The optimal management of a large intracoronary thrombus in patients with acute coronary syndromes without an urgent need of revascularization is unclear. We investigated whether deferring percutaneous coronary intervention (PCI) after a course of intensive antithrombotic therapy (ATT) (glycoprotein IIb/IIIa inhibitors, enoxaparin, aspirin, and clopidogrel) improves the outcomes compared with immediate PCI. We studied 133 stable patients with ACS and a large intracoronary thrombus and without an urgent need for revascularization at angiography. The angiographic and in-hospital outcomes of a prospective cohort of 89 patients who had undergone deferred angiography with or without PCI after ATT (d-PCI) were compared with a historical cohort of 44 patients who had undergone immediate PCI, matched for age, gender, and Thrombolysis In Myocardial Infarction thrombus grade. The absolute thrombus volume was measured before and after ATT using dual quantitative coronary angiography. All d-PCI patients remained stable during ATT (60.0 ± 30.8 hours). A significant reduction in the Thrombolysis In Myocardial Infarction thrombus grade (4, range 4 to 5, vs 3, range 2 to 4; p <0.001), thrombus volume (51.1, range 32.1 to 83, vs 38.1, range 21.7 to 50.7 mm 3 ; p <0.001), stenosis severity (73.8 ± 25.8% vs 60.3 ± 32.5%; p <0.001) and better Thrombolysis In Myocardial Infarction flow (2, range 0 to 3, vs 3, 1.5 to 3; p <0.001) were noted after ATT. PCI, stenting, and thrombus aspiration were performed less frequently in the d-PCI group (76.4% vs 100%, p <0.001; 70.8% vs 93.2%, p = 0.003; and 21% vs 100%, p <0.001, respectively). However, distal embolization and slow and/or no-reflow were more common during immediate PCI (31.8% vs 9%; p = 0.001). No life-threatening or severe hemorrhagic complications were observed, although the rate of mild and/or moderate bleeding was similar between the 2 groups (6.8% in immediate PCI vs 7.9% in d-PCI; p = 0.829). In conclusion, compared with immediate PCI, d-PCI after ATT in selected, stabilized patients with ACS and a large intracoronary thrombus and without an urgent need for revascularization is probably safe and associated with a reduction in thrombotic burden, angiographic complications, and the need of revascularization. These benefits were observed without an increase in hemorrhagic complications.
In patients with acute coronary syndromes (ACS), a large intracoronary thrombus (LIT) increases the risk of distal embolization, no-reflow, abrupt closure, stent thrombosis, repeat revascularization, myocardial infarction, and death. Antithrombotic and antiplatelet therapies can reduce the thrombotic burden, and thrombectomy and embolic protection devices can effectively remove variable fractions of LIT. However, their effectiveness is often suboptimal ; therefore, the optimal treatment of LIT remains a major, unsolved problem frequently faced during percutaneous coronary intervention (PCI). Although in some presentations of ACS, such as acute ST-elevation myocardial infarction, PCI must be performed ad hoc, and thrombus burden reduction relies mainly on thrombectomy, the risk/benefit ratio of performing immediate PCI in patients with ACS and LIT who are clinically stable and without an urgent need of revascularization is less clear. Accordingly, the aim of the present study was to investigate whether in stable patients with ACS and LIT and without an urgent need for revascularization, deferral of PCI (d-PCI) after a course of intensive antithrombotic therapy (ATT), would be effective in reducing the thrombotic load and improve the in-hospital outcomes compared with ad hoc immediate PCI.
Methods
Patients admitted with ACS, LIT, and controlled symptoms, who were hemodynamically stable and without an urgent need for revascularization, were included in the present study. ACS were defined according to current clinical practice guidelines. Subacute ST-elevation myocardial infarction was defined as a history of typical chest pain lasting for >30 minutes, with ST-segment elevation >1 mm in 2 consecutive leads or new-onset complete left bundle branch block and arriving to the hospital >12 hours after the onset of symptoms. Unstable angina was defined as at rest, new-onset, progressive, or postinfarct chest pain, and non–ST-elevation myocardial infarction as the occurrence of troponin elevation with electrocardiographic changes or angina. The definition of controlled symptoms required the presence of all of the following at angiography: the absence of anginal symptoms or signs of acute heart failure, significant arrhythmias, complications of myocardial infarction, arrival to the hospital >12 hours after symptom onset, and no need for urgent revascularization, as judged by the operator. Primary PCI, ongoing/recurrent angina, hemodynamic instability, and unstable arrhythmias were the exclusion criteria.
The treatment group consisted of a prospective cohort of patients with ACS, LIT, and controlled symptoms who underwent deferred PCI (d-PCI), after a period of intensive ATT and antiplatelet therapy. ATT consisted of glycoprotein IIb/IIIa inhibitors, enoxaparin, aspirin, and clopidogrel for 48 hours after the diagnostic angiography but before PCI. Their angiographic and in-hospital outcomes were compared with those of a historical cohort of patients, with controlled symptoms, who had been treated ad hoc with PCI (immediate PCI) at our institution during the same period. The control patients were ≈ 1:2 frequency-matched for age, gender, and Thrombolysis In Myocardial Infarction thrombus grade.
Coronary angiograms were analyzed off-laboratory by experienced personnel before and after PCI. According to Yip et al, LIT was diagnosed if ≥1 of the 6 following features were present: (1) cutoff pattern of occlusion in the infarct-related artery, (2) accumulated thrombus (>5 mm) proximal to the occlusion, (3) the presence of floating thrombus, (4) persistent dye stasis distal to the obstruction, (5) thrombus in the infarct-related artery >4 mm, and (6) incomplete obstruction with the presence of accumulated thrombus >3 times the infarct-related artery luminal diameter. Coronary flow was assessed using the Thrombolysis In Myocardial Infarction flow grade classification (Thrombolysis In Myocardial Infarction grade 0 to 3). The Thrombolysis In Myocardial Infarction thrombus grade scale was used to assess the change in thrombotic burden before and after the interventions: grade 0, no angiographic characteristics of thrombus; grade 1, possible thrombus, seen as reduced contrast density, haziness, irregular lesion contour, or a smooth convex “meniscus” at the site of total occlusion suggestive, but not diagnostic, of thrombus; grade 2, definite thrombus, with the greatest dimensions ≤½ the vessel diameter; grade 3, definite thrombus, with the greatest linear dimension >½ but <2 vessel diameters; grade 4, definite thrombus, with the largest dimension ≥2 vessel diameters; and grade 5, total occlusion. To assess the effect of ATT on thrombotic burden, the absolute thrombus volume was measured using dual quantitative coronary angiography before and after ATT in cases suitable for this analysis (Thrombolysis In Myocardial Infarction flow ≥1 and absence of significant vessel foreshortening or overlapping). A detailed description of the development and validation of dual quantitative coronary angiography for thrombus volume quantification has been previously published. In brief, dual quantitative coronary angiography calculates the intracoronary thrombus volume by combining 2 quantitative coronary angiographic modalities: edge detection and video densitometry. The discrepancy between the luminal volumes calculated with both techniques constitutes an estimate of thrombotic volume. The CAAS-II quantitative coronary angiography system (Pie Medical, Einthoven, The Netherlands) was used.
The angiographic complications recalled were defined as follow. Distal embolization was defined as the presence of filling defects in or cut-off of a distal branch; slow flow as Thrombolysis In Myocardial Infarction flow grade 2 at the end of the procedure; and, finally, no reflow as Thrombolysis In Myocardial Infarction grade ≤1 flow in the distal infarct-related artery in the absence of an occlusion at the treatment site or evidence of distal embolization. The clinical complications and in-hospital evolution were reviewed, including recurrent angina, hemodynamic instability, and urgent revascularization during the ATT period. Hemorrhagic complications were collected as defined by the Global Utilization of Streptokinase and Tissue-Plasminogen Activator for Occluded Coronary Arteries (GUSTO) investigators : (1) severe or life-threatening, intracranial hemorrhage or bleeding that causes hemodynamic compromise and requires intervention, (2) moderate, bleeding requiring blood transfusion but not causing hemodynamic instability, and (3) mild, bleeding not meeting the criteria for severe or moderate bleeding.
All continuous variables are presented as the mean ± SD or median (interquartile range), according to their normal or not normal distribution. Categorical variables are presented as numbers or percentages. Before the statistical analysis, the normalcy and homogeneity of the variances were tested using the Kolmogorov-Smirnov and Levene tests. Continuous variables were compared using the t test or Mann-Whitney U test, as appropriate. Categorical variables were compared using Pearson’s chi-square or Fisher’s exact test, as appropriate. A paired t test or Wilcoxon test was used to compare the angiographic differences before and after ATT and PCI. A p value <0.05 was considered significant. The SPSS, version 20.0 (SPSS, Chicago, Illinois), statistical software package was used for all calculations.
Results
The baseline characteristics of the study population are listed in Table 1 . Non–ST-elevation myocardial infarction was the dominant cause of admission. About 40% of patients (n = 54) were in the subacute phase of ST-elevation myocardial infarction treated either with fibrinolysis (9%, n = 12) or had not received reperfusion therapy owing to a late (>12 hours) arrival to the hospital and controlled symptoms. Most patients had 1-vessel disease, with a preponderance of LIT in the right coronary artery. No significant differences with the controls were observed for diabetes, hypertension, dyslipidemia, and smoking or in the cause of admission, number of diseased vessels, thrombus location, or pre-PCI treatment with glycoprotein IIb/IIIa inhibitors. Patients in the d-PCI group were more likely to have a greater stenosis grade. Thrombotic vessel occlusion was found in 29 (33%) d-PCI and 21 (48%) immediate PCI patients (p = 0.090).
| Variable | Total Population (n = 133) | d-PCI (n = 89) | i-PCI (n = 44) | p Value |
|---|---|---|---|---|
| Age (yrs) | 58 ± 13 | 58 ± 13 | 58 ± 12 | 0.866 |
| Men | 115 (87) | 77 (87) | 38 (86) | 0.981 |
| Diabetes mellitus | 25 (19) | 20 (23) | 5 (11) | 0.123 |
| Presentation | 0.051 | |||
| Unstable angina pectoris | 11 (8) | 11 (12) | 0 | |
| Non–STEMI | 68 (51) | 43 (48) | 25 (57) | |
| STEMI (subacute phase) | 54 (41) | 35 (39) | 19 (43) | |
| Peak troponin during admission (ng/ml) | 9 (2–27) | 8 (2–27) | 10 (3–25) | 0.564 |
| Ejection fraction (%) | 58 ± 15 | 57 ± 15 | 59 ± 13 | 0.543 |
| Glycoprotein IIb/IIIa inhibitors before angiography | 25 (19) | 13 (15) | 12 (27) | 0.079 |
| No. of coronary arteries narrowed | 0.160 | |||
| 1 | 95 (71) | 61 (69) | 34 (77) | |
| 2 | 26 (20) | 17 (19) | 9 (21) | |
| 3 | 12 (9) | 11 (12) | 1 (2) | |
| Thrombus location | 0.180 | |||
| Left anterior descending artery | 47 (35) | 27 (30) | 20(46) | |
| Circumflex artery | 15 (11) | 11 (12) | 4 (9) | |
| Right coronary artery | 66 (50) | 46 (52) | 20 (46) | |
| Saphenous vein graft | 5 (4) | 5 (6) | 0 | |
| TIMI flow | 2 (0–3) | 2 (0–3) | 1 (0–3) | 0.080 |
| TIMI thrombus grade | 4 (4–5) | 4 (4–5) | 4 (4–5) | 0.289 |
| Absolute thrombotic volume (mm 3 ) ∗ | 32 (51–83) | 56 (38–90) | 35 (26–79) | 0.148 |
| Stenosis grade (%) | 79 ± 23 | 74 ± 26 | 90 ± 11 | <0.001 |
∗ Calculated using dual quantitative coronary angiography in 44 patients suitable for this analysis.
All d-PCI patients remained asymptomatic and without recurrent angina during the ATT period (60 ± 31 hours). Tirofiban was the most frequently used glycoprotein IIb/IIIa inhibitor (63%), followed by abciximab (33%). The angiographic data for the d-PCI group are listed in Table 2 . After the ATT period, the Thrombolysis In Myocardial Infarction grade flow, TTG, and other indexes of thrombotic burden and coronary flow significantly improved ( Figure 1 and Table 2 ). The number of vessels completely occluded by LIT decreased significantly with ATT. In the 44 patients suitable for this analysis, dual quantitative coronary angiography ( Figure 2 ) demonstrated a significant reduction in the absolute thrombus volume of 37% ( Figure 3 ).
| Variable | Before ATT | After ATT | p Value |
|---|---|---|---|
| TIMI flow | 2 (0–3) | 3 (1.5–3) | <0.001 |
| TIMI thrombus grade | 4 (4–5) | 3 (2–4) | <0.001 |
| Absolute thrombotic volume (mm 3 ) ∗ | 51 (32–83) | 38 (22–51) | <0.001 |
| Stenosis grade (%) | 74 ± 26 | 61 ± 36 | <0.001 |
| Stenosis length (mm) | 14 ± 8 | 10 ± 7 | <0.001 |
| Totally occluded vessel | 29 (33) | 18 (20) | <0.001 |
∗ Calculated using dual quantitative coronary angiography in 44 patients suitable for this analysis.
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