Primary coronary angioplasty compared with intravenous thrombolytic therapy for acute myocardial infarction: six-month follow up and analysis of individual patient data from randomized trials.

BACKGROUND: Overviews of trials suggest that percutaneous transluminal coronary angioplasty (PTCA) may be more effective than thrombolysis. However, whether these effects are sustained beyond hospital discharge, and the extent to which the results are applicable to a broad cross section of patients and the wider community are unknown. We compared the effectiveness of primary PTCA and thrombolysis in acute myocardial infarction during a 6-month follow-up period. METHODS: Detailed individual patient data were collected from randomized trials commenced from 1989 to 1996 that compared primary PTCA with thrombolysis. Data were combined to produce estimates of relative reduction in events at 30 days and 6 months for the group and for predefined clinical subgroups. Treatment effects were also assessed in relation to several study-related factors. RESULTS: Eleven trials were identified. The mortality rate at 30 days was 4.3% for 1348 patients randomized to undergo PTCA, and 6.9% for 1377 patients assigned to thrombolytic therapy (relative risk [RR] 0.62, 95% CI 0.44-0.86, P =.004). At 6 months, the mortality rate was 6.2% for PTCA and 8.2% for thrombolysis (RR 0.73, 95% CI 0.55-0.98, P =.04). Combined death and reinfarction rates at 30 days were 7.0% for PTCA and 12.9% for thrombolysis, with a sustained effect at 6 months (RR 0.60, 95% CI 0.48-0.75, P <.0001). The risk of hemorrhagic stroke at 30 days was lower in the PTCA group (RR 0.06, 95% CI 0.0-0.50, P =.009). The relative treatment effect did not vary across clinically important subgroups, but the absolute benefit varied according to baseline risk. The relative treatment effect varied across the trials and according to the thrombolytic comparator used, the delay in performing PTCA, and the recruitment rate. CONCLUSION: In the context of these trials, primary PTCA was more effective than thrombolytic therapy in reducing death, reinfarction, and stroke, with the greatest absolute benefit in patients who were at the highest risk. These benefits appear to be sustained for 6 months. The effect of treatment varied significantly across the trials, and this raises issues about how widely the results can be applied.

Clinical characteristics and outcome of patients with early (<2 h), intermediate (2-4 h) and late (>4 h) presentation treated by primary coronary angioplasty or thrombolytic therapy for acute myocardial infarction.

AIMS: We examined the clinical characteristics and outcome of patients with early (<2 h), intermediate (2-4 h) and late (>4 h) presentation treated by primary angioplasty or thrombolytic therapy for acute myocardial infarction. METHODS AND RESULTS: We studied 2635 patients enrolled in 10 randomized trials of primary angioplasty (n=1302) vs thrombolytic therapy (n=1333) in acute myocardial infarction, and baseline characteristics of the two groups were comparable. Increase in presentation delay is associated with older age, female gender, diabetes and an increased heart rate. We classified the patients according to the time delay from symptom onset to presentation into three categories: early presentation (<2 h), intermediate presentation (2-4 h), and late presentation (>or=4 h). At 30 days the combined rate of death, non-fatal reinfarction and stroke in patients presenting early was 5.8% in the angioplasty group vs 12.5% in the thrombolysis group, in patients with intermediate presentation, 8.6% vs 14.2%, respectively, and in patients presenting late 7.7% vs 19.4%, respectively. With increasing time from symptom onset to presentation, all major adverse cardiac event rates show a trend to a larger increase in the thrombolysis group compared to the angioplasty group, both at 30 days and at 6 months after the acute event. CONCLUSIONS: Major adverse cardiac event rates are lower after angioplasty compared to thrombolysis, irrespective of time to presentation. With increasing time to presentation major adverse cardiac event rates increase after thrombolysis but appear to remain relatively stable after angioplasty.

Cost-effectiveness of coronary stenting in acute myocardial infarction: results from the stent primary angioplasty in myocardial infarction (stent-PAMI) trial.

BACKGROUND: Although several randomized trials have demonstrated that coronary stenting improves angiographic and clinical outcomes for patients with acute myocardial infarction (AMI), the cost-effectiveness of this practice is unknown. The objective of the present study was to evaluate the long-term costs and cost-effectiveness (C/E) of coronary stenting compared with primary balloon angioplasty as treatment for AMI. Methods and Results- Between December 1996 and November 1997, 900 patients with AMI were randomized to undergo balloon angioplasty (PTCA, n=448) or coronary stenting (n=452). Detailed resource utilization and cost data were collected for each patient's initial hospitalization and for 1 year after randomization. Compared with conventional PTCA, stenting increased procedural costs by approximately $2000 per patient ($6538+/-1778 versus $4561+/-1598, P<0.001). During the 1-year follow-up period, stenting was associated with significant reductions in the need for repeat revascularization and rehospitalization. Although follow-up costs were significantly lower with stenting ($3613+/-7743 versus $4592+/-8198, P=0.03), overall 1-year costs remained approximately $1000/patient higher with stenting than with PTCA ($20 571+/-10 693 versus 19 595+/-10 990, P=0.02). The C/E ratio for stenting compared with PTCA was $10 550 per repeat revascularization avoided. In analyses that incorporated recent changes in stent technology and pricing, the 1-year cost differential fell to <$350/patient, and the C/E ratio improved to $3753 per repeat revascularization avoided. The cost-utility ratio for primary stenting was <$50 000 per quality-adjusted life year gained only if stenting did not increase 1-year mortality by >0.2% compared with PTCA. CONCLUSIONS: As performed in Stent-PAMI, primary stenting for AMI increased 1-year medical care costs compared with primary PTCA. The overall cost-effectiveness of primary stenting depends on the societal value attributed to avoidance of symptomatic restenosis, as well as on the relative mortality rates of primary PTCA and stenting.

Importance of time to reperfusion on outcomes with primary coronary angioplasty for acute myocardial infarction (results from the Stent Primary Angioplasty in Myocardial Infarction Trial).

The mortality benefit of thrombolytic therapy for acute myocardial infarction (AMI) is strongly dependent on time to treatment. Recent observations suggest that time to treatment may be less important with primary percutaneous transluminal coronary angioplasty (PTCA). Patients with AMI of <12 hours duration, without cardiogenic shock, who were treated with primary PTCA from the Stent PAMI Trial (n = 1,232) were evaluated to assess the effect of time to reperfusion on outcomes. Thrombolysis In Myocardial Infarction grade 3 flow was achieved in a high proportion of patients regardless of time to treatment. Improvement in ejection fraction from baseline to 6 months was substantial with reperfusion at <2 hours but was modest and relatively independent of time to reperfusion after 2 hours (<2 hours, 12.3% vs > or =2 hours, 4.2%, p = 0.004). There were no differences in 1- or 6-month mortality by time to reperfusion (6-month mortality: <2 hours [5.5%], 2 to <4 hours [4.6%], 4 to <6 hours [4.5%], >6 hours [4.2%], p = 0.97). There were also no differences in other clinical outcomes by time to reperfusion, except that reinfarction and infarct artery reocclusion at 6 months were more frequent with later reperfusion. The lack of correlation between time to treatment and mortality in patients without cardiogenic shock suggests that the survival benefit of primary PTCA may be related principally to factors other than myocardial salvage. These data may also have implications regarding the triage of patients with AMI for primary PTCA.

Clinical pharmacology of higher dose eptifibatide in percutaneous coronary intervention (the PRIDE study).

This study describes the dose-exploration phase of the PRIDE trial, an investigation of the clinical pharmacology of higher dose eptifibatide in patients who underwent elective percutaneous coronary intervention (PCI). Outcomes of treatment with the platelet glycoprotein IIb/IIIa inhibitors were dependent upon proper dosing selection. In this multicenter, placebo-controlled clinical study, 127 patients were randomized 1:1:2:2 into 1 of the following treatment groups: placebo; eptifibatide as a 135 microg/kg bolus followed by a 0.75 microg/kg/min infusion; eptifibatide as a 180 microg/kg bolus with a 2.0 microg/kg/min infusion; or eptifibatide as a 250 microg/kg bolus with a 3.0 microg/kg/min infusion. Light transmission aggregometry was used to determine platelet aggregation in response to 20 microM adenosine diphosphate, and platelet receptor occupancy was also determined. Eptifibatide exhibited linear pharmacokinetics over the dose range studied. Inhibition of platelet aggregation was greater in samples collected in sodium citrate compared with those collected in D-phenylalanyl-L-prolyl-L-arginine chloromethyl ketone. The 180/2.0 dosing regimen achieved 90% inhibition of platelet aggregation immediately (5 minutes) and at steady state (8 to 24 hours). At 1 hour, mean inhibition of platelet aggregation was 80%. Eptifibatide exhibited dose-dependent pharmacodynamics that were dependent upon choice of anticoagulant. A 180 microg/kg bolus followed by a 2.0 microg/kg/min infusion at steady state achieved >80% inhibition of platelet aggregation. With the single-bolus regimen, however, there was an early loss of the inhibition of platelet aggregation before steady state was reached. Additional dose-exploration studies may further optimize eptifibatide dosing.

Quality of life after balloon angioplasty or stenting for acute myocardial infarction. One-year results from the Stent-PAMI trial.

OBJECTIVES: The goal of this study was to compare the impact of primary stenting or percutaneous transluminal coronary angioplasty (PTCA) on health-related quality of life (HRQOL) in patients undergoing direct angioplasty for acute myocardial infarction (AMI). BACKGROUND: Previous studies have demonstrated that coronary stenting reduces clinical and angiographic restenosis compared with PTCA. However, the impact of stenting on HRQOL from the patient's perspective remains unknown. METHODS: We administered the Seattle Angina Questionnaire and the Medical Outcomes Study Short-form Survey at 1, 6 and 12 months after initial treatment to all North American patients in the Stent-Primary Angioplasty for Myocardial Infarction trial (Stent-PAMI) (n = 509)-a randomized trial comparing primary stenting to conventional PTCA for patients with AMI. RESULTS: At one month, most HRQOL measures were similar for the two groups, but stent patients reported less bodily pain than PTCA patients (p = 0.03). At six-month follow-up, stenting resulted in significant improvements in several dimensions of HRQOL including reduced anginal frequency and bodily pain as well as improved disease perception (all p < or = 0.03) and a trend towards better anginal stability (p = 0.056). By 12-month follow-up, however, none of these differences remained statistically significant. These differences in HRQOL were largely explained by the greater need for ischemia-driven target-vessel repeat revascularization procedures in PTCA patients during the first six months (16.0% vs. 6.2%, p < 0.001). CONCLUSIONS: In patients undergoing revascularization for AMI, initial stent placement is associated with improvements in several dimensions of health status during the first six months of follow-up. In the absence of differences in mortality, these findings add to the overall argument in favor of initial stenting in patients treated with mechanical reperfusion for myocardial infarction.

Normal flow (TIMI-3) before mechanical reperfusion therapy is an independent determinant of survival in acute myocardial infarction: analysis from the primary angioplasty in myocardial infarction trials.

BACKGROUND: Whereas survival after lytic therapy for myocardial infarction is strongly dependent on early administration, it is unknown whether the otherwise excellent outcomes in patients undergoing primary PTCA for acute myocardial infarction, in whom TIMI-3 flow rates of >90% may be achieved, can be further improved by early reperfusion. METHODS AND RESULTS: Among 2507 patients enrolled in 4 PAMI trials undergoing primary PTCA, spontaneous reperfusion (TIMI-3 flow) was present in 16% at initial angiography. Compared with patients without TIMI-3 flow, those with TIMI-3 flow before PTCA had greater left ventricular ejection fraction (57+/-10% versus 53+/-11%, P=0.003) and were less likely to present in heart failure (7.0% versus 11.6%, P=0.009). Patients with initial TIMI-3 flow had significantly lower in-hospital rates of mortality, new-onset heart failure, and hypotension and had a shorter hospital stay. Cumulative 6-month mortality was 0.5% in patients with initial TIMI-3 flow, 2.8% with TIMI-2 flow, and 4.4% with initial TIMI-0/1 flow (P=0.009). By multivariate analysis, TIMI-3 flow before PTCA was an independent determinant of survival (odds ratio 2.1, P=0.04), even when corrected for by postprocedural TIMI-3 flow. CONCLUSIONS: Patients undergoing primary PTCA in whom TIMI-3 flow is present before angioplasty present with greater clinical and angiographic evidence of myocardial salvage, are less likely to develop complications related to left ventricular failure, and have improved early and late survival. These data warrant prospective randomized trials of pharmacological strategies to promote early reperfusion before definitive mechanical intervention in acute myocardial infarction.

Initial experience with multivessel percutaneous coronary intervention during mechanical reperfusion for acute myocardial infarction.

The feasibility and safety of simultaneous multivessel percutaneous coronary intervention during mechanical reperfusion for acute myocardial infarction was analyzed in a retrospective, case-controlled study. Patients who underwent multivessel coronary intervention had a higher risk of adverse clinical outcomes through 6 months compared with matched controls in whom coronary intervention was limited to the infarct-related artery.

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.

Predictive value of the Killip classification in patients undergoing primary percutaneous coronary intervention for acute myocardial infarction.

The predictive value of Killip classification of acute myocardial infarction (AMI) in patients undergoing percutaneous coronary intervention (PCI) is not well established. We performed a pooled analysis of 2,654 patients with AMI enrolled in 3 primary angioplasty trials. Of these, 2,305 patients were class I, 302 were class II, and 47 were class III (class IV patients were excluded). Univariate and multivariate analyses were performed to determine if Killip class at admission was a predictor of in-hospital and 6-month mortality. Higher Killip classification was associated with greater in-hospital (2.4%, 7%, and 19% for class I, II, and III, respectively) and 6-month mortality (4%, 10%, and 28% for class I, II, and III, respectively). Higher Killip class was associated with increased age (p <0.001), history of diabetes (p <0.02), lower systolic blood pressure and higher heart rate at presentation (p <0.0001 for both), more 3-vessel disease (p <0.001), lower left ventricular ejection fraction (p <0.0001), and higher peak creatine phosphokinase (p <0.0001). With each increasing Killip class, there was an increased need for an intra-aortic balloon counterpulsation (p <0.001) and greater incidence of renal failure (p <0.001), major arrhythmia (p <0.001), and major bleeding (p <0.001). After controlling for potential confounding variables, Killip classification remained a multivariate predictor of mortality at both time end points. Killip classification at hospital admission remains a simple and useful independent predictor of in-hospital and 6-month mortality in patients with AMI who are undergoing primary PCI.

Enoxaparin and abciximab adjunctive pharmacotherapy during percutaneous coronary intervention.

Randomized controlled trials of patients with non-ST segment elevation acute coronary syndromes have established the superiority of enoxaparin (versus unfractionated heparin) for reducing adverse ischemic outcomes. Furthermore, adjunctive abciximab therapy during percutaneous coronary intervention (PCI) is associated with improved clinical outcomes. Since algorithms for integrating these pharmacotherapies have not been determined, patients undergoing elective PCI were enrolled into 2 distinct and separate studies conducted by the National Investigators Collaborating on Enoxaparin (NICE) study groups (NICE 1 and NICE 4 studies). Patients in NICE 1 were administered enoxaparin 1.0 mg/kg intravenously (without abciximab) and those enrolled in NICE 4 were administered a reduced dose (0.75 mg/kg) of enoxaparin in combination with standard-dose abciximab intravenously during PCI. Bleeding events and ischemic outcomes assessed in-hospital and at 30-days post-PCI were infrequent with either pharmacologic regimen. In the dose regimens studied, enoxaparin with or without abciximab appears to provide safe and effective anticoagulation during PCI. The combination of reduced-dose enoxaparin and abciximab was associated with a low incidence of adverse outcomes (bleeding or ischemic events). Additional studies may be required to establish the relative safety and efficacy of this new adjunctive pharmacologic strategy when compared with the combination of low-dose, weight-adjusted unfractionated heparin and abciximab.

Interventional procedures in acute myocardial infarction.

BACKGROUND: Acute myocardial infarction (MI) remains a leading cause of death in the United States. There is evidence that primary (direct) percutaneous intervention (PCI) may improve survival and reduce morbidity in patients with acute MI. METHODS: We present a concise, comprehensive, evidence-based literature review of modern techniques of primary PCI in patients with acute MI. A comparison to thrombolytic therapy, especially in selected patient subgroups is made. Rescue angioplasty is also addressed. Adjunctive pharmacology, economic implications, and feasibility of implementation are discussed. A brief discussion of experimental therapies is included. RESULTS: Primary PCI is an acceptable alternative to thrombolytic therapy in patients with acute MI and may result in superior outcomes in select patient populations, especially the elderly, patients with prior coronary artery bypass surgery, those with congestive heart failure, and those in cardiogenic shock. CONCLUSIONS: Clinical trials support the use of primary PCI as first-line therapy for acute myocardial infarction. Patients in whom thrombolytic therapy is contraindicated or known to have reduced efficacy are also excellent candidates for this therapy. Ongoing advancements in equipment and adjunctive therapies continue to enhance delivery of this treatment as well as improve patient outcome.

A time-to-treatment analysis in the medicine versus angiography in thrombolytic exclusion (MATE) trial.

Patients with acute coronary syndromes who are considered ineligible for thrombolytic therapy are at high risk of recurrent ischemia and death. This trial randomized 201 patients to triage angiography in the first 24 hours of hospital admission versus conventional medical care. Of the 165 patients who underwent angiography that was either protocol-driven or on the basis of physician preference, those who underwent angiography within 6 hours of symptom onset had a reduction in early and late adverse events. The rates of in-hospital recurrent ischemia were 15.4%, 15.4%, 17.5%, 32.4%, and 38.5%, respectively (P = 0.01 for trend), and rates of cumulative recurrent myocardial infarction or death were 0%, 12.8%, 10.0%, 11.8%, and 7.7%, respectively (P = 0.48 for trend) for patients who underwent angiography at 0-6, 6-12, 12-24, 24-48, and over 48 hours, respectively from symptom onset. Future trials of invasive versus conservative therapy should focus on performing angiography within 6 hours of symptom onset.

Role of prolonged intravenous heparin in unstable angina patients prior to coronary angioplasty.

BACKGROUND: The optimal timing of coronary angioplasty in unstable angina patients is controversial. Early reports suggested using 3-5 days of intravenous heparin and aspirin for plaque stabilization before angioplasty. There is no clearcut data in this regard from the published literature. The purpose of this study was to evaluate whether delaying the angioplasty in order to stabilize the plaque affected the outcome. METHODS: We reviewed the hospital course of patients who were admitted with unstable angina through the emergency room and ruled out for myocardial infarction, and who required angioplasty during the index hospitalization. To diminish the influence of coronary stenting and glycoprotein IIb/IIIa receptor blockade, we reviewed all patients admitted during 1994. RESULTS: Of the 305 patients, 166 patients received < or = 48 hours and 139 patients received > 48 hours of intravenous heparin infusion before angioplasty. Both groups were well-matched. The procedural success was similar in both the groups (98% vs 97%, P = 0.72). The complication rate was similar in both groups, including abrupt closure, emergency bypass surgery, myocardial infarction and death. Length of hospital stay was significantly prolonged in the group with > 48 hours of heparin infusion (4.4 +/- 3.0 vs 7.4 +/- 3.6 days; P < 0.001). CONCLUSION: In patients with unstable angina undergoing angioplasty, prolonged duration of heparin infusion influenced the procedural outcome or postprocedural complications, but prolonged the hospital stay. These data suggest that early angioplasty of unstable angina patients is safe and may be cost-effective, even in the absence of stenting and potent antiplatelet agents. However, prospective, randomized trials are needed to clarify the need for and duration of heparin infusion prior to angioplasty in unstable angina patients.

One-year follow-up after primary coronary intervention for acute myocardial infarction in diabetic patients. A substudy of the STENT PAMI trial.

OBJECTIVE: This analysis was undertaken to determine the composite incidence of cumulative adverse events (death, reinfarction, disabling stroke, and target vessel revascularization) at the end of the first year after acute myocardial infarction, in diabetic patients who underwent coronary stenting or primary coronary balloon angioplasty. METHODS: From the STENT PAMI trial, we analyzed the 6-month angiographic and 1-year clinical outcomes of 135 diabetic (112, noninsulin dependent) patients who underwent the randomization process of the trial and compared them with 758 nondiabetic patients. RESULTS: Coronary stenting did not significantly reduce the primary composite clinical end point when compared with PTCA (20 vs. 30%, p=0.2). A significant benefit from stenting was observed in patients with noninsulin dependent diabetes, with a trend toward a lesser need for new revascularization procedures (10 vs. 21%, p<.001), with a significant reduction in the primary composite clinical end point at 1 year (12 vs. 28%, p=. 04). At 6 months, the restenosis rate were significantly reduced only in nondiabetic patients (18 vs. 33%, p<. 001). Diabetic patients had the same restenosis rate (38%) either with stenting or balloon PTCA. CONCLUSIONS: Coronary Stenting in diabetics noninsulin dependent offered a significant reduction in the composite incidence of major clinical adverse events compared with balloon PTCA.

Impaired culprit vessel flow in acute coronary syndromes ineligible for thrombolysis.

The majority of patients with acute myocardial infarction and other acute coronary syndromes (ACS) are considered ineligible for thrombolysis and do not routinely receive reperfusion therapy. We hypothesized that predictors and outcomes of angiographically impaired culprit vessel flow can be identified and compared. This trial evaluated the outcomes following triage angiography in acute coronary syndromes ineligible for thrombolytic therapy. Eligible patients (n=201) with<24 hours of symptoms were randomized to early triage angiography and subsequent therapies based on the angiogram versus conventional medical therapy. This analysis was performed in 165 patients, from experimental and control arms, in whom angiography was performed on the index hospitalization with the outcome of interest being target vessel flow (Thrombolysis In Myocardial Infarction [TIMI] grades 0 to 2) on initial angiography. Patients with and without impaired culprit lesion flow were similar with respect to age, gender, diabetes, and prior coronary disease. A family history of premature coronary disease was more common in those with impaired flow, 50.0 versus 28.5% (p=0.02). Abnormal culprit vessel flow was found in 19.2% of patients who underwent angiography within 6 hours of symptom onset; however, after 24 hours this rate was reduced to 11.7%. Impaired culprit lesion flow can be expected in approximately 20% of patients presenting with ACS who are ineligible for reperfusion therapy by conventional guidelines and therefore represents an opportunity for early intervention within 6 hours of the onset of symptoms in these patients.

Combination Enoxaparin and Abciximab During Percutaneous Coronary Intervention: A New Standard of Care?

Evidence from randomized trials supports the administration of platelet glycoprotein (GP) IIb/IIIa blockade both to patients undergoing percutaneous coronary intervention (PCI) and those presenting with non-ST elevation acute coronary syndromes (ACSs). Similarly, the low molecular weight heparin (LMWH), enoxaparin, has demonstrated superior efficacy when compared with unfractionated heparin (UFH) in the treatment of patients with non-ST elevation ACS. Algorithms for seamless integration of pharmacotherpy through the course of hospitalization for patients who present with ACS and who require PCI will likely combine therapy with enoxaparin and platelet GP IIb/IIIa blockade (abciximab). Our preliminary experience with combination enoxaparin and abciximab as adjunctive pharmacotherapy for PCI suggests that this strategy is safe and effective and may offer advantages over a conventional strategy, which employs UFH.

Optimization of platelet therapy.

Percutaneous coronary intervention produces vessel wall injury and activation of platelets that are responsible for producing peri-procedural ischemic complications. The importance of adequate antiplatelet therapy during coronary intervention to reduce platelet mediated ischaemic complications has been recognized for some time. Until recently, adjunctive treatment with aspirin was the only available antiplatelet therapy after coronary intervention that had demonstrated benefit. During the last decade, newer and more potent agents have demonstrated consistent reductions in ischaemic events after intervention and appear to have some enduring effect. Additionally, optimization of antiplatelet therapy with aspirin and the thienopyridines after coronary stenting has been an important advance allowing for the current liberal use of coronary stents.