Low-molecular-weight heparin versus unfractionated heparin in acute ST-segment elevation myocardial infarction patients undergoing primary percutaneous coronary intervention with drug-eluting stents

Article Outline

• Abstract
• Methods
  • Study population and antithrombotic regimens
  • PCI procedure and other medical treatment
  • Study definitions and clinical follow-up
  • Statistical analysis
• Results
• Discussion
  • Study strengths and limitations
• Conclusions
• Appendix. Korea Acute Myocardial Infarction Registry (KAMIR) Investigators
• References
• Copyright

Background

Whether low-molecular-weight heparin (LMWH) is superior to unfractionated heparin (UFH) in acute ST-segment elevation myocardial infarction (STEMI) patients undergoing primary percutaneous coronary intervention (PCI) with drug-eluting stents (DESs) remains unclear.

Methods

A total of 3,372 STEMI patients who underwent primary PCI with DESs received either LMWH (n = 1,531 patients, subcutaneous enoxaparin 1 mg/kg, bid for 3-5 days plus reduced dose of UFH [50 U/kg] during PCI) or UFH alone (n = 1,841 patients, intravenous bolus injection of 5,000 U, followed by 24,000 U/d infusion for at least 48 hours). The bleeding events and clinical outcomes during in-hospital and at 8 months were compared.

Results

The incidences of major and minor bleeding events were similar between the 2 groups. Multivariable Cox regression analysis showed that LMWH group had lower incidences of cardiac death (adjusted odds ratio [OR] 0.55, 95% CI 0.39-0.77, P < .001), total death (adjusted OR 0.50, 95% CI 0.37-0.68, P < .001), and total major adverse cardiac events (adjusted OR 0.77, 95% CI 0.62-0.95, P = .017) at 8 months as compared with UFH group. Similar results were obtained across different subgroups including different DESs, age, and sex.

Conclusions

The LMWH enoxaparin combined with reduced dose of UFH (50 U/kg) administration as an adjunctive antithrombotic therapy in STEMI patients undergoing primary PCI with DESs seems to be safe and efficacious. However, randomized clinical trials are needed to confirm this conclusion.

Drug-eluting stents (DESs) have drastically changed the landscape of percutaneous coronary intervention (PCI) with significant reductions in angiographic restenosis rate and the need for repeated revascularization.¹ Although there is no recommendation from current guidelines, the off-label use of DESs in acute myocardial infarction (AMI) setting has been very common in the real world clinical practice.² However, concerns have been raised regarding the safety of DESs in patients with AMI due to the risk of stent thrombosis.³ Several previous studies have shown that the DESs implantation in AMI was associated with an increased risk for acute and subacute stent thrombosis.³, ⁴ Not only the delayed endothelial healing due to the DESs itself but also the altered environment with high thrombin activity and markedly increased platelet reactivity was proven in the early period of AMI in patients undergoing primary PCI.⁵, ⁶

Although low-molecular-weight heparins (LMWHs) have several well-established potential advantages over unfractionated heparin (UFH) as antithrombin agents,⁷ it is still controversial whether the LMWHs can be optimal antithrombin agents in the AMI setting.⁸, ⁹ Moreover, little has been known to date that whether LMWHs are superior or similar to UFH in the off-label use of DESs in AMI.¹⁰, ¹¹ Therefore, the present study was aimed to evaluate the safety and efficacy of LMWH versus UFH specifically in patients with acute ST-segment elevation myocardial infarction (STEMI) who underwent primary PCI with DESs, in Korea Acute Myocardial Infarction Registry (KAMIR).

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Methods 

KAMIR is a Korean prospective multicenter online registry designed to reflect the “real world” clinical practice in Asian patients with AMI in the DES era with support from Korean Circulation Society since November 2005. A total of 41 university or community hospitals that were high-volume centers with facilities for primary PCI and on-site cardiac surgery participated in this study. Data were collected at each site by a trained study coordinator using a standardized case report form. Standardized definitions of all patient-related variables and clinical diagnoses were used. The study protocol was approved by the ethics committee and institutional review board at each participating institution. We enrolled patients presenting with AMI including both STEMI and non-ST-segment elevation myocardial infarction (NSTEMI). No extramural funding was used to support this work. The authors are solely responsible for the design and conduct of this study, all study analyses, and the drafting and editing of the article and its final contents.

Study population and antithrombotic regimens 

From November 2005 to December 2007, there were 13,632 patients diagnosed with AMI. In the present study, the inclusion criterion was patients with STEMI who underwent primary PCI with DESs. The exclusion criteria included NSTEMI, STEMI with bare-metal stenting or without stenting, STEMI with elective PCI, conservative treatment without PCI, contraindication to antithrombotic agents, known bleeding disorders, thrombocytopenia (<100 × 10⁹/L), administration of oral anticoagulants, administration of thrombolytic or fibrinolytic medications for AMI, infarction related to the grafted vessel, and estimated life expectancy of <12 months.

Therefore, a total of 3,372 eligible STEMI patients who underwent primary PCI with DESs were enrolled and divided into 2 groups according to the antithrombotic therapies: LMWH enoxaparin group (n = 1,531 patients) and UFH group (n = 1,841 patients). According to KAMIR study design, the antithrombotic therapies started after the patients' arrival in the hospital. The dose adjustment of antithrombotics was left to the decision of individual physician. Most of the patients in LMWH group received subcutaneous enoxaparin (Clexane; Bristol-Myers Squibb, New York, USA and Sanofi-Aventis, Paris, France) 1 mg/kg, bid for 3 to 5 days from the emergency department plus reduced dose of UFH (50 U/kg) during PCI. The additional intravenous bolus of UFH (2,000-3,000 U) was given to maintain activated clotting time between 200 and 300 seconds. Patients in UFH group received a bolus of intravenous UFH 5,000 U at emergency department, and 50 to 70 U/kg were given during the primary PCI with the target activated clotting time of 200 to 300 seconds, followed by 24,000 U/d infusions for 2 days but could be continued for a longer period at the physician's discretion.

PCI procedure and other medical treatment 

Diagnostic coronary angiography was performed via femoral or radial artery. During primary PCI, DESs were deployed after predilation or thrombus aspiration. The choice of DESs was depended upon the physician's discretion. The administration of cilostazol as the third antiplatelet agent (triple antiplatelet therapy) and platelet glycoprotein IIb/IIIa receptor blockers was left to individual operator's decision. The successful PCI was defined as the achievement of an angiographic residual stenosis <30% in the presence of TIMI grade III flow.

Loading doses of aspirin and clopidogrel were administered immediately after the patients agreed to receive primary PCI. The loading/maintenance doses were 200 to 300 mg/100 mg qd for aspirin and 300 to 600 mg/75 mg qd for clopidogrel. Aspirin and clopidogrel were administered throughout the follow-up period. Aspirin was recommended for lifelong administration and clopidogrel for at least >1 year. Patients were encouraged to maintain the essential medications including β-blockers, angiotensin-converting enzyme inhibitors (ACEIs), angiotensin II receptor blockers (ARBs) for the patients intolerant to ACEIs, and statins.

Study definitions and clinical follow-up 

All deaths were considered as cardiac death unless noncardiac death could be ruled out. Recurrent myocardial infarction (MI) was defined as the development of either pathologic Q waves in at least 2 contiguous leads on ECG or an increase in the creatine kinase MB isoenzyme level to more than twice the upper limit of normal. Target lesion revascularization (TLR) was defined as ischemia-driven PCI of target lesion due to restenosis or reocclusion within the stent or in the adjacent 5 mm of the distal or proximal segment. Total major adverse cardiac events (MACE) was defined as the composite of (1) total death, (2) nonfatal MI, and (3) repeated PCI or coronary artery bypass grafting. Major bleeding was defined as any intracranial bleeding, bleeding associated with the need for blood transfusion, or any other clinically relevant bleeding as judged by the investigator. Minor bleeding was any clinically relevant bleeding that did not qualify as major.

All the enrolled patients in the present study received routine clinical follow-up up to 8 months. The incidences of major and minor bleeding events and major clinical outcomes at 8 months were evaluated between LMWH enoxaparin group and UFH group.

Statistical analysis 

For continuous variables, differences between groups were evaluated by unpaired t test or Mann-Whitney rank sum test. For discrete variables, differences were expressed as counts and percentages and were analyzed with χ² (or Fisher exact) test between groups as appropriate. To adjust for potential confounders, a propensity score analysis was performed by use of a logistic regression model, testing the propensity to receive enoxaparin rather than UFH. We tested all available variables that could be relevant to the choice of antithrombotic therapies including age, sex, Killip classes on admission, traditional cardiovascular risk factors (hypertension, dyslipidemia, smoking, diabetes mellitus, family history of coronary heart disease), prior MI, chronic heart failure, prior cerebrovascular disease, chronic renal disease, and peripheral arterial disease. The logistic model by which the propensity scores were estimated showed good predictive value (C-statistic = 0.731). Multivariable Cox regression analysis was then performed using propensity scores, antithrombotic therapies (enoxaparin or UFH), the aforementioned variables and target lesions, number of diseased vessel, stent types, postprocedural TIMI blood flow, and cardiovascular medications (aspirin, clopidogrel, cilostazol, glycoprotein IIb/IIIa receptor blockers, ACEIs, ARBs, β-blockers, calcium channel blockers, and statins) to figure out the impact of the different antithrombotic regimens on the in-hospital and 8-month clinical outcomes. Cox's regression models adjusted with the propensity scores and the aforementioned variables were also used to assess odds ratios of various MACE in subgroups of patients. All continuous variables were described as mean ± SD. All analyses were 2-tailed, with clinical significance defined as P <.05. All statistical processes were done using SPSS 13.0 (Statistical package for the social sciences; SPSS-PC Inc, Chicago, IL). The authors are solely responsible for the design and conduct of this study, all study analyses, and the drafting and editing of the article and its final contents.

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Results 

As shown in Table I, enoxaparin group and UFH group had similar baseline clinical characteristics except that patients in enoxaparin group had more prior MI and chronic heart failure than those in UFH group. The baseline angiographic and PCI procedural characteristics also were similar between these 2 groups except that the patients in enoxaparin group received longer stents and a trend toward fewer stents per patients than those in UFH group (Table II).

Table I. Baseline clinical characteristics

Variables, n (%)	UFH (n = 1841)	Enoxaparin (n = 1531)	P
Age, y	62.61 ± 12.57	62.23 ± 12.66	.377
Body mass index, kg/m2	24.00 ± 3.09	23.93 ± 3.13	.494
Male	1383 (75.1)	1122 (73.3)	.224
History
Hypertension	828 (45.0)	685 (44.7)	.892
Diabetes mellitus	487 (26.5)	368 (24.0)	.108
Current smoking	906 (49.2)	744 (48.6)	.861
Dyslipidemia	152 (8.3)	88 (5.7)
Family history of CAD	126 (6.8)	86 (5.6)
MMI	83 (4.5)	48 (3.1)	.040
Chronic heart failure	22 (1.2)	8 (0.5)	.038
Peripheral artery disease	24 (1.3)	15 (1.0)	.381
Cerebrovascular disease	112 (6.1)	78 (5.1)	.215
Peptic ulcer disease	7 (0.4)	1 (0.1)	.061
Chronic renal disease	14 (0.8)	17 (1.1)	.289
Killip class on admission			<.001
Class I	1410 (76.6)	1096 (71.6)
Class II	204 (11.1)	248 (16.2)
Class III	109 (5.9)	83 (5.4)
Class IV	118 (6.4)	104 (6.8)
Onset to PCI (h, IQR)	4.21 (1.77-7.40)	4.15 (1.72-7.38)	.812

CAD, Coronary artery disease; IQR, interquartile range.

Table II. Baseline angiographic and PCI procedural characteristics

Variables, n (%)	UFH (n = 1841)	Enoxaparin (n = 1531)	P
Target vessel			.496
Left anterior descending	961 (52.2)	806 (52.6)
Right coronary artery	678 (36.8)	558 (36.5)
Left circumflex	172 (9.4)	151 (9.9)
Left main	30 (1.6)	16 (1.0)
No. of diseased vessels			.195
Single-vessel disease	872 (47.4)	735 (48.0)
Two-vessel disease	531 (28.9)	473 (30.9)
Three-vessel disease	397 (21.6)	294 (19.2)
Left main disease	41 (2.2)	29 (1.9)
Preprocedure TIMI flow			.129
TIMI 0	1081 (58.7)	948 (62.0)
TIMI I	206 (11.2)	147 (9.6)
TIMI II	247 (13.4)	208 (13.6)
TIMI III	306 (16.6)	228 (14.9)
Stent type			.739
Sirolimus-eluting stent	853 (46.3)	719 (47.0)
Paclitaxel-eluting stent	659 (35.8)	548 (35.8)
Zotarolimus-eluting stent	114 (6.2)	114 (6.7)
Others drug-eluting stent	215 (11.7)	162 (10.6)
Stent length, mm	25.15 ± 5.96	25.98 ± 6.03	<.001
Stent diameter, mm	3.19 ± 0.39	3.18 ± 0.42	.362
Total stent number per patient	1.46 ± 0.79	1.41 ± 0.72	.060
Postprocedure TIMI flow			.126
TIMI 0	20 (1.1)	14 (0.9)
TIMI I	15 (0.8)	6 (0.4)
TIMI II	75 (4.0)	83 (5.4)
TIMI III	1731 (94.0)	1428 (93.3)

The in-hospital medications were listed in Table III. Patients in enoxaparin group had higher use rates of aspirin and ARBs but lower use rates of cilostazol, glycoprotein IIb/IIIa receptor blockers, β-blockers, ACEIs, calcium channel blockers, and statins than those in UFH group.

Table III. In-hospital medications

GP, Glycoprotein.

In-hospital clinical outcomes showed that enoxaparin group had significantly lower incidences of cardiac death and total death than UFH group. The incidences of recurrent MI and major and minor bleeding events were similar between the 2 groups (Table IV). The cumulative clinical outcomes at 8 months also showed that enoxaparin group had significantly lower incidences of cardiac death, total death, and a trend toward lower incidence of total MACE than UFH group. Despite the similar incidence of TLR, enoxaparin group had a higher incidence of repeated PCI than UFH group, possibly due to more non-TLR target vessel revascularization in enoxaparin group. The incidences of recurrent MI and coronary artery bypass grafting were similar between the 2 groups (Table IV).

Table IV. Cumulative clinical outcomes up to 8 months

Variables, n (%)	UFH (n = 1841)	Enoxaparin (n = 1531)	P
In-hospital outcomes
Cardiac death	87 (4.7)	34 (2.2)	<.001
Total death	116 (6.3)	45 (2.9)	<.001
Recurrent MI	8 (0.4)	2 (0.1)	.106
Major bleeding events	11 (0.6)	8 (0.5)	.772
Minor bleeding events	21 (1.1)	16 (1.0)	.790
Outcomes at 8 m
Cardiac death	103 (5.6)	55 (3.6)	.006
Total death	140 (7.6)	69 (4.5)	<.001
Recurrent MI	11 (0.6)	5 (0.3)	.254
CABG	2 (0.1)	1 (0.1)	1.000
TLR	26 (1.4)	27 (1.8)	.414
Re-PCI	60 (3.3)	73 (4.8)	.025
Total MACE	213 (11.6)	149 (9.7)	.086

CABG, Coronary artery bypass grafting; re-PCI, repeated percutaneous coronary intervention.

Multivariable Cox regression analysis showed that Enoxaparin group had significantly lower incidences of in-hospital cardiac death and total death than UFH group. The adjusted clinical outcomes at 8 months showed that enoxaparin group had significantly lower incidences of cardiac death, total death, and total MACE, but the incidence of repeated PCI was significantly higher in enoxaparin group as compared with UFH group (Table V, Figure 1).

Table V. Adjusted cumulative clinical outcomes up to 8 months of enoxaparin as compared with UFH (Cox regression analysis using propensity score)

Variables	Unadjusted OR (95% CI)	P	Adjusted OR (95% CI)	P
In-hospital outcomes
Cardiac death	0.46 (0.31-0.68)	<.001	0.28 (0.16-0.48)	<.001
Total death	0.45 (0.32-0.64)	<.001	0.27 (0.17-0.43)	<.001
Recurrent MI	0.30 (0.06-1.41)	.128	0.28 (0.06-1.38)	.117
Outcomes at 8 m
Cardiac death	0.63 (0.45-0.88)	.007	0.55 (0.39-0.77)	<.001
Total death	0.57 (0.43-0.77)	<.001	0.50 (0.37-0.68)	<.001
Recurrent MI	0.54 (0.19-1.57)	.262	0.66 (0.22-1.95)	.452
CABG	0.60 (0.05-6.63)	.678	0.36 (0.03-4.23)	.417
Re-PCI	1.49 (1.05-2.11)	.026	1.47 (1.03-2.09)	.033
TLR	1.25 (0.73-2.16)	.415	1.27 (0.73-2.22)	.392
Total MACE	0.82 (0.66-1.03)	.086	0.77 (0.62-0.95)	.017

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• Figure 1. 

  Adjusted cumulative incidences in patients received enoxaparin or UFH of cardiac death (A), total death (B), and total MACE (C) at 8 months. Cum prob, cumulative probability; OR, odds ratio.

As shown in Figure 2, subgroup analysis showed that enoxaparin group had significantly lower incidences of cardiac death and total death up to 8 months across different DESs, sex, and age subgroups as compared with UFH group.

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• Figure 2. 

  Adjusted odds ratios for incidences of cardiac death (A), total death (B), and total MACE (C) associated with enoxaparin therapy in all study population and various subgroups of patients according to different stents, sex, and age.

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Discussion 

The main finding of this present study shows that the administration of subcutaneous enoxaparin for 3 to 5 days combined with reduced dose of UFH (50 U/kg) during PCI in Asian STEMI patients undergoing primary PCI with DESs significantly improved the clinical outcomes including significant reduction in incidences of in-hospital and 8-month cardiac death, total death, and total MACE as compared with UFH alone. Although the present study is not prospectively randomized, this is the first study to evaluate the safety and efficacy of combined enoxaparin with reduced dose of UFH versus UFH alone in acute STEMI patients undergoing primary PCI with the off-label use of DESs.

The off-label use of DESs has become common in the real world clinical practice of AMI,² and a recent meta-analysis showed that the use of DESs in acute STEMI patients was safe and improved clinical outcomes by reducing the risk of reintervention as compared with BMS.¹² In KAMIR data, DES use rate was >92% due to widely spread expected advantages of DESs among Korean physicians. Because of the stent thrombosis issues and the increased systemic thrombosis milieu in the early period of AMI patients, especially in STEMI patients undergoing primary PCI with DESs, proper antithrombotic and antiplatelet regimens would be crucial.⁵, ⁶ However, little has been known regarding the optimal antithrombotics in this clinical setting.

Numerous studies comparing the safety and efficacy of enoxaparin with UFH in acute STEMI have demonstrated that the antithrombotic therapy with enoxaparin is superior to UFH with significantly improved clinical outcomes and similar rates of bleeding events.⁹, ¹³, ¹⁴ However, most of these studies used enoxaparin as an adjunctive antithrombin therapy to thrombolysis, and very limited data to date are available about the comparison of enoxaparin versus UFH in patients with primary PCI.¹⁵, ¹⁶ In addition, although the recent OASIS 6 trial¹⁷ showed that fondaparinux significantly reduced the risk of death, recurrent MI, and severe bleeds as an adjunct to thrombolytic therapy, the results of antithrombotic agents with fibrinolytics cannot be translated to primary PCI.

Recently, an observational study¹⁵ has evaluated the safety and efficacy of combination of intravenous and subcutaneous enoxaparin as compared with intravenous UFH in 83 STEMI patients undergoing primary PCI. Because of the limited case number, this study showed that there was no difference in the rate of mortality, MACE, or major bleeding between these 2 regimens. Zeymer et al¹⁶ retrospectively analyzed the safety and efficacy of enoxaparin (n = 609) and UFH (n = 5,690) in STEMI patients who received various treatments including primary PCI in the ACOS registry. Their results showed that enoxaparin was associated with a reduction in the combined end point of death and nonfatal recurrent MI without any increase, even a trend toward fewer bleeding complications, in the subgroup of patients treated with primary PCI. However, in their study, the difference in patient numbers between 2 groups was considerably high. Furthermore, although they performed a subgroup analysis in patients who received primary PCI, they did not give any detail information about the PCI procedure and stent types. In contrast to that study, the present study compared the safety and efficacy of enoxaparin versus UFH between 2 groups with comparable numbers of patients, and we only enrolled STEMI patients undergoing primary PCI who exclusively received DESs. In addition, WEST study¹⁸ evaluated the use of subcutaneous enoxaparin in the setting of primary PCI. However, it showed that, of 36 initial patients treated with primary PCI, 3 patients had complications of extensive thrombosis within coronary catheters and on PCI equipment, suggesting unacceptable catheter thrombus rates during primary PCI with subcutaneous enoxaparin alone. Different from WEST study, in the present study, most of the patients in LMWH group received reduced dose of UFH (50 U/kg) or intravenous enoxaparin during PCI procedure. It may explain the result that rare cases had the complications of thrombosis during primary PCI in the present study.

The advantages and disadvantages of LMWHs and UFH have been extensively discussed. Low-molecular-weight heparins have several well-established potential advantages over UFH as antithrombin agents.⁷ Low-molecular-weight heparins have a more predictable pharmacologic profile than UFH without the need for close therapeutic drug monitoring. In contrast, UFH shows an unpredictable pharmacologic profile that needs close monitoring of anticoagulation levels. In addition, UFH shows prothrombotic properties related to poor control of von Willebrand factor release, as well as platelet activation and rebound of thrombin generation after discontinuation.¹⁹, ²⁰ These differences between LMWHs and UFH might be one of the important explanations for our results. Unfractionated heparin needs closely monitoring, which might be achieved with a more stable level of anticoagulation in clinical trials rather than in real world clinical practice. However, the efficacy and safety of LMWHs does not depend on close monitoring, except for an adjustment of the doses in some patients with renal dysfunction. This advantage of LMWHs over UFH seems to be more important in clinical practice. In addition, according to administration pattern of LMWHs and UFH in the present study, the use of LMWHs usually maintained for 3 to 5 days, whereas the use of UFH usually continued for 48 hours. Therefore, the longer administration period might be another potential reason for the benefits of enoxaparin over UFH as shown in the present study.

Notably, the subgroup analysis in the present study showed that all patients in different subgroups could get benefits from enoxaparin therapy as compared with UFH therapy, suggesting the antithrombotic therapy with enoxaparin might be beneficial for all patients with acute STEMI undergoing primary PCI with DESs regardless of different DESs, age, and sex.

Study strengths and limitations 

The strengths of the KAMIR study included its prospective design and large multicenter population base. The registry provides a comprehensive view of the contemporary treatments and outcomes in a series of Asian patients with AMI in the DESs era.

However, the present study also had some limitations. First, although there were a relative larger number of patients in the present study because of the nonrandomized nature of the registry study, there were baseline differences in several important prognostic factors between our primary comparison groups. Fortunately, we included most confounders into the multivariable Cox regression model including propensity scores to control the baseline biases. However, the present study showed that the degree of mortality reduction by LMWH was even larger than the effect of primary PCI itself, suggesting residual confounding might still persist. This multicenter registry may provide rational for future randomized trials regarding this issue. Second, although the antithrombotic regimens were prospectively designed in KAMIR study, we did not have detail information about the activated partial thromboplastin time achieved with UFH, the exact duration of administration of both LMWH and UFH, and dose adjustment of LMWH in patients who had renal insufficiency. In addition, of 41 centers, 2 centers (n = 143 patients) used intravenous enoxaparin during PCI instead of reduced dose of UFH. All of the above factors might have influenced the rate of clinical events. However, the potential differences in the above factors reflect the real world clinical practice.

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Conclusions 

The present study showed that antithrombotic therapy with subcutaneous enoxaparin plus reduced dose UFH (50 U/kg) during PCI in acute STEMI patients undergoing primary PCI with DESs showed lower incidences of in-hospital cardiac deaths and total deaths without significant difference in bleeding and vascular complications as compared with UFH alone. Predominantly due to this consistent mortality benefit, enoxaparin plus reduced dose UFH (50 U/kg) during PCI was translated into significantly lower incidence of total MACE at 8 months as compared with UFH. Because the results of present study are hypothesis generating, a further randomized trial with larger study population is needed to confirm this conclusion.

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Appendix. Korea Acute Myocardial Infarction Registry (KAMIR) Investigators 

Myung Ho Jeong, MD; Young Jo Kim, MD; Chong Jin Kim, MD; Myeong Chan Cho, MD; Young Keun Ahn, MD; Jong Hyun Kim, MD; Shung Chull Chae, MD; Seung Ho Hur, MD; In Whan Seong, MD; Taek Jong Hong, MD; Dong Hoon Choi, MD; Jei Keon Chae, MD; Jae Young Rhew, MD; Doo Il Kim, MD; In Ho Chae, MD; Jung Han Yoon, MD; Bon Kwon Koo, MD; Byung Ok Kim, MD; Myoung Yong Lee, MD; Kee Sik Kim, MD; Jin Yong Hwang, MD; Seok Kyu Oh, MD; Nae Hee Lee, MD; Kyoung Tae Jeong, MD; Seung Jea Tahk, MD; Jang Ho Bae, MD; Seung Woon Rha, MD; Keum Soo Park, MD; Kyoo Rok Han, MD; Tae Hoon Ahn, MD; Moo Hyun Kim, MD; Ju Young Yang, MD; Chong Yun Rhim, MD; Hyeon Cheol Gwon, MD; Seong Wook Park, MD; Young Youp Koh, MD; Seung Jae Joo, MD; Soo Joong Kim, MD; Dong Kyu Jin, MD; Jin Man Cho, MD; Jeong Gwan Cho, MD; Wook Sung Chung, MD; Yang Soo Jang, MD; Ki Bae Seung, MD; and Seung Jung Park, MD

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References 

1. Daemen J, Serruys PW. Drug-eluting stent update 2007: part I. A survey of current and future generation drug-eluting stents: meaningful advances or more of the same?. Circulation. 2007;116:316–328
   • View In Article
   • CrossRef
2. Rao SV, Shaw RE, Brindis RG, et al. On- versus off-label use of drug-eluting coronary stents in clinical practice (report from the American College of Cardiology National Cardiovascular Data Registry [NCDR]). Am J Cardiol. 2006;97:1478–1481
   • View In Article
   • Abstract
   • Full Text
   • Full-Text PDF (176 KB)
   • CrossRef
3. Luscher TF, Steffel J, Eberli FR, et al. Drug-eluting stent and coronary thrombosis: biological mechanisms and clinical implications. Circulation. 2007;115:1051–1058
   • View In Article
   • CrossRef
4. Daemen J, Wenaweser P, Tsuchida K, et al. Early and late coronary stent thrombosis of sirolimus-eluting and paclitaxel-eluting stents in routine clinical practice: data from a large two-institutional cohort study. Lancet. 2007;369:667–678
   • View In Article
   • Abstract
   • Full Text
   • Full-Text PDF (218 KB)
   • CrossRef
5. Gawaz M, Neumann FJ, Ott I, et al. Platelet function in acute myocardial infarction treated with direct angioplasty. Circulation. 1996;93:229–237
   • View In Article
   • MEDLINE
6. Muller I, Seyfarth M, Rudiger S, et al. Effect of a high loading dose of clopidogrel on platelet function in patients undergoing coronary stent placement. Heart. 2001;85:92–93
   • View In Article
7. Antman EM. The search for replacements for unfractionated heparin. Circulation. 2001;103:2310–2314
   • View In Article
8. Dumaine R, Borentain M, Bertel O, et al. Intravenous low-molecular-weight heparins compared with unfractionated heparin in percutaneous coronary intervention: quantitative review of randomized trials. Arch Intern Med. 2007;167:2423–2430
   • View In Article
   • CrossRef
9. Murphy SA, Gibson CM, Morrow DA, et al. Efficacy and safety of the low-molecular weight heparin enoxaparin compared with unfractionated heparin across the acute coronary syndrome spectrum: a meta-analysis. Eur Heart J. 2007;28:2077–2086
   • View In Article
   • CrossRef
10. ADVANCE MI Investigators . Facilitated percutaneous coronary intervention for acute ST-segment elevation myocardial infarction: results from the prematurely terminated ADdressing the Value of facilitated ANgioplasty after Combination therapy or Eptifibatide monotherapy in acute Myocardial Infarction (ADVANCE MI) trial. Am Heart J. 2005;150:116–122
    • View In Article
    • Abstract
    • Full Text
    • Full-Text PDF (113 KB)
    • CrossRef
11. Zeymer U, Gitt A, Zahn R, et al. Efficacy and safety of enoxaparin in combination with and without GP IIb/IIIa inhibitors in unselected patients with ST segment elevation myocardial infarction treated with primary percutaneous coronary intervention. EuroIntervention. 2009;4:524–528
    • View In Article
    • CrossRef
12. Kastrati A, Dibra A, Spaulding C, et al. Meta-analysis of randomized trials on drug-eluting stents vs. bare-metal stents in patients with acute myocardial infarction. Eur Heart J. 2007;28:2706–2713
    • View In Article
    • CrossRef
13. Antman EM, Louwerenburg HW, Baars HF, et al. Enoxaparin as adjunctive antithrombin therapy for ST-elevation myocardial infarction: results of the ENTIRE-Thrombolysis in Myocardial Infarction (TIMI) 23 Trial. Circulation. 2002;105:1642–1649
    • View In Article
    • CrossRef
14. Antman EM, Morrow DA, McCabe CH, et al. Enoxaparin versus unfractionated heparin with fibrinolysis for ST-elevation myocardial infarction. N Engl J Med. 2006;354:1477–1488
    • View In Article
    • CrossRef
15. Khoobiar S, Mejevoi N, Kaid K, et al. Primary percutaneous coronary intervention for ST-elevation myocardial infarction using an intravenous and subcutaneous enoxaparin low molecular weight heparin regimen. J Thromb Thrombolysis. 2008;26:85–90
    • View In Article
    • CrossRef
16. Zeymer U, Gitt A, Junger C, et al. Efficacy and safety of enoxaparin in unselected patients with ST-segment elevation myocardial infarction. Thromb Haemost. 2008;99:150–154
    • View In Article
17. Peters RJ, Joyner C, Bassand JP, et al. The role of fondaparinux as an adjunct to thrombolytic therapy in acute myocardial infarction: a subgroup analysis of the OASIS-6 trial. Eur Heart J. 2008;29:324–331
    • View In Article
    • CrossRef
18. Buller CE, Pate GE, Armstrong PW, et al. Catheter thrombosis during primary percutaneous coronary intervention for acute ST elevation myocardial infarction despite subcutaneous low-molecular-weight heparin, acetylsalicylic acid, clopidogrel and abciximab pretreatment. Can J Cardiol. 2006;22:511–515
    • View In Article
    • Abstract
    • Full-Text PDF (143 KB)
    • CrossRef
19. Montalescot G, Philippe F, Ankri A, et al. Early increase of von Willebrand factor predicts adverse outcome in unstable coronary artery disease: beneficial effects of enoxaparin. French Investigators of the ESSENCE Trial. Circulation. 1998;98:294–299
    • View In Article
    • MEDLINE
20. Montalescot G, Collet JP, Lison L, et al. Effects of various anticoagulant treatments on von Willebrand factor release in unstable angina. J Am Coll Cardiol. 2000;36:110–114
    • View In Article
    • Abstract
    • Full Text
    • Full-Text PDF (200 KB)
    • CrossRef