Association Between Platelet Glycoprotein IIb/IIIa Inhibition and In-Hospital Outcomes in ST-Elevation Myocardial Infarction Patients Treated with Coronary Thrombus Aspiration: Findings from the CCC-ACS Project

doi:10.21203/rs.3.rs-1949081/v1

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Research Article

Association Between Platelet Glycoprotein IIb/IIIa Inhibition and In-Hospital Outcomes in ST-Elevation Myocardial Infarction Patients Treated with Coronary Thrombus Aspiration: Findings from the CCC-ACS Project

https://doi.org/10.21203/rs.3.rs-1949081/v1

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published 07 Nov, 2022

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Purpose: Thrombus aspiration in ST-elevation myocardial infarction (STEMI) with high thrombus burden did not improve clinical outcomes. The clinical efficacy of bailout use of platelet glycoprotein IIb/IIIa inhibitors (GPIs) in this clinical scenario remains unknown.

Methods: We assessed associations between GPI use and in-hospital major bleeds, ischemic events, and mortality among STEMI patients treated with percutaneous coronary intervention (PCI) and thrombus aspiration in a nationwide acute coronary syndrome registry (the Improving Care for Cardiovascular Disease in China-Acute Coronary Syndrome project).

Results: A total of 5,896 STEMI patients who received thrombus aspiration were identified, among which 56.3% received GPI therapy. In a 1-to-1 propensity-score-matched cohort, compared with STEMI patients not treated with GPI, GPI use was associated with a 69% increase in major in-hospital bleeds, with an odds ratio (OR) of 1.69, a 95% confidence interval (CI) of 1.08 to 2.65, and a nonsignificant reduction in ischemic events (OR: 0.61, 95% CI: 0.36 to 1.06), as well as a neutral effect on mortality (OR: 0.93, 95% CI: 0.55 to 1.58). However, among patients aged < 65 years, GPI use was associated with a reduction in ischemic events (OR: 0.26, 95% CI: 0.08 to 0.77), and no significant increase in major bleeds (OR: 1.23, 95% CI: 0.67 to 2.25) was observed.

Conclusion: In a nationwide registry, routine use of GPI following thrombus aspiration was not associated with reduced in-hospital ischemic events and mortality, but at the cost of increased major bleeding. However, for patients aged < 65 years, there may be a potential net benefit.

Platelet Glycoprotein IIb/IIIa Inhibitors

ST-elevation myocardial infarction

Percutaneous coronary intervention

Bleeding

Intracoronary thrombosis-induced acute vascular occlusion is the primary pathophysiological basis segment elevation myocardial infarction (STEMI).¹ Recent progress in reperfusion strategies, including primary percutaneous coronary intervention (PCI) and thrombolysis, as well as high-density antiplatelet and anticoagulation therapy, has greatly improved clinical outcomes in STEMI patients.^{2, 3} However, high thrombus burden is still a clinical challenge in STEMI management and is associated with a greater risk of no- or slow-reflow phenomena, stent thrombosis, transmural necrosis, and death.⁴ Although thrombus aspiration was designed to reduce distal embolization in patients with high thrombus burden, this approach has not been recommended as a routine procedure in high thrombus burden because of insufficient evidence of its clinical efficacy in recent meta-analysis,⁵although it may be considered in selective or bailout situations under recent clinical guidelines.^{2, 3, 6-9}

Glycoprotein IIb/IIIa inhibitor (GPI) is a rapidly acting and potent antiplatelet agent. In recent years, with a new generation of drug-eluting stents and more potent oral P2Y₁₂ receptor inhibitors (prasugrel and ticagrelor), GPI recommendations in STEMI guidelines have been scaled back from routine therapy to bailout use or selected-patients only in contemporary iterations.^{2, 3} East Asians are at increased risk for bleeding complications when treated with the standard dose of antithrombotic agents, a phenomenon known as the “East Asian Paradox.”¹⁰ Notably, GPI is not recommended in Japan and is only considered in other East Asian countries and regions as a bailout strategy when there is evidence of large thrombus burden, slow- or no-reflow, and other thrombotic complications.^6-9 A previous meta-analysis based on an East Asian population suggested a possible synergistic effect between thrombus aspiration and GPI,¹¹ but this study was inconclusive because of the insufficient data and low quality of studies included. Nevertheless, a recent Korean registry study suggested that dual antiplatelet therapy (DAPT) plus a GPI regimen may increase the bleeding risk in acute myocardial infarction patients who present with intracoronary thrombus.¹² Thus, with potent platelet inhibition and wide use of the drug-eluting stent, evidence for the use of GPI in high thrombus burden STEMI patients who need thrombus aspiration remains elusive.

The Improving Care for Cardiovascular Disease in China-Acute Coronary Syndrome (CCC-ACS) project is a collaborative effort of the American Heart Association and the Chinese Society of Cardiology aimed at improving the quality of care for acute coronary syndrome (ACS) patients in China.¹³ Based on the CCC-ACS project, the current study evaluates the association between GPI use and in-hospital outcomes of STEMI patients with high thrombus burden who were treated with thrombus aspiration during the indexed PCI.

Study Design and Population

Our analysis was based on the CCC-ACS project, which is a nationwide registry jointly initiated by the American Heart Association and the Chinese Society of Cardiology from 2014. The CCC-ACS project was approved by the institutional review board of Beijing Anzhen Hospital, Capital Medical University, with a waiver for informed consent. This study is registered at the following URL: https://clinicaltrial.gov (unique identifier: NCT02306616).

A total of 104,516 ACS patients were enrolled in the CCC-ACS project from November 2014 to July 2019. As shown in Figure 1, we included 5,896 patients (3,322 GPI users and 2,574 non-GPI users) for analysis after excluding the following groups: those admitted with a diagnosis of non-ST-elevation myocardial infarction; those who were not treated with PCI; those with a missing value for body weight; those who were not treated by thrombus aspiration therapy; and those who received GPI after the occurrence of an ischemic event during hospitalization. GPIs used in the CCC-ACS project included tirofiban, eptifibatide, abciximab, or others at any time during the indexed hospitalization.

Study Covariates

The following variables were treated as covariates for multivariable adjustment and propensity score matching: demographics (age, sex, and body weight); previous history (diabetes, hypertension, dyslipidemia, smoking, MI, PCI, coronary artery bypass grafting, atrial fibrillation, heart failure, renal failure, ischemic stroke, hemorrhagic stroke, peripheral vascular disease, chronic obstructive pulmonary disease); on-admission clinical features [Killip class, peak levels of creatine kinase-MB (CK-MB) isoform, serum levels of low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C) and triglycerides (TG), levels of systolic and diastolic blood pressure (SBP and DBP), heart rate, estimated glomerular filtration rate (eGFR) and baseline hemoglobin)]; prehospital medications (prehospital thrombolysis, aspirin, P2Y₁₂ inhibitors, statins, β-blockers, angiotensin converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs), aldosterone antagonists and oral anticoagulants); in-hospital medications [DAPT status, P2Y₁₂ inhibitors (clopidogrel or ticagrelor), statins, β-blockers, ACEIs/ARBs, aldosterone antagonists, oral anticoagulants, and perioperative anticoagulants (unfractionated heparin, low molecular weight heparin (LMWH) and others)]; and PCI-related characteristics [PCI types (primary PCI < 12 hours after symptom onset, primary PCI ≥ 12 hours after symptom onset, rescue PCI, and elective PCI) and radial route for PCI or not]. Estimated glomerular filtration rate (eGFR) was calculated according to the equation by chronic kidney disease.¹⁴ DAPT status within the first 24 hours was defined by one of the following three categories: non-loading DAPT (DAPT not in loading dose), single-loading DAPT, and both-loading DAPT (DAPT both in loading dose). The loading dose of aspirin was defined as ≥ 150 mg. The loading dose of the P2Y₁₂ receptor inhibitor was defined as ≥ 300 mg for clopidogrel and ≥ 180 mg for ticagrelor. The definitions of the abovementioned study variables are listed in Supplemental Table 1.

Study Outcomes

The primary study outcome concerned major in-hospital bleeds, defined by any of the following three major bleeding definitions that occurred during hospitalization: (a) Bleeding Academic Research Consortium (BARC) type 3b (defined as a hemoglobin drop of ≥ 5 g/dL or cardiac tamponade or bleeding requiring surgical intervention or bleeding requiring intravenous vasoactive agents), 3c (intracranial hemorrhage) and type 5 (fatal bleeding); (b) Thrombolysis in Myocardial Infarction (TIMI) major bleeding (defined as intracranial hemorrhage or clinically overt bleeding associated with a hemoglobin drop of ≥ 5 g/dL, or fatal bleeding); and (c) PLATelet inhibition and patient Outcomes (PLATO) life-threatening bleeding (defined as fatal bleeding, intracranial bleeding, intraoperative bleeding with cardiac tamponade, severe hypotension, hypovolemic shock because of bleeding and requiring either vasopressor or surgery, a hemoglobin drop of ≥ 5 g/dL, or the need for transfusion > 4 U of whole blood or packed red blood cells). Coronary artery bypass-grafting-related bleeding was excluded. Other study outcomes included in-hospital mortality and less severe but clinically significant in-hospital bleeds (defined as a hemoglobin drop of 3 to 5 g/dL). The associations between GPI use and ischemic events and all-cause in-hospital mortality were also examined. We defined ischemic events as the occurrence of reinfarction, ischemic stroke, non-bleeding related fatal events, and in-stent thrombosis. The data of study outcomes above for this study were collected from their medical records.

Statistical Analysis

Results obtained from continuous data with normal distribution are presented as means and standard deviations. Those from non-normal continuous data are presented as medians with 25^th and 75^th percentiles, and those from categorical data are presented as numbers and percentages. The absolute standardized difference (ASD), which is superior to rank-sum tests or t-tests because it is independent of sample size, was used for between-group comparisons. The between-group imbalances were considered ideal if the ASD was less than 10% (Stata command “stddiff”). We used propensity score matching to balance the differences in patient demographics, medical history, and pre-admission and in-hospital management strategies between GPI users and non-GPI users. We developed a non-parsimonious multivariable logistic regression model to estimate a propensity score for GPI status (yes or no) as the dependent variable. Then, a propensity score matching of a maximal ratio of 1-to-1, without replacement, with a caliper width of 0.02 was performed (Stata command “calipmatch”). The risk of in-hospital bleeding, ischemic events, and mortality in the matched groups was assessed using a logistic regression model on the matched pairs.

We performed the following interaction tests and subgroup analyses based on matched population, including age (< 65 and ≥ 65 years), sex, eGFR, Killip class (Class I vs. > Class I), DAPT status (full loading or not), and Low Molecular Weight Heparin LWMH (use or not).

Finally, we performed the following sensitivity analyses based on the matching cohort that excluded the following: (a) patients who died within 48 hours of admission; (b) patients with Killip Class IV; (c) patients receiving ticagrelor; (d) patients receiving DAPT with both in loading dose; (e) femoral PCI; and (f) patients receiving unfractionated heparin (nonoperative, unfractionated heparin use). Additionally, an inverse probability weighting based on multivariate logistic regression (Stata command “teffects ipw”) was used as a sensitivity analysis to validate the primary findings.

We imputed data for variables with missing values using the sequential regression multiple imputation method by IVEware (version 0.2; Survey Research Center, University of Michigan, Ann Arbor, MI), as previously described.¹⁵ The missing rates of the study variables are shown in Supplemental Table 2. We used Stata version 15.1 (StataCorp, College Station, TX) for analysis. A two-tailed p < 0.05 was considered statistically significant.

Patient Characteristics

Among 3,322 GPI users and 2,574 non-GPI users, as shown in Supplemental Table 3, GPI users were younger, more likely to be male and dyslipidemia patients, with higher levels of body weight and hemoglobin, and less likely to receive prehospital thrombolysis and prehospital medications (aspirin, P2Y₁₂ inhibitors, statins, β-blocker, and aldosterone antagonist). After propensity score matching, a cohort comprising 2,219 GPI users (66.7% of the total GPI population) and 2,219 non-GPI users was constructed, with well-balanced clinical characteristics in terms of demographics, pre-admission characteristics, medical history, admission characteristics, and in-hospital management strategies. The baseline characteristics of the post-matching cohort are shown in Table 1, and the ASD between pre- and post-matched cohorts is shown in Figure 2.

Associations Among GPI, Major In-Hospital Bleeds, Ischemic Events, and Mortality

In the propensity-score-matched cohort, a total of 83 composite major bleeds, 55 ischemic events, and 56 deaths were recorded, with incidence rates of 1.90%, 1.20%, and 1.30%, respectively. Compared with non-GPI users, GPI use was associated with a 69% increase in major bleeds, with an odds ratio (OR) of 1.69, a 95% confidence interval (CI) of 1.08 to 2.65, and a nonsignificant reduction in ischemic events (OR: 0.61, 95% CI: 0.36 to 1.06), as well as a neutral effect on in-hospital mortality (OR: 0.93, 95% CI: 0.55 to 1.58). Notably, GPI-associated increase in bleeding risk was consistent for BARC- (OR: 1.63, 95% CI: 0.99 to 2.66), TIMI- (OR: 1.83, 95% CI: 1.09 to 3.09), and PLATO- (OR: 1.80, 95% CI: 1.13 to 2.88) defined major bleeds (Figure 3). By using inverse probability weighting, we also confirmed the abovementioned findings (Supplemental Figure 1). As shown in Figure 4 and Supplemental Figure 2, there was no significant interaction across subgroups, and GPI-associated bleeding risk was more pronounced in patients with advanced age (OR: 2.52, 95% CI: 1.27 to 5.00), in males (OR: 1.82, 95% CI: 1.11 to 2.97), and in patients receiving LMWH therapy (OR: 2.26, 95% CI: 1.22 to 4.17). Similarly, the association of GPI use with ischemic events (Figure 4 and Supplemental Figure 3) and mortality (Figure 4 and Supplemental Figure 4) across subgroups was generally in agreement with the main findings. Notably, as shown in Figure 4, a significant interaction between age subgroup and ischemic events was observed among patients aged < 65 years (OR: 0.26, 95% CI: 0.08 to 0.77) versus patients aged ≥ 65 years. Considering the nonsignificant increase in major bleeding risk in this subgroup (Figure 4), these results indicate a potential benefit of GPI use in STEMI patients aged < 65 years following thrombus aspiration.

Sensitivity Analysis

Figure 5 displays the sensitivity analyses for major in-hospital bleeding. GPI use-associated risk for major bleeds remained consistent in multiple sensitivity analyses. In terms of in-hospital ischemic events and mortality, additional sensitivity analyses revealed similar results that agreed with the main findings. (Supplemental Figures 5 and 6).

In a nationwide registry of STEMI patients receiving contemporary management, we demonstrated that GPI use following thrombus aspiration was not associated with reduced in-hospital ischemia events and mortality, but at the cost of increased major bleeding. These findings were found to be consistent using multiple sensitivity analyses. However, our analysis also showed a possible beneficial GPI-use effect in STEMI patients aged < 65 years, in terms of a significant reduction in ischemic events and a nonsignificant increase in major bleeds. Therefore, the study’s evidence does not support routine GPI use following thrombus aspiration, but STEMI patients aged < 65 years may benefit from this bailout strategy.

Most patients included in the study received the standard treatment recommended by the guidelines.^{2, 3, 6-9} For example, about 97% of the patients received at least one loading dose of DAPT treatment, and about 84% received parenteral anticoagulant agents. Ticagrelor accounted for about 40% of P2Y₁₂ inhibitors, and clopidogrel accounted for about 60%; 92% of patients were administered transradial access for PCI, which had been proven to significantly reduce the risk of bleeding.

Sufficient clinical evidence shows that high thrombus burden still appears to be an important risk factor for STEMI patients. Large thrombus burden increases the risk of no- or slow-reflow and distal embolization,^{4, 15} which may lead to more cardiovascular death, heart failure, or cardiogenic shock.¹⁶ Distal embolization of micro-thrombi and plaque-material-induced obstruction of the microvasculature may be one important mechanism of poor prognosis,¹⁷ and there is evidence that intrinsic platelet reactivity was higher with greater thrombus burden, which predicts the thrombus burden may be a risk marker of system ischemic risk as well as a therapeutic target.¹⁸ In view of these mechanisms, the potential effective schemes considered in the current treatment of high thrombus burden may be thrombus aspiration alone or with GPI. In support of these pathological mechanisms, a recent randomized controlled trial showed that even under the current intensive treatment measures (60.8% ticagrelor and 50.7% thrombus aspiration), GPI use in STEMI patients with high thrombus burden is capable of improving myocardial perfusion, as shown by lower TIMI frame counts.¹⁹ However, this study was underpowered to detect differences in bleeding and mortality risk.

Thrombus aspiration can be used to evacuate coronary thrombus prior to stent deployment, so it may improve the blood flow of coronary microcirculation and reduce the risk of no-reflow.²⁰ However, even in patients with high thrombotic load, it was demonstrated that routine thrombus aspiration does not improve outcomes.¹⁶ Limitations of the current manual thrombus aspiration technique probably include downstream thromboembolism, limited ability to deal with large organized thrombi, and embolization of thrombus to other vascular territories during removal of the aspiration catheter.⁵ GPI was considered to have a synergistic effect with thrombus aspiration because it could further dissolve residual thrombus in the microvasculature after most thrombotic materials were retrieved by thrombus aspiration.²¹

The advantage of GPIs is their rapid and powerful antiplatelet effect. Although there is no clinical evidence, GPI could be a bailout therapy in the event of a large thrombus and other thrombotic complications.^{2, 3} However, our study, based on the Chinese population, found that in the era of wide use of new P2Y₁₂ and new-generation drug-eluting stents, routine GPI use in STEMI patients who received thrombus aspiration did not decrease in-hospital ischemic events, but significantly increased the risk of bleeding. These findings are consistent with other recent clinical studies on the application of GPI bailout use.^{22, 23} However, an important finding in the present study was a statistically significant interaction between aging (≥ 65 years vs. < 65 years) and GPI-associated major bleeding risk: Patients aged ≥ 65 years had increased risk of major bleeding, while those aged < 65 years may benefit from GPI treatment, as shown by a reduction in ischemic events and a nonsignificant increase in major bleeding risk. Indeed, advanced age is generally regarded as a risk factor for bleeding risk among patients receiving antithrombotic therapy. ^24-26 Mechanistically, age-related physiological changes ²⁷ (i.e., the increasing levels of fibrinogen, factor [F] VII, FVIII, plasminogen activator inhibitor-1, and thrombin-activatable fibrinolysis inhibitor) made the formation of thrombus in the elderly more intricate, which may limit the efficacy of platelet glycoprotein IIb/IIIa inhibition. However, decline of liver or kidney function and age-related amyloid angiopathy may heighten the risk of bleeding. Therefore, advanced age seems to be a key factor affecting the risk and benefit to GPI users.

To our knowledge, the present work is the largest sample size empirical study on the association between GPI use and in-hospital outcomes in STEMI patients treated with coronary thrombus aspiration. Although multiple statistical approaches have confirmed the key findings, several limitations should, nonetheless, be acknowledged. First, in an observational study, we cannot exclude the possible impact of unmeasured factors. For example, according to existing STEMI guidelines, thrombus aspiration is only suitable for patients with high thrombus burden, so this study assumes all patients undergoing thrombus aspiration have high thrombus burden, but it lacks any quantitative analysis of thrombus load. Second, the entire included population was Chinese. Because ethnic differences affect the risks of bleeding and ischemia, the conclusions of this study should be extended to other populations with caution.

In conclusion, in a nationwide ACS registry in China, the routine use of GPI did not reduce the incidence of in-hospital ischemic events in STEMI patients treated with thrombus aspiration, but significantly increased the risk of major bleeding. However, a reduced risk for ischemic events and nonsignificant increase in major bleeding risk was observed in patients aged < 65 years old, indicating the potential benefit of GPI use in this subgroup. These findings need to be validated in other populations.

Author Declarations

Funding

This work was supported by a collaborative program of the American Heart Association and the Chinese Society of Cardiology. The American Heart Association was funded by Pfizer and AstraZeneca for the quality improvement initiative through an independent grant for learning and change. This work was also supported by the National Key R&D Program of China (Nos. 2020YFC2004700, 2020YFC2004706), National Natural Science Foundation of China (No. 81970304) and Tianjin Municipal Science and Technology Commission (No. 18ZXZNSY00290).

Conflicts of interest/Competing interests

The authors declare that there are no conflicts of interest or competing interests to report.

Availability of data and material

Not applicable.

Code availability

Not applicable.

Authors' contributions

The article was written on behalf of the CCC-ACS project investigators. XZ, QY and YL conceived and designed the study, supervised the analysis process, interpreted the data and revised the manuscript. WL and ZL analyzed the data and drafted the manuscript. WL, ZL, TY, GA, HS, HL, XS, ZJ and LL helped to analyze the data and table and figure generation. YH, JL and DZ supervised the CCC-ACS project, and interpreted the data. All authors read and approved the final manuscript.

Ethics approval

The CCC-ACS project was approved by the institutional review board of Beijing Anzhen Hospital, Capital Medical University, with a waiver for informed consent.

Consent to participate

Not applicable.

Consent for publication

Not applicable.

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Table 1 Baseline characteristics between GPI patients and non-GPI patients in post-matched cohorts

Characteristics	No. of Patients n=4438	GPI n=2219	Non-GPI n=2219	ASD, %
Demographics
Age, year	59.8±12.7	59.7±12.4	60.0±12.9	2.69
Male, n (%)	3669(82.7)	1837(82.8)	1832 (82.6)	0.60
Weight, kg	70.0 (64.0-76.0)	70.0 (63.0-76.0)	70.0 (64.0-76.0)	0.42
Medical history
Smoking, n (%)	2450 (55.2)	1222 (55.1)	1228 (55.3)	0.54
Hypertension, n (%)	2055 (46.3)	1019 (45.9)	1036 (46.7)	1.54
Diabetes, n (%)	841 (18.9)	417 (18.8)	424 (19.1)	0.81
Dyslipidemia, n (%)	297 (6.70)	150 (6.80)	147 (6.60)	0.54
MI, n (%)	229 (5.20)	118 (5.30)	111 (5.00)	1.43
PCI, n (%)	230 (5.20)	116 (5.20)	114 (5.10)	0.41
CABG, n (%)	7 (0.20)	4 (0.20)	3 (0.10)	1.14
COPD, n (%)	51 (1.10)	24 (1.10)	27 (1.20)	1.27
Heart failure, n (%)	11 (0.20)	6 (0.30)	5 (0.20)	0.91
Renal failure, n (%)	36 (0.80)	19 (0.90)	17 (0.80)	1.01
Atrial fibrillation, n (%)	71 (1.60)	35 (1.60)	36 (1.60)	0.36
Ischemic stroke, n (%)	285 (6.40)	148 (6.70)	137 (6.20)	2.02
Hemorrhagic stroke, n (%)	23 (0.50)	10 (0.50)	13 (0.60)	1.88
Peripheral vascular disease, n (%)	28 (0.60)	15 (0.70)	13 (0.60)	1.14
Clinical variables
SBP, mmHg	125.2±22.7	124.9±23.2	125.5±22.2	2.79
DBP, mmHg	77.2±14.9	77.1±15.3	77.3±14.5	1.31
Heart rate, bpm	77.3±16.0	77.4±15.8	77.3±16.1	0.79
Killip Class >I, No. (%)	1080 (24.3%)	523 (23.6%)	557 (25.1%)	3.57
CK-MB peak, μg/L	48.9 (16.8-120)	48.8 (17.8-120)	49.0 (15.6-119.7)	0.71
LDL-C, mg/dL	107 (85.0-132)	107 (86.0-131)	106 (84.0-133)	0.41
HDL-C, mg/dL	40.0 (34.0-48.0)	41.0 (34.0-48.0)	40.0 (34.0-48.0)	1.01
TG, mg/dL	130 (89.0-190)	130 (90.0-188)	130 (89.0-194)	0.85
eGFR, mL/min/1.73m²	87.2±22.8	87.3±22.3	87.0±23.3	1.29
Hemoglobin on admission, g/dL	142 (130-153)	142 (130-153)	141.4 (129-153)	0.16
Pre-hospital medications
Pre-hospital thrombolysis, n (%)	47(1.10)	21 (0.90)	26 (1.20)	2.20
Aspirin, n (%)	655 (14.8)	326 (14.7)	329 (14.8)	0.38
P2Y₁₂ inhibitor, n (%)	523 (11.8)	264 (11.9)	259 (11.7)	0.70
Statin, n (%)	478 (10.8)	230 (10.4)	248 (11.2)	2.62
Oral anticoagulants, n (%)	12 (0.30)	7 (0.30)	5 (0.20)	1.74
β-blocker, n (%)	229 (5.20)	110 (5.00)	119 (5.40)	1.83
ACEI/ARB, n (%)	303 (6.80)	155 (7.00)	148 (6.70)	1.25
Aldosterone antagonist, n (%)	32 (0.70)	16(0.70)	16(0.70)	<0.01
In-hospital medications
DAPT status after admission, n (%)				2.69
DAPT was not in loading dose	105 (2.40)	70 (3.20)	35 (1.60)
One of DAPT in loading dose	1279 (28.8)	589 (26.5)	690 (31.1)
DAPT both in loading dose	3054 (68.8)	1560 (70.3)	1494 (67.3)
P2Y₁₂ inhibitor, n (%)
Ticagrelor	1820 (41.0)	915 (41.2)	905 (40.8)	0.92
Clopidogrel	2790 (62.9)	1392 (62.7)	1398 (63.0)	0.56
Anticoagulation therapy, n (%)
Unfractionated heparin	396 (8.90)	201 (9.1)	195 (8.80)	0.95
LMWH	3120 (70.3)	1571 (70.8)	1549 (69.8)	2.17
Others	133 (3.00)	69 (3.10)	64 (2.90)	1.32
Oral anticoagulants, n (%)	25 (0.60)	14.0 (0.60)	11 (0.50)	1.81
Statin, n (%)	4189 (94.4)	2099 (94.6)	2090 (94.2)	1.76
β-blocker, n (%)	2147 (48.4)	1077 (48.5)	1070 (48.2)	0.63
ACEI/ARB, n (%)	1749 (39.4)	876 (39.5)	873 (39.3)	0.28
Aldosterone antagonist, n (%)	668 (15.1)	326 (14.7)	342 (15.4)	2.02
PCI related
Radial route for PCI, n (%)	4058 (91.4)	2032 (91.6)	2026 (91.3)	0.97
PCI type, n (%)				2.76
Primary, <12 h	3568 (80.4)	1782 (80.3)	1786 (80.5)
Primary, ≥12 h	524 (11.8)	275 (12.4)	249 (11.2)
Rescue	55 (1.20)	32 (1.40)	23 (1.00)
Elective	291 (6.60)	130 (5.90)	161 (7.30)

Abbreviations: ACEI, angiotensin converting enzyme inhibitor; ARB, angiotensin receptor blocker; CABG, coronary artery bypass grafting; CK-MB, creatine kinase MB isoform; COPD, chronic obstructive pulmonary disease; DAPT, dual antiplatelet therapy; DBP, diastolic blood pressure; GPI, glycoprotein IIb/IIIa inhibitors; HDL-C, high density lipoprotein cholesterol; LDL-C, low density lipoprotein cholesterol; LMWH, low molecular weight heparin; MI, myocardial infarction; PCI, percutaneous coronary intervention; SBP, systolic blood pressure; TG, triglycerides.

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Association Between Platelet Glycoprotein IIb/IIIa Inhibition and In-Hospital Outcomes in ST-Elevation Myocardial Infarction Patients Treated with Coronary Thrombus Aspiration: Findings from the CCC-ACS Project

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