Eric A. Cohen

Comparison of two platelet glycoprotein IIb/IIIa inhibitors, tirofiban and abciximab, for the prevention of ischemic events with percutaneous coronary revascularization.

BACKGROUND In the setting of percutaneous coronary revascularization, agents in the class known as platelet glycoprotein IIb/IIIa inhibitors have significantly reduced the incidence of death or nonfatal myocardial infarction at 30 days. We assessed whether there are differences in safety or efficacy between two such inhibitors, tirofiban and abciximab. METHODS Using a double-blind, double-dummy design at 149 hospitals in 18 countries, we randomly assigned patients to receive either tirofiban or abciximab before undergoing percutaneous coronary revascularization with the intent to perform stenting. The primary end point was a composite of death, nonfatal myocardial infarction, or urgent target-vessel revascularization at 30 days. The trial was designed and statistically powered to demonstrate the noninferiority of tirofiban as compared with abciximab. RESULTS The primary end point occurred more frequently among the 2398 patients in the tirofiban group than among the 2411 patients in the abciximab group (7.6 percent vs. 6.0 percent; hazard ratio, 1.26; one-sided 95 percent confidence interval of 1.51, demonstrating lack of equivalence, and two-sided 95 percent confidence interval of 1.01 to 1.57, demonstrating the superiority of abciximab over tirofiban; P=0.038). The magnitude and the direction of the effect were similar for each component of the composite end point (hazard ratio for death, 1.21; hazard ratio for myocardial infarction, 1.27; and hazard ratio for urgent target-vessel revascularization, 1.26), and the difference in the incidence of myocardial infarction between the tirofiban group and the abciximab group was significant (6.9 percent and 5.4 percent, respectively; P=0.04). The relative benefit of abciximab was consistent regardless of age, sex, the presence or absence of diabetes, or the presence or absence of pretreatment with clopidogrel. There were no significant differences in the rates of major bleeding complications or transfusions, but tirofiban was associated with a lower rate of minor bleeding episodes and thrombocytopenia. CONCLUSIONS Although the trial was intended to assess the noninferiority of tirofiban as compared with abciximab, the findings demonstrated that tirofiban offered less protection from major ischemic events than did abciximab.

Myonecrosis After Revascularization Procedures

The detection of elevated cardiac enzyme levels and the occurrence of electrocardiographic (ECG) abnormalities after revascularization procedures have been the subject of recent controversy. This report represents an effort to achieve a consensus among a group of researchers with data on this subject. Creatine kinase (CK) or CK-MB isoenzyme (CK-MB) elevations occur in 5% to 30% of patients after a percutaneous intervention and commonly during coronary artery bypass graft surgery (CABG). Although Q wave formation is rare, other ECG changes are common. The rate of detection is highly dependent on the intensity of enzyme and ECG measurement. Because most events occur without the development of a Q wave, the ECG will not definitively diagnose them; even the ECG criteria for Q wave formation signifying an important clinical event have been variable. At least 10 studies evaluating > 10,000 patients undergoing percutaneous intervention have demonstrated that elevation of CK or CK-MB is associated not only with a higher mortality, but also with a higher risk of subsequent cardiac events and higher cost. Efforts to identify a specific cutoff value below which the prognosis is not impaired have not been successful. Rather, the risk of adverse outcomes increases with any elevation of CK or CK-MB and increases further in proportion to the level of intervention. This information complements similar previous data on CABG. Obtaining preprocedural and postprocedural ECGs and measurement of serial cardiac enzymes after revascularization are recommended. Patients with enzyme levels elevated more than threefold above the upper limit of normal or with ECG changes diagnostic for Q wave myocardial infarction (MI) should be treated as patients with an MI. Patients with more modest elevations should be observed carefully. Clinical trials should ensure systematic evaluation for myocardial necrosis, with attention paid to multivariable analysis of risk factors for poor long-term outcome, to determine the extent to which enzyme elevation is an independent risk factor after considering clinical history, coronary anatomy, left ventricular function and clinical evidence of ischemia. In addition, tracking of enzyme levels in clinical trials is needed to determine whether interventions that reduce periprocedural enzyme elevation also improve mortality.

Routine Early Angioplasty after Fibrinolysis for Acute Myocardial Infarction

BACKGROUND Patients with a myocardial infarction with ST-segment elevation who present to hospitals that do not have the capability of performing percutaneous coronary intervention (PCI) often cannot undergo timely primary PCI and therefore receive fibrinolysis. The role and optimal timing of routine PCI after fibrinolysis have not been established. METHODS We randomly assigned 1059 high-risk patients who had a myocardial infarction with ST-segment elevation and who were receiving fibrinolytic therapy at centers that did not have the capability of performing PCI to either standard treatment (including rescue PCI, if required, or delayed angiography) or a strategy of immediate transfer to another hospital and PCI within 6 hours after fibrinolysis. All patients received aspirin, tenecteplase, and heparin or enoxaparin; concomitant clopidogrel was recommended. The primary end point was the composite of death, reinfarction, recurrent ischemia, new or worsening congestive heart failure, or cardiogenic shock within 30 days. RESULTS Cardiac catheterization was performed in 88.7% of the patients assigned to standard treatment a median of 32.5 hours after randomization and in 98.5% of the patients assigned to routine early PCI a median of 2.8 hours after randomization. At 30 days, the primary end point occurred in 11.0% of the patients who were assigned to routine early PCI and in 17.2% of the patients assigned to standard treatment (relative risk with early PCI, 0.64; 95% confidence interval, 0.47 to 0.87; P=0.004). There were no significant differences between the groups in the incidence of major bleeding. CONCLUSIONS Among high-risk patients who had a myocardial infarction with ST-segment elevation and who were treated with fibrinolysis, transfer for PCI within 6 hours after fibrinolysis was associated with significantly fewer ischemic complications than was standard treatment. (ClinicalTrials.gov number, NCT00164190.)

Complementary clinical benefits of coronary-artery stenting and blockade of platelet glycoprotein IIb/IIIa receptors

BACKGROUND Inhibition of the platelet glycoprotein IIb/IIIa receptor with the monoclonal-antibody fragment abciximab reduces the acute ischemic complications associated with percutaneous coronary revascularization, whereas coronary-stent implantation reduces restenosis. We conducted a trial to determine the efficacy of abciximab and stent implantation in improving long-term outcome. METHODS A total of 2399 patients were randomly assigned to stent implantation and placebo, stent implantation and abciximab, or balloon angioplasty and abciximab. The patients were followed for six months. RESULTS At six months, the incidence of the composite end point of death or myocardial infarction was 11.4 percent in the group that received a stent and placebo, as compared with 5.6 percent in the group that received a stent and abciximab (hazard ratio, 0.47; 95 percent confidence interval, 0.33 to 0.68; P<0.001) and 7.8 percent in the group assigned to balloon angioplasty and abciximab (hazard ratio, 0.67; 95 percent confidence interval, 0.49 to 0.92; P=0.01). The hazard ratio for stenting plus abciximab as compared with angioplasty plus abciximab was 0.70 (95 percent confidence interval, 0.48 to 1.04; P=0.07). The rate of repeated revascularization of the target vessel was 10.6 percent in the stent-plus-placebo group, as compared with 8.7 percent in the stent-plus-abciximab group (hazard ratio, 0.82; 95 percent confidence interval, 0.59 to 1.13; P=0.22) and 15.4 percent in the angioplasty-plus-abciximab group (hazard ratio, 1.49; 95 percent confidence interval, 1.13 to 1.97; P=0.005). The hazard ratio for stenting plus abciximab as compared with angioplasty plus abciximab was 0.55 (95 percent confidence interval, 0.41 to 0.74; P<0.001). Among patients with diabetes, the combination of abciximab and stenting was associated with a lower rate of repeated target-vessel revascularization (8.1 percent) than was stenting and placebo (16.6 percent, P=0.02) or angioplasty and abciximab (18.4 percent, P=0.008). CONCLUSIONS For coronary revascularization, abciximab and stent implantation confer complementary long-term clinical benefits.

Outcomes at 1 year and economic implications of platelet glycoprotein IIb/IIIa blockade in patients undergoing coronary stenting: results from a multicentre randomised trial

BACKGROUND We assessed in a randomised trial the long-term outcomes for potent adjunctive antiplatelet therapy given at the time of coronary stenting. METHODS In 63 hospitals in the USA and Canada, 2399 patients were randomly assigned stenting with abciximab, stenting with placebo, or balloon angioplasty with abciximab. Standard adjunctive therapy with aspirin, ticlopidine, and heparin was used. The major outcomes of death and myocardial infarction were assessed at 1-year follow-up by intention to treat. We also investigated the 1-year cost-effectiveness of combined stenting and abciximab therapy. FINDINGS At 1-year follow-up, eight (1.0%) of 794 patients in the stent plus abciximab group had died, compared with 19 (2.4%) of 809 in the stent plus placebo group (hazard ratio 0.43 [95% CI 0.19-0.97], p=0.037). The combined endpoint of death or large myocardial infarction occurred in 42 (5.3%) and 89 (11.0%), respectively (0.46 [0.32-0.67], p<0.001). By multivariate modelling, the factors independently associated with improved survival were assignment to stenting with abciximab (p=0.027) and greater preprocedural stenosis (p=0.002); those associated with worse survival were age greater than 70 years (p<0.001), previous heart failure (p=0.001), diabetes treated with insulin (p=0.02), and postprocedural occlusion (p<0.001). Relative to stenting plus placebo and balloon angioplasty plus abciximab, the incremental 1-year costs of stenting plus abciximab were US

A Comparison of Directional Atherectomy with Balloon Angioplasty for Lesions of the Left Anterior Descending Coronary Artery

581 and

Rimonabant for prevention of cardiovascular events (CRESCENDO) : a randomised, multicentre, placebo-controlled trial.

932. The corresponding cost-effectiveness ratios were US

Randomized Trial of Percutaneous Coronary Intervention for Subacute Infarct-Related Coronary Artery Occlusion to Achieve Long-Term Patency and Improve Ventricular Function. The Total Occlusion Study of Canada (TOSCA)-2 Trial

5291 and

Impact of Patient and Target-Vessel Characteristics on Arterial and Venous Bypass Graft Patency Insight From a Randomized Trial

6213 per added life-year. INTERPRETATION Coronary stenting with abciximab, compared with stenting alone or balloon angioplasty with abciximab, is associated with improved survival and is an economically attractive therapy by conventional standards.

Multi-year follow-up of abciximab therapy in three randomized, placebo-controlled trials of percutaneous coronary revascularization.

BACKGROUND Restenosis is a major limitation of coronary angioplasty. Directional coronary atherectomy was developed with the expectation that it would provide better results than angioplasty, including a lower rate of restenosis. We undertook a randomized, multicenter trial to compare the rates of restenosis for atherectomy and angioplasty when used to treat lesions of the proximal left anterior descending coronary artery. METHODS Of 274 patients referred for first-time, non-surgical revascularization of lesions of the proximal left anterior descending coronary artery, 138 were randomly assigned to undergo atherectomy and 136 to undergo angioplasty; 257 of 265 eligible patients (97 percent) underwent follow-up angiography at a median of 5.9 months. Computer-assisted quantitative measurements of luminal dimensions were determined from the angiograms obtained before and immediately after the procedure and at follow-up. The primary end point of restenosis was defined as stenosis of more than 50 percent of the vessels diameter at follow-up. RESULTS Quantitative analysis showed that the procedural success rate was higher in patients who underwent atherectomy than in those who had angioplasty (94 percent vs. 88 percent, P = 0.061); there was no significant difference in the frequency of major in-hospital complications (5 percent vs. 6 percent). At follow-up, the rate of restenosis was 46 percent after atherectomy and 43 percent after angioplasty (P = 0.71). Despite a larger initial gain in the minimal luminal diameter with atherectomy (mean [+/- SD], 1.45 +/- 0.47 vs. 1.16 +/- 0.44 mm; P < 0.001), there was a larger late loss (0.79 +/- 0.61 vs. 0.47 +/- 0.64 mm; P < 0.001), resulting in a similar minimal luminal diameter in the two groups at follow-up (1.55 +/- 0.60 vs. 1.61 +/- 0.68, P = 0.44). The clinical outcomes at six months were not significantly different between the two groups. CONCLUSIONS The role of atherectomy in percutaneous coronary revascularization remains to be fully defined. However, as compared with angioplasty, atherectomy did not result in better late angiographic or clinical outcomes in patients with lesions of the proximal left anterior descending coronary artery.