Abstract
Objectives
This multicenter registry aimed to assess the ClearWay™ (CW) perfusion catheter in reduction of thrombus burden and improvement of the coronary flow during percutaneous coronary intervention (PCI).
Background
The presence or development of thrombus during PCI is associated with poor prognosis.
Methods
The utility of the CW perfusion catheter was assessed in patients who presented with intracoronary thrombus and were subjected to PCI. Data were collected by online survey from 15 US sites. Angiographic assessment of the coronary thrombus burden and the coronary flow after intracoronary infusion of glycoprotein (GP) IIb/IIIa inhibitors via the CW catheter was evaluated at baseline, immediately after infusion, and at the end of the procedure. The cohort included 102 patients; 71.6% presented with ST-elevation myocardial infarction (MI), 21.6% with non-ST-elevation MI, 5.9% with stable angina pectoris, and 2.9% with silent ischemia. The mean cohort age was 59.9 ± 14.5 years and comprised mostly of men (72.5%).
Results
GP IIb/IIIa inhibitors were infused via the CW catheter on average 1.1 ± 0.3 times, with a mean pressure of 4.2 ± 2.7 atm and a mean infusion time of 55 ± 55 s. Following the infusion, Thrombolysis In Myocardial Infarction (TIMI) flow improved by 1° in 71 patients (69.6%) and by 2° in 51 patients (50%), while visible thrombus was reduced by 52% ( p < 0.001). In the final angiogram, TIMI flow was restored in 90.2% and clearance of a visible thrombus was obtained in 91.8% of the lesions.
Conclusion
Intracoronary infusion of GP IIb/IIIa inhibitors via the perfusion CW catheter is associated with significant reduction in thrombus burden and with improvement of the coronary flow in patients presenting or developing thrombus burden during PCI.
Percutaneous coronary intervention (PCI) in patients with a large thrombus burden has been associated with impaired clinical outcome . Large thrombus burden predicts distal embolization and myocardial reperfusion in patients undergoing primary PCI . Proximal aspiration devices have improved myocardial perfusion and ST-segment elevation resolution in patients with ST-elevation myocardial infarction (MI) undergoing primary PCI . A high concentration of in vitro glycoprotein (GP) IIb/IIIa inhibitors promotes disaggregation of fresh thrombus . Small clinical series have suggested the utility of intracoronary GP IIb/IIIa inhibitors to improve post-procedural coronary flow, myocardial perfusion, and ventricular function as compared to systemically infused drugs . The ClearWay™ (CW) catheter (Atrium Medical Corporation, Hudson, NH, USA) is a low-pressure, low-profile occlusion balloon specially designed for drug infusion that theoretically allows for high local drug concentration. Accordingly, via a multicenter survey, this study aimed to assess the clinical utility of the intracoronary infusion of GP IIb/IIIa inhibitors via the CW perfusion catheter to reduce thrombus burden in patients who presented or developed intracoronary thrombus during PCI.
1
Methods
The utility of the CW perfusion catheter was assessed in 102 patients who presented or developed intracoronary thrombus during PCI. Data were collected by online survey from 15 US high-volume sites (ClinicalTrials.gov identifier number NCT00804024). Angiographic improvement on coronary thrombus burden and flow after intracoronary drug infusion via the CW catheter was evaluated at baseline, immediately after infusion, and at the end of the procedure. The primary study end points were the rate of treatment success defined as decreased thrombus burden and normal Thrombolysis In Myocardial Infarction (TIMI) 3 flow.
PCI was performed according to guidelines current at the time of the procedure. In all cases, the interventional strategy was at the discretion of the responsible physician. Intra-procedural anticoagulation was ensured using bivalirudin or unfractionated heparin to achieve an activated clotting time of > 250 s in all patients. All patients received an aspirin loading dose of ≥ 100 mg and were encouraged to continue this regimen indefinitely. After a clopidogrel loading dose of 300–600 mg, additional antiplatelet therapy with a 75-mg clopidogrel maintenance dose was instituted in all patients. Patients were advised to continue this regimen for ≥ 1 year.
After angiographic documentation of intracoronary filling defect consistent with thrombus, an intracoronary 200-μg bolus of nitroglycerin was administered through the guiding catheter and a repeat coronary angiogram was obtained. In cases of persistent filling defect, a CW perfusion catheter system was advanced over a 0.014-inch guidewire in the culprit vessel, and GP IIb/IIIa inhibitors were given in bolus: Abxicimab (Lilly, Indianapolis, IN, USA) at 0.25 mg/kg or Eptifibatide (Merck, Whitehouse Station, NJ, USA) at 180 μg/kg buffered with 2 ml of 8.4% sodium bicarbonate solution. At the end of drug infusion, the CW catheter was removed, and a coronary angiogram was obtained.
Additionally, this study included a simple survey to evaluate the performance of the CW catheter. Physicians were asked to score the performance and the importance of the following characteristics: trackability, deliverability, flexibility, and ease of use using a subjective scale from 1 to 10 (1 = unacceptable; 10 = excellent).
MI was defined as the association of ≥ 1 clinical and ≥ 1 biological criteria: acute onset chest pain and/or typical modification on electrocardiogram (ST or T-wave modification or new left bundle branch block) and an elevation of troponin value above the 99th percentile of the upper reference limit . Angiographic type lesions were sorted as A, B or C using the American College of Cardiology/American Heart Association (ACC/AHA) classification . Chronic renal insufficiency was defined as the presence of previously documented renal failure and/or a baseline serum creatinine > 2.0 mg/dl.
All angiograms were reviewed and analyzed “offline” at each site. Coronary flow was graded using the TIMI flow scale (as defined by the Thrombolysis In Myocardial Infarction trial) before intervention, immediately after GP IIb/IIIa inhibitor infusion, and at the end of the procedure. Thrombus burden was objectivized as presence or absence of angiographic filling defect at baseline, after GP IIb/IIIa inhibitor infusion, and at the end of the procedure.
Continuous variables are expressed as mean ± standard deviation. Discrete variables are presented as absolute numbers and percentages. Differences in TIMI flow and thrombus burden before and after GP IIb/IIIa inhibitor infusion, and at the end of the procedure were evaluated by chi-square test. Probability values < 0.05 (two-tailed) were considered significant.
2
Results
Table 1 summarizes the baseline clinical characteristics. The population presented with a mean age of 60 years and a relatively high prevalence of cardiovascular risk factors. ST-elevation MI was the most common presentation (71.6%), followed by acute coronary syndrome without ST elevation (21.6%), stable angina pectoris (5.9%) and silent ischemia (2.9%).
| Variable | ( n = 102) |
|---|---|
| Clinical characteristics | |
| Age, years ± SD | 59.9 ± 14.5 |
| Men | 74 (72.5%) |
| Diabetes mellitus | 21 (20.6%) |
| Systemic hypertension a | 61 (59.8%) |
| Current smoking | 38 (37.2%) |
| Hypercholesterolemia b | 55 (53.9%) |
| Chronic renal insufficiency c | 2 (2.0%) |
| History of coronary artery disease | 28 (27.5%) |
| Clinical presentation | |
| ST-elevation myocardial infarction | 73 (71.6%) |
| Acute coronary syndrome | 22 (21.6%) |
| Stable angina pectoris | 6 (5.9%) |
| Silent ischemia | 3 (2.9%) |
a History of systemic hypertension diagnosed and/or treated with medication or currently being treated with diet and/or medication by a physician.
b Includes patients with a previously documented diagnosis of hypercholesterolemia. The patient may be treated with diet or medication. A new diagnosis can be made during this hospitalization with an elevated total cholesterol > 160 mg/dl. Does not include elevated triglycerides.
c CRI previously diagnosed or treated with medication, diet or dialysis by a physician. Diagnosis at admission if a baseline creatinine of > 2.0 mg/dl is found.
Table 2 depicts the angiographic and procedural characteristics. The most common involved vessel was the right coronary artery (52.0%). Most of the lesions were complex (B–C type ACC/AHA class) with a TIMI flow of 0 in 58.8% of the cases. Interventional therapies are displayed as prior to and after CW catheter use ( Table 2 ). Balloon dilatation and thrombectomy were commonly used prior to CW catheter use. Drug-eluting stents and bare-metal stents were implanted in 61 (59.9%) and 37 (36.3%) patients, respectively, more commonly after CW use. However, balloon dilatation was frequently used after GP IIb/IIIa inhibitor infusion via the CW catheter (44.1%) and thrombectomy in 16.7%.
| ( n = 102) | |
|---|---|
| Angiographic characteristics | |
| Coronary vessel | |
| Left anterior descending | 34 (33.3%) |
| Left circumflex | 15 (14.7%) |
| Right coronary | 53 (52.0%) |
| Venous graft | 0 |
| Vessel location | |
| Proximal | 40 (39.2%) |
| Mid | 41 (40.2%) |
| Ostial | 4 (3.9%) |
| Total occlusion (initial TIMI flow 0) | 60 (58.8%) |
| ACC/AHA class B1-B2 | 51 (50.0%) |
| ACC/AHA class C | 41 (40.2%) |
| Adjuvant devices | |
| Prior to ClearWay catheter use | |
| Balloon dilatation | 40 (39.2%) |
| Thrombectomy | 35 (34.3%) |
| Drug-eluting stent | 7 (6.9%) |
| Bare-metal stent | 4 (3.9%) |
| Laser | 4 (3.9%) |
| Atherectomy | 1 (1.0%) |
| After ClearWay catheter use | |
| Drug-eluting stent | 54 (52.9%) |
| Bare-metal stent | 33 (32.4%) |
| Thrombectomy | 17 (16.7%) |
| Balloon dilatation | 45 (44.1%) |
| Laser | 1 (1.0%) |
| Atherectomy | 0 |
GP IIb/IIIa inhibitors were infused via the CW catheter on average 1.1 ± 0.3 times, at a mean pressure of 4.2 ± 2.7 atm and at a mean infusion time of 55 ± 55 s. Abxicimab was used in 60 patients (58.8%), whereas eptifibatide was infused in 42 cases (41.2%). After CW catheter infusion, TIMI flow improved by 1° in 71 patients (69.6%) and by 2° in 51 patients (50%), and visible thrombus was absolutely reduced by 52% ( p < 0.001) ( Table 3 , Fig. 1 ). Overall, normal TIMI flow was restored in 90.2% of the studied population, without visible thrombus in 91.8% of the patients by the end of the procedure ( Table 3 , Fig. 1 ). After CW catheter infusion, patients treated with abxicimab showed a greater improvement in TIMI flow compared to patients treated with eptifibatide (improved by 1° in 81.7% vs. 52.4%, p = 0.003; and by 2° in 63.3% vs. 31.0%, p = 0.002), and had higher resolution of visible thrombus (62.7% with abxicimab vs. 39.1% with eptifibatide, p = 0.03). Nonetheless, by the end of the procedure, the rate of normal TIMI flow (88.3% with abxicimab vs. 92.9% with eptifibatide, p = 0.68) and the absence of thrombus (8.3% with abxicimab vs. 9.5% with eptifibatide, p = 0.88) were similar among patients treated with either GP IIb/IIIa inhibitor.
