines, with specific recommendations for the use of
5
4.16 4.17
small-molecule GPIIb/IIIa inhibitors (eptifibatide or tirofiban) pre-
4 angiography (‘upstream’) and abciximab in patients proceeding immediately
to catheterization with PCI.
3,4,48
However, despite a substantial amount of
3
supportive evidence, GPIIb/IIIa receptor inhibitors remain vastly underutilized
2
in NSTE-ACS, as reflected in large-scale registry data, which note that fewer
% in-hospital mortality
1
than 50% of eligible patients receive GPIIb/IIIa receptor inhibitors within the
first 24 hours of admission.
49,50
To some degree, underutilization may stem
0
≤25% 25–50% 50–75% ≥75% from uncertainties related to the combination and timing of antiplatelet
Hospital composite quality quartiles
therapies. Dual antiplatelet therapy early in the treatment course is
Adjusted Unadjusted
recommended, but the specific combination is left to the clinician.
Clopidogrel offers proven efficacy and ease of administration and may be
Link between overall guidlines adherence and in-hospital mortality in the CRUSADE Registry.
appropriate for long-term continuation in the majority of ACS patients.
Cummulative CRUSADE data through September 2003.
Concerns of bleeding in the small proportion of ACS patients requiring in-
for NSTE-ACS versus aspirin alone.
37
While the benefit of dual antiplatelet hospital coronary artery bypass grafting temper its usage, however. The
therapy (aspirin and clopidogrel) was noted across all risk strata, these GPIIb/IIIa receptor inhibitors also show early ischemic benefit that is at least
findings were most pronounced in the highest-risk groups and in those comparable to that seen with clopidogrel, although no direct large-scale
patients undergoing PCI.
38
The time to plateau platelet inhibition with comparison exists. Additionally, the small-molecule GPIIb/IIIa inhibitors
clopidogrel is significantly shortened with initial administration of an oral
loading dose; however, questions remain regarding the optimal dose.
Several investigations have examined this issue in the context of ACS and
PCI. The available data suggest that the non-US Food and Drug
Efforts to improve the process and
Administration (FDA)-approved 600mg loading dose is safe and more
quality of acute coronary syndrome care
rapidly efficacious than FDA-approved regimens.
39–41
However, despite
broad demonstrations of efficacy, a persistent concern is that of
should continue on individual,
clopidogrel hypo-response. This phenomenon appears to be
institutional, and national levels.
multifactorial in etiology, is prevalent in up to one-third of ACS or PCI
patients, remains difficult to predict, and is strongly associated with
increased cardiac events in high-risk patient groups.
42
Investigational
antiplatelet agents such as the thienopyridine compound prasugrel offer eptifibatide and tirofiban are parenteral compounds with relatively short
greater potency than clopidogrel with a lower rate of non-response and half-lives. Therefore, these agents rapidly achieve steady-state platelet
faster onset of action. In the TRITON-TIMI 38 study, which compared inhibition and can be discontinued at short notice should clinical
prasugrel with clopidogrel in NSTE-ACS with planned PCI, prasugrel circumstances warrant.
decreased ischemic events and stent thrombosis at the cost of increased
bleeding rates.
43
Current recommendations strongly support early With a staggering amount of complex and sometimes contradictory
(pre-angiography) initiation of dual antiplatelet therapy with aspirin plus scientific data to navigate by, and a necessary degree of ambiguity in the
either clopidogrel or a GPIIb/IIIa receptor inhibitor. practice guidelines, how is a clinician to decide on an appropriate care
plan? While several antiplatelet/anticoagulant strategies are currently
Intravenous Platelet Inhibitors supported by the available evidence, one unifying principle that should
GPIIb/IIIa receptor inhibitors have demonstrated benefit in guide therapy is that higher-risk patients should receive more intensive
NSTE-ACS management independent of other pharmacological strategies therapies earlier in their hospital course. Deferral of dual antiplatelet
and revascularization. Approved agents include the monocolonal therapy until the time of angiography allows for the occurrence of many
antibody abciximab and the two small-molecule agents eptifibatide and potentially preventable ischemic events within the first 24–48 hours. Triple
tirofiban. GPIIb/IIIa receptor inhibitors bind to the conformationally antiplatelet therapy (aspirin plus clopidogrel and GPIIb/IIIa receptor
active platelet GPIIb/IIIa receptor, thereby preventing cross-linking of inhibitors) may also be considered in selected high-risk patients undergoing
activated platelets via binding with soluble fibrinogen. Vascular clot burden an early invasive strategy with likely PCI. However, importantly, the
is reduced not only by the prevention of new thrombus formation, but also ischemic benefits of antiplatelet therapy must be balanced with the
by disaggregation of the existing thrombus.
44
Several large meta-analyses attendant bleeding risks. Therapeutic choices must be tailored to specific
found that GPIIb/IIIa receptor inhibitors conferred a 9% reduction in 30-day clinical scenarios, assessed early and often for adequacy of treatment
odds of death or MI in all NSTE-ACS patients, 26% 30-day mortality effect, and revised as warranted.
20 US CARDIOLOGY
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