Ronald S. Gottlieb

Bleeding Complications With the Chimeric Antibody to Platelet Glycoprotein IIb/IIIa Integrin in Patients Undergoing Percutaneous Coronary Intervention

BACKGROUND The potential for novel antiplatelet and antithrombin agents to contribute to periprocedural bleeding complications of percutaneous coronary revascularization is poorly defined. In the Evaluation of c7E3 Fab in Preventing Ischemic Complications of High-Risk Angioplasty (EPIC) trial, the periprocedural use of aspirin, heparin, and a chimeric antibody to the platelet glycoprotein IIb/IIIa integrin c7E3 Fab in 2099 patients significantly reduced postprocedural ischemic complications and 6-month clinical restenosis but was associated with increased procedural bleeding complications. We review these complications and describe clinical and procedural variables associated with increased bleeding complications in the EPIC trial. METHODS AND RESULTS Patients with high-risk clinical or lesion morphological characteristics were randomized to receive placebo bolus plus placebo infusion, c7E3 Fab bolus plus placebo infusion, or c7E3 Fab bolus plus c7E3 Fab infusion. Patients received periprocedural aspirin and intravenous heparin continued for a minimum of 12 hours after the procedure. Outcomes reflecting bleeding complications were measured: transfusions, decreased hemoglobin, and an index including both parameters. Major bleeding complications unrelated to bypass surgery occurred in 3.3%, 8.6%, and 10.6%, and blood product transfusions were used in 7.5%, 14.0%, and 16.8% of patients treated with placebo, bolus c7E3 Fab, and bolus plus infusion c7E3 Fab, respectively (both P < .001). Most major bleeding complications occurred at the femoral access site, regardless of treatment. Intracranial hemorrhage (0.3%) and death (0.09%) attributable to major bleeding complications were rare. Multivariable regression analyses identified several variables significantly and independently related to major bleeding complications or greater blood loss, including greater age, female sex, lower weight, c7E3 Fab therapy, and duration and complexity of the index procedure. Major bleeding complications and blood loss in patients receiving bolus plus infusion were not significantly greater than in those receiving bolus alone (P = .38 and P = .14, respectively). CONCLUSIONS Bleeding complications unrelated to bypass surgery were two to three times more frequent in patients receiving c7E3 Fab than in those receiving placebo, but most were transient and well tolerated. Risk-factor analysis and modification of concomitant antithrombotic and antiplatelet treatment strategies may aid in reducing bleeding complications and enhancing clinical benefit in patients receiving c7E3 Fab during percutaneous coronary revascularization.

A multicenter, randomized trial of coronary angioplasty versus directional atherectomy for patients with saphenous vein bypass graft lesions

BACKGROUND Directional coronary atherectomy and percutaneous transluminal coronary angioplasty have both been used in symptomatic patients with coronary saphenous vein bypass graft stenoses. The relative merits of plaque excision and removal versus balloon dilatation remain uncertain. We compared outcomes after directional coronary atherectomy or angioplasty in patients with de novo bypass graft stenoses. METHODS AND RESULTS Fifty-four North American and European sites randomized 305 patients with de novo vein graft lesions to atherectomy (n = 149) or angioplasty (n = 156). Quantitative coronary angiography at a core laboratory assessed initial and 6-month results. Initial angiographic success was greater with atherectomy (89.2% versus 79.0%), as was initial luminal gain (1.45 versus 1.12 mm, P < .001). Distal embolization was increased with atherectomy (P = .012), and a trend was shown toward more non-Q-wave myocardial infarction (P = .09). Although the 6-month net minimum luminal diameter gain was 0.68 mm for atherectomy and 0.50 mm for angioplasty, the restenosis rates were similar, 45.6% for atherectomy and 50.5% for angioplasty (P = .491). At 6 months, there was a trend toward decreased repeated target-vessel interventions for atherectomy (P = .092); in addition, 13.2% of patients treated with atherectomy versus 22.4% of the angioplasty patients (P = .041) required repeated percutaneous intervention of the initial target lesion. CONCLUSIONS Atherectomy of de novo vein graft lesions was associated with improved initial angiographic success and luminal diameter but also with increased distal embolization. There was no difference in 6-month restenosis rates, although primary atherectomy patients tended to require fewer target-vessel revascularization procedures.

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.

Directional atherectomy versus balloon angioplasty for coronary ostial and nonostial left anterior descending coronary artery lesions: Results from a randomized multicenter trial

OBJECTIVES We hypothesized that atherectomy would be superior to balloon angioplasty for ostial and nonostial left anterior descending coronary artery lesions. BACKGROUND Balloon angioplasty of ostial coronary artery lesions has been associated with a lower procedural success rate and a higher rate of complications and of restenosis than angioplasty of nonostial stenoses. Directional coronary atherectomy has been proposed as an alternative therapy for ostial lesions. METHODS In the Coronary Angioplasty Versus Excisional Atherectomy Trial (CAVEAT-I), 1,012 patients were randomized to undergo either procedure; 563 patients had proximal left anterior descending coronary artery lesions, of which 74 were ostial. We compared balloon angioplasty with directional atherectomy for early and 6-month results for ostial as well as nonostial proximal left anterior descending coronary artery lesions. RESULTS Directional atherectomy led to an initially higher gain in minimal lumen diameter for ostial lesions (1.13 vs. 0.56 mm, respectively, p < 0.001) but a higher rate of adjudicated non-Q wave myocardial infarction (24% vs. 13%, respectively, p < 0.001) than balloon angioplasty and no improvement in restenosis rates (48% vs. 46%, respectively). In the nonostial proximal left anterior descending coronary artery lesions, angiographic restenosis was reduced (51% vs. 66%, p = 0.012), but this was also associated with a higher rate of periprocedural myocardial infarction (8% vs. 2%, p = 0.008 by site and 24% vs. 8%, p < 0.001 by adjudication) and no difference in the need for subsequent coronary artery bypass surgery (7.3% vs. 8.4%, respectively) or repeat percutaneous coronary intervention (24% vs. 26%, respectively). CONCLUSIONS For ostial left anterior descending coronary artery stenoses, both procedures yielded similar rates of initial success and restenosis, but atherectomy was associated with more non-Q wave myocardial infarction. In this trial the predominant angiographic benefit (increased early gain and less angiographic restenosis) of atherectomy for the left anterior descending coronary artery was in proximal nonostial lesions. However, the tradeoffs for this angiographic advantage were more in-hospital myocardial infarctions and no decrease in clinical restenosis.

Abrupt closure: The CAVEAT I experience

Objectives. This study sought to assess the incidence and consequences of abrupt closure in a series of patients undergoing directional coronary atherectomy versus percutaneous coronary angioplasty. Background. Abrupt closure with coronary angioplasty has been associated with adverse outcome. The results from the Coronary Angioplasty Versus Excisional Atherectomy Trial (CAVEAT) I, a randomized trial of coronary angioplasty versus directional coronary atherectomy, were analyzed. Method. This multicenter trial enrolled 1,012 patients from 1991 to 1992. All records from patients with abrupt closure, which was coded as a discrete complication, were reviewed. Results. Abrupt closure occurred in 60 patients (5.9%) and was associated with a significantly longer hospital stay (median 8 vs. 3 days). Severe proximal target vessel tortuosity was more common in patients with abrupt closure (20.3% vs. 11.6%, p = 0.046), as was preexistent coronary artery thrombus (30.5% vs. 18.3%, p = 0.02). Abrupt closure was associated with a marked increase in subsequent complications (myocardial infarction 46.7% vs. 2.1%, emergency bypass surgery 383% vs. 0.32%, death 33% vs. 0%) and occurred more frequently in the directional coronary atherectomy group (8.0% vs. 3.8%, p = 0.005). In the coronary angioplasty group, the occlusion usually occurred at the target lesion (91%), presumably related to the effects of barotrauma. In the directional coronary atherectomy group, the site of the occlusion was the target lesion in only 58% (p = 0.045). The remaining occlusions related to problems with the technique (guide catheter or nose cone trauma), reflecting the fact that directional coronary atherectomy is a more complex procedure. Conclusions. Abrupt closure remains the principal determinant of adverse outcome after percutaneous procedures for the treatment of coronary artery disease. Although abrupt closure is more common with directional atherectomy than angioplasty, the sequelae are similar.

Coronary angiographic assessment of left posterior hemiblock

The ECGs of 1,095 patients with coronary angiographic evidence of significant coronary artery disease (greater than or equal to 50% obstructive lesion in at least one major coronary artery) were reviewed. Five patients had left posterior hemiblock (LPHB), an incidence of 0.5%. Three of five patients also had a right bundle branch block (RBBB). Of the five patients with LPHB, all had significant right coronary artery (RCA) disease (four complete occlusions, one 90% obstructive lesion). All five patients having LPHB also had evidence of critical disease (greater than or equal to 75% obstruction) of at least one of the major branches of the left coronary artery; four of the five had complete occlusion of the left anterior descending coronary artery (LAD). The left circumflex coronary artery (CFx) was critically diseased in three patients. The ECGs of four patients showed evidence of only one myocardial infarction while one patient had evidence of an anterior and an inferior infarction. It is concluded that the presence of LPHB in patients with coronary artery disease is an ominous electrocardiographic finding, and is associated with extensive coronary artery disease.