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Original Research: THROMBOSIS |

Increased Major Bleeding Complications Related to Triple Antithrombotic Therapy Usage in Patients With Atrial Fibrillation Undergoing Percutaneous Coronary Artery Stenting FREE TO VIEW

Sergio Manzano-Fernández, MD; Francisco J. Pastor, MD; Francisco Marín, MD, PhD; Francisco Cambronero, MD; Cesar Caro, MD; Domingo A. Pascual-Figal, MD, PhD; Iris P. Garrido, MD; Eduardo Pinar, MD, PhD; Mariano Valdés, MD, PhD; Gregory Y. H. Lip, MD; for the CREDO Investigators; for the SYNERGY Trial Investigators; for the GRACE Investigators
Author and Funding Information

*From the Department of Cardiology (Drs. Manzano-Fernández, Pastor, Marín, Cambronero, Caro, Pascual-Figal, Garrido, Pinar, and Valdés), University Hospital Virgen de la Arrixaca, Murcia, Spain; and University Department of Medicine (Dr. Lip), City Hospital, Birmingham, UK.

Correspondence to: Gregory Y. H. Lip, MD, University Department of Medicine, City Hospital, Birmingham B18 7QH, UK; e-mail: g.y.h.lip@bham.ac.uk


The authors have no conflicts of interest to disclose.

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (www.chestjournal.org/misc/reprints.shtml).


Chest. 2008;134(3):559-567. doi:10.1378/chest.08-0350
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Background:  The optimal antithrombotic therapy strategy for atrial fibrillation (AF) patients who undergo percutaneous coronary intervention with stent implantation (PCI-S) is unknown. We assessed the safety of antithrombotic therapy strategies in AF patients with indication for oral anticoagulation (OAC) undergoing PCI-S.

Methods:  We studied consecutive AF patients with indication for OAC who underwent PCI-S. We compared patients that received triple antithrombotic therapy (TT) [aspirin, clopidogrel, and coumadin] against other regimes (non-TT) after PCI-S. The primary end point was defined as the occurrence of major bleeding complications that were termed as early major bleeding (EMB) [≤ 48 h] or late major bleeding (LMB) [> 48 h]. Clinical follow-up was performed, and complications were recorded.

Results:  We studied 104 patients (mean age ± SD, 72 ± 8 years; 70% men); TT was used in 51 patients (49%). TT was associated with a higher incidence of LMB (21.6% vs non-TT, 3.8%; p = 0.006) but not of EMB (5.8% vs non-TT, 11.3%; p = 0.33). In multivariate analyses, glycoprotein (GP) IIb/IIIa inhibitor use (hazard ratio [HR], 13.5; 95% confidence interval [CI], 1.7 to 108.3; p = 0.014) and PCI-S of three vessels or left main artery disease (HR, 7.9; 95% CI, 1.6 to 39.2; p = 0.01) were independent predictors for EMB. TT use (HR, 7.1; 95% CI, 1.5 to 32.4; p = 0.012), the occurrence of EMB (HR, 6.7; 95% CI, 1.8 to 25.3; p = 0.005), and baseline anemia (HR, 3.8; 95% CI, 1.2 to 12.5; p = 0.027) were independent predictors for LMB. No differences in major cardiovascular events were observed in patients treated with TT vs non-TT (25.5% vs 21.0%; p = 0.53).

Conclusion:  A high rate of major bleeding is observed in AF patients with indication for OAC undergoing PCI-S who receive TT. GP IIb/IIIa inhibitor use and multivessel/left main artery disease during PCI-S were independent predictors for EMB, while TT use, occurrence of EMB, and baseline anemia were independent predictors for LMB.

Figures in this Article

There has been a marked increase in the use of percutaneous coronary interventions with stent implantation (PCI-S) in the elderly population.1 Given that the incidence of atrial fibrillation (AF) increases steadily with age and is present in approximately 5% subjects > 65 years old,2 it is increasingly common that patients who undergo PCI-S have concomitant AF.3 In addition, PCI-S is being performed in increasingly complex patients with multiple comorbidities, resulting in a high risk for hemorrhagic and thromboembolic complications. With the wide use of multiple antithrombotic agents in this clinical scenario, postprocedural bleeding complications are common and may result in significant morbidity and mortality.4

The optimal antithrombotic treatment of AF patients with indication for long-term oral anticoagulation (OAC) undergoing PCI-S is unknown. There are no randomized trials assessing the best antithrombotic regimen in this setting, and the management of this population is challenging. In general, the combination of aspirin and clopidogrel (A+C) is the recommended antithrombotic treatment for preventing stent thrombosis.5,6 Conversely, OAC is the optimal antithrombotic therapy to prevent stroke and thromboembolism in AF patients at high risk of stroke, and has been demonstrated to be superior to A+C in AF patients.7

We recently reported that anticoagulation therapy significantly reduced the occurrence of mortality and cardiovascular events in AF patients undergoing PCI-S.8 Few observational studies have shown that the overall efficacy of triple antithrombotic therapy (TT) may be superior to other strategies adopted in the prevention of cardiovascular events.9,10 However, concerns have been raised that the safety of TT may be suboptimal, with a fivefold increase in overall hemorrhagic complications, when compared to A+C alone.9,1115

The aim of this study was to assess safety of antithrombotic drug management strategies adopted after PCI-S in AF patients with indication for OAC, with specially regard to the occurrence of major bleeding complications. We hypothesized that baseline characteristics (ie, age, anemia, previous major bleeding) and type of antithrombotic regimen could influence major bleeding events and the time of bleeding occurrence. We tested this hypothesis by comparing those AF patients who subsequently received TT vs other antithrombotic therapy regimes (ie, non-TT) after undergoing PCI-S.

A retrospective analysis of our computerized database including all patients who were discharged from our hospital after PCI-S between January 2002 and December 2006 was performed. All AF patients with indication for OAC16 who had undergone PCI-S and belonged to our local patient catchment area (a population of 226,000) were included in the analysis.

We recorded clinical and demographic characteristics of the patients, stroke risk factors, and antithrombotic therapy use before percutaneous coronary intervention (PCI) and at discharge. Stroke risk scores were calculated in all patients according to Gage et al.17 All medical records of the cases were carefully reviewed, and patients were contacted by telephone to obtain the length of antithrombotic therapy and incidence of major bleeding and other clinical events during the follow-up period.

Individual clinical management decisions and PCI lesions were treated according to current standard interventional techniques, at the operator's discretion. Hospital records and death certificates from the central statistics office of Spain were used to record and classify deaths. We classified all patients as those receiving TT or non-TT after PCI-S. The study protocol was approved by the ethics committees of our hospital, and all the subjects gave informed consent to participation.

Primary and secondary end points were defined as in the Appendix. The primary end point was defined as the occurrence of major bleeding complications (fatal bleeding, a decrease in the blood hemoglobin level > 4 g/dL, need for transfusion of ≥ 2 U of blood, need for corrective surgical intervention, the occurrence of intracranial or retroperitoneal bleeding, or any combinations of these events18) that were subclassified in two groups: (1) early major bleeding (EMB) as that occurring within 48 h after PCI-S; and (2) late major bleeding (LMB), which occurs after 48 h after PCI-S. The secondary end points consisted of cardiovascular death, myocardial infarction, need of new revascularization, stent thrombosis, or thromboembolic complications (major adverse cardiovascular events [MACEs]) during the follow-up. The international normalized ratio (INR) at the time of the event was recorded in addition to other potentially contributing factors such as a fall. The occurrences of adverse events were recorded at hospital discharge and during the follow-up.

Statistical Analysis

Normally distributed data are presented as mean ± SD, and nonnormally distributed data are presented as median (interquartile range [IQR]). Categorical variables are expressed as percentages. Categorical data were compared using the χ2 test, and a Fisher exact test was performed, if relevant. Categorized analyses were performed according antithrombotic regimen at discharge: TT vs non-TT. Baseline differences between groups were evaluated by unpaired Student t test, and a Mann-Whitney U test, as relevant. The overall recurrence-free survival rates were calculated using the Kaplan-Meier method, and the differences were determined using the log-rank test. The independent effect of variables on prognosis was calculated using a Cox proportional hazards regression model, using the values that showed p < 0.15 in the univariate analysis. All p values < 0.05 were accepted as a statistically significant.

We identified 104 patients with AF who had undergone PCI-S over the study period (Table 1). Of the 104 study patients, only 7 patients had been included in our earlier report8 on mortality and outcomes in AF patients undergoing PCI. Median follow-up was 12 months (IQR, 10 to 12 months). All patients were followed up for at least 6 months, although 1-year follow-up was completed in 68% of the study population. The study population was elderly, with a high prevalence of comorbidities. The indications for PCI-S, as well as the procedural characteristics of our study patients, are summarized in Table 2. Acute myocardial infarction was the most common indication for PCI-S in 38 patients (37%). There were high rates of drug-eluting stent (DES) use (66%) and a high prevalence of three-vessel or left main artery disease (25%).

Table Graphic Jump Location
Table 1 Baseline Characteristics of Study Cohort*

*Data are presented as mean ± SD, No. (%), or median (IQR) unless otherwise indicated. CHADS = chronic heart failure, hypertension, age > 75 yr, diabetes, prior transient ischemic attack or stroke.17

Table Graphic Jump Location
Table 2 Procedural Characteristics*

*Data are presented as No. (%), or median (IQR).

Antithrombotic Regimens Used

There was wide variability in the antithrombotic therapy regimen adopted at discharge (Fig 1). TT was the most commonly used regimen (51 patients, 49%). Ticlopidine was used in only one patient who was included in the clopidogrel group. Patients discharged receiving TT were more often receiving acenocoumarol (a coumadin) before hospital admission (73% vs 25%, p < 0.001). Patients who received TT were younger than patients who received other antithrombotic regimens (p = 0.003).

Figure Jump LinkFigure 1 Antithrombotic treatment during follow-up (at discharge, at 6 months, at 12 months).Grahic Jump Location

The duration of clopidogrel prescription was variable (median, 10 months; IQR, 1 to 12 months), with 61% of patients receiving clopidogrel for at least 6 months and 42% for at least 1 year. As expected, clopidogrel treatment was significantly longer in patients receiving DES than in patients with bare metal stents (BMSs) [12 months; IQR, 8 to 12 months; vs 1 month; IQR, 1 to 3 months; p < 0.0001]. The duration of clopidogrel therapy was higher in the TT group (12 months; IQR, 1 to 12 months; vs 7 months; IQR, 1 to 12 months; p = 0.06). During the follow-up, TT was discontinued in 39% of patients, major bleeding being the reason for discontinuation in 6% of cases.

EMB

There were no significant differences in the occurrence of EMB (5.8% vs 11.3%, p = 0.33) between the two antithrombotic therapy groups (TT vs non-TT) [see online supplementary material]. Kaplan-Meier survival analysis of EMB events at 48 h after PCI showed that the event-free survival period was similar in both groups (94% vs 88%; log-rank test, p = 0.32) [Fig 2]. In a univariate model, glycoprotein (GP) IIb/IIIa inhibitor use and PCI-S of three vessels or left main artery disease were associated with EMB (hazard ratio [HR], 13.1; 95% confidence interval [CI], 1.6 to 105.0; p = 0.015; and HR, 7.4; 95% CI, 1.5 to 36.0; p = 0.013, respectively). In multivariate analysis, GP IIb/IIIa inhibitor use (HR, 13.5; 95% CI, 1.7 to 108.3; p = 0.014) and PCI-S of three vessels or left main artery disease (HR, 7.9; 95% CI, 1.6 to 39.2; p = 0.01) remained significantly independent predictors for EMB (Table 3).

Figure Jump LinkFigure 2 Kaplan-Meier survival analysis of EMB complications (log-rank test, p = 0.33).Grahic Jump Location
Table Graphic Jump Location
Table 3 Univariate and Multivariate Analysis of EMB Complications
LMB

During the follow-up, TT was associated with higher rate of LMB (21.6% vs non-TT, 3.8%; p = 0.006) [shown in online supplementary material]. Among patients receiving TT, two fatal intracranial bleedings occurred: one of them was secondary to a mild craniocerebral trauma with an INR value on the day of the bleeding event of 6.8; the other intracranial bleeding occurred spontaneously without acenocoumarol overdose. The majority of INR values on the day of LMB were within the therapeutic range, and only two major bleeding events occurred with an INR value > 3 (6.8 and 6.9, respectively). All major GI bleeding events occurred in patients with baseline anemia. In both groups, most LMB events (85%) occurred principally during the first 6 months of follow-up.

Kaplan-Meier survival analysis of LMB events at 12 months showed that use of TT was associated with shorter event-free survival period (78% vs 96%; log-rank test, p = 0.009) [Fig 3]. On univariate analyses, TT use (HR, 5.8; 95% CI, 1.3 to 26.3; p = 0.022), presence of EMB (HR, 4.4; 95% CI, 1.2 to 16.1; p = 0.024), number of stents implanted per procedure (HR, 1.6; 95% CI, 1.1 to 2.4; p = 0.026), and baseline anemia (HR, 3.5; 95% CI, 1.1 to 11.4; p = 0.036) were associated with LMB. In multivariate analyses, TT use (HR, 7.1; 95% CI, 1.5 to 32.4; p = 0.012), the presence of EMB (HR, 6.7; 95% CI, 1.8 to 25.3; p = 0.005), and baseline anemia (HR, 3.8; 95% CI, 1.2 to 12.5; p = 0.027) remained significant independent predictors for LMB during follow-up (Table 4).

Figure Jump LinkFigure 3 Kaplan-Meier survival analysis of LMB complications (log-rank test, p = 0.009). See Figure 1 for expansion of abbreviation.Grahic Jump Location
Table Graphic Jump Location
Table 4 Univariate and Multivariate Analysis of LMB Complications
MACEs

The rate of MACEs did not differ significantly between the two groups (25.5% vs 21.0%, p = 0.53). In the TT group, three patients had cardiovascular death during the follow-up: two patients died due to a hemorrhagic stroke (details shown above), and the other patient died suddenly 1 month after PCI. In the latter patient (who had a DES implanted), clopidogrel treatment was prematurely stopped 10 days before the event occurred. In the non-TT group, two patients receiving dual antiplatelet treatment with A+C had nonfatal acute stent thrombosis and subsequent reinfarction. One of them had been treated with BMS and the other with DES. Also, four cardiovascular deaths occurred in this group: two patients died suddenly, one patient died due to an acute myocardial infarction, and one patient died after a massive ischemic stroke. The first three patients were receiving A+C, and the other patient was receiving acenocoumarol plus clopidogrel. The two patients who died suddenly had been treated with DES, while the other two had BMS. The incidence of thromboembolic complications was similar between the two groups (p = 0.38).

Four patients receiving TT had thromboembolic events during the follow-up, compared to two patients in the non-TT group. The two patients of this last group who had thromboembolic events were receiving A+C and acenocoumarol plus clopidogrel, respectively. All INR values on the day of thromboembolic events were below therapeutic range (1.2 to 1.9).

Kaplan-Meier survival analysis of MACE at 12 months showed no significant difference event-free survival period between the treatment groups (71% vs 78%; log-rank test, p = 0.59) [Fig 4].;F4> In univariate model, previous PCI (HR, 2.67; 95% CI, 1.21 to 5.90; p = 0.015), diabetes mellitus (HR, 3.15; 95% CI, 1.32 to 7.58; p = 0.011), and previous chronic heart failure (HR, 2.49; 95% CI, 1.12 to 5.55; p = 0,026) were associated with the occurrence of MACE. In multivariate analysis, diabetes mellitus (HR, 3.55; 95% CI, 1.46 to 8.62; p = 0.005) and previous chronic heart failure (HR, 2.74; 95% CI, 1.21 to 6.20; p = 0.016) remained significant independent predictors for the secondary end points.

Figure Jump LinkFigure 4 Kaplan-Meier survival analysis of MACEs (log-rank test, p = 0.59). See Figure 1 for expansion of abbreviation.Grahic Jump Location

The present study has the following major findings in regard to bleeding in our AF patients undergoing PCI-S: (1) a high incidence of short-term and long-term major bleeding complications; (2) the identification of different predictors of major bleeding according to the time from the PCI-S: GP IIb/IIIa inhibitor use and the presence of multivessel/left main artery disease were independent predictors of EMB, while TT regimen and EMB were independent predictors of LMB; and (3) a high complexity of the study cohort, being elderly and with multiple comorbidities, resulting in a high risk for hemorrhagic and/or thrombotic complications. To the best of our knowledge, our study represents the first study that differentiates EMB and LMB complications after PCI-S in AF patients to determine specific predictors of early or late bleeding.

Our results confirm earlier studies9,1115 that had shown a high rate of major bleeding complications after PCI-S in patients who need OAC. The reasons for these findings have not been specifically studied but are likely to be multifactorial, including various clinical and therapeutic characteristics. Possible explanations are elderly, high prevalence of comorbidities (eg, anemia, renal dysfunction, and previous major bleeding), and the high DES use (66%). Indeed, 61% of patients received clopidogrel for at least 6 months and 42% for at least 1 year. Our previous series (from a different hospital area)8 focused mainly on MACE in a cohort of AF patients after PCI-S with or without anticoagulation at discharge, and did report a nonsignificant difference in the overall incidence of major bleeding in the anticoagulated group vs nonanticoagulated group (14.9% vs 9.0%, respectively). In contrast to the present analysis, our previous study8 only considered overall major bleeding complications without differentiating early and late bleeding, nor examined the factors influencing these events.8

Trials1920 conducted in high-risk populations with high rates of use of GP IIb/IIIa inhibitors and coronary intervention have not shown a significant improvement in outcomes but have shown some evidence of increased bleeding, especially when enoxaparin and unfractionated heparin were administered simultaneously. However, scarce data exist about the safety of GP IIb/IIIa inhibitors administration in AF patients undergoing PCI-S, especially in the real-world setting. In agreement with previous studies,1920 we found that GP IIb/IIIa inhibitor use was the most powerful independent predictor of EMB. However, the presence of multivessel/left main artery disease was also identified as an important independent predictor of EMB. This finding may be related to complexity of the procedure and high incidence of vascular access site-related complications.

Several studies2124 have shown that the risk of procedural hemorrhagic events is significantly increased in elderly patients. In the present study, we were unable to show age as independent predictor of EMB. Interestingly, we did not find significant differences in the rate of EMB between TT and other antithrombotic regimens. Indeed, EMBs were mainly related to periprocedural variables and not to antithrombotic regimen adopted, as previously described. Nguyen et al25 published a global registry that included 800 patients who underwent PCI-S owing to an acute coronary syndrome, and were subsequently discharged receiving TT or warfarin and single antiplatelet therapy. Similarly to our findings, these authors concluded that there were no differences in hospital major bleeding complications. These authors did not include patients receiving dual antiplatelet therapy alone or data on long-term bleeding outcomes.

To date, there are few studies that have focused on the long-term bleeding outcomes after PCI-S in patients who have additional indications for long-term OAC. In previous studies,9,11,14,15 there was heterogeneity in the study population, a wide variability in the definitions of major bleeding complications and in the antithrombotic regimen compared. Our study—which was performed in AF patients with indication for OAC only—shows that TT may be an independent predictor of LMB. Almost all major bleeding events occurred during the first 6 months of follow-up. This may be attributed to a more intensive antithrombotic regimen during these first months after PCI-S and make this period extremely important to a closer INR control. Interestingly, Palareti et al26 showed similar results in an outpatient populations following initiation of their first OAC course (most commonly for venous thromboembolism), thus emphasizing that the majority of bleeding complications occur within 3 months. In our population, we did not find differences in major bleeding between patients who underwent PCI but were receiving longstanding anticoagulant therapy vs those in which anticoagulants were started at the time of the current admission.

Of note, in this study, patients who had EMB were more likely to present with LMB. Thus, prior major bleeding is an important factor that should be kept in mind when post-PCI major bleeding risk factors are assessed. Anemia also appears to be a high-risk marker for mortality and hemorrhagic complications in patients undergoing PCI.2729 In our population, baseline anemia and the likelihood of LMB were strongly correlated. The risk of LMB was almost quadrupled in patients presenting with baseline anemia. Importantly, all GI major bleeding occurred in patients with baseline anemia, emphasizing the importance of a thorough search for predisposing bleeding sites and/or hemorrhagic diatheses. However, we were unable to show renal insufficiency as a independent predictor of LMB.

With regard to MACE, we did not observe significant differences between the two therapy groups, neither in the subgroup with cardiac events nor in thromboembolic complications. In a larger population of AF patients undergoing PCI-S from a different center, we previously showed that OAC reduces the occurrence of cardiovascular events.8 In this cohort, both study population and antithrombotic regimen compared were significantly different. In the present study, we found a higher incidence of major bleeding complications, and its implications on mortality may explain these results. In agreement with previous data,7 the fact that all ischemic strokes were reported in patients with INR values below therapeutic range or in patients receiving dual antiplatelet therapy enhances the importance of OAC for the prevention of thromboembolic complications in our population. On the basis of these and previous data,30 TT should not be used after PCI-S in those AF patients with high bleeding risk profile. A combination of a single antiplatelet agent plus OAC may be a safer treatment option.

Limitations

This study is limited by its single-center retrospective registry study design, although we have included consecutive patients on our database. There were also significant baseline differences between the two treatment groups that may account for the increased major bleeding and all-cause mortality in the TT group. However, we have tried to adjust for these differences by multivariate analyses adjusting for confounding variables. The small sample size also makes it difficult to draw firm conclusions. A final limitation is the possible change of antithrombotic treatment during the follow-up period, sometimes in relation to the presence of thrombotic or hemorrhagic complications.

This study shows that AF patients with indication for OAC who undergo PCI-S represent a complex population with multiple comorbidities and a high rate of short-term and long-term major bleeding complications. Moreover, different predictors of major bleeding according to the time from the PCI-S were identified, being GP IIb/IIIa inhibitors and TT use being the main factors implicated in EMB and LMB, respectively. Although TT may theoretically represent the best antithrombotic therapy option for the prevention of cardiac and thromboembolic events, its safety in this context is doubtful, with a significant risk of LMB. Further studies are required to assess the bleeding and thrombotic risk with different post-PCI strategies in these patients, in order to facilitate the development of management guidelines.

A+C

aspirin and clopidogrel

AF

atrial fibrillation

BMS

bare metal stent

CI

confidence interval

DES

drug-eluting stent

EMB

early major bleeding

GP

glycoprotein

HR

hazard ratio

INR

international normalized ratio

IQR

interquartile range

LMB

late major bleeding

MACE

major adverse cardiovascular event

OAC

oral anticoagulation

PCI

percutaneous coronary intervention

PCI-S

percutaneous coronary intervention with stent implantation

TT

triple antithrombotic therapy

Appendix: Definitions of End Points

  1. Major bleeding was defined as fatal, decrease in the blood hemoglobin level > 4 g/dL, need for transfusion of ≥ 2 U of blood, need for corrective surgery intervention, the occurrence of intracranial or retroperitoneal bleeding, or any combinations of these events.18

  2. Thromboembolic complications were defined as any clinical manifestation of acute cerebral or peripheral ischemia that was ascertained by objective diagnostic testing.

  3. Myocardial infarction was defined as either the development of pathologic Q waves in at least two contiguous leads with an elevated troponin level or, in the absence of pathologic Q waves, any troponin levels elevation with symptoms suggestive for acute coronary syndromes.

  4. The need for new revascularization was defined as a repeat intervention driven by any significant coronary lesion. Indication for repeat revascularization was based on anginal symptoms and/or proven myocardial ischemia in any vessel territory, and a significant luminal stenosis (> 50% diameter stenosis).

  5. Stent thrombosis was considered to have occurred when an intraluminal filling defect resulting in an occluded or suboccluded coronary artery was detected at angiography, when death was sudden and unexplained, or when a myocardial infarction occurred in the territory of the treated vessel and stent thrombosis could not be definitively excluded.

  6. “Procedural success” was defined as a residual stenosis < 30% by visual analysis in the presence of Thrombolysis in Myocardial Infarction31 flow grade 3 without death, occurrence of Q-wave myocardial infarction, or coronary artery bypass graft surgery.

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Januzzi JL Jr, Sabatine MS, Wan Y, et al. Interactions between age, outcome of acute coronary syndromes, and tirofiban therapy. Am J Cardiol. 2003;91:457-461. [PubMed]
 
Nguyen MC, Lim YL, Walton A, et al. for the GRACE Investigators Combining warfarin and antiplatelet therapy after coronary stenting in the Global Registry of Acute Coronary Events: is it safe and effective to use just one antiplatelet agent? Eur Heart J. 2007;28:1717-1722. [PubMed]
 
Palareti G, Leali N, Coccheri S, et al. Hemorrhagic complications of oral anticoagulant therapy: results of a prospective multicenter study ISCOAT (Italian Study on Complications of Oral Anticoagulant Therapy). G Ital Cardiol. 1997;27:231-243. [PubMed]
 
Nikolsky E, Mehran R, Aymong ED, et al. Impact of anemia on outcomes of patients undergoing percutaneous coronary interventions. Am J Cardiol. 2004;94:1023-1027. [PubMed]
 
Nikolsky E, Aymong ED, Halkin A, et al. Impact of anemia in patients with acute myocardial infarction undergoing primary percutaneous coronary intervention: analysis from the Controlled Abciximab and Device Investigation to Lower Late Angioplasty Complications (CADILLAC) Trial. J Am Coll Cardiol. 2004;44:547-553. [PubMed]
 
Voeltz MD, Patel AD, Feit F, et al. Effect of anemia on hemorrhagic complications and mortality following percutaneous coronary intervention. Am J Cardiol. 2007;99:1513-1517. [PubMed]
 
Watson T, Lip GY. Combining antiplatelet drugs and oral anticoagulant therapy in atrial fibrillation: acute coronary syndromes and/or percutaneous coronary intervention/stenting revisited. Stroke. 2007;38:e107-e108. [PubMed]
 
TIMI Study Group The Thrombolysis in Myocardial Infarction (TIMI) trial: phase I findings. N Engl J Med. 1985;312:932-936. [PubMed]
 

Figures

Figure Jump LinkFigure 1 Antithrombotic treatment during follow-up (at discharge, at 6 months, at 12 months).Grahic Jump Location
Figure Jump LinkFigure 2 Kaplan-Meier survival analysis of EMB complications (log-rank test, p = 0.33).Grahic Jump Location
Figure Jump LinkFigure 3 Kaplan-Meier survival analysis of LMB complications (log-rank test, p = 0.009). See Figure 1 for expansion of abbreviation.Grahic Jump Location
Figure Jump LinkFigure 4 Kaplan-Meier survival analysis of MACEs (log-rank test, p = 0.59). See Figure 1 for expansion of abbreviation.Grahic Jump Location

Tables

Table Graphic Jump Location
Table 1 Baseline Characteristics of Study Cohort*

*Data are presented as mean ± SD, No. (%), or median (IQR) unless otherwise indicated. CHADS = chronic heart failure, hypertension, age > 75 yr, diabetes, prior transient ischemic attack or stroke.17

Table Graphic Jump Location
Table 2 Procedural Characteristics*

*Data are presented as No. (%), or median (IQR).

Table Graphic Jump Location
Table 3 Univariate and Multivariate Analysis of EMB Complications
Table Graphic Jump Location
Table 4 Univariate and Multivariate Analysis of LMB Complications

References

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Porter A, Konstantino Y, Iakobishvili Z, et al. Short-term triple therapy with aspirin, warfarin, and a thienopyridine among patients undergoing percutaneous coronary intervention. Catheter Cardiovasc Interv. 2006;68:56-61. [PubMed]
 
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Ferguson JJ, Antman EM, Bates ER, et al. Combining enoxaparin and glycoprotein IIb/IIIa antagonists for the treatment of acute coronary syndromes: final results of the National Investigators Collaborating on Enoxaparin-3 (NICE-3) study. Am Heart J. 2003;146:628-634. [PubMed]
 
Ferguson JJ, Califf RM, Antman EM, et al. for the SYNERGY Trial Investigators Enoxaparin vs unfractionated heparin in high-risk patients with non-ST-segment elevation acute coronary syndromes managed with an intended early invasive strategy: primary results of the SYNERGY randomized trial. JAMA. 2004;292:45-54. [PubMed]
 
Graham MM, Norris CM, Galbraith PD, et al. Quality of life after coronary revascularization in the elderly. Eur Heart J. 2006;27:1690-1698. [PubMed]
 
Reddy VS, Parikh SM, Drinkwater DC Jr, et al. Morbidity after procurement of radial arteries in diabetic patients and the elderly undergoing coronary revascularization. Ann Thorac Surg. 2002;73:803-807. [PubMed]
 
Avezum A, Makdisse M, Spencer F, et al. GRACE Investigators: impact of age on management and outcome of acute coronary syndrome: observations from the Global Registry of Acute Coronary Events (GRACE). Am Heart J. 2005;149:67-73. [PubMed]
 
Januzzi JL Jr, Sabatine MS, Wan Y, et al. Interactions between age, outcome of acute coronary syndromes, and tirofiban therapy. Am J Cardiol. 2003;91:457-461. [PubMed]
 
Nguyen MC, Lim YL, Walton A, et al. for the GRACE Investigators Combining warfarin and antiplatelet therapy after coronary stenting in the Global Registry of Acute Coronary Events: is it safe and effective to use just one antiplatelet agent? Eur Heart J. 2007;28:1717-1722. [PubMed]
 
Palareti G, Leali N, Coccheri S, et al. Hemorrhagic complications of oral anticoagulant therapy: results of a prospective multicenter study ISCOAT (Italian Study on Complications of Oral Anticoagulant Therapy). G Ital Cardiol. 1997;27:231-243. [PubMed]
 
Nikolsky E, Mehran R, Aymong ED, et al. Impact of anemia on outcomes of patients undergoing percutaneous coronary interventions. Am J Cardiol. 2004;94:1023-1027. [PubMed]
 
Nikolsky E, Aymong ED, Halkin A, et al. Impact of anemia in patients with acute myocardial infarction undergoing primary percutaneous coronary intervention: analysis from the Controlled Abciximab and Device Investigation to Lower Late Angioplasty Complications (CADILLAC) Trial. J Am Coll Cardiol. 2004;44:547-553. [PubMed]
 
Voeltz MD, Patel AD, Feit F, et al. Effect of anemia on hemorrhagic complications and mortality following percutaneous coronary intervention. Am J Cardiol. 2007;99:1513-1517. [PubMed]
 
Watson T, Lip GY. Combining antiplatelet drugs and oral anticoagulant therapy in atrial fibrillation: acute coronary syndromes and/or percutaneous coronary intervention/stenting revisited. Stroke. 2007;38:e107-e108. [PubMed]
 
TIMI Study Group The Thrombolysis in Myocardial Infarction (TIMI) trial: phase I findings. N Engl J Med. 1985;312:932-936. [PubMed]
 
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