Impact of Baseline Platelet Count in Patients Undergoing Primary

Percutaneous Coronary Intervention in Acute Myocardial

Infarction (from the CADILLAC Trial)
Eugenia Nikolsky, MD, PhDa, Cindy L. Grines, MDb, David A. Cox, MDc, Eulogio Garcia, MDe,
James E. Tcheng, MDd, Mehrdad Sadeghi, MDb, Roxana Mehran, MDa, Alexandra J. Lansky, MDa,
Yingbo Na, MSca, and Gregg W. Stone, MDa,*
Despite the well-recognized role of platelets in the pathogenesis of acute myocardial
infarction (AMI) and in the vascular responses to angioplasty, the relation between platelet
count and outcomes after primary percutaneous coronary intervention (PCI) in AMI is
unknown. We therefore determined the effect of baseline platelet count on clinical and
angiographic outcomes of patients with AMI undergoing primary PCI. In the prospective,
randomized CADILLAC trial, platelet count on admission was available in 2,021 of 2,082
patients (97.0%). Angiographic results and outcomes at 30 days and 1 year were stratified
by quartiles of platelet count. Median platelet count was 231 ⴛ 109/L (range 38 to 709).
Primary PCI angiographic success rates were independent of platelet count. The 30-day
incidence of target vessel thrombosis or reocclusion increased steadily across the higher
quartiles of baseline platelet count (0.2%, 0.6%, 1.0%, and 2.0%, p ⴝ 0.027). At 1 year,
patients with a baseline platelet count >234 versus <234 ⴛ 109/L had higher rates of death
or reinfarction (8.9% vs 4.5%, p <0.0001), death (5.8% vs 3.1%, p ⴝ 0.002), and reinfarction
(3.4% vs 1.6%, p ⴝ 0.008). By multivariable analysis, a higher baseline platelet count was
the strongest predictor of 1-year death or reinfarction (hazard ratio [HR] per 10,000
increase in platelet count 1.02, 95% confidence interval [CI] 1.02 to 1.07, p <0.0001) and
independently predicted reinfarction (HR 1.06, 95% CI 1.02 to 1.09, p ⴝ 0.002) and cardiac
mortality (HR 1.03, 95% CI 1.00 to 1.06, p ⴝ 0.055) at 1 year. In conclusion, a higher
baseline platelet count in patients with AMI is a powerful independent predictor of death
and reinfarction within the first year after primary PCI. © 2007 Elsevier Inc. All rights
reserved. (Am J Cardiol 2007;99:1055–1061)

The critical role of platelets in the pathogenesis of acute
myocardial infarction (AMI) has been well documented.1
However, few studies have evaluated the relation between
platelet count and outcomes in AMI, and contradictory
findings have been reported. In the Hirulog Early Reperfu-
sion/Occlusion (HERO-1) trial, higher platelet count at pre-
sentation of AMI was an independent predictor of Throm-
bolysis In Myocardial Infarction (TIMI) grade 3 flow 90
minutes after streptokinase administration.2 In contrast, in a
pooled analysis from clinical trials of fibrinolytic therapy
for ST-segment elevation AMI, a higher baseline platelet
count was associated with the presence of residual thrombus
in the infarct-related artery3 and higher rates of adverse
composite cardiac events at 30 days.4 Moreover, despite the
well-known response of platelets to balloon-mediated vas-
cular injury,5,6 the relation between baseline platelet count
a
Columbia University Medical Center and the Cardiovascular Research
Foundation, New York, New York; bWilliam Beaumont Hospital, Royal
Oak, Michigan; cMid Carolina Cardiology, Charlotte, and dDuke Clinical
Research Institute, Durham, North Carolina; and eHospital Gregorio Ma-
ranon, Madrid, Spain. Manuscript received September 29, 2006; revised
manuscript received and accepted November 16, 2006.
*Corresponding author: Tel: 212-851-9304; fax: 212-851-9396.
E-mail address: gs2184@columbia.edu (G.W. Stone).
and outcomes after primary percutaneous coronary inter-
vention (PCI) in AMI have not been assessed. We therefore
examined the database from the large, multicenter, random-
ized Controlled Abciximab and Device Investigation to
Lower Late Angioplasty Complications (CADILLAC) trial
to determine the effect of baseline platelet count on out-
comes in patients with AMI treated with primary PCI.
Methods
Patient population and treatments: Full details of the
CADILLAC protocol have been previously reported.7
Briefly, 2,082 patients of any age with AMI within 12
hours of onset who underwent primary PCI and eligible
for stent implantation were randomized in a 2 ⫻ 2 fac-
torial design to 1 of 4 mechanical reperfusion strategies:
balloon angioplasty with/without abciximab versus stent-
ing with the Multilink stent (Guidant Corp., Santa Clara,
California) with/without abciximab. Major exclusion cri-
teria were cardiogenic shock, gastrointestinal or genito-
urinary bleeding within 6 months, stroke within 2 years
or any permanent residual neurologic defect, history of
thrombocytopenia, leucopenia, hepatic or renal dysfunc-
tion, current thrombolytic administration, and noncardiac
illness with a life expectancy ⬍1 year. Patients received
chewable aspirin 324 mg, ticlopidine 500 mg or clopi-
dogrel 300 mg, a 5,000-U heparin bolus, and intravenous

0002-9149/07/$ – see front matter © 2007 Elsevier Inc. All rights reserved. www.AJConline.org
doi:10.1016/j.amjcard.2006.11.066
1056 The American Journal of Cardiology (www.AJConline.org)
␤ blockade in the absence of contraindications before
catheterization. Abciximab was administered as a bolus of
0.25 mg/kg followed by a 12-hour infusion at 0.125 ␮g/kg/
min (10 ␮g/min maximum). Heparin dosing was guided by
nomogram to achieve an activated clotting time ⱖ350 sec-
onds in the absence of abciximab and 200 to 300 seconds if
randomized to abciximab. After PCI, medical therapy in-
cluded aspirin 325 mg/day in addition to ␤ blockers and
angiotensin-converting enzyme inhibitors if not contraindi-
cated. Patients receiving stents were treated with ticlopidine
or clopidogrel for 4 weeks. Clinical follow-up was per-
formed at 1 month and 6 and 12 months, and angiographic
follow-up was carried out at 7 months in a prespecified
cohort of 656 patients.7 All baseline and follow-up films
were analyzed at an independent angiographic core labora-
tory blinded to clinical events. Complete blood counts were
measured at a minimum at baseline, 24 hours after admis-
sion, and at discharge.
The primary composite end point included death from
any cause, reinfarction (recurrent ischemic symptoms or
electrocardiographic changes plus a creatine kinase level
⬎2 times the upper limit of normal range or ⬎50% higher
than the previous value), target vessel revascularization
(TVR) as a result of ischemia, and disabling stroke.7 Mod-
erate bleeding was overt bleeding requiring blood transfu-
sion, and severe bleeding was hemorrhage with hemody-
namic compromise or hemorrhagic stroke. Anemia was
defined using World Health Organization criteria, i.e., base-
line hematocrit ⬍39% for men and ⬍36% for women.8
Statistical analysis: For the purpose of this study, pa-
tients were categorized into quartiles of baseline platelet
count (first and fourth quartiles corresponding to the lowest
and highest values, respectively). Continuous variables are
expressed as medians with interquartile ranges, and cate-
gorical data are presented as frequencies. Differences
among groups were compared using analysis of variance for
continuous variables and chi-square statistics for categorical
variables. All analyses were 2-sided, and significance was
established at the 0.05 level. Correlations between vari-
ables were described using Spearman rank-correlation
coefficients.
Survival was estimated by the Kaplan-Meier method and
compared by log-rank test. Multivariable analysis of pre-
dictors of death and reinfarction were performed using Cox
proportional hazards regression, and multivariable corre-
lates of stent thrombosis were examined using stepwise
logistic regression with entry/exit criteria of a p value ⬍0.1.
Candidate variables entered in the model included age,
gender, diabetes mellitus, hypertension, hypercholesterol-
emia, current smoking, previous MI or bypass graft surgery,
Killip class II/III, creatinine clearance, left anterior descend-
ing artery infarct vessel, 3-vessel disease, randomization to
abciximab or stent, time from symptom onset to first balloon
inflation, reference vessel diameter, final percent diameter
stenosis, target lesion location at bifurcation, presence of
dissection or thrombus on final angiogram, final TIMI grade
flow, baseline anemia, baseline white blood cell (WBC)
count, and baseline platelet count as a continuous variable.
The outcome-oriented method proposed by Contal and
O’Quigley,9 based on the log-rank test statistic, was used to
Figure 1. Frequency histogram of baseline platelet counts.
define a cut-off value for the continuous variable of platelet
count that most strongly corresponded with outcomes.
Results
Baseline characteristics: Baseline platelet count on ad-
mission was available in 2,021 of 2,082 randomized patients
(97.0%; Figure 1). Mean ⫾ SD baseline platelet count was
238 ⫾ 66.4 ⫻ 109/L (range 38 to 709), and median platelet
count (interquartile range) was 231 ⫻ 109/L (193 to 274).
As presented in Table 1, patients in the higher quartiles were
younger, more frequently were women and current smokers,
were less likely to have renal insufficiency, previous MI,
PCI, and coronary bypass surgery, had higher baseline
WBC count and lower baseline hemoglobin and hematocrit,
and were less frequently treated with aspirin and ␤ blockers
on admission. Patients with higher platelet counts more
frequently had anterior MI (p ⫽ 0.053) and less frequently
had inferior MI (p ⫽ 0.02). A weak but statistically
significant positive correlation was observed between
baseline platelet count and baseline WBC count (r ⫽
0.29, p ⬍0.0001; Figure 2), but not with baseline hemat-
ocrit (r ⫽ ⫺0.02, p ⫽ 0.34). By multivariable analysis,
higher baseline platelet count was associated with female
gender (p ⬍0.0001), younger age (p ⬍0.0001), current
smoking (p ⫽ 0.003), absence of diabetes mellitus (p ⫽
0.02), no previous MI (p ⫽ 0.039), higher baseline WBC
count (p ⬍0.0001), and lower baseline hematocrit (p ⫽
0.016).
Procedural and in-hospital outcomes: Angiographic
characteristics including lumen dimensions before and after
PCI, presence of thrombus and/or dissection, TIMI flow
grades, peak activated clotting time, and rates of procedural
success did not differ significantly across quartiles of base-
line platelet count (Table 2). However, patients with higher
baseline platelet counts had higher peak creatine kinase
levels (medians 1,234, 1,251, 1,513, and 1,470 U/L for first
to fourth quartiles, respectively, p ⫽ 0.007).
Patients with higher baseline platelet counts were less
likely to develop mild thrombocytopenia (platelet count 50
to 100 ⫻ 109/L; 8.0%, 0.6%, 1.6%, and 0.4% for first to
fourth quartiles, respectively; p ⬍0.0001); a strong trend
 Coronary Artery Disease/Platelet Count and Primary Angioplasty 1057

Table 1
Clinical characteristics, angiographic features, and medication use stratified by baseline platelet count
Variable Platelet Count (⫻109/L) p Value

⬍193 ⱖ193–⬍231 ⱖ231–⬍274 ⱖ274

(n ⫽ 501) (n ⫽ 508) (n ⫽ 506) (n ⫽ 506)

Men 82.0% 75.8% 74.7% 59.7% ⬍0.0001

Age (yrs) 63 (53–71) 62 (52–70) 57 (49–66) 56 (49–65) ⬍0.0001
Diabetes mellitus 17.6% 17.9% 15.4% 15.4% 0.57
Hypertension 50.3% 47.6% 44.9% 47.8% 0.39
Hyperlipidemia 38.7% 40.6% 36.0% 36.0% 0.35
Current smoker 38.5% 36.8% 49.2% 48.2% ⬍0.0001
Previous MI 17.6% 15.6% 12.5% 9.3% 0.0008
Previous percutaneous coronary intervention 13.8% 12.4% 9.7% 8.7% 0.037
Previous coronary bypass surgery 3.2% 2.8% 1.0% 0.8% 0.008
Previous stroke or transient ischemic attack 3.6% 2.8% 2.2% 3.6% 0.45
History of peripheral vascular disease 3.4% 2.0% 2.6% 2.8% 0.57
History of gastrointestinal bleeding 1.4% 1.0% 0.4% 2.0% 0.79
Killip class ⱖII 10.6% 9.9% 10.7% 12.7% 0.53
Body mass index (kg/m2) 27.0 (24.7–29.9) 27.3 (24.8–30.8) 27.3 (24.6–31.0) 27.3 (24.8–30.2) 0.57
Baseline hemoglobin (g/dl) 14.6 (13.5–15.6) 14.8 (13.6–15.7) 14.8 (13.8–15.6) 14.5 (13.4–15.5) 0.04
Baseline hematocrit (%) 42.7 (39.7–45.6) 43.4 (40.2–46.3) 43.3 (40.5–45.9) 42.7 (39.7–45.3) 0.025
Baseline WBC count (⫻109/L) 8.6 (6.9–10.6) 9.4 (7.5–11.7) 10.4 (8.5–12.6) 9.8 (7.9–12.2) ⬍0.0001
Baseline platelet count (⫻109/L) 170 (152–183) 212 (203–222) 248 (240–260) 307 (288–342) ⬍0.0001
Baseline serum creatinine (mg/dl) 1.0 (0.9–1.2) 1.0 (0.9–1.2) 1.0 (0.9–1.1) 1.0 (0.8–1.2) ⬍0.0001
Renal insufficiency* (%) 21.8% 17.7% 14.9% 17.3% 0.049
ST-segment elevation or left bundle branch block 85.8% 86.8% 89.8% 88.2% 0.24
Symptom onset to balloon inflation (h) 4.1 (3.0–6.3) 4.1 (2.9–6.5) 3.7 (2.8–5.7) 3.9 (2.9–6.1) 0.10
No. of coronary arteries narrowed
1 48.5% 49.4% 54.0% 53.2% 0.22
2 33.5% 35.4% 32.2% 31.0% 0.48
3 18.0% 15.2% 13.8% 15.8% 0.33
Left ventricular ejection fraction (%) 50 (40–59) 50 (40–57.5) 50 (40–55) 46.5 (40–55) 0.09
Infarct-related artery
Left anterior descending 35.5% 33.3% 41.1% 38.5% 0.053
Left circumflex 15.4% 18.3% 18.6% 17.4% 0.53
Right coronary 48.9% 47.6% 40.1% 43.7% 0.02
Medications before admission
Aspirin 33.3% 27.4% 23.7% 23.9% 0.001
Thienopyridine 3.4% 2.8% 2.0% 2.6% 0.57
ACE inhibitor or ARB 11.2% 8.5% 8.9% 9.1% 0.46
␤ Blocker 17.8% 17.5% 13.2% 10.9% 0.003
Statin 13.8% 11.8% 11.7% 10.5% 0.44
Medications at discharge
Aspirin 96.4% 97.8% 96.4% 96.7% 0.49
Thienopyridine 67.8% 63.7% 68.7% 69.8% 0.18
ACE inhibitor or ARB 36.0% 33.5% 38.4% 31.7% 0.13
␤ Blocker 74.6% 77.0% 84.2% 80.4% 0.001
Statin 25.2% 28.3% 34.9% 30.2% 0.007

* Estimated creatinine clearance ⬍60 ml/min.

ACE ⫽ angiotensin-converting enzyme; ARB ⫽ angiotensin receptor blocker.

was also present for a lower incidence of acquired severe
thrombocytopenia (platelet count ⬍50 ⫻ 109/L) in patients
with the highest baseline platelet counts (1.6%, 1.0%, 0.2%,
and 0.4%; p ⫽ 0.06). No significant difference was present
in the incidence of moderate or severe bleeding across
platelet count quartiles (3.0%, 2.6%, 2.0%, and 4.2%;
p ⫽ 0.21), although the rate of red blood cell transfusion
was highest in the quartile with the highest baseline
platelet count (4.2%, 2.4%, 3.9%, and 6.1%; p ⫽ 0.03).
At discharge, more patients in the higher quartiles of
baseline platelet count were prescribed ␤ blockers and
statins (Table 1).
Thirty-day and 1-year outcomes: The 30-day inci-
dence of target vessel thrombosis or reocclusion increased
steadily across higher quartiles of baseline platelet count
(0.2%, 0.6%, 1.0%, and 2.0%; p ⫽ 0.027). Reinfarction and
ischemic TVR rates at 30 days were also significantly
higher in patients with increased baseline platelet counts,
resulting in higher rates of cumulative major adverse car-
diac events (Table 3).
At 1-year follow-up, patients in the highest platelet count
quartile had the highest rates of all-cause and cardiac mor-
tality, reinfarction, ischemic TVR, and composite major
adverse cardiac events, whereas disabling stroke was not
1058 The American Journal of Cardiology (www.AJConline.org)
Figure 2. Correlation between baseline platelet and WBC counts.
related to baseline platelet count (Table 3). One-year sur-
vival free from MI was significantly lower in patients in the
higher quartiles of baseline platelet count (Figure 3). A
baseline platelet amount of 234 ⫻ 109/L was identified as
the cut-off point that corresponded to the most significant
relation between platelet count and 1-year death/reinfarction
(Figure 4). At 1 year, patients with a baseline platelet count
ⱖ234 versus ⬍234 ⫻ 109/L had higher rates of death or
reinfarction (8.9% vs 4.5%, p ⬍0.0001), death (5.8% vs
3.1%, p ⫽ 0.002), and reinfarction (3.4% vs 1.6%, p ⫽
0.008).
Because of a significant correlation between baseline
WBC and platelet counts, additional analyses were per-
formed to determine a possible linkage between the 2 on
adverse clinical outcomes. When analyzed by quartiles of
baseline platelet and WBC counts (Figure 5), rates of 1-year
death/reinfarction in 16 subgroups varied from 1.4% to
11.5%. There was no interaction between baseline platelet
and WBC counts in the occurrence of 1-year death (p ⫽
0.58), reinfarction (p ⫽ 0.22), or death/reinfarction (p ⫽
0.49).
By multivariable analysis, a higher baseline platelet
count was the only independent predictor of reinfarction at
30 days (hazard ratio [HR] per 10,000 increase in platelet
count 1.08, 95% confidence interval [CI] 1.02 to 1.12, p ⫽
0.008). Higher baseline platelet count also independently
predicted reinfarction at 1 year (HR 1.06, 95% CI 1.02 to
1.09, p ⫽ 0.002). Trends were present for baseline platelet
count as an independent predictor of 1-year cardiac mortal-
ity (HR 1.03, 95% CI 1.00 to 1.06, p ⫽ 0.055) and all-cause
mortality (HR 1.02, 95% CI 0.99 to 1.05, p ⫽ 0.12). Base-
line platelet count was the most powerful predictor of 1-year
death/MI (HR 1.04, 95% CI 1.02 to 1.07, p ⬍0.0001) in
addition to older age (p ⫽ 0.0001), left anterior descending
artery infarct vessel (p ⫽ 0.0002), final TIMI grade ⬍3 flow
(p ⫽ 0.003), baseline anemia (p ⫽ 0.015), chronic renal
insufficiency (p ⫽ 0.012), 3-vessel disease (p ⫽ 0.024), and
hypertension (p ⫽ 0.038). Results remained unchanged af-
ter inclusion of moderate/severe bleeding and blood product
transfusion into the multivariable model of the analyzed
clinical end points.
Discussion
The present study, to our knowledge the first investigation
of the effect of quantitative platelet count in patients under-
going primary PCI, demonstrates that, although procedural
success rates are independent of platelet amount, a higher
baseline platelet count is a significant and independent pre-
dictor of early reinfarction and of late death and reinfarction
after primary PCI in patients with AMI.
Reinfarction after primary PCI is uncommon. In the
pooled analysis from 7 Primary Angioplasty in Acute Myo-
cardial Infarction (PAMI) studies, 30-day reinfarction oc-
curred in 77 of 3,646 patients (2.1%) and was predicted by
admission Killip class ⬎I, left ventricular ejection fraction
⬍50%, final coronary stenosis ⬎30%, and presence of cor-
onary dissection and thrombus on the final angiogram.10
The influence of platelet count was not examined in that
study. In the present large-scale, multicenter, randomized
trial of mechanical reperfusion therapies in AMI, the 30-day
reinfarction rate was only 1.6%. Notably, when the platelet
count was considered in a multivariable model, the only
independent predictor of 30-day reinfarction was baseline
platelet count; none of the clinical or angiographic charac-
teristics identified in the previous PAMI report was predic-
tive. Reinfarction rates at 1 year were also 2 times as
frequent in patients with a baseline platelet count ⱖ234 ⫻
109/L than in patients with lower baseline platelet counts
(3.4% vs 1.6%, respectively).
Higher baseline platelet counts in the present study were
associated with increased cardiac mortality at 1 year. Rein-
farction is 1 of the most common causes of death in patients
undergoing reperfusion therapy and likely contributed to the
late mortality risk in patients with higher baseline platelet
counts.11 Moreover, increased platelet counts were associ-
ated with more frequent anterior infarcts and larger infarcts
as estimated by peak creatine kinase level, which may also
partly explain the poor prognosis in these patients.12
The mechanisms through which higher baseline plate-
let counts increase reinfarction rates and late cardiac
mortality are uncertain. Consistent with previous studies,
patients with higher platelet counts were more frequently
women,13 who have a worse prognosis in AMI compared
with men.14 –16 However, although female gender was an
important independent determinant of mortality in the
CADILLAC study, women compared with men did not
have higher rates of 30-day reinfarction (1.1% vs 0.7%,
respectively, p ⫽ 0.41).16
Cigarette smoking, which in the present study was also
associated with a higher baseline platelet count, may result
in a hypercoagulable state and provoke thrombosis by oxi-
dative stress, endothelial dysfunction, and platelet activa-
tion.17,18 Previous studies have demonstrated that smokers
with AMI or sudden death have a higher incidence of
platelet-rich thrombus, which may theoretically increase the
likelihood of early reinfarction.19 However, previous pri-
mary PCI studies have found similar or lower rates of
reinfarction after primary PCI in current smokers compared
with nonsmokers.20,21
At discharge, ␤-blocker and statin use, which decrease
death and/or reinfarction in AMI after primary PCI, was
paradoxically more frequent in patients with higher baseline
 Coronary Artery Disease/Platelet Count and Primary Angioplasty 1059

Table 2
Angiographic results stratified by baseline platelet count
Variable Platelet Count (⫻109/L) p Value

⬍193 ⱖ193–⬍231 ⱖ231–⬍274 ⱖ274

(n ⫽ 501) (n ⫽ 508) (n ⫽ 506) (n ⫽ 506)

TIMI flow
Baseline
Grade 0 or 1 67.7% 67.5% 70.1% 65.7% 0.54
Grade 2 11.8% 9.6% 9.2% 9.6% 0.52
Grade 3 20.5% 22.9% 20.7% 24.6% 0.34
Final
Grade 0 or 1 2.0% 0.8% 1.0% 1.8% 0.28
Grade 2 2.4% 4.0% 2.6% 3.2% 0.47
Grade 3 95.5% 95.2% 96.4% 95.0% 0.72
Reference diameter (mm)
Baseline 3.00 (2.67–3.38) 2.99 (2.65–3.37) 2.97 (2.64–3.34) 2.96 (2.60–3.36) 0.36
Final 2.94 (2.66–3.28) 2.99 (2.63–3.37) 2.94 (2.66–3.28) 2.99 (2.63–3.37) 0.36
Minimal luminal diameter (mm)
Baseline 0 (0–0.74) 0 (0–0.69) 0 (0–0.69) 0 (0–0.76) 0.66
Final 2.47 (2.10–2.80) 2.48 (2.10–2.85) 2.46 (2.08–2.79) 2.44 (2.05–2.81) 0.75
Diameter stenosis (%)
Baseline 100 (74.2–100) 100 (75.5–100) 100 (75.9–100) 100 (75.2–100) 0.66
Final 24.0 (17.4–31.5) 22.5 (16.5–29.1) 23.8 (16.9–32.6) 23.6 (16.9–32.1) 0.19
Thrombus
Baseline 52.7% 53.9% 57.1% 57.6% 0.32
Final 4.9% 5.5% 2.8% 4.5% 0.21
Final dissection 12.2% 9.4% 9.0% 10.6% 0.35
Procedural success 91.9% 90.8% 93.4% 88.8% 0.078
Peak activated clotting time (s) 307 (253–371) 301 (249–363) 320 (259–372) 315 (250–374) 0.076
Stent implanted 54.9% 55.5% 61.7% 55.3% 0.094
Per randomization 51.0% 48.2% 53.2% 47.0% 0.48
As bailout for complications 4.8% 8.9% 9.7% 8.9% 0.016
Abciximab administered 54.7% 53.0% 53.0% 51.6% 0.80
Per randomization 51.6% 51.6% 50.8% 47.6% 0.20
As bailout for complications 3.8% 2.2% 2.2% 4.2% 0.75

Table 3
In-hospital, 30-day, and one-year outcomes stratified by baseline platelet count
Platelet Count (⫻109/L) p Value

⬍193 ⱖ193–⬍231 ⱖ231–⬍274 ⱖ274

(n ⫽ 501) (n ⫽ 508) (n ⫽ 506) (n ⫽ 506)

All-cause mortality
30 d 1.6% 1.4% 2.4% 3.0% 0.26
1 yr 4.1% 2.4% 5.2% 5.9% 0.038
Cardiac mortality
30 d 1.0% 0.8% 2.2% 2.0% 0.17
1 yr 2.9% 1.2% 4.4% 3.5% 0.022
Noncardiac mortality
30 d 0.6% 0.6% 0.2% 1.0% 0.44
1 yr 1.2% 1.2% 0.8% 2.5% 0.14
Disabling stroke
30 d 0.4% 0.0% 0.0% 0.2% 0.29
1 yr 0.6% 0.2% 1.1% 0.4% 0.35
Reinfarction
30 d 0.4% 0.2% 1.2% 1.6% 0.047
1 yr 1.7% 1.6% 2.9% 3.5% 0.12
TVR
30 d 3.0% 3.4% 2.0% 5.6% 0.015
1 yr 12.5% 14.1% 10.9% 16.2% 0.064
Composite adverse events
30 d 5.2% 4.7% 4.8% 8.5% 0.024
1 yr 16.4% 16.6% 16.5% 21.8% 0.048
1060 The American Journal of Cardiology (www.AJConline.org)
Figure 3. One-year survival free from MI in quartiles of baseline platelet
count.
Figure 4. One-year survival free from MI in patients with a cut-point value
of baseline platelet count (234 ⫻ 109/L) that corresponded to the most
significant relation with death or reinfarction at 1 year.
Figure 5. Rates of 1-year death or reinfarction in relation to baseline
platelet count (first to fourth quartiles ⬍193, ⱖ193 to ⬍231, ⱖ231 to
⬍274, and ⱖ274 ⫻ 109/L, respectively) and baseline WBC count (first to
fourth quartiles ⬍7.88, ⱖ7.88 to ⬍9.88, ⱖ9.88 to ⬍12.2, and ⱖ12.2 ⫻
109/L, respectively).
platelet counts. Thus, differences in medical management
cannot account for the adverse outcomes in patients with
higher baseline platelet counts.22,23
Previous studies have demonstrated that platelets in pa-
tients with acute coronary syndromes are hyperaggregable
and that angioplasty-injured blood vessels are highly throm-
bogenic1,24 despite administration of antiplatelet agents.
Persistent platelet activation may thus be more prominent in
patients with larger numbers of platelets and contribute to
more frequent reocclusion after primary PCI.
Several recent studies have demonstrated that higher
baseline WBC counts, as a marker of systemic inflamma-
tion, are associated with impaired epicardial and myocardial
perfusion, more extensive atherosclerotic disease, and
higher mortality in patients with acute coronary syn-
dromes.25–27 In the present study, a positive correlation
existed between baseline platelet and WBC counts, which
might suggest that an inflammatory state contributed to the
adverse outcomes in patients in the higher quartiles of
platelet count. However, platelets, as an acute-phase reac-
tant, may also increase in number in response to various
stimuli (systemic infection, inflammatory conditions, bleed-
ing, and tumors), resulting in overproduction of proinflam-
matory cytokines.28,29 Despite the correlation between base-
line platelet and WBC counts in the CADILLAC study, the
influence of a higher platelet count on 1-year mortality and
reinfarction was independent of baseline WBC count. It thus
remains possible that an increased baseline platelet count in
patients undergoing primary PCI for AMI reflects a height-
ened underlying inflammatory state (independent of WBC
count) that is associated with recurrent ischemic events and
late mortality.
The present post hoc analysis was not prespecified in the
original trial and has inherent limitations. Increased mean
platelet volume and platelet size, which may contribute to
reinfarction and death,30 were not measured in this study.
Biochemical indexes of platelet activation, including throm-
boxanes, prostacyclin, and P-selectin, also unavailable in
the CADILLAC trial, may provide insight to the association
between platelet count and reinfarction.
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