Improved Procedural Results in Coronary Thrombosis Are Obtained with Delayed Percutaneous Coronary Interventions

ABSTRACT: We investigated the efficacy of percutaneous coronary intervention (PCI) in coronary thrombotic lesions according to the timing of the procedure. Eighty-two patients who underwent immediate PCI (IPCI) were compared to 24 patients who underwent PCI 4.9 ± 3 days after the diagnostic catheterization [delayed PCI (DPCI)]. DPCI was associated with a lower rate of thrombus-related angiographic events (4% versus 27%; p p = NS), no-reflow phenomenon (0% versus 8%; p = NS), acute closure (0% versus 10%; p = NS), stent thrombosis (4% versus 1%; p = NS) and residual thrombus (0% versus 17%; p = 0.03). No differences were seen in the hospital clinical outcome, including non-fatal myocardial infarction (4% versus 9%; p = NS), death (4% versus 0%; p = NS) or major bleeding (4% versus 3%). Delayed PCI after pharmacological treatment is a safe and efficient strategy of treatment for coronary thrombus.

Key words: complications, coronary thrombus, percutaneous coronary angioplasty

Coronary thrombus is the pathophysiological substrate in the majority of cases with acute coronary syndrome, and is angiographically identifiable in 6–30% of patients undergoing coronary catheterization.¹ Visible coronary thrombus has been associated with increased risk of angiographic complications (no-reflow, distal embolization, acute closure, stent thrombosis)^1–5 and clinical complications (myocardial infarction, urgent coronary surgery and death) during percutaneous coronary interventions (PCI).^6–8 The most appropriate approach to thrombotic lesions has not yet been defined. Multiple pharmacological and mechanical strategies have been applied during the percutaneous treatment of this type of lesion.^8–11 In the recent past, before the introduction of stents and platelet glycoprotein IIb/IIIa inhibitors to the field of interventional cardiology, a policy of PCI delay was recommended in patients with acute coronary events regardless of the angiographic characteristics, in order to decrease procedural complications.^12,13 This study compares whether this delayed approach is valid in the present era versus immediate intervention of thrombotic lesions. Methods This was an historical, prospective cohort trial that analyzed 106 patients who underwent PCI in the presence of angiographically visible coronary thrombus. These patients were selected from a population of 5,230 patients catheterized at the Soroka Medical Center between 1995 and 1999. A comparison between the angiographic results and hospital outcomes was performed between 82 patients (mean age, 58.2 ± 11 years) undergoing immediate PCI (IPCI) and 24 patients (mean age, 60.3 ± 10 years) undergoing delayed PCI (DPCI). The timing of the PCI was decided by the operator. Baseline demographic, clinical, angiographic and procedural characteristics of the patients were analyzed. The data analyzed were prospectively recorded in a computerized database at the time of the procedure. Additional review of the electronic records, patient charts and catheterization films was performed for validation of the computerized data. Endpoints for comparison were: 1) angiographic events related to the presence of thrombus, occurring during or after the procedure, including no-reflow phenomenon, coronary embolism, acute closure, residual thrombus, acute or subacute thrombosis; and 2) clinical events during the hospitalization period, including death, myocardial infarction and major bleeding. Definitions. Coronary thrombosis was defined as the presence of an intraluminal globular filling defect in multiple angiographic views or in an occluded vessel by the presence of a convex margin and staining with contrast. Immediate PCI was defined as PCI performed in the setting of diagnostic catheterization. Delayed PCI was defined as PCI performed after pharmacological treatment for at least 24 hours after the diagnostic catheterization. Exclusion criteria were patients undergoing primary or rescue PCI in the setting of acute myocardial infarction or unstable angina refractory to the medical treatment. Statistical analysis. Continuous variables are expressed as means and standard deviations and were analyzed with t-test for two independent samples. Categorical variables are expressed as percentages and were analyzed with the Chi-square test. P-values less than 0.05 were considered statistically significant. Results Baseline clinical and angiographic characteristics were similar in both groups, with the exception of a higher frequency of diabetes and peripheral vascular disease as well as smaller diameter stenoses in the DPCI group (Table 1). Time to DPCI was 4.9 ± 3 days after diagnostic catheterization. Before the angioplasty, a more frequent use of unfractionated heparin (86% versus 51%; p p p = 0.02) was observed in the group of DPCI in comparison to IPCI. During PCI, all patients received unfractionated heparin. The use of abciximab (39% versus 49%; p = NS) and stent implantation (69% versus 75%; p = NS) was similar in both groups (Table 2). A higher frequency of angiographic events related to the presence of coronary thrombus was seen in patients undergoing IPCI (27% versus 4%; p = 0.03). They included coronary embolism (7% for IPCI versus 0% for DPCI; p = NS); no-reflow phenomenon (8% for IPCI versus 0% for DPCI; p = NS) and acute closure (10% for IPCI versus 0% for DPCI; p = NS). Stent thrombosis occurred in 1% of the IPCI group versus 4% of the DPCI group (p = NS). The presence of residual thrombosis identifiable angiographically at the end of the procedure was seen in 17% of cases in the IPCI group in comparison to 0% in the DPCI group (p = 0.03) (Table 3). The rate of in-hospital clinical events, including non-fatal myocardial infarction, bleeding, major bleeding, death and a combined endpoint, was similar in both treatment groups. During the delay period in the DPCI group, no episode of myocardial infarction or death was observed. Recurrent angina was observed in 2 patients (8%) (Table 3). Discussion Angiographically visible coronary thrombus is considered an independent predictor of adverse outcomes during and after PCI. This group of patients is characterized by an increased rate of adverse vascular phenomena during angioplasty, including abrupt closure, distal embolization, no-reflow phenomenon and subacute stent thrombosis.^1–5 In addition, a worse final result and residual thrombus are frequently seen after PCI, contributing to the higher rate of restenosis observed in thrombotic lesions.^14,15 Together with the angiographic complications, an increased incidence of clinical events (including death, non-fatal myocardial infarction and urgent revascularization) has been associated with the angioplastic treatment of thrombus-laden coronary lesions.^6,7 Multiple therapeutic strategies have been applied to overcome the adverse outcomes associated with angioplasty in the presence of thrombus, including mechanical devices and pharmacological measures. Transluminal extraction catheter atherectomy/thrombectomy, the Possis AngioJet, rheolytic thrombectomy, the X-sizer catheter system, covered stents, heparin-coated stents, ultrasound thrombolysis, protective devices, thrombolytic drugs, glycoprotein IIb/IIIa inhibitors, unfractionated and low molecular weight heparins have been used during the percutaneous treatment of this type of lesion with moderate success.^8–10,16 At this time, there is no clearly effective and safe approach for thrombotic lesions. Although not always angiographically visible, coronary thrombus is the anatomic substrate in the majority of cases of acute coronary syndrome (ACS).¹ A higher rate of adverse angiographic and clinical phenomena has been associated with PCI during ACS in comparison to stable coronary artery disease. Previous trials support the concept that delayed PCI in ACS patients is associated with a better outcome. Laskey reported a lower PCI success rate (81% versus 91%) and higher incidence of post-procedural thrombotic vessel occlusion (8.3% versus 1.5%) and coronary embolism (12.4% versus 1.5%) in patients with unstable angina not treated with heparin before the heart catheterization.^12,13 Stabilization of the culprit lesion as a result of interruption of the activated thrombogenic mechanisms and partial resolution as well as organization of the thrombus could explain a lower tendency for acute closure or distal embolization. However, this issue has not been appropriately evaluated in cases with angiographically visible thrombus. In our patients, a significant decrease in the incidence of adverse angiographic events during PCI was observed in those cases treated with delayed angioplasty after the diagnostic catheterization. Acute closure, distal embolization and no-reflow phenomenon were not observed in this group. In contrast, the high frequency of adverse angiographic events in the immediate PCI group is comparable with previously reports.¹² Residual thrombus after angioplasty was significantly more frequent in cases treated with early PCI. The implications of residual thrombus after PCI are not completely understood. Uncontrolled data, however, suggest that enlargement of the thrombus burden after PCI can occur, leading to acute closure, additional clinical events and potentially to a higher restenosis rate.^17,18 Smaller thrombotic masses or evolution in the thrombus structure could explain the benefit of delayed PCI on these phenomena.¹⁹ No differences in clinical outcomes were observed between the two PCI strategies analyzed. However, the value of this observation is limited by the small size of the study population and secondary small statistical power for demonstration of differences between groups. A delayed approach to PCI in the presence of intracoronary thrombus should be weighed against the potential of additional ischemic and bleeding episodes during the waiting period until performing the angioplasty under the effects of intensive anticoagulation. An encouraging 8% rate of recurrent angina, with no myocardial infarction or death, was observed in the delayed PCI group in our study, in contrast to the higher rate of events reported in the literature for thrombotic coronary lesions treated medically. More efficient medical treatment, including the use of glycoprotein IIb/IIIa inhibitors in 36% of cases, could explain this improvement. In addition, a similar frequency of bleeding complications in both groups supports the strategy described. Conclusion. A strategy of delayed PCI after intensive pharmacological treatment for thrombotic coronary lesions is associated with a significant reduction of angiographic complications during the procedure in comparison to immediate PCI. The implementation of this strategy is safe and not associated with more bleeding or increased rates of ischemic complications during the waiting time. No clinical advantage was demonstrated in the analysis of this small population of patients. However, potential clinical benefits could exist, on the basis of the demonstrated reduction in thrombus-related complications. This fact should be investigated in a larger population of patients. Study limitations. This is a non-randomized trial and selection bias to immediate or delayed strategies on the basis of angiographic or clinical characteristics of the patients could have occurred. A comparison of thrombus characteristics was not performed. Differences in the thrombus size, form and mobility can influence the selection of the therapeutic approach and can change the tendency for thrombotic complications. The study population was small and therefore not statistically powered for the demonstration of differences in the clinical complications observed between the groups. Only 49% of the patients in the immediate PCI group were treated with a glycoprotein IIb/IIIa antagonist. This is a relatively low figure for a high-risk population undergoing PCI. Moreover, a strategy of upstream glycoprotein IIb/IIIa antagonist before the diagnostic catheterization was not instituted. Recent reports show that the adverse effects from coronary thrombus during PCI significantly decrease when glycoprotein IIb/IIIa is administered early,^4,8 increasing efficacy and safety of an immediate PCI strategy.