Need For Urgent Revascularization Research Articles

Addition of Clopidogrel to Aspirin and Fibrinolytic Therapy for Myocardial Infarction with ST-Segment Elevation

A substantial proportion of patients receiving fibrinolytic therapy for myocardial infarction with ST-segment elevation have inadequate reperfusion or reocclusion of the infarct-related artery, leading to an increased risk of complications and death. We enrolled 3491 patients, 18 to 75 years of age, who presented within 12 hours after the onset of an ST-elevation myocardial infarction and randomly assigned them to receive clopidogrel (300-mg loading dose, followed by 75 mg once daily) or placebo. Patients received a fibrinolytic agent, aspirin, and when appropriate, heparin (dispensed according to body weight) and were scheduled to undergo angiography 48 to 192 hours after the start of study medication. The primary efficacy end point was a composite of an occluded infarct-related artery (defined by a Thrombolysis in Myocardial Infarction flow grade of 0 or 1) on angiography or death or recurrent myocardial infarction before angiography. The rates of the primary efficacy end point were 21.7 percent in the placebo group and 15.0 percent in the clopidogrel group, representing an absolute reduction of 6.7 percentage points in the rate and a 36 percent reduction in the odds of the end point with clopidogrel therapy (95 percent confidence interval, 24 to 47 percent; P<0.001). By 30 days, clopidogrel therapy reduced the odds of the composite end point of death from cardiovascular causes, recurrent myocardial infarction, or recurrent ischemia leading to the need for urgent revascularization by 20 percent (from 14.1 to 11.6 percent, P=0.03). The rates of major bleeding and intracranial hemorrhage were similar in the two groups. In patients 75 years of age or younger who have myocardial infarction with ST-segment elevation and who receive aspirin and a standard fibrinolytic regimen, the addition of clopidogrel improves the patency rate of the infarct-related artery and reduces ischemic complications.

A prospective, nonrandomized, open-labeled pilot study investigating the use of magnesium in patients undergoing nonacute percutaneous coronary intervention with stent implantation.

Magnesium has recently been shown to inhibit acute stent thrombosis in animal models. This study tested the feasibility of magnesium administration in patients undergoing nonacute percutaneous coronary intervention with stent implantation. Twenty-one patients undergoing nonemergent percutaneous coronary intervention were enrolled and received intravenous magnesium sulfate (2-g bolus over 20 minutes prepercutaneous coronary intervention, followed by 14 g over 12 hours infusion). safety outcomes--hypotension, bradycardia, bleeding complications and heart block within first 24 hours; angiographic outcomes--acute thrombotic occlusion and need for platelet glycoprotein IIb/IIIa inhibitor bailout; and clinical outcomes--death, myocardial infarction, recurrent ischemia, and need for urgent revascularization at 48 hours and 30 days. No significant effects on heart rate or blood pressure, major bleeding complication, or new electrocardiographic changes were observed. Angiographic thrombus was visualized in two cases, and coronary artery dissection in one case poststent deployment. None of these cases required the use of glycoprotein inhibitors for bailout. Death, myocardial infarction, recurrent ischemia, and need for urgent revascularization were not observed. The serum magnesium level increased from 2.1 +/- 0.3 mg/dL at baseline to 3.5 +/- 0.8 mg/dL at the end of the infusion (P <.0001). Platelet activation was significantly inhibited at the end of the magnesium sulfate infusion. Intravenous magnesium sulfate has been demonstrated as a feasible and safe agent in patients undergoing nonacute percutaneous coronary intervention with stent implantation. A randomized clinical trial comparing magnesium with glycoprotein inhibitors during percutaneous coronary intervention is warranted.

Reperfusion therapy for acute myocardial infarction with fibrinolytic therapy or combination reduced fibrinolytic therapy and platelet glycoprotein IIb/IIIa inhibition: the GUSTO V randomised trial

Plasminogen activator therapy for acute myocardial infarction is limited by lack of achievement of early, complete, and sustained reperfusion in a substantial proportion of patients. Many phase II trials have supported the potential of combined fibrinolytic therapy and platelet glycoprotein IIb/IIIa inhibition for improving reperfusion. We did a randomised, open-label trial to compare the effect of reteplase alone with reteplase plus abciximab in patients with acute myocardial infarction. 16588 patients in the first 6 h of evolving ST-segment elevation myocardial infarction were randomly assigned standard-dose reteplase (n=8260) or half-dose reteplase and full-dose abciximab (n=8328). The primary endpoint was 30-day mortality, and secondary endpoints included various complications of myocardial infarction. Analysis was by intention to treat. At 30 days, 488 (5.9%) of patients in the reteplase group had died, compared with 468 (5.6%) in the combined reteplase and abciximab group (odds ratio 0.95 [95% CI 0.83-1.08], p=0.43). There were fewer deaths or non-fatal reinfarctions with the combination than with reteplase alone, and there was less need for urgent revascularisation and fewer major non-fatal ischaemic complications of acute myocardial infarction. On the other hand, there were more non-intracranial bleeding complications in the combination group. The rates of intracranial haemorrhage and non-fatal disabling stroke were similar. Although combined reteplase and abciximab was not superior to standard reteplase, the 0.3% absolute (5% relative) decrease in 30-day mortality fulfilled the criteria of non-inferiority. Combination therapy led to a consistent reduction in key secondary complications of myocardial infarction including reinfarction, which was partly counterbalanced by increased non-intracranial bleeding complications.

Increased mortality with oral platelet glycoprotein IIb/IIIa antagonists: a meta-analysis of phase III multicenter randomized trials.

Numerous clinical trials have established the benefits of intravenous glycoprotein IIb/IIIa inhibition in the management of coronary artery disease. In contrast, the recent large-scale, placebo-controlled, randomized trials of the oral glycoprotein IIb/IIIa antagonists have failed to provide commensurate reductions in late composite ischemic end points despite potent inhibition of platelet aggregation. The ORs for death, myocardial infarction, urgent revascularization, and major bleeding from the 4 large-scale, placebo-controlled, randomized trials with oral glycoprotein IIb/IIIa inhibitors were calculated and combined. Stratification by low-dose or high-dose therapy and the use of concurrent aspirin was also undertaken. In 33 326 patients followed for >30 days, a consistent and statistically significant increase in mortality was observed with oral glycoprotein IIb/IIIa therapy (OR, 1.37; 95% CI, 1.13 to 1.66; P:=0.001). This effect was evident regardless of aspirin coadministration and treatment with either low-dose or high-dose therapy. Although a reduction in urgent revascularization was observed with oral glycoprotein IIb/IIIa inhibition, pooled analysis favored an increase in myocardial infarction that did not demonstrate statistical significance. Although we found a highly significant excess in mortality consistent across 4 trials with 3 different oral glycoprotein IIb/IIIa inhibitor agents, this was associated with a reduction in the need for urgent revascularization and no increase in myocardial infarction. These findings suggest the potential for a direct toxic effect with these agents and argue against a prothrombotic mechanism. Further investigation to elucidate the cause of this increased fatality risk is warranted.

Part 7: The Era of Reperfusion

Part 7: The Era of Reperfusion

Randomised placebo-controlled and balloon-angioplasty-controlled trial to assess safety of coronary stenting with use of platelet glycoprotein-IIb/IIIa blockade

Summary Background Coronary stenting with use of heparin, aspirin, and ticlopidine for thromboprophylaxis is performed in more than 500 000 patients per year worldwide. We did a randomised controlled trial to assess the role of platelet glycoprotein-IIb/IIIa blockade for use in elective stenting. Methods At 63 hospitals in the USA and Canada, 2399 patients with ischaemic heart disease and suitable coronary-artery lesions were randomly assigned stenting plus placebo (n=809), stenting plus abciximab, a IIb/IIIa inhibitor (n=794), or balloon angioplasty plus abciximab (n=796). The primary endpoint was a combination of death, myocardial infarction, or need for urgent revascularisation in the first 30 days. All patients received heparin, aspirin, and standard pharmacological therapy. Findings The primary endpoint occurred in 87 (10·8%) of 809 patients in the stent plus placebo group, 42 (5·3%) of 794 in the stent plus abciximab group (hazard ratio 0·48 [95% CI 0·33–0.69] p Interpretation Platelet glycoprotein-IIb/IIIa blockade with abciximab substantially improves the safety of coronary-stenting procedures. Balloon angioplasty with abciximab is safer than stenting without abciximab.

The use of dobutamine stress echocardiography for the determination of myocardial viability.

Determining the presence of viable myocardium has prognostic and therapeutic implications in the treatment of ischemic heart disease. Dobutamine stress echocardiography (DSE) is one possible technique to help identify both hibernating and stunned but viable myocardium. Low-dose dobutamine infusion has an increased inotropic effect, while higher doses cause both inotropic and chronotropic effects. Thus, at lower doses cardiac augmentation occurs, and at higher doses regions of ischemia may be produced in the presence of significant coronary artery disease. This is manifested echocardiographically as changes in segmental wall motion. In theory, therefore, areas of viable myocardium should show improved wall motion at low doses, and areas of irreversible myocardial damage will remain akinetic. Five studies have investigated DSE for determining viability in the setting of acute myocardial infarction, thus looking for stunned but viable myocardium. DSE was shown to compare favorably with positron emission tomography and was highly sensitive and specific for predicting functional myocardial recovery. Five additional studies examined DSE for determining the presence of hibernating myocardium. The sensitivity and specificity of DSE were found to range from 71 to 92% and from 73 to 93%, respectively. The benefits of DSE include lower cost, convenience to both patient and physician, additional ancillary information, and determination of the possible need for urgent revascularization. Limitations of DSE include occasional technical difficulty in obtaining and interpreting studies and the need for larger volumes of viable myocardium to detect changes predictive of functional recovery. Larger trials are currently underway to confirm DSE as a reliable technique for determining myocardial viability.

Usefulness of esmolol in unstable angina pectoris

Esmolol is a new cardioselective β blocker with unique pharmacokinetic properties resulting in a half-life of only 9 minutes. The present multicenter, randomized, placebo-controlled study examined the hemodynamic and antiischemic effects of this compound given as an adjunctive to conventional medical therapy in 113 patients with unstable angina. Fifty-nine patients received esmolol and 54 received matching placebo infusions. Esmolol was titrated in a step-wise manner at dosages of 2 to 24 mg/min until a 25% reduction in the double product was achieved; thereafter, esmolol was continuously infused for up to 72 hours. Esmolol caused a significant and persistent decline in heart rate and blood pressure throughout the entire study period. Clinical events, such as development of acute myocardial infarction or the need for urgent revascularization, occurred in 3 esmolol compared with 9 placebo patients (p = 0.06). There was also a trend toward reduction of silent ischemia as judged by Holter monitoring (mean [± standard deviation] duration/patient/24 hours, 21 ± 81 minutes in the esmolol and 35 ± 128 minutes in the placebo groups). Esmolol-related adverse effects were mostly cardiovascular in origin and could be managed promptly by downward dose titration or cessation of drug infusion. Thus, esmolol appears to be a safe and effective drug for patients with unstable angina because it permits a large degree of flexibility in adapting the desired level of β blockade to the patient's changing clinical presentation.