Dual Antiplatelet Agent Failure: A New Syndrome or a Clinical Non-Entity?
Geoffrey D. Barnes, Jin Li, Eva Kline-Rogers, Rebecca Juliar, David F. Armstrong, James B. Froehlich, MD,
Kim A. Eagle, MD, Hitinder S. Gurm, MD, University of Michigan Medical Center, Ann Arbor, MI
METHODS
Background: Aspirin (ASA) resistance is a welldocumented laboratory finding but the effects of clinical ASA
failure on patients with acute coronary syndrome (ACS)
have been debated. Likewise, there is some recognition of
clopidogrel resistance, but the effects of clopidogrel failure
are not well understood. We sought to determine the 6month outcomes of patients who developed an ACS while
on ASA or dual antiplatelet agents.
Methods: Of all patients admitted to the University of
Michigan between 1999 and 2005 with a diagnosis of ACS,
6-month follow up data was available for 3126. Those were
divided into three groups based on medication history: no
prior antiplatelet agent, ASA only and ASA + clopidogrel (or
ticlopidine). Primary endpoint was the rate of death, MI and
stroke or composite major adverse cardiac events (MACE)
at 6-months.
Results: Aside from a lower rate of MI in patients without
any prior antiplatelet agent usage, there were no significant
differences in 6-month stroke, death or MACE between the
three medication cohorts. In the propensity-adjusted
model, while dual antiplatelet status was not an independent
predictor of 6-month mortality or MACE, there was a trend
towards lower 6-month death rates for prior ASA use
patients (OR 0.72, 95% CI 0.51-1.04, P = 0.08).
Conclusions: Patients who “fail” antiplatelet therapy
do not have overall worse prognosis. Our data do not
support ASA or dual antiplatelet agent failure as a distinct
clinical entity.
BACKGROUND
• Several studies have reported higher rates of adverse short-term
outcomes in patients who fail ASA therapy.
• More recent studies have failed to demonstrate an adverse
outcome with ASA failure.
• The American Heart Association/American College of Cardiology
clinical guidelines currently recommends dual antiplatelet therapy
in patients with non-ST elevation ACS.
• Biochemical resistance to simultaneous ASA and clopidogrel and
the associated clinical outcomes of medication failure are not yet
well documented.
OBJECTIVE
• To evaluate the 6-month clinical outcomes in patients who fail
ASA-only or dual antiplatelet therapy
• Population of all consecutive patients with a diagnosis of an
ACS admitted to the University of Michigan between 1999 and
2005 with 6-12 month follow up.
• Prior medication use was defined as medications the patients
was taking upon admission to the hospital, excluding
medications given only by EMS or upon arrival at the
emergency department.
• Patients were separated into three cohorts based on chronic
anti-platelet medication usage on admission:
1. no antiplatelet medications
2. ASA only
3. ASA and thienopyridine (clopidogrel or ticlopidine).
• Failure was defined as chronic daily medication use in an ACS
patient.
• Our primary outcome of interest was major adverse coronary
events (MACE), defined as all-cause death, MI or stroke, in the
6-months following discharge.
RESULTS
Baseline Characteristics
Event Rates for medication groups
No Antiplatelet ASA Only
1397 (45.6%)
1413 (46.1%)
Dual Agent
255 (8.3%)
P-value
61.1± 14.0
66.0± 12.9
64.8± 13.7
<0.0001
12
Gender (% male) 927 (66.4%)
916 (64.8%)
150 (58.8%)
0.007
10
Hx MI
292 (20.9%)
781 (55.3%)
186 (72.9%)
<0.0001
Hx CAD/Cath
324 (23.2%)
909 (64.3%)
231 (90.6%)
<0.0001
Hx PCI
143 (10.2%)
539 (38.2%)
180 (70.6%)
<0.0001
Hx CABG
132 (9.5%)
448 (31.7%)
91 (35.7%)
<0.0001
4
Hx HTN
797 (57.1%)
1093 (77.4%)
228 (89.4%)
<0.0001
2
Hx PAD
123 (8.8%)
239 (16.9%)
53 (20.8%)
<0.0001
0
Hx TIA/CVA
93 (6.7%)
171 (12.1%)
46 (18.0%)
<0.0001
Hx Smoker
899 (64.4%)
826 (58.5%)
132 (51.8%)
<0.0001
Age
14
% Patients
ABSTRACT
8
P=0.40
P=0.74
P=0.009
6
P=0.57
6-Month Death
6-Month MI
No Antiplatelet Agents
ASA Only
6-Month Stroke
Dual Antiplatelet Agents
Propensity Adjusted Outcomes
STATISTICAL METHODS
• Comparison of the demographics and clinical characteristics of
patients in each of the three study groups was performed using
chi-square tests for categorical variables and Kruskal-Wallis test
for continuous variables.
• Logistic regression modeling with propensity scores was used
to compare odds ratios for death and MACE in ASA-failure, dual
antiplatelet failure and no-antiplatelet medication patients.
RESULTS
Characteristics of the Study Population:
• There were 3126 patients with ACS and 6 month follow up.
• 61 patients were excluded for clopidogrel or ticlopidine only
medication history.
• 255 patients had received dual antiplatelet therapy. 1413
patients received ASA only. 1397 had no prior antiplatelet
medication history.
• Patients with ASA-only or dual agent use were more likely to be
older and have a history or MI, coronary artery disease, previous
PCI, previous bypass surgery, hypertension, peripheral artery
disease, previous TIA or stroke, and have a history of diabetes.
They were less likely to have a smoking history.
6-Month MACE
CONCLUSION
• We did not find a difference in outcomes of ACS patients who were on prior
antiplatelet therapy. If confirmed in larger studies, then our findings are consistent
with antiplatelet failure not affecting clinical decision making.
• We did note a trend towards better outcomes with prior ASA usage.
• Additional studies on larger data sets would add to the understanding and
implications of this process.