Biomedical subjects

A M Lincoff

Publications and source records attributed to A M Lincoff.

At least 73 records · Page 4Linked to original sources

PubMed1999

Chest pain--a strong predictor of adverse cardiac events following precutaneous intervention (from the Evaluation of Platelet IIb/IIIa Inhibitor for Stenting Trial [EPISENT])].

Postprocedural chest pain remains a common problem, and irrespective of electrocardiographic changes, is associated with a higher incidence of early cardiac events. A return to the catheterization laboratory is unlikely to benefit patients with postprocedural chest pain without electrocardiographic changes with documented irreversible intraprocedural complications, or those with late postprocedural pain.

Abciximab↗

PubMed1999

Attainment and maintenance of platelet inhibition through standard dosing of abciximab in diabetic and nondiabetic patients undergoing percutaneous coronary intervention.

BACKGROUND: Although the effectiveness of abciximab (c7E3 Fab; ReoPro) in large populations of patients undergoing a percutaneous coronary intervention has been consistently proved in clinical trials, it is unknown whether all patients achieve and maintain target inhibition during treatment. Diabetic patients in particular are a subgroup of patients with known underlying platelet abnormalities whose long-term response to abciximab has been shown to vary from that of nondiabetic patients. METHODS AND RESULTS: Forty-nine diabetic and 51 nondiabetic patients who received adjunctive abciximab therapy during percutaneous coronary interventions were evaluated prospectively. The degree of platelet function inhibition was determined immediately after the abciximab bolus, 8 hours after the bolus (during the 12-hour abciximab infusion), and the next morning (13 to 26 hours after the bolus) with the use of a rapid platelet function assay (Accumetrics). After the abciximab bolus, platelet function was inhibited by 95+/-4% (mean+/-SD). By 8 hours, the average percent inhibition had decreased to 88+/-9%, with 13% of patients with <80% inhibition. The next morning (mean 19 hours after the bolus), mean inhibition was 71+/-14%. A difference was not found between diabetics and nondiabetics, nor was any physiological parameter found to be predictive of the response to abciximab. CONCLUSIONS: Although the majority of patients achieve and maintain >/= 80% platelet inhibition during the 12-hour infusion with standard-dose abciximab, there is substantial variability among patients. Diabetic status does not appear to influence this variability.

Abciximab↗

PubMed1999

Complementary clinical benefits of coronary-artery stenting and blockade of platelet glycoprotein IIb/IIIa receptors. Evaluation of Platelet IIb/IIIa Inhibition in Stenting Investigators.

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.

Abciximab↗

PubMed1999

Clinical significance of thrombocytopenia during a non-ST-elevation acute coronary syndrome. The platelet glycoprotein IIb/IIIa in unstable angina: receptor suppression using integrilin therapy (PURSUIT) trial experience.

BACKGROUND: The significance of thrombocytopenia in patients experiencing an acute coronary syndrome (ACS) has not been examined systematically. We evaluated this condition in a large non-ST-elevation ACS clinical trial, with particular interest paid to its correlation with clinical outcomes. METHODS AND RESULTS: Patients presenting without persistent ST elevation during an ACS were randomized to receive a double-blind infusion of the platelet glycoprotein (GP) IIb/IIIa inhibitor eptifibatide or placebo in addition to other standard therapies including heparin and aspirin. The primary end point was death/nonfatal myocardial infarction (MI) at 30 days, whereas bleeding and stroke were the main safety outcomes. Thrombocytopenia (nadir platelet count <100x10(9)/L or <50% of baseline) occurred in 7.0% of enrolled patients. The time to onset was a median of 4 days in both treatment arms. Patients with thrombocytopenia were older, weighed less, were more likely nonwhite, and had more cardiac risk factors. These patients experienced significantly more bleeding events: they were more than twice as likely to experience moderate/severe bleeding after adjustment for confounders. Univariably, ischemic events (stroke, MI, and death) occurred significantly (P<0.001) more frequently in patients with thrombocytopenia; multivariable regression modeling preserved this association with death/nonfatal MI at 30 days. Neither the use of heparin or eptifibatide was found to independently increase thrombocytopenic risk. CONCLUSIONS: Although causality between thrombocytopenia and adverse clinical events could not be established definitively, thrombocytopenia was highly correlated with both bleeding and ischemic events, and the presence of this condition identified a more-at-risk patient population.

Acute Disease↗

PubMed1999

Stroke in patients with acute coronary syndromes: incidence and outcomes in the platelet glycoprotein IIb/IIIa in unstable angina. Receptor suppression using integrilin therapy (PURSUIT) trial. The PURSUIT Investigators.

BACKGROUND: The incidence of stroke in patients with acute coronary syndromes has not been clearly defined because few trials in this patient population have been large enough to provide stable estimates of stroke rates. METHODS AND RESULTS: We studied the 10 948 patients with acute coronary syndromes without persistent ST-segment elevation who were randomly assigned to placebo or the platelet glycoprotein IIb/IIIa receptor inhibitor eptifibatide in the Platelet Glycoprotein IIb/IIIa in Unstable Angina: Receptor Suppression Using Integrilin Therapy (PURSUIT) trial to determine stroke rates, stroke types, clinical outcomes in patients with stroke, and independent baseline clinical predictors for nonhemorrhagic stroke. Stroke occurred in 79 (0.7%) patients, with 66 (0.6%) nonhemorrhagic, 6 intracranial hemorrhages, 3 cerebral infarctions with hemorrhagic conversion, and 4 of uncertain cause. There were no differences in stroke rates between patients who received placebo and those assigned high-dose eptifibatide (odds ratios and 95% confidence intervals 0.82 [0.59, 1.14] and 0.70 [0.49, 0.99], respectively). Of the 79 patients with stroke, 17 (22%) died within 30 days, and another 26 (32%) were disabled by hospital discharge or 30 days, whichever came first. Higher heart rate was the most important baseline clinical predictor of nonhemorrhagic stroke, followed by older age, prior anterior myocardial infarction, prior stroke or transient ischemic attack, and diabetes mellitus. These factors were used to develop a simple scoring nomogram that can predict the risk of nonhemorrhagic stroke. CONCLUSIONS: Stroke was an uncommon event in patients with acute coronary syndromes in the PURSUIT trial. These strokes are, however, associated with substantial morbidity and mortality rates. The majority of strokes were of nonhemorrhagic causes. Eptifibatide was not associated with an increase in intracranial hemorrhage, and no significant effect on nonhemorrhagic stroke was observed. We developed a useful nomogram for assigning baseline nonhemorrhagic stroke risk in this patient population.

Acute Disease↗

PubMed1999

Sustained suppression of ischemic complications of coronary intervention by platelet GP IIb/IIIa blockade with abciximab: one-year outcome in the EPILOG trial. Evaluation in PTCA to Improve Long-term Outcome with abciximab GP IIb/IIIa blockade.

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.

Abciximab↗

PubMed1999

Prior aspirin use predicts worse outcomes in patients with non-ST-elevation acute coronary syndromes. PURSUIT Investigators. Platelet IIb/IIIa in Unstable angina: Receptor Suppression Using Integrilin Therapy.

Aspirin is beneficial in the prevention and treatment of cardiovascular events, but patients who have events while taking aspirin may have worse outcomes than those not on aspirin. We investigated the association between prior aspirin use and clinical outcomes in 9,461 patients with non-ST-elevation acute coronary syndromes enrolled in the Platelet IIb/IIIa in Unstable angina: Receptor Suppression Using Integrilin Therapy (PURSUIT) trial, before and after adjustment for baseline factors. We also examined whether eptifibatide has a differential treatment effect in prior aspirin users. Prior aspirin users were less likely to have an enrollment myocardial infarction (MI) (vs unstable angina) (43.9% vs 48.8%, p = 0.001) but more likely to have death or MI at 30 days (16.1% vs 13.0%, p = 0.001) and at 6 months (19.9% vs 15.9%, p = 0.001). After adjustment, prior aspirin users remained less likely to have an enrollment MI (odds ratio 0.88, 95% confidence interval 0.79 to 0.97) and more likely to have death or MI at 30 days (odds ratio 1.16, 95% confidence interval 1.00 to 1.33) but not at 6 months (odds ratio 1.14, 95% confidence interval 0.98 to 1.33). In a multivariable model, eptifibatide did not have a different treatment effect in prior aspirin users compared with nonusers (p = 0.534). Prior aspirin users had fewer enrollment MIs but worse long-term outcomes than nonusers. We found no evidence for a different treatment effect of eptifibatide in prior aspirin users.

Acute Disease↗

PubMed1999

Rapid platelet-function assay: an automated and quantitative cartridge-based method.

BACKGROUND: The platelet glycoprotein (GP) IIb/IIIa receptor is important in mediating platelet thrombus formation, and the GP IIb/IIIa antagonist abciximab (c7E3 Fab; ReoPro) is effective in preventing thrombotic ischemic cardiovascular complications of unstable angina and percutaneous coronary interventions. Small-molecule antagonists of GP IIb/IIIa based on the Arg-Gly-Asp (RGD) sequence show similar benefit, and some of these agents are orally active. However, there may be significant interindividual variation in response to such antagonists, especially with chronic oral therapy. It will be essential to balance the beneficial antithrombotic effect of these drugs with their potential for causing bleeding. In response to this need, we have developed a rapid platelet-function assay (RPFA), a point-of-care system that provides a quantitative measure of the competence of the GP IIb/IIIa receptor as reflected in the ability of platelets to agglutinate fibrinogen-coated beads. METHODS AND RESULTS: Polystyrene beads were coated with fibrinogen and placed in a cartridge along with a lyophilized peptide that activates the thrombin receptor. Anticoagulated whole blood was added to the cartridge, and then a microprocessor-controlled operation mixed the reagents and detected agglutination between platelets and coated beads. Quantitative digital results were displayed within 3 minutes. Because there is no dilution of the blood, the assay can be used to measure platelet activity in samples that have been treated with GP IIb/IIIa antagonists with high dissociation rates. RPFA results of whole-blood samples treated with different GP IIb/IIIa antagonists correlated well with both conventional turbidimetric platelet aggregation (r2=0.95) and the percentage of free GP IIb/IIIa molecules in the sample (r2=0.96). The mean difference in measurements between RPFA and aggregometry was -4% (+/-4% SD), and the mean difference in measurements between RPFA and free GP IIb/IIIa receptors was -2% (+/-6% SD). CONCLUSIONS: The RPFA provides rapid information on platelet function that mirrors turbidimetric platelet aggregation and reflects GP IIb/IIIa receptor blockade.

Abciximab↗

PubMed1999

Effect of institutional volume and academic status on outcomes of coronary interventions: the IMPACT-II experience.

BACKGROUND: Rates of morbidity and mortality after interventional procedures are reported to be inversely associated with institutional volume. METHODS: This study assessed both procedural volume and academic status at the 82 US centers that participated in the IMPACT-II trial. Interventional volumes at the sites ranged from 90 to 3300 cases per year. Patients were randomly assigned to a platelet glycoprotein IIb/IIIa inhibitor (eptifibatide) or placebo during procedures done by experienced operators. The primary end point was the composite of death, myocardial infarction, nonelective repeat coronary intervention, or nonelective coronary artery bypass surgery at 30 days, or placement of an intracoronary stent for abrupt closure during the initial procedure. RESULTS: Baseline patient characteristics and median length of stay were similar between the academic and nonacademic centers. In univariable analysis, volume as a continuous variable had a nonlinear relation with the incidence of the composite end point, with better outcomes noted at the highest volume institutions. Academic status did not predict outcome. When added to a predictive model that contained the variables unstable angina, weight, prior coronary artery bypass grafting, heart rate, and platelet count, procedural volume continued to be associated with the composite outcome (P =.04). CONCLUSIONS: We conclude that among hospitals participating in this trial, there is a nonlinear relation between annual interventional volume and outcomes. This relation is complex, involving variations in periprocedural infarction rates and additional, undefined institutional differences (other than academic status) that result in differences in procedural outcome.

Academic Medical Centers↗

PubMed1999

Clinical outcomes after detection of elevated cardiac enzymes in patients undergoing percutaneous intervention. IMPACT-II Investigators. Integrilin (eptifibatide) to Minimize Platelet Aggregation and Coronary Thrombosis-II.

OBJECTIVES: We examined the relations of elevated creatine kinase (CK) and its myocardial band isoenzyme (CK-MB) to clinical outcomes after percutaneous coronary intervention (PCI) in patients enrolled in Integrilin (eptifibatide) to Minimize Platelet Aggregation and Coronary Thrombosis-II (trial) (IMPACT-II), a trial of the platelet glycoprotein IIb/IIIa inhibitor eptifibatide. BACKGROUND: Elevation of cardiac enzymes often occurs after PCI, but its clinical implications are uncertain. METHODS: Patients undergoing elective, scheduled PCI for any indication were analyzed. Parallel analyses investigated CK (n=3,535) and CK-MB (n=2,341) levels after PCI (within 4 to 20 h). Clinical outcomes at 30 days and 6 months were stratified by postprocedure CK and CK-MB (multiple of the site's upper normal limit). RESULTS: Overall, 1,779 patients (76%) had no CK-MB elevation; CK-MB levels were elevated to 1 to 3 times the upper normal limit in 323 patients (13.8%), to 3 to 5 times normal in 84 (3.6%), to 5 to 10 times normal in 86 (3.7%), and to >10 times normal in 69 patients (2.9%). Elevated CK-MB was associated with an increased risk of death, reinfarction, or emergency revascularization at 30 days, and of death, reinfarction, or surgical revascularization at 6 months. Elevated total CK to above three times normal was less frequent, but its prognostic significance paralleled that seen for CK-MB. The degree of risk correlated with the rise in CK or CK-MB, even for patients with successful procedures not complicated by abrupt closure. CONCLUSIONS: Elevations in cardiac enzymes, including small increases (between one and three times normal) often not considered an infarction, are associated with an increased risk for short-term adverse clinical outcomes after successful or unsuccessful PCI.

Aged↗

PubMed1999

Comparing physician-specific two-year patient outcomes after coronary angiography: methodologic issues and results.

OBJECTIVES: We sought to evaluate methodologies to compare physician-related long-term patient outcomes appropriately. BACKGROUND: Evaluation of physicians on the basis of short-term patient outcome is becoming widely practiced. These analyses fail to consider the importance of long-term outcome, and methods appropriate to such an analysis are poorly defined. METHODS: All patients undergoing coronary angiography between 1992 and 1994 who received all of their cardiac care at our institution were followed for 27+/-13 months (mean+/-SD). Patients (n = 754) were cared for by one or more of 17 staff physicians. Risk-adjusted models were developed for four candidate clinical end points and cost. Physicians were then evaluated for each outcome measure. RESULTS: Of the clinical end points, death could be modeled most accurately (c-statistic = 0.83). The c-statistics for other end points ranged from 0.63 to 0.70. Physicians with outcomes statistically different (p < 0.05) from other physicians were identified more commonly than would be expected from the play of chance (p = 0.005). However, improvement in the c-statistics by the addition of physician identifiers was very modest. Physician's evaluations by the four measures of clinical outcome were variably correlated (r = .00 to .85). Graphic display of clinical and cost results for each physician did identify certain physicians who might be judged to provide more cost-effective care than others. CONCLUSIONS: Although comparisons of groups of physicians on the basis of long-term patient outcomes may have merit, individual physician-to-physician comparisons will be more difficult, owing to 1) multiple physicians contributing care to individual patients; 2) the poor predictive capacity of models other than that for survival; and 3) the modest apparent impact of differences in physician providers on long-term patient outcome. With these caveats in mind, modeling to compare patient outcomes of individual physicians with homogeneous patient populations or to identify gross outliers (good or bad) may be practicable in some patient-care systems, but may be inappropriate in others.

Aged↗

PubMed1999

Is all unstable angina the same? insights from the Coronary Angioplasty Versus Excisional Atherectomy Trial (CAVEAT-I). The CAVEAT-Investigators.

BACKGROUND: Certain characteristics of unstable angina have been associated with worse clinical outcomes after percutaneous revascularization procedures. METHODS AND RESULTS: We compared outcomes of patients with (n = 690) and those without (n = 320) unstable angina in the Coronary Angioplasty Versus Excisional Atherectomy Trial (CAVEAT-I) by unstable angina subgroup: rest chest pain, postinfarction chest pain, chest pain with ischemic electrocardiographic changes, chest pain with recent acceleration, and no chest pain. Regression models were constructed to predict in-hospital and 6-month composite end point death, infarction, bypass surgery, percutaneous revascularization, and abrupt closure (in-hospital) or restenosis (6 months) for each subgroup. Only chest pain with electrocardiographic changes predicted the composite in-hospital outcome (24% vs 17% with no chest pain, P =.0374.) This subgroup also had a greater acute gain, more late loss, and more restenosis than patients in the other subgroups. Rest chest pain carried a higher incidence of the composite 6-month outcome (39.9% vs 29% with no chest pain, P =.0472). For all unstable angina categories, atherectomy was associated with worse overall outcomes than angioplasty. CONCLUSIONS: Patients with unstable angina have more complications of percutaneous revascularization than patients without unstable angina, but event rates vary by anginal subgroup. The clinical presentation may help to identify unstable angina patients at particularly high risk for adverse outcomes.

Angina, Unstable↗

PubMed1999

Clinical risk factors for ischemic complications after percutaneous coronary interventions: results from the EPIC trial. The EPIC Investigators.

BACKGROUND: Most analyses of complications after percutaneous coronary intervention have been limited to angiographic predictors of abrupt closure. We sought to determine the relation between baseline clinical and angiographic characteristics and clinical ischemic events and whether treatment with the platelet glycoprotein IIb/IIIa receptor antagonist c7E3 reduced ischemic events differentially in patients with distinct lesion morphologic characteristics. In the EPIC trial, a bolus and infusion of c7E3 decreased the 30-day incidence of death, myocardial infarction, and need for revascularization by 35% in 2099 high-risk patients. METHODS: We used logistic regression modeling to determine the relations between these patients' baseline clinical and angiographic characteristics and the composite primary end point. We also constructed multivariable models with interaction terms to assess treatment effect on prespecified, core laboratory-assessed, coronary morphologic characteristics. RESULTS: The most important predictors of a poor outcome were low weight (chi-square = 10.5, P =.001) and preprocedural percent stenosis (chi-square = 15.0, P <.001). History of hypertension, nonwhite race, and peripheral vascular disease were also associated with an increased risk, as were all measures of lesion complexity except calcification and presence of a side branch. The treatment benefit with abciximab was significantly greater with less complex than with more complex lesion morphologic characteristics. CONCLUSIONS: Future risk models should include these baseline characteristics to define the risk for ischemic complications in individual patients, and treatment with abciximab should not be predicated on lesion morphologic findings alone.

Abciximab↗

PubMed1998

Reduction in complications of angioplasty with abciximab occurs largely independently of baseline lesion morphology. EPIC and EPILOG Investigators. Evaluation of 7E3 for the Prevention of Ischemic Complications. Evaluation of PTCA To Improve Long-term Outcome with abciximab GPIIb/IIIa Receptor Blockade.

OBJECTIVES: We investigated the hypothesis that abciximab might lead to a differential effect among patients with different lesion morphologies; hence, its cost/benefit ratio would be optimized if it were used selectively on the basis of baseline angiographic findings. BACKGROUND: Major complications of coronary angioplasty occur in 4% to 9% of patients. In the Evaluation of 7E3 for the Prevention of Ischemic Complications (EPIC) and Evaluation of PTCA To Improve Long-term Outcome with abciximab GPIIb/IIIa Receptor Blockade (EPILOG) trials, abciximab decreased the ischemic complications after intervention by 35% to 56%. However, the cost of this agent is appreciable, and there remain concerns about the safety of its readministration. METHODS: There were 1,362 patients in EPIC and 2,792 patients in EPILOG randomized to either bolus plus an infusion of abciximab or placebo, administered with aspirin and heparin at the time of the coronary intervention. Data from these studies were combined, and a differential effect of abciximab in relation to baseline lesion morphology on 30-day risk of death, myocardial infarction or urgent intervention was investigated using the Breslow Day test for statistical interaction. RESULTS: Abciximab consistently reduced the relative risk of complications across all lesion morphologies studied, with the possible exception of patients treated with degenerated saphenous vein grafts (risk with placebo 16.3% vs. risk with abciximab 18.6%, Breslow Day test for interaction, p=0.08). However, the absolute reduction of risk was somewhat greater in patients with more complex B2 or C lesions (7.6% and 5.8%, respectively) than in patients with morphologically simpler A or B1 lesions (3.7% and 3.2%, respectively). CONCLUSIONS: The reduction of early adverse ischemic events associated with angioplasty by abciximab occurs largely independent of pretreatment morphology.

Abciximab↗

PubMed1998

Reduction in the need for unplanned stenting with the use of platelet glycoprotein IIb/IIIa blockade in percutaneous coronary intervention.

Data from the 5 large randomized, double-blind, placebo-controlled trials that used glycoprotein IIb/IIIa inhibitors during percutaneous transluminal coronary angioplasty were pooled for a total of 10,691 patients. We found that the use of glycoprotein IIb/IIIa inhibitors in percutaneous coronary interventions significantly decreases the need for unplanned stenting for abrupt closure.

Angioplasty, Balloon, Coronary↗

PubMed1998

Trials of platelet glycoprotein IIb/IIIa receptor antagonists during percutaneous coronary revascularization.

Selective inhibition of the platelet glycoprotein (GP) IIb/ IIIa surface receptor is a potent mechanism to inhibit platelet aggregation and thrombus formation. Over 15,000 patients have been enrolled in pivotal trials of GP IIb/IIIa receptor blockade with the parenteral inhibitors abciximab, eptifibatide, and tirofiban during coronary intervention, unequivocally establishing the clinical efficacy of this class of therapy in this setting. Reductions of up to 50-60% in the risk of important clinical endpoints have been achieved with these agents, a treatment effect that extends to all components of the composite clinical endpoints (death, myocardial infarction, and emergency revascularization). Inhibition of ischemic events by GP IIb/IIIa blockade is achieved early and almost invariably maintained without attenuation over long-term follow-up, although an influence of these agents on the risk of restenosis has not been consistently observed. All patients undergoing intervention appear to benefit from this class of therapy, irrespective of their risk profile or indication for revascularization, and clinical benefit is independent of the device or modality (stent, balloon, atherectomy) used. Patients undergoing coronary revascularization for acute ischemic syndromes such as unstable angina may derive exceptional treatment effect. Excessive bleeding risk associated with these agents may be markedly diminished without loss of efficacy by reduction in conjunctive heparin dosing.

Abciximab↗

PubMed1998

Platelet glycoprotein IIb/IIIa receptor blockade with abciximab reduces ischemic complications in patients undergoing directional coronary atherectomy. EPILOG Investigators. Evaluation of PTCA to Improve Long-term Outcome by c7E3 GP IIb/IIIa Receptor Blockade.

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.

Abciximab↗

PubMed1998

Diabetes mellitus, glycoprotein IIb/IIIa blockade, and heparin: evidence for a complex interaction in a multicenter trial. EPILOG Investigators.

BACKGROUND: After angioplasty, major complications and ischemic events occur more frequently in diabetic than nondiabetic patients. To determine whether treatment with abciximab is effective in reducing these events in diabetics, we analyzed characteristics and outcomes of diabetic patients enrolled in a large multicenter study (EPILOG). METHODS AND RESULTS: Of 2792 patients enrolled, 638 (23%) were diabetic. Diabetic patients were older, shorter, and heavier; more likely to be female and have three-vessel disease, prior coronary artery bypass graft surgery, a history of hypertension, or a recent myocardial infarction; and less likely to be current smokers than their nondiabetic counterparts. During hospitalization, death, myocardial infarction, or urgent revascularization occurred in 7.1% of diabetics and 7.5% of nondiabetics. By 6 months, the composite of death and myocardial infarction had occurred in 8.8% of diabetic patients and 7.4% of nondiabetics, whereas death, myocardial infarction, or revascularization had occurred in 27.2% and 22.6%, respectively. Abciximab treatment reduced death or myocardial infarction among diabetic and nondiabetic patients (hazard ratios, 0.28 [95% confidence interval (CI), 0.13 to 0.57] and 0.47 [95% CI, 0.33 to 0.70] at 30 days for diabetics and nondiabetics, respectively, and 0.36 [95% CI, 0.21 to 0.61] and 0.60 [95% CI, 0.44 to 0.82] at 6 months for diabetics and nondiabetics, respectively). Abciximab reduced target vessel revascularization among nondiabetic patients (hazard ratio, 0.78 [95% CI, 0.63 to 0.96]) but not among diabetics (hazard ratio, 1.4 [95% CI, 0.94 to 2.08]). When standard- and low-dose heparin adjuncts were compared, diabetics receiving abciximab with standard-dose heparin had marginally greater reductions in the composite of death and myocardial infarction and in target vessel revascularization than diabetics assigned to abciximab with low-dose heparin. CONCLUSIONS: Abciximab treatment in diabetic patients led to a reduction in the composite of death and myocardial infarction, which was at least as great as that seen in nondiabetic patients. However, target vessel revascularization was reduced in nondiabetic but not diabetic patients. This effect may be associated in part with lower doses of heparin. These differences may be related to differences in the platelet and coagulation systems between diabetics and nondiabetics, the greater extent of coronary artery disease in diabetics, or patient selection and management factors.

Abciximab↗