Thomas A. Kelly

Sustained Suppression of Ischemic Complications of Coronary Intervention by Platelet GP IIb/IIIa Blockade With Abciximab One-Year Outcome in the EPILOG Trial

BACKGROUND Blockade of the platelet glycoprotein IIb/IIIa receptor with the monoclonal antibody fragment abciximab was shown in a placebo-controlled randomized trial to reduce the incidence of acute ischemic complications within 30 days among a broad spectrum of patients undergoing percutaneous coronary revascularization. The durability of clinical benefit in this setting has not been established. METHODS AND RESULTS A total of 2792 patients enrolled in the Evaluation in PTCA to Improve Long-term Outcome with abciximab GP IIb/IIIa blockade (EPILOG) trial were followed with maintenance of double-blinding for 1 year. Patients had been assigned at the time of their index coronary interventional procedure to receive placebo with standard-dose, weight-adjusted heparin (100 U/kg initial bolus), abciximab with standard-dose, weight-adjusted heparin, or abciximab with low-dose, weight-adjusted heparin (70 U/kg initial bolus). The primary outcome was the composite of death, myocardial infarction, or urgent repeat revascularization by 30 days; this composite end point and its individual components were also assessed at 6 months and 1 year. Rates of any repeat revascularization (urgent or elective), target vessel revascularization, and a composite of death, myocardial infarction, or any repeat revascularization were also reported. Follow-up at 1 year was 99% complete for survival status and 97% complete for other end points. By 1 year, the incidence of the primary composite end point was 16.1% in the placebo group, 9.6% in the abciximab with low-dose heparin group (P<0.001), and 9.5% in the abciximab with standard-dose heparin group (P<0.001). Each of the components of this composite end point was reduced to a similar extent. Nonurgent or target vessel repeat revascularization rates were not significantly decreased by abciximab therapy. Mortality rates over 1 year increased with increasing levels of periprocedural creatine kinase MB fraction elevation. CONCLUSIONS Acute reductions in ischemic events after percutaneous coronary intervention by abciximab are sustained over follow-up to at least 1 year. Early periprocedural myocardial infarctions suppressed by this therapy are associated with long-term mortality rates.

Outcomes of Direct Coronary Angioplasty for Acute Myocardial Infarction in Candidates and Non-Candidates for Thrombolytic Therapy

Coronary angioplasty without prior thrombolytic therapy was performed in 383 patients with acute myocardial infarction (AMI). Patients were divided into 2 groups depending on whether they were candidates or non-candidates for thrombolytic therapy. Patients were not considered thrombolytic candidates if they: (1) presented in cardiogenic shock, (2) were greater than or equal to 75 years of age, (3) had had coronary artery bypass surgery or, (4) had a reperfusion time of greater than 6 hours. Thrombolytic and nonthrombolytic candidates had similar rates of reperfusion (92 vs 88%), nonfatal reinfarction (6.0 vs 5.9%) and recurrent myocardial ischemia (1.8 vs 0%). Thrombolytic candidates had a lower mortality rate (3.9 vs 24%, p less than 0.0001) and a lower incidence of bleeding (4.6 vs 10.9%, p less than 0.05). Improvement in left ventricular ejection fraction at follow-up angiography was 4.4% in thrombolytic and 10.5% in nonthrombolytic candidates (p less than 0.002). Ejection fraction improved most in patients with anterior wall AMI (7.7% in thrombolytic candidates, 15.1% in nonthrombolytic candidates) and in patients with reperfusion times greater than 6 hours (14.2%). These outcomes suggest that direct coronary angioplasty is a viable alternative method of reperfusion in patients with AMI who are candidates for thrombolytic therapy. Nonthrombolytic candidates are a high-risk group of patients. Direct coronary angioplasty may be beneficial in certain subgroups, especially for patients in cardiogenic shock and for patients presenting greater than 6 hours after the onset of chest pain with evidence of ongoing ischemia.

Importance of infarct-related artery patency for recovery of left ventricular function and late survival after primary angioplasty for acute myocardial infarction

OBJECTIVES The purpose of this study was to evaluate the importance of late infarct-related artery patency for recovery of left ventricular function and late survival after primary angio-plasty for acute myocardial infarction. BACKGROUND Infarct-related artery patency is thought to improve late survival by its effect on preservation of left ventricular function. Patency may also enhance late survival by preventing left ventricular dilation and reducing arrhythmias, independent of myocardial salvage. However, most studies have not shown patency to be an independent predictor of survival when late left ventricular function is taken into account. METHODS We followed up 576 hospital survivors of acute myocardial infarction treated with primary angioplasty for 5.3 years. Ejection fraction and infarct-related artery patency were determined at follow-up catheterization at 6 months. Predictors of late cardiac survival were determined using Cox regression models. RESULTS Patients with patent arteries had more improvement and a better late ejection fraction than patients with occluded arteries (56.3% vs. 47.9%, p = 0.001). In patients with acute ejection fraction < 45%, late survival was better in those with patent versus occluded arteries (89% vs. 44%, p = 0.003), but patency was not a significant predictor after improvement in ejection fraction was taken into account. In patients with a large anterior infarction, patency was a significant independent predictor of late survival. CONCLUSIONS Infarct-related artery patency is important for recovery of left ventricular function, and in patients with acute ejection fraction < 45%, patency is important for late survival. Our data are consistent with the hypothesis that the survival benefit is due primarily to the effect of patency on recovery of left ventricular function. In patients with a large anterior infarction, patency appears to provide an additional late survival benefit independent of myocardial salvage. These observations support the need for additional clinical trials of late reperfusion in patients with a large anterior infarction.

Abciximab and bleeding during coronary surgery: results from the EPILOG and EPISTENT trials ∗

BACKGROUND Abciximab during percutaneous coronary revascularization reduces ischemic complications, but concern exists regarding increased bleeding risk should emergency coronary surgical procedures be required. METHODS Outcomes were assessed among 85 patients who required coronary artery bypass grafting operations after coronary intervention in two randomized placebo-controlled trials of abciximab. Comparisons were made between patients in the pooled placebo and abciximab groups. RESULTS The incidence of coronary surgical procedures was 2.17% and 1.28% among patients randomized to placebo and abciximab, respectively (p = 0.021). Platelet transfusions were administered to 32% and 52% of patients in the placebo and abciximab groups, respectively (p = 0.059). Rates of major blood loss were 79% and 88% in the placebo and abciximab groups, respectively (p = 0.27); transfusions of packed red blood cells or whole blood were administered in 74% and 80% of patients, respectively (p = 0.53). Surgical reexploration for bleeding was required in 3% and 12% of patients, respectively. Death and myocardial infarction tended to occur less frequently among patients who had received abciximab. CONCLUSIONS Urgent coronary artery bypass grafting operations can be performed without an incremental increase in major hemorrhagic risk among patients on abciximab therapy.

Timing and mechanism of death determined clinically after primary angioplasty for acute myocardial infarction.

We reviewed the timing and mechanism of death in 1,184 consecutive patients with acute myocardial infarction (AMI) treated with primary angioplasty from 1984 to 1995. Of 98 deaths, 48 (49%) occurred early on day 0 or 1. The mechanisms of death were pump failure in 60 patients (61%), reinfarction in 7 patients (7.1%), left ventricular rupture in 5 patients (5.1%), arrhythmia in 3 patients (3.1%), other cardiac causes in 5 patients (5.1%), stroke in 6 patients (6.1%), anoxic encephalopathy in 7 patients (7.1%), and procedure-related deaths in 5 patients (5.1%). The strongest predictors of mortality were cardiogenic shock and unsuccessful reperfusion. Our data indicate that mortality after primary angioplasty, like thrombolytic therapy, is highest in the early hours and is usually due to pump failure. In contrast to thrombolytic therapy, the incidence of death from myocardial rupture and bleeding complications is low. Future treatment strategies will need to focus on the large number of patients with early death due to pump failure, especially patients with cardiogenic shock.

Platelet glycoprotein IIb/IIIa receptor blockade with abciximab reduces ischemic complications in patients undergoing directional coronary atherectomy

We determined the efficacy of abciximab, a platelet glycoprotein IIb/IIIa receptor antagonist, combined with low-dose weight-adjusted heparin in reducing ischemic complications in patients undergoing directional coronary atherectomy (DCA). The Evaluation of IIb/IIIa platelet receptor antagonist 7E3 in Preventing Ischemic Complications (EPIC) trial demonstrated a reduction in the incidence of non-Q-wave myocardial infarction in DCA patients who were treated with abciximab bolus and infusion plus heparin. This benefit, however, was associated with increased bleeding complications. Of the 2,792 patients who had coronary intervention in the Evaluation of PTCA to Improve Long-term Outcome by c7E3 GP IIb/IIIa receptor blockade (EPILOG) trial, 144 (5%) underwent DCA. Patients were randomly assigned to 3 treatment groups: placebo with standard-dose, weight-adjusted heparin; abciximab with low-dose weight-adjusted heparin; or abciximab with standard-dose weight-adjusted heparin. Study end points included 30-day and 6-month composite incidence of death, myocardial infarction, or revascularization. Compared with those undergoing percutaneous transluminal coronary angioplasty (PTCA), DCA patients had a higher rate of myocardial infarction (11.1 % vs 4.9%, p = 0.001) and predominantly non-Q-wave myocardial infarction (9.7% vs 4.4%, p = 0.004). Abciximab was associated with a 57% lower combined rate of death, myocardial infarction, or urgent revascularization within 30 days following DCA (20% placebo vs 8.7% abciximab with low-dose heparin) without excess risk of bleeding complications. A combined analysis of data from the EPIC and EPILOG trials demonstrates a reduction in the rate of death or myocardial infarction (19.9% vs 8.4%, p = 0.008) at 30 days that was sustained for up to 6 months in the abciximab-treated patients. These findings support the premise that non-Q-wave myocardial infarction in DCA patients are platelet mediated.

Importance of a patent infarct-related artery for hospital and late survival after direct coronary angioplasty for acute myocardial infarction

The importance of a patent infarct-related artery (IRA) for hospital and late survival was examined in 383 patients with acute myocardial infarction treated with direct coronary angioplasty. At hospital discharge, 317 of 348 patients (91%) had a patent IRA and mean follow-up left ventricular (LV) ejection fraction (EF) was 58%. Cardiac survival after hospital discharge at 1, 3 and 6 years was 99, 95 and 90%. Patency of the IRA was the most important determinant of hospital mortality: patent versus occluded IRA, 5 vs 39% mortality, p less than 0.001. Follow-up LVEF was the most important determinant of late cardiac mortality: follow-up LVEF greater than or equal to 45 versus less than 45%, 2 versus 24% mortality, p less than 0.001. Patency of the IRA was not a significant predictor of late cardiac mortality in the group as a whole: patent versus occluded IRA, 4.7 versus 6.5% mortality, p = 0.67. In the subgroup of patients with depressed initial LVEF less than 45%, patency was a significant predictor of late cardiac mortality: patent versus occluded IRA, 9.2 versus 40% mortality, p = 0.03. Patients with a patent IRA had better recovery of LV function than patients with an occluded IRA (follow-up LVEF 58.5 versus 47.6%, p less than 0.001). When late cardiac mortality was adjusted for differences in follow-up LVEF, patency was no longer a significant predictor of late mortality. Our results indicate patency of the IRA is the most important determinant of hospital survival, and LV function (measured after recovery) is the most important determinant of late cardiac survival.(ABSTRACT TRUNCATED AT 250 WORDS)

Benefit of late coronary reperfusion in patients with acute myocardial infarction and persistent ischemic chest pain

The benefit of thrombolytic therapy given late after the onset of acute myocardial infarction (AMI) has been controversial because of low reperfusion rates and limited myocardial salvage. Persistent chest pain has been used as a criteria for late intervention, but there is little documentation to validate this practice. Clinical outcomes and myocardial salvage were evaluated in 74 patients with AMI and persistent chest pain who underwent late reperfusion (> 6 hours) with direct coronary angioplasty, and these were compared with outcomes in 460 patients with early reperfusion (< or = 6 hours). Patients with late reperfusion had a high infarct artery patency rate (96%), a low hospital mortality rate (5.4%), and a low incidence of reinfarction (1.4%) and recurrent ischemia that were similar to patients with early reperfusion. Patients with late reperfusion had surprisingly good recovery of left ventricular function with improvement in ejection fraction from 50% to 60% at follow-up angiography. Patients with late reperfusion had a greater incidence of collateral flow (45% vs 22%, p < 0.001) and a lower value of peak creatine kinase (1,357 vs 2,057 U/liter, p < 0.001) than patients with early reperfusion. This study emphasizes the importance of persistent chest pain as a marker of continued myocardial viability in patients who present late after AMI. These data suggest that the probable mechanism of continued viability is preserved flow to the infarct zone. Patients with AMI and persistent chest pain may benefit from reperfusion therapy beyond 6 to 12 hours.