Eptifibatide-induced thrombocytopenia

Glycoprotein (GP) IIb/IIIa inhibitors reduce major adverse coronary events in patients with acute coronary syndromes undergoing percutaneous coronary interventions (PCI). Unlike the other GPIIb/IIIa inhibitors, eptifibatide is rarely associated with thrombocytopenia with only a few cases reported in the medical literature. Here we report a case of a 34-year-old man presenting with a non ST-elevation myocardial infarction (NSTEMI) who underwent primary PCI with stenting and developed stent thrombosis 5 days after the procedure. He underwent repeat PCI with readministration of eptifibatide and subsequently developed profound thrombocytopenia within 4 h. This report adds another case of eptifibatide associated thrombocytopenia to the literature and reinforces the importance of platelet count monitoring after therapy with this agent.     

An audit of the use and complications of glycoprotein IIb/IIIa inhibitors in percutaneous coronary intervention against national UK standards

Coronary thrombosis is a pivotal event in the pathogenesis of acute coronary syndromes and ischemic complications resulting from coronary intervention. Activation of the platelet glycoprotein (GP) IIb/IIIa receptor is the final common pathway leading to platelet aggregation, coronary thrombus formation, and myocardial ischemia. Inhibitors of platelet GP IIb/IIIa are potent agents to prevent progression to myocardial infarction and death.

We prospectively surveyed the indications, frequency, and complications associated with the use of GP IIb/IIIa inhibitors in percutaneous coronary intervention in a tertiary center setting.

A total of 170 patients underwent screening over a period of 6 weeks. One hundred four (61%) had coronary intervention, out of which eight (8%) had failed intervention. Glycoprotein IIb/IIIa inhibitors were used in 57 (55%) patients; 47 (45%) did not have any agent periprocedure. Eptifibatide was the most commonly used agent in 35 (33%), followed by abciximab in 19 (18%) and tirofiban in 3 (3%).

Out of 57 patients in whom GP IIb/IIIa agents were used, 22 (38%) had visible intracoronary thrombus, 22 (38%) had diffuse disease, 8 (14%) had complex intervention, and 5 (9%) had diabetes.

The overall incidence of complications was not increased by the use of GP IIb/IIIa inhibitors; serious complications were rare with the use of GP IIb/IIIa agents; no stroke, thrombocytopenia, gastrointestinal bleed, or death was recorded. The overall use in emergency settings was not associated with increased complications. Bradycardia and vomiting were more common with abciximab group, whereas puncture site pain was commoner in eptifibatide group.     

Eptifibatide-induced thrombocytopenia and thrombosis

Glycoprotein (GP) IIb/IIIa inhibitors have been shown to reduce morbidity and mortality in patients with acute coronary syndromes undergoing percutaneous coronary interventions (PCI). With their widespread use, there is a growing body of literature describing adverse outcomes, including severe thrombocytopenia. Here we report a case of a 75-year-old man who presented with an ST-elevation myocardial infarction, underwent primary PCI and stenting, and subsequently developed profound thrombocytopenia and thrombosis after eptifibatide administration. This report adds to the literature regarding eptifibatide-induced thrombocytopenia and also raises the possibility of a new syndrome of eptifibatide-induced thrombosis. A case is made to examine available databases for thrombosis after administration of eptifibatide and other GPIIb/IIIa inhibitors.     

Clinical trials of glycoprotein IIb/IIIa inhibitors

Glycoprotein (GP) IIb/IIIa inhibitors were developed to block platelet aggregation and potentially to abolish thrombus formation. Clinical trials have demonstrated that GP IIb/IIIa inhibitors are more potent antithrombotic agents than aspirin and heparin alone. GP IIb/IIIa inhibitors reduce short- and long-term complications of percutaneous revascularization. These agents also are effective as adjuncts to various treatment strategies for the management of patients with unstable angina (UA) or non-Q-wave myocardial infarction (NQMI). Furthermore, recent clinical trials with a small number of patients suggest that GP IIb/IIIa inhibitors in combination with low-dose fibrinolytics are safe and effective for the treatment of ST segment elevation myocardial infarction. The clinical trials of GP IIb/IIIa inhibitors summarized here examined different patient populations managed under different strategies. Moreover, these agents have different indications for clinical use and varying safety profiles.     

Does platelet glycoprotein IIb/IIIa receptor antibody improve in-hospital outcome of coronary stenting in high-risk thrombus containing lesions?

Coronary stenting in acute coronary syndromes probably increases the risk of acute stent thrombosis. Recently, use of platelet glycoprotein IIb/IIIa receptor antibody has been shown to improve percutaneous transluminal coronary angioplasty (PTCA) outcomes in high risk lesions. The purpose of this analysis was to determine safety and efficacy of platelet glycoprotein IIb/IIIa receptor antibody administration in patients receiving coronary stents in high-risk lesions. Between October 1995 and November 1996, 282 patients with acute ischemic syndromes received coronary stents at our center: 73 had thrombus containing lesions—40 presented with AMI and 33 with unstable angina and make up the study population. The mean age of these patients was 61 ± 13 years, 56 were male, 35 had a history of myocardial infarctions (MI), 21 had prior coronary artery bypass graft (CABG), and 21 had prior PTCA. Coronary stenting was used for suboptimal result in 46 patients (63%), threatened closure in 25 patients (34%), and acute closure in 2 patients (3%). Platelet glycoprotein IIb/IIIa receptor antibody was administered during the procedure in 74% and after the procedure in 26%. A total of 115 stents were deployed (Gianturco-Roubin 80, Palmaz-Schatz 29, and Wallstent 6) in 24 LAD, 21 RCA, 15 LCX, and 13 saphenous vein graft (SVG) lesions. Procedural success was 100%. The mean diameter stenosis before and after intervention was 60% ± 31% and 4% ± 14%, respectively. In-hospital events included 1 Q-wave MI (1.4%), 13 non–Q-wave MI (18%), and 1 death (1.4%). There was no subacute stent thrombosis, emergency CABG, or repeat PTCA. Significant in-hospital bleeding complications were noted in seven (10%) patients, with five patients (6.8%) requiring blood transfusions. In this series of patients with acute ischemic syndromes associated with angiographic evidence of thrombus, combined use of platelet glycoprotein IIb/IIIa receptor antibody and stenting resulted in a very low incidence of subacute stent thrombosis and emergency target lesion revascularization. However, bleeding complications were higher than expected with conventional antiplatelet therapy following routine stenting. Cathet. Cardiovasc. Intervent. 46:415–420, 1999. © 1999 Wiley-Liss, Inc.     

A Review of Clinical Trials with Eptifibatide in Cardiology

Glycoprotein (GP) IIb/IIIa receptor antagonists inhibit the binding of ligands to activated platelet GP IIb/IIIa receptors and, therefore, prevent the formation of platelet thrombi. Additional antithrombin therapy should be given in connection with GP IIb/IIIa administration. Eptifibatide is a small heptapeptide, which is highly selective and rapidly dissociates from its receptor after cessation of therapy. In clinical trials (IMPACT‐II and ESPRIT) concomitant administration of eptifibatide to patients undergoing percutaneous coronary intervention (PCI) reduced thrombotic complications. In the PURSUIT trial, in patients with non‐ST‐elevation acute coronary syndromes, eptifibatide, compared to placebo, significantly reduced the primary endpoint of death and nonfatal myocardial infarction at 30 days. In patients with STEMI eptifibatide has been studied as an adjunct to fibrinolysis and primary PCI; it improved epicardial flow and tissue reperfusion. Current studies are evaluating eptifibatide as upstream therapy in high‐risk patients with NSTE‐ACS, in the EARLY‐ACS and in comparison with abciximab in patients with primary PCI in the EVA‐AMI trial.     

Periprocedural creatine kinase-MB elevations: long-term impact and clinical implications

Since the introduction of percutaneous transluminal coronary angioplasty (PTCA), percutaneous intervention with balloon catheters, stents, and atherectomy devices has become a widely accepted practice. The persistent complication of non-Q-wave myocardial infarction (MI), as evidenced by increased cardiac enzyme levels after intervention, has aroused only moderate concern because its incidence was perceived to be small and not clinically relevant. With more systematic assessments of cardiac enzymes--specifically, creatine kinase (CK) and its MB isoform--evidence has begun to clarify both the incidence and the prognosis of periprocedural non-Q-wave MI: It appears to occur nearly three times more often than is clinically evident across all device types (8 to 9% of all interventions) and is directly and continuously associated with adverse outcomes, including late death. Although directional and rotational atherectomy improve angiographic outcome compared with PTCA, periprocedural infarction occurs at least twice as often with these newer technologies; the incidence associated with stent placement is comparable to and possibly higher than that of PTCA. Factors that may cause elevated CK-MB levels include distal embolization, side branch occlusion, thrombus, and coronary spasm. Analyses of the major trials of platelet glycoprotein (GP) IIb/IIIa receptor inhibitors, a class of potent antiplatelet agents, show striking effectiveness of these drugs in reducing the incidence of "enzyme-only" or "silent" MI and in improving long-term clinical outcomes. The findings implicate platelet mediation in the occurrence of periprocedural infarction and suggest an important role for antiplatelet therapy, particularly GP IIb/IIIa receptor inhibition, in protecting patients undergoing percutaneous intervention.     

Reduced vascular complications after percutaneous coronary interventions with a nonmechanical suture device: results from the randomized RACE study.

The objective of this study was to evaluate the safety and efficacy of a novel nonmechanical percutaneous suture device, X-Press, after diagnostic catheterization and percutaneous coronary interventions (PCIs) in the setting of glycoprotein IIb/IIIa inhibitor usage. Current percutaneous vascular suture devices remain mechanically complex and expensive and have not been shown to reduce major vascular complications. Using a 2:1 randomization scheme (2:1 ratio, device vs. compression), 393 patients undergoing diagnostic catheterization (n = 133) or PCI (n = 260) were randomized in the prospective Rapid Ambulation After Closure (RACE) study and evaluated for time to ambulation, time to hemostasis, treatment success, and incidence of major vascular complications. Glycoprotein IIb/IIIa inhibitors were used in 52% of PCI patients. There was a significant reduction in the primary efficacy endpoint of median time to ambulation for device compared to control with both diagnostic (2.2 vs. 6.2 hr; P = 0.0001) and PCI patients (4.1 vs. 14.7 hr; P = 0.0001). Device malfunction occurred in 3.1% patients without clinical sequalae. Equivalence in the primary safety endpoint, the incidence of major complications (vascular repair, ultrasound-guided compression, transfusion, or infection) at 14 days, was observed with the X-Press device (1/261; 0.4%) compared to control (3/132; 2.3%; P = 0.11). In PCI patients, half of whom received glycoprotein IIb/IIIa inhibitors, there was a significant reduction in the incidence of vascular complications in patients using the device (0/172; 0%) compared to control (3/88; 3.4%; P = 0.037). In diagnostic catheterization and PCI, a novel nonmechanical suture device reduced the time to ambulation and demonstrated equivalence in major complications compared to conventional compression techniques. The incidence of major complications after PCI was reduced with the device.     

Use of Glycoprotein IIb/IIIa Inhibition Plus Fibrinolysis in Acute Myocardial Infarction

Pharmacological reperfusion therapy for acute myocardial infarction with intravenous fibrinolytic agents improves survival yet fails to achieve early and complete coronary blood flow in nearly half of treated patients. In principle, glycoprotein (GP) IIb/IIIa inhibitors, potent antiplatelet agents, might improve the efficacy and clinical outcomes associated with fibrinolysis. Preclinical research suggests more rapid and effective reperfusion with combined platelet GP IIb/IIIa inhibition and fibrinolysis. Early clinical studies confirm improved early patency and more rapid electrocardiographic resolution, but increased bleeding complications, with the addition of GP IIb/IIIa antagonists to conventional fibrinolysis. Future studies may combine reduced-dose fibrinolytic therapy with GP IIb/IIIa inhibition to optimize efficacy and safety.     

Oral Glycoprotein IIb/IIIa Antagonists: New Insights from the SYMPHONY Trial

Platelet aggregation plays a central role in the pathophysiology of acute coronary syndromes, and the platelet glycoprotein IIb/IIIa receptor has been identified as the critical final mediator of this process. Antagonists of this receptor used parenterally during both acute coronary syndromes and percutaneous coronary interventions reduce the likelihood of subsequent major cardiac complications. However, after the treatment period little further benefit accrues. Based on these observations and that of the significant benefit of aspirin in cardiovascular secondary prevention, oral glycoprotein IIb/IIIa receptor antagonists are being evaluated with the goal of extending the benefit of glycoprotein IIb/IIIa inhibition into chronic secondary prevention. This paper will review the results of the SYMPHONY study of one such oral agent, sibrafiban, and the current state of the oral glycoprotein IIb/IIIa inhibitor field.     

Platelet Function and Myocardial Injury During Percutaneous Coronary Intervention

Background: Several studies have shown that inhibition of the glycoprotein IIb/IIIa receptor can reduce myocardial injury during percutaneous coronary intervention (PCI). The present study was performed to investigate platelet function, using a bedside diagnostic system, to test the hypothesis that patients with activated platelets have an increased risk for myocardial injury during PCI. Such information would be valuable to guide the PCI operator to whom he or she should give a glycoprotein IIb/IIIa inhibitor during and after the procedure. Methods: 155 consecutive patients undergoing PCI were included in the study. 94 of the patients had stable angina pectoris and the remaining patients had unstable angina pectoris or ongoing myocardial infarction. Troponin T levels were measured in serum before PCI and at 6 am the day after PCI by an immunoassay. Platelet function was analyzed in arterial blood before PCI using the platelet function analyzer PFA-100® by Dade Behring. Results: The platelet function analyzer PFA-100® could not discriminate between patients with or without myocardial injury during the procedure but between patients with or without acetyl salicylic acid. Conclusion: The platelet function analyzer PFA-100® cannot be used to guide the PCI operator to whom he or she should give a glycoprotein IIb/IIIa inhibitor but the results indicate that PFA-100® can be used to monitor platelet effects of ASA therapy.     

Adjunctive Antiplatelet Therapy in Acute Myocardial Infarction: The Road to Improved Infarct-Related Artery Patency

A direct relationship exists between infarct artery patency and survival in patients with acute myocardial infarction. Currently available thrombolytic regimens produce 90 minute patency rates on the order of 80%. Preliminary trials suggest that adjunctive anti-platelet therapy with glycoprotein IIb/IIIa inhibitors, in conjunction with thrombolytic therapy, may significantly improve 90 minute infarct related artery patency and thereby survival, in patients with acute myocardial infarction.     

Association of glycoprotein IIb/IIIa inhibitors and long-term survival following administration during percutaneous coronary intervention for acute myocardial infarction

Objectives: We sought to evaluate the impact of GP IIb/IIIa receptor blockers on long-term mortality in patients undergoing PCI for AMI. Background: Glycoprotein (GP) IIb/IIIa inhibitors are potent suppressors of platelet aggregation and when used during percutaneous coronary intervention (PCI) for the treatment of acute myocardial infarction (AMI) may improve short-term clinical outcomes, including survival. However, the impact of GP IIb/IIIa treatment during PCI for AMI on long-term survival is unknown. Methods: Patients undergoing primary or rescue PCI for AMI within 24 hours of symptom onset with or without GP IIb/IIIa inhibitor treatment were identified from a multicenter PCI database. All cause mortality at a mean follow-up of 3 years was the primary end point. Results: Of the 269 patients treated with primary or rescue PCI for AMI, 107 (40%) received a GP IIb/IIIa antagonist. Patients treated with GP inhibitors were more likely to present with or develop heart failure (13% vs. 6.2%, P = 0.052). Left ventricular ejection fraction was reduced in those treated with GP IIb/IIIa antagonists (44% vs. 48%, P = 0.051). The extent of coronary artery disease did not differ between groups. Stent use was 80% in both groups. Procedural success was high and did not differ between groups. In-hospital mortality was low and did not differ between groups. The mortality at a mean follow-up of 3 years was 1.9% among patients treated with a GP IIb/IIIa antagonist and 15% for those who were not treated (log-rank P = 0.0005). Treatment with a GP IIb/IIIa antagonist was independently associated with a significant reduction in the hazard of long-term mortality (Hazard Ratio, 0.159; 95% Confidence Interval, 0.034–0.729; P = 0.018). Conclusions: Treatment of patients undergoing PCI for AMI with GP IIb/IIIa antagonists appears to be associated with a profound reduction in late mortality.     

Complementary effects of thienopyridine pretreatment and platelet glycoprotein IIb/IIIa integrin blockade with eptifibatide in coronary stent intervention; results from the ESPRIT trial.

OBJECTIVES: This analysis sought to investigate the complementary effect of thienopyridine pretreatment and platelet glycoprotein (GP) IIb/IIIa integrin blockade in coronary stent intervention. BACKGROUND: Definitive evidence supporting combined antiplatelet therapy consisting of thienopyridine pretreatment and GP IIb/IIIa receptor blockade in patients undergoing percutaneous coronary intervention (PCI) with stent implantation is limited. METHODS: We retrospectively analyzed clinical outcomes by thienopyridine use in the 2,040 patients randomized to eptifibatide or placebo who underwent PCI in the ESPRIT trial. RESULTS: A total of 901 patients received a loading dose of thienopyridine before PCI (group 1), 123 received thienopyridine pretreatment without a loading dose (group 2), and 1,016 were not treated with thienopyridine before PCI (group 3). The composite incidence of death or myocardial infarction at 30 days was significantly lower in group 1 than in groups 2 and 3 combined (OR, 0.71 [95%CI, 0.52-0.99]; P = 0.0417). A similar trend was seen for the composite of death, myocardial infarction, or urgent target vessel revascularization (unadjusted OR, 0.77 [0.57-1.05]; P = 0.1025). After adjusting for baseline characteristics, these differences were no longer significant. No interactions were identified with eptifibatide assignment for any of the group comparisons. CONCLUSIONS: Pretreatment with a loading dose of thienopyridine lowers the rate of ischemic complications regardless of treatment with a GP IIb/IIIa inhibitor. Conversely, the efficacy of eptifibatide is maintained whether or not a loading dose of a thienopyridine is administered. Optimal outcomes are achieved in patients receiving thienopyridine pretreatment along with platelet GP IIb/IIIa inhibitor therapy.     

Platelet Glycoprotein IIb/IIIa Integrin Blockade in Coronary Artery Disease: Current State of the Art

Platelets have been shown to play an important role in the pathogenesis of atherosclerosis, acute coronary syndromes, and ischemic complications after percutaneous coronary intervention. Fibrinogen binding via platelet surface glycoprotein (GP) IIb/IIIa receptors constitutes the "final pathway" in platelet aggregation leading to thrombus formation. The GP IIb/IIIa receptor inhibitors, a new class of antiplatelet agents that have emerged in recent years, show great promise in reducing complications of coronary angioplasty and acute coronary syndromes. This review will examine the biology of platelet GP IIb/IIIa receptors, the various classes of GP IIb/IIIa receptor antagonists, the results of the latest clinical trials, and their implications in current clinical practice.     

Platelet glycoprotein IIb/IIIa inhibition in acute coronary syndromes. Gradient of benefit related to the revascularization strategy.

AIMS: To assess the efficacy of platelet glycoprotein IIb/IIIa inhibitors in patients with acute coronary syndromes primarily medically managed. METHODS AND RESULTS: We performed a meta-analysis of the randomized clinical trials of platelet glycoprotein IIb/IIIa inhibitor therapy in the medical management of non-ST-elevation acute coronary syndromes. Among 29570 patients, IIb/IIIa integrin blockade was associated with a reduction in death or non-fatal myocardial infarction at 30 days, from 11.5% to 10.7% (odds ratio 0.91,P =0.02). Patients undergoing percutaneous coronary intervention during index hospitalization sustained a greater reduction in ischaemic events (odds ratio 0.82, P=0.01) than patients medically managed (odds ratio 0.95, P=0.27). Among patients undergoing intervention, the benefit was more pronounced if the procedure was performed during glycoprotein IIb/IIIa inhibitor infusion (odds ratio 0.74; P=0.02), than if revascularization was performed after drug discontinuation (odds ratio 0.87,P =0.17). CONCLUSION: This analysis, including the entire large-scale trial experience of intravenous glycoprotein IIb/IIIa inhibitors in patients with acute coronary syndromes primarily medically managed, demonstrates an overall significant, albeit moderate, reduction in 30-day death or myocardial infarction associated with therapy. Although not based on a prospectively defined hypothesis, the findings suggest a gradient of benefit conferred by these agents depending on the revascularization strategy used.     

The Efficacy and Safety of Perioperative Antiplatelet Therapy

Widespread adoption of the antiplatelet agents into everyday clinical practice has revolutionized contemporary care of the cardiovascular patient. Major adverse cardiovascular events including death, myocardial infarction, stroke, and recurrent angina have all been shown to be significantly decreased when these agents are employed in the treatment of coronary atherosclerosis, acute coronary syndromes, myocardial infarction, and in the setting of percutaneous coronary intervention. As a growing number of patients on antiplatelet therapy are undergoing various surgical procedures, the potential risks and benefits these drugs pose perioperatively will become increasingly important. Available data indicate that, when used appropriately, these drugs can be used safely prior to surgery. Efficacy in improving surgical outcomes and in preventing adverse cardiovascular events postoperatively has also been demonstrated. The purpose of this review is to examine the perioperative safety and efficacy of the most widely used antiplatelet agents: aspirin; the thienopyridine clopidogrel; and the glycoprotein (GP) IIb/IIIa inhibitors abciximab, eptifibatide, and tirofiban. This information, coupled with emerging platelet monitoring techniques, may help provide additional assistance to the clinician to manage therapy and guide appropriate timing of both cardiac and noncardiac surgery.     

The Efficacy and Safety of Perioperative Antiplatelet Therapy

Widespread adoption of the antiplatelet agents into everyday clinical practice has revolutionized contemporary care of the cardiovascular patient. Major adverse cardiovascular events including death, myocardial infarction, stroke, and recurrent angina have all been shown to be significantly decreased when these agents are employed in the treatment of coronary atherosclerosis, acute coronary syndromes, myocardial infarction, and in the setting of percutaneous coronary intervention. As a growing number of patients on antiplatelet therapy are undergoing various surgical procedures, the potential risks and benefits these drugs pose perioperatively will become increasingly important. Available data indicate that, when used appropriately, these drugs can be used safely prior to surgery. Efficacy in improving surgical outcomes and in preventing adverse cardiovascular events postoperatively has also been demonstrated. The purpose of this review is to examine the perioperative safety and efficacy of the most widely used antiplatelet agents: aspirin; the thienopyridine clopidogrel; and the glycoprotein (GP) IIb/IIIa inhibitors abciximab, eptifibatide, and tirofiban. This information, coupled with emerging platelet monitoring techniques, may help provide additional assistance to the clinician to manage therapy and guide appropriate timing of both cardiac and noncardiac surgery.     

Point-of-care testing shows clinically relevant variation in the degree of inhibition of platelets by standard-dose abciximab therapy during percutaneous coronary intervention.

Administration of GP IIb/IIIa inhibitors during percutaneous coronary intervention (PCI) has proven clinical benefit, but is administered at a dose allowing for the patients' weight but not other variables. This study of 75 patients evaluated platelet inhibition achieved by standard-dose abciximab therapy during PCI as measured by two point-of-care (POC) instruments, Plateletworks (PW) and whole blood aggregation (WB). Results were related to the decrease of platelet activation produced as well as patients' return of angina within 30 days. Flow cytometric measurement showed abciximab suppressed platelet-monocyte aggregates (P < 0.001) and activated glycoprotein IIb/IIIa (P < 0.001) but not P-selectin. Greater POC-measured inhibition corresponded to less postabciximab expression of platelet-monocyte aggregates (P < 0.01). Patients above the lowest quartile of POC inhibition with PW demonstrated a relative risk of experiencing return of angina within 30 days of 0.48 (0.23-0.99). In conclusion, POC measurements reflect platelet activation suppression, higher PW measurements being associated with a decreased risk of return of angina.     

Glycoprotein IIb/IIIa Combination Therapy in Acute Myocardial Infarction: Tailoring Therapies to Optimize Outcome

Numerous randomized trials have unequivocally shown that fibrinolytic therapy in the treatment of ST-segment elevation myocardial infarction substantially reduces mortality when administered within 12 hours of symptom-onset. Although fibrinolytic therapy initially restores antegrade flow in the infarct vessel in the majority of patients, sustained tissue-level reperfusion occurs in only approximately 25% of patients. Thrombin and platelets are two additional constituents of a coronary thrombus that contribute to the tendency for vessel reocclusion after initially successful reperfusion. Therefore, adjunctive therapy with potent antithrombins and antiplatelets is essential in the successful treatment of a coronary thrombus. Recent studies including GUSTO-V and ASSENT-III have studied the use of combination drug therapy with glycoprotein IIb/IIIa inhibition and reduced-dose fibrinolytics in the treatment of acute myocardial infarction. These studies demonstrated that combination therapy reduces reinfarction rates. However, this therapy is associated with increased bleeding complications especially in elderly patients. This article reviews the results and clinical implications of these major trials of combination drug therapy in acute myocardial infarction and provides recommendations for tailoring their use in clinical practice.