The aim of the present study was to compare 600- and 300-mg clopidogrel loading doses in patients with ST-segment elevation myocardial infarctions who underwent primary percutaneous coronary intervention (PCI). Two hundred fifty-five consecutive patients presenting with ST-segment elevation myocardial infarctions who underwent primary PCI were enrolled. Patients were divided into 2 groups on the basis of the loading dose of clopidogrel received before the procedure (600 vs 300 mg). Procedural angiographic end points and 1-year major adverse cardiac events were compared between the 2 groups. Major adverse cardiac events were defined as death, nonfatal myocardial infarction, and target vessel revascularization. There were no significant differences in baseline clinical and angiographic features between the 2 groups: 157 (62%) in the clopidogrel 600 mg group and 98 (38%) in the 300 mg group. Patients receiving 600-mg loading dose of clopidogrel showed a significantly lower incidence of post-PCI myocardial blush grade 0 or 1 (odds ratio 0.64, 95% confidence interval 0.43 to 0.96, p = 0.03) and significantly less common no-reflow phenomenon (odds ratio 0.38, 95% confidence interval 0.15 to 0.98, p = 0.04) compared to those in the 300-mg group. Propensity-adjusted Cox analysis showed significantly higher survival free of major adverse cardiac events in patients receiving 600-mg loading dose of clopidogrel compared to those receiving the lower dose (hazard ratio 0.57, 95% confidence interval 0.33 to 0.98, p = 0.04). In conclusion, a 600-mg loading dose of clopidogrel is associated with improvements in procedural angiographic end points and 1-year clinical outcomes in patients with ST-segment elevation myocardial infarction who undergo primary PCI compared to a 300-mg dose.
In the present study, we analyzed whether a 600-mg loading dose of clopidogrel is associated with better procedural and 1-year clinical outcomes compared to a 300-mg loading dose in a single-center registry of patients with ST-segment elevation myocardial infarction (STEMI) who underwent primary percutaneous coronary intervention (PCI).
Methods
From January 2006 to December 2007, 384 consecutive patients presenting with STEMI and occluded infarct-related arteries (Thrombolysis In Myocardial Infarction [TIMI] flow grade 0 or 1) underwent primary PCI <12 hours after symptom onset at the Cardiovascular Center (Aalst, Belgium). STEMI was diagnosed in the presence of chest pain lasting >30 minutes and typical electrocardiographic changes (ST-segment elevation >1 mm in ≥2 contiguous leads). To be included in this registry, patients needed to be administered clopidogrel loading doses before intervention. Patients receiving fibrinolytic treatment were excluded.
Coronary angiography and PCI were performed according to standard practice. The decision as to which dose of clopidogrel to administer before PCI was left at the physician’s discretion. Depending on the clopidogrel loading dose administered, patients were divided into 600- and 300-mg groups. All patients received anticoagulation therapy with weight-adjusted unfractionated heparin and dual-antiplatelet therapy with aspirin (500 mg) and clopidogrel before the procedure. Use of glycoprotein IIb/IIIa inhibitors and catheter thrombus aspiration was at the physician’s discretion. Postprocedural antiplatelet therapy consisted of aspirin 100 mg/day and clopidogrel 75 mg/day.
Baseline clinical features and laboratory data were collected from the patient database at OLV Hospital (Aalst, Belgium). TIMI flow grade, TIMI frame count, and myocardial blush grade (MBG) were evaluated before and after disocclusion of the infarct-related artery. Post-PCI no reflow was defined as TIMI flow grade <2 not attributable to dissection, occlusive thrombosis, or epicardial spasm. Two independent expert interventionalists, unaware of treatment strategies and outcomes, reviewed all coronary angiograms. Interobserver coefficients of variation were 6% for TIMI flow grade and 10% for MBG. In case of disagreement, a third operator was involved to reach a consensus.
Clinical follow-up was performed using hospital records and telephone interviews. All events were classified and adjudicated by a physician not involved in the follow-up process. Major adverse cardiac events (MACEs) were defined as death, nonfatal myocardial infarction, or target vessel revascularization. This study complied with the Declaration of Helsinki and was approved by the local ethics committee, and all patients gave written informed consent.
Statistical analysis was performed using SPSS version 15.0 (SPSS, Inc., Chicago, Illinois). Continuous variables are expressed as mean ± SD. Categorical variables are reported as frequencies and percentages. Student’s t test was used to compare continuous variables. Comparisons between categorical variables were evaluated using 2-tailed Fisher’s exact tests or Pearson chi-square tests as appropriate. A propensity score was built with a nonparsimonious method to account for potential differences in treatment allocation and then entered into a logistic regression model. In particular, all variables listed in Table 1 were incorporated into the model and the score was then used in proportional-hazards analyses as a covariate. Overall survival and MACE-free survival were evaluated using the Kaplan-Meier method and Cox proportional-hazards analysis. A p value <0.05 was considered statistically significant.
| Variable | Clopidogrel Dose (mg) | p Value | |
|---|---|---|---|
| 600 (n = 157) | 300 (n = 98) | ||
| Age (years) | 64 ± 13 | 65 ± 13 | 0.43 |
| Men | 117 (75%) | 67 (68%) | 0.29 |
| Systemic hypertension ⁎ | 75 (48%) | 53 (54%) | 0.33 |
| Diabetes mellitus | 39 (25%) | 23 (23%) | 0.80 |
| Dyslipidemia † | 84 (54%) | 49 (50%) | 0.59 |
| Current smoking | 48 (31%) | 32 (33%) | 0.73 |
| Previous myocardial infarction | 17 (11%) | 15 (15%) | 0.29 |
| Previous PCI | 19 (12%) | 15 (15%) | 0.46 |
| Previous coronary artery bypass graft | 6 (4%) | 1 (1%) | 0.18 |
| Body mass index (kg/m 2 ) | 27 ± 5 | 27 ± 5 | 0.31 |
| Symptom-to-balloon time (minutes) | 369 ± 234 | 378 ± 266 | 0.45 |
| First medical contact–to–balloon time (minutes) | 107 ± 69 | 112 ± 71 | 0.58 |
| Clopidogrel-to-balloon time (minutes) | 86 ± 73 | 90 ± 61 | 0.64 |
| Glycoprotein IIb/IIIa inhibitors | 85 (54%) | 53 (54%) | 0.95 |
| Upstream | 45 (53%) | 23 (23%) | 0.34 |
| Procedural | 42 (47%) | 30 (57%) | 0.34 |
| Left ventricular ejection fraction (%) | 58 ± 15 | 59 ± 15 | 0.54 |
| Number of narrowed vessels | 1.73 ± 0.8 | 1.68 ± 0.8 | 0.68 |
| Infarct-related coronary artery | 0.42 | ||
| Left anterior descending | 68 (43%) | 41 (42%) | |
| Left circumflex | 20 (13%) | 17 (17%) | |
| Right | 66 (42%) | 40 (41%) | |
| Saphenous vein graft | 3 (2%) | — | |
| Thrombolysis in myocardial infarction flow grade | 0.34 | ||
| 0 | 122 (78%) | 35 (22%) | |
| 1 | 71 (72%) | 27 (28%) | |
| Thrombolysis in myocardial infarction frame count | 88 ± 29 | 85 ± 30 | 0.55 |
| Angiographically visible thrombus | 102 (65%) | 66 (67%) | 0.70 |
⁎ Systolic blood pressure >140 mm Hg and/or diastolic blood pressure >90 mm Hg or current antihypertensive treatment.
Results
We prospectively included 255 patients: 157 (62%) in the clopidogrel 600 mg group and 98 (38%) in the 300 mg group. There were no significant differences in baseline clinical and angiographic features between the 2 groups ( Table 1 ).
Patients receiving 600-mg loading dose of clopidogrel showed a significantly lower incidence of post-PCI MBG 0 or 1 (odds ratio 0.64, 95% confidence interval [CI] 0.43 to 0.96, p = 0.03) and no-reflow phenomenon (odds ratio 0.38, 95% CI 0.15 to 0.98, p = 0.04) compared to those in the 300-mg group ( Figure 1 ). A trend toward more frequent postprocedural TIMI flow grade 3 and lower TIMI frame count was also found in patients in the 600-mg group ( Table 2 ).
| Variable | Clopidogrel Dose (mg) | p Value | |
|---|---|---|---|
| 600 (n = 157) | 300 (n = 98) | ||
| Direct stenting | 72 (46%) | 45 (46%) | 0.99 |
| Drug-eluting stents | 25 (16%) | 17 (17%) | 0.77 |
| Length of stented segment (mm) | 24 ± 12 | 25 ± 12 | 0.27 |
| Diameter of stented segment (mm) | 3.2 ± 0.4 | 3.2 ± 0.4 | 0.55 |
| Thrombus aspiration | 105 (69%) | 60 (61%) | 0.36 |
| Intra-aortic balloon pump | 12 (8%) | 11 (11%) | 0.33 |
| Procedure length (minutes) | 60 ± 28 | 62 ± 24 | 0.61 |
| TIMI frame count | 19 ± 16 | 23 ± 18 | 0.07 |
| TIMI flow grade 3 | 134 (85%) | 75 (77%) | 0.08 |
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