Benefit of abciximab in patients with refractory unstable angina in relation to serum troponin T levels.

BACKGROUND: In patients with refractory unstable angina, the platelet glycoprotein IIb/IIIa-receptor antibody abciximab reduces the incidence of cardiac events before and during coronary angioplasty. We investigated whether serum troponin T levels identify patients most likely to benefit from therapy with this drug. METHODS: Among 1265 patients with unstable angina who were enrolled in the c7E3 Fab Antiplatelet Therapy in Unstable Refractory Angina (CAPTURE) trial, serum samples drawn at the time of randomization to abciximab or placebo were available from 890 patients; we used these samples for the determination of troponin T and creatine kinase MB levels. Patients with postinfarction angina were not included. RESULTS: Serum troponin T levels at the time of study entry were elevated (above 0.1 ng per milliliter) in 275 patients (30.9 percent). Among patients receiving placebo, the risk of death or nonfatal myocardial infarction was related to troponin T levels. The six-month cumulative event rate was 23.9 percent among patients with elevated troponin T levels, as compared with 7.5 percent among patients without elevated troponin T levels (P<0.001). Among patients treated with abciximab, the respective six-month event rates were 9.5 percent for patients with elevated troponin T levels and 9.4 percent for those without elevated levels. As compared with placebo, the relative risk of death or nonfatal myocardial infarction associated with treatment with abciximab in patients with elevated troponin T levels was 0.32 (95 percent confidence interval, 0.14 to 0.62; P=0.002). The lower event rates in patients receiving abciximab were attributable to a reduction in the rate of myocardial infarction (odds ratio, 0.23; 95 percent confidence interval, 0.12 to 0.49; P<0.001). In patients without elevated troponin T levels, there was no benefit of treatment with respect to the relative risk of death or myocardial infarction at six months (odds ratio, 1.26; 95 percent confidence interval, 0.74 to 2.31; P=0.47). CONCLUSIONS: The serum troponin T level, which is considered to be a surrogate marker for thrombus formation, identifies a high-risk subgroup of patients with refractory unstable angina suitable for coronary angioplasty who will particul

Thrombolysis with tissue plasminogen activator in acute myocardial infarction: no additional benefit from immediate percutaneous coronary angioplasty

A randomised trial of 367 patients with acute myocardial infarction was performed to determine whether an invasive strategy combining thrombolysis with recombinant tissue-type plasminogen activator (rTPA), heparin, and acetylsalicylic acid, and immediate percutaneous transluminal coronary angioplasty (PTCA) would be superior to a noninvasive strategy with the same medical treatment but without immediate angiography and PTCA. Intravenous infusion of 100 mg rTPA was started within 5 h after onset of symptoms (median 156 min). Angiography was performed 6-165 min later in 180 out of 183 patients allocated to the invasive strategy; 184 patients were allocated to the non-invasive strategy. Immediate PTCA reduced the percentage stenosis of the infarc

Link Between the Angiographic Substudy and Mortality Outcomes in Large Randomized Trial of Myocardial Reperfusion

BACKGROUND: The Global Utilization of Streptokinase and TPA for Occluded Coronary Arteries (GUSTO-I) trial was designed to test whether thrombolytic strategies achieving more complete, early, sustained coronary artery patency would lead to further reductions in mortality in patients with acute myocardial infarction. An angiographic substudy within GUSTO-I provided a unique opportunity to examine the relation between mortality and degrees of patency among the regimens. METHODS AND RESULTS: Four thrombolytic strategies were compared in 41,021 patients in GUSTO-I: streptokinase with subcutaneous or intravenous heparin, accelerated tissue plasminogen activator (TPA) with intravenous heparin, and combination streptokinase plus TPA with intravenous heparin. Accelerated TPA was associated with lower 30-day mortality (6.3%) than the other strategies (7.2%, 7.4%, and 7.0%, respectively). Among the 1210 patients in the angiographic substudy randomized to angiography 90 minutes after starting treatment, there was improved patency, particularly Thrombolysis in Myocardial Infarction (TIMI) grade 3 flow, with accelerated TPA over the other regimens (P < .0001). Coronary artery perfusion (TIMI grade 3) at 90 minutes was also a significant predictor of 30-day survival (P < .01). To determine whether differences in mortality among the four strategies matched differences in 90-minute patency, a model was developed for predicting mortality differences in the main trial from the angiographic substudy. The model assumed that any differences in treatment effects on 30-day mortality were mediated through differences in 90-minute patency for the four treatments. The predicted rates were then compared with observed mortality rates of the remaining patients in the main trial for each treatment group. The predicted and observed 30-day mortality rates of the four treatments were streptokinase with subcutan

Safety and preliminary efficacy of one month glycoprotein IIb/IIIa inhibition with lefradafiban in patients with acute coronary syndromes without ST-elevation; a phase II study.

AIMS: Oral glycoprotein IIb/IIIa inhibitors might enhance the early benefit of an intravenous agent and prevent subsequent cardiac events in patients with acute coronary syndromes. We assessed the safety and preliminary efficacy of 1 month treatment with three dose levels of the oral GP IIb/IIIa blocker lefradafiban in patients with unstable angina or myocardial infarction without persistent ST elevation. METHODS: The Fibrinogen Receptor Occupancy STudy (FROST) was designed as a dose-escalation trial with 20, 30 and 45 mg lefradafiban t.i.d. or placebo. Five hundred and thirty-one patients were randomized in a 3:1 ratio to lefradafiban or placebo in a double-blind manner. Efficacy was assessed by the incidence of death, myocardial infarction, coronary revascularization and recurrent angina. Safety was evaluated by the occurrence of bleeding classified according to the TIMI criteria and by measuring clinical laboratory parameters. RESULTS: There was a trend towards a reduction in cardiac events with lefradafiban 30 mg when compared with placebo and lefradafiban 20 mg. The benefit was particularly apparent in patients with a positive (> or = O.1 ng. ml(-1)) troponin I test at baseline and less so in those with a negative test result. In patients receiving lefradafiban, the cardiac event rate decreased with increasing minimal levels of fibrinogen receptor occupancy. There was a dose-dependent increase in the incidence of bleeding: the composite of major or minor bleeding occurred in 1% of placebo patients, 5% of patients receiving lefradafiban 20 mg and in 7% of patients receiving 30 mg, with an excessive risk (15%) in the 45 mg group which resulted in early discontinuation of this dose level. Gingival and arterial or venous puncture site bleedings were most common and accounted for more than 60% of all haemorrhagic events. There was an increased incidence of neutropenia (neutrophils <1. 5 x 10(9)/l) in the lefradafiban groups (5.2% vs 1.5% in the placebo group), which did not result from bone marrow depression but rather from a reversible redistribution of neutrophils by margination or clustering. CONCLUSION: One month's treatment with the oral glycoprotein IIb/IIIa inhibitor lefradafiban in patients with unstable angina and myocardial infarction without persistent ST elevation resulted in a decrease in cardiac events with lefradafiban 30 mg and a dose-dependent increase in haemorrhagic events. The observed favourable trend toward

Patients with acute coronary syndromes without persistent ST elevation undergoing percutaneous coronary intervention benefit most from early intervention with protection by a glycoprotein IIb/IIIa receptor blocker.

BACKGROUND: Many patients with acute coronary syndromes are offered percutaneous coronary intervention. However, the appropriate indications for, and optimal timing of, such procedures are uncertain. We analysed timing of intervention and associated events (death and myocardial infarction) in the PURSUIT trial in which 9461 patients received a platelet glycoprotein IIb/IIIa inhibitor, eptifibatide, or placebo for 72 h. Other treatment was left to the investigators. 2430 patients underwent percutaneous coronary intervention within 30 days. Four groups were distinguished, who underwent percutaneous coronary intervention on day 1; on days 2 or 3; at 4 to 7 days; or between 8 until 30 days, for eptifibatide- and placebo-treated patients. RESULTS: The four groups treated with placebo demonstrated total 30-

Clinical and therapeutic profile of patients presenting with acute coronary syndromes who do not have significant coronary artery disease.The Platelet Glycoprotein IIb/IIIa in Unstable Angina: Receptor Suppression Using Integrilin Therapy (PURSUIT) Trial Investigators

BACKGROUND: A proportion of patients who present with suspected acute coronary syndrome (ACS) are found to have insignificant coronary artery disease (CAD) during coronary angiography, but these patients have not been well characterized. METHODS AND RESULTS: Of the 5767 patients with non-ST-segment elevation ACS who were enrolled in the Platelet Glycoprotein IIb/IIIa in Unstable Angina: Receptor Suppression Using Integrilin (Eptifibatide) Therapy (PURSUIT) trial and who underwent in-hospital angiography, 88% had significant CAD (any stenosis >50%), 6% had mild CAD (any stenosis >0% to </=50%), and 6% had no CAD (no stenosis identified). The frequency of death or nonfatal myocardial infarction at 30 days was reduced with eptifibatide treatment in patients with significant CAD (18.3% versus 15.6% for placebo, P=0.006) but not in those with mild CAD (6.6% versus 5.4%, P=0.62) and with no CAD (3.0% versus 1. 2%, P=0.28). We identified independent baseline predictors of insignificant CAD (mild or no CAD) and used them to develop a simple predictive nomogram of the probability of insignificant CAD for use at hospital presentation. This nomogram was validated in a separate population of patients with non-ST-segment elevation ACS. CONCLUSIONS: Patients with suspected ACS found to have insignificant CAD have a low risk of adverse outcomes, do not appear to benefit from treatment with eptifibatide, and can be predicted with a simple nomogram drawn from baseline characteristics. Because patients with significant CAD appear to have an enhanced benefit from eptifibatide treatment, the predictive nomogram developed can be used to determine indications for glycoprotein IIb/IIIa blockade

Acute coronary thrombolysis with recombinant human tissue-type plasminogen activator: initial patency and influence of maintained infusion on reocclusion rate

An intravenous infusion of 40 mg of recombinant tissue-type plasminogen activator (rt-PA) was given intravenously over 90 minutes to 123 patients with acute myocardial infarction (AMI) of less than 4 hours' duration. A coronary angiogram was recorded at the end of the infusion in 119 patients. Central assessment of the angiograms revealed a patent infarct-related artery in 78 patients (patency rate 66%, 95% confidence limits 57 to 74%). Patients with a patent infarct-related artery at the first angiogram were randomized in a double-blind manner to receive a subsequent 6-hour infusion of either 30 mg of rt-PA or placebo. All patients had received an initial bolus of 5,000 IU of heparin and then 1,000 IU/hour until a second angiogram was recorded 6 to 24 hours after the start of the second perfusion. At central assessment of the second coronary angiogram the reocclusion rate was 2 of 36 patients who received rt-PA at the second infusion and 3 of 37 patients not receiving this drug (or the 2 groups combined 7%, 95% confidence limits 2 to 15%). Three of 60 patients (5%, 95% confidence limits 1 to 14%) with patent arteries on both previous angiograms had a later occ

Thrombolysis with rt-PA in acute myocardial infarction: no additional benefit of immediate PTCA

A randomised trial of 367 patients with acute myocardial infarction was performed to determine whether an invasive strategy combining thrombolysis with recombinant tissue-type plasminogen activator (rTPA), heparin, and acetylsalicylic acid, and immediate percutaneous transluminal coronary angioplasty (PTCA) would be superior to a noninvasive strategy with the same medical treatment but without immediate angiography and PTCA. Intravenous infusion of 100 mg rTPA was started within 5 h after onset of symptoms (median 156 min). Angiography was performed 6-165 min later in 180 out of 183 patients allocated to the invasive strategy; 184 patients were allocated to the non-invasive strategy. Immediate PTCA reduced the percentage stenosis of the infarct-related segment, but this was offset by a high rate of transient (16%) and sustained (7%) reocclusion during the procedure and recurrent ischaemia during the first 24 h (17%). The clinical course was more favourable after non-invasive therapy, with a lower incidence of recurrent ischaemia within 24 h (3%), bleeding complications, hypotension, and ventricular fibrillation. Mortality at 14 days was lower in patients allocated to non-invasive treatment (3%) than in the group allocated to invasive treatment (7%). No difference between the treatment groups was observed in infarct size estimated from myocardial release of alpha-hydroxybutyrate dehydrogenase or in left ventricular ejection fraction after 10-22 days. Since immediate PTCA does not provide additional benefit there seems to be no need for immediate angiography and PTCA in patients with acute myocardial infarction treated with rTPA