Facilitated PCI: Ist das Konzept gescheitert?

BACKGROUND: Direct percutaneous coronary intervention (PCI) can be considered the gold standard of reperfusion therapy. For patients with need for transfer, the question of antithrombotic pretreatment arises. CONCEPT OF FACILITATED PCI: With the concept of facilitated PCI the advantages of fibrinolysis, namely the rapid and ubiquitous availability, should be combined with the advantages of immediate PCI. With a pretreatment using fibrinolytics, glycoprotein IIb/IIIa inhibitors (GPI) or the combination of both (in that case a fibrinolytic in half dosage only), it was aimed to achieve reperfusion before a planned PCI. Facilitated PCI was expected to improve the rate of open vessels prior to PCI, thereby reducing infarct size, improving clinical outcome, and the success rate of PCI. CLINICAL TRIALS: The concept of facilitated PCI was evaluated in two major randomized trials (ASSENT-4 PCI, FINESSE) as well as in one meta-analysis. Despite an increase of 20% of patients with patent infarct-related arteries (TIMI 3) before PCI, the clinical outcome, especially mortality, reinfarction rate and heart failure rate, did not improve. Moreover, the bleeding rate increased and even a higher rate of cerebral bleeds was seen, predominantly with full-dose fibrinolysis. POSSIBLE REASONS FOR THE LACK OF SUCCESS WITH FACILITATED PCI: Patency (TIMI 3) of the coronary arteries was 20% higher in the facilitated PCI arms of the trials. However, all patients were at risk of bleeding complications. Also the inclusion of patients with myocardial infarction in a later phase and the inclusion of patients at lower risk may have contributed to the somewhat disappointing results of facilitated PCI. GUIDELINES: Recent American College of Cardiology/American Heart Association (ACC/AHA) guidelines recommend facilitated PCI (class IIb), if all of the following criteria are met: (1) patients at high risk, (2) PCI not available within 90 min, (3) low risk of bleed. A planned reperfusion strategy using full-dose fibrinolysis followed by immediate PCI may be harmful (class III). In addition, a further restriction to patients in the early phase of myocardial infarction (< 3 h) should be considered. In the small subset of carefully selected patients, a combination of GPI and half-dose fibrinolytic could be appropriate.     

Comparison of bivalirudin versus heparin plus glycoprotein IIb/IIIa inhibitors in patients undergoing an invasive strategy: A meta-analysis of randomized clinical trials

Objective

This meta-analysis was performed to assess the efficacy and safety of bivalirudin compared with unfractionated heparin or enoxaparin plus glycoprotein (GP) IIb/IIIa inhibitors in patients undergoing percutaneous coronary intervention (PCI).

Background

Pharmacotherapy for patients undergoing PCI includes bivalirudin, heparin, and GP IIb/IIIa inhibitors. We sought to compare ischemic and bleeding outcomes with bivalirudin versus heparin plus GP IIb/IIIa inhibitors in patients undergoing PCI.

Methods

A literature search was conducted to identify fully published randomized trials that compared bivalirudin with heparin plus GP IIb/IIIa inhibitors in patients undergoing PCI.

Results

A total of 19,772 patients in 5 clinical trials were included in the analysis (9785 patients received bivalirudin and 9987 patients received heparin plus GP IIb/IIIa inhibitors during PCI). Anticoagulation with bivalirudin, as compared with heparin plus glycoprotein IIb/IIIa inhibitors, results in no difference in major adverse cardiovascular events (odds ratio [OR] 1.07, 95% confidence interval [CI] 0.96 to 1.19), death (OR 0.93, 95% CI 0.72 to 1.21), or urgent revascularization (OR 1.06, 95% CI 0.86 to 1.30). There is a trend towards a higher risk of myocardial infarction (OR 1.12, 95% CI 0.99 to 1.28) but a significantly lower risk of TIMI major bleeding with bivalirudin (OR 0.55, 95% CI 0.44 to 0.69).

Conclusion

In patients who undergo PCI, anticoagulation with bivalirudin as compared with unfractionated heparin or enoxaparin plus GP IIb/IIIa inhibitors results in similar ischemic adverse events but a reduction in major bleeding.     

Improved clinical outcomes with abciximab therapy in acute myocardial infarction: a systematic overview of randomized clinical trials

Background

Investigations of glycoprotein (GP) IIb/IIIa inhibition in primary percutaneous coronary intervention (PCI) have suggested the efficacy of abciximab in improving clinical and angiographic outcomes, but sample-size limitations and variability in trial design preclude the ability to generalize these results to a broader patient population.

Methods

Meta-analytic techniques were used to evaluate clinical outcomes from randomized trials comparing GP IIb/IIIa inhibition with placebo or control therapy in primary PCI for acute myocardial infarction (MI).

Results

In 3266 patients, treatment with abciximab significantly reduced the 30-day composite end point of death, reinfarction, or ischemic or urgent target-vessel revascularization (TVR; odds ratio [OR], 0.54; 95% CI, 0.40-0.72), with trends toward reduced 30-day death and death or reinfarction. Abciximab resulted in an increased likelihood of major bleeding (OR, 1.74; 95% CI, 1.11-2.72). By 6 months, abciximab significantly reduced the occurrence of death, reinfarction, or any TVR (OR, 0.80; 95% CI, 0.67-0.97), and there were positive trends favoring a decrease in mortality alone and the composite of death or reinfarction.

Conclusions

Treatment with abciximab significantly reduces early adverse ischemic events, a clinical benefit that is maintained at 6-month follow-up. These findings support the use of adjunctive GP IIb/IIIa inhibition in primary PCI.     

Bleeding complications associated with glycoprotein IIb/IIIa inhibitors in patients 80 years of age and older undergoing percutaneous coronary intervention

BACKGROUND:

Treatment of symptomatic coronary artery disease with percutaneous intervention requires antithrombotic therapy. Patients with elevated thromboembolic risk benefit from therapy with glycoprotein IIb/IIIa inhibitors. The safety and effectiveness of glycoprotein IIb/IIIa inhibition have been well documented in clinical trials. Drug-induced bleeding complications in elderly patients have not been specifically addressed.

METHODS:

Between 2006 and 2009, a total of 439 unselected patients 80 years of age and older undergoing percutaneous intervention for symptomatic coronary artery disease were included in the present nonrandomized retrospective study. In one-half of the patients, glycoprotein IIb/IIIa inhibitors were administered peri-interventionally. The in-hospital occurrence of bleeding complications (access site, gastrointestinal and cerebral) were analyzed in the groups with and without glycoprotein IIb/IIIa inhibitors.

RESULTS:

The mean age of the patients was 84 years. Nearly all patients (95%) received dual antiplatelet therapy. Patients treated with glycoprotein IIb/IIIa inhibitors had more complex coronary lesions and bypass graft interventions, and a tendency toward more access site bleeding complications than patients without inhibitors, which included femoral hematomas (4.6% versus 2.3%, respectively; P not significant) and femoral pseudoaneurysms (6% versus 3.2%, respectively; P not significant). The rate of blood transfusion was equal in both groups (0.9%). Major hemorrhagic events did not occur. Vessel closure devices were used more often in patients without glycoprotein inhibition.

CONCLUSIONS:

An increase in minor bleedings must be expected when using glycoprotein IIb/IIIa inhibitors in patients 80 years of age and older. However, this issue must not prevent this treatment option from being offered to elderly patients. There appears to be no elevated risk for major bleeding complications. Broadened use of vascular closure devices in this specific patient population may lower the rate of access site complications.     

Effectiveness of a change in reperfusion strategy to primary percutaneous coronary intervention in a nonselected population

BACKGROUND

Randomized controlled trials have established the clinical superiority of primary percutaneous coronary intervention (PCI) over fibrinolysis for ST segment elevation myocardial infarction (STEMI) in selected populations. However, the clinical effectiveness of the primary PCI strategy with modern adjunctive antiplatelet therapy deserves further evaluation.

OBJECTIVE

To validate results from randomized controlled trials in a nonselected Canadian population.

METHODS

A retrospective study of 243 consecutive patients who presented with a STEMI at a single academic centre was performed. Baseline characteristics, treatment strategies and in-hospital outcomes of patients treated in 2004 to 2005 (n=129) were compared with those of patients treated in 1999 to 2000 (n=114). Logistic regression was used to adjust for imbalanced baseline characteristics.

RESULTS

Patients in the 2004 to 2005 cohort versus those in the 1999 to 2000 cohort were older and more likely to be hypertensive and to present in Killip class 2 to 4. All of the patients treated in 2004 to 2005 underwent a primary PCI strategy compared with 32.5% in the 1999 to 2000 cohort. The in-hospital incidence of death, reinfarction or stroke was reduced from 21.9% in 1999 to 2000, to 15.5% in 2004 to 2005 (adjusted OR 0.462; P=0.055), largely due to a reduction in reinfarction (10.5% to 3.1%, adjusted OR 0.275; P=0.041). In-hospital mortality and stroke rates did not change significantly. The median length of stay was reduced from eight to six days in the recent cohort (P=0.002).

CONCLUSIONS

In the present nonselected population, the change in reperfusion strategy from fibrinolysis to primary PCI in the treatment of STEMI reduced the length of hospitalization by two days and was associated with an adjusted 54% relative reduction in adverse in-hospital events, which was largely due to a significant reduction in reinfarction.     

Bridging the Gap with New Strategies in Acute ST Elevation Myocardial Infarction: Bolus Thrombolysis,Glycoprotein IIb/IIIa Inhibitors,Combination Therapy,Percutaneous Coronary Intervention,and “Facilitated” PCI

Achieving early reperfusion with thrombolytic agents or primary percutaneous coronary intervention (PCI) in patients with acute myocardial infarction (AMI) is the cornerstone of current therapy. Two advances in pharmacologic therapy are: (1) bolus thrombolysis, which simplifies therapy, reduces door-to-needle time, and reduces the potential for medication errors, and (2) Low-dose fibrinolytic therapy combined with a glycoprotein (GP) IIb/IIIa inhibitor which can achieve higher rates of reperfusion than fibrinolytic therapy alone. In addition, the IIb/IIIa inhibitor as part of the reperfusion regimen will support any acute-phase interventions that are performed. The combination of fibrinolytic therapy and GP IIb/IIIa inhibition to facilitate PCI is being examined in TIMI-14, SPEED, and GUSTO IV. Early findings in the SPEED trial have shown promising results with facilitated PCI when patency is achieved before PCI is attempted. Results of these trials will further define the role of combination therapy in facilitating mechanical interventions.     

Timing of glycoprotein IIb/IIIa inhibitor use and outcomes among patients with non-ST-segment elevation myocardial infarction undergoing percutaneous coronary intervention (results from CRUSADE)

Although glycoprotein (GP) IIb/IIIa inhibitors are recommended for patients with unstable angina and non-ST-segment elevation myocardial infarction who undergo percutaneous coronary intervention (PCI), the American College of Cardiology/American Heart Association guidelines do not specify optimal timing for their initiation. We compared patient characteristics and clinical outcomes in 30,830 patients with non-ST-segment elevation myocardial infarction included in the CRUSADE initiative (January 2001 to December 2004) who underwent PCI with upstream (>1 hour before PCI) or periprocedural use of GP IIb/IIIa inhibitors. GP IIb/IIIa inhibitors were administered upstream in 43% of patients versus periprocedurally in 57%. Time from arrival to PCI was longer for patients who received GP IIb/IIIa inhibitors upstream (median 25.6 hours) compared with periprocedurally (18.2 hours). Unadjusted incidence of in-hospital death or reinfarction was lower with upstream GP IIb/IIIa inhibitor use (3.8% vs 4.3%, p = 0.046), but after adjusting for patient and hospital characteristics, this difference was not statistically significant. Treatment with upstream GP IIb/IIIa inhibitors was associated with a lower incidence of unadjusted death or reinfarction in patients who underwent PCI <12 hours from hospital arrival. In conclusion, in this observational analysis, overall ischemic outcomes were similar between the 2 groups, but clinical trials are needed to solve the controversy over optional timing of GP IIb/IIIa inhibitor use.     

Combining enoxaparin and glycoprotein IIb/IIIa antagonists for the treatment of acute coronary syndromes: final results of the National Investigators Collaborating on Enoxaparin-3 (NICE-3) study

Background

In high-risk patients with acute coronary syndromes (ACS), there have been concerns relating to the safety of using low molecular weight heparins (LMWH) in combination with a glycoprotein (GP) IIb/IIIa antagonist, and the continued use of LMWH in patients brought to the cardiac catheterization laboratory for percutaneous coronary intervention (PCI).

Methods

The National Investigators Collaborating on Enoxaparin-3 (NICE-3) study was an open-label observational study of enoxaparin in combination with any 1 of 3 available GP IIb/IIIa antagonists in patients presenting with non-ST-elevation ACS. The primary end point was the incidence of major bleeding not related to coronary artery bypass graft (CABG) surgery. Data were also recorded on the incidence of death, myocardial infarction (MI), and urgent revascularization for repeat ischemia.

Results

A total of 671 patients with validated data were treated with enoxaparin; 628 of these patients also received a GP IIb/IIIa antagonist (tirofiban, n = 229; eptifibatide, n = 272; abciximab, n = 127); 283 of 628 underwent percutaneous coronary intervention (PCI). The 30-day incidence of non-CABG major bleeding was 1.9%, and was not significantly higher than a prespecified historical control rate of 2.0%. Outcome events included death (1.0% at hospital discharge and 1.6% at 30 days), MI (3.5% and 5.1%, respectively), and urgent revascularization (2.7% and 6.8%, respectively).

Conclusions

The safety of enoxaparin plus a GP IIb/IIIa antagonist was comparable to that of unfractionated heparin plus a GP IIb/IIIa antagonist, as reported in other recent major trials. Patients undergoing PCI can be safely managed with enoxaparin and a GP IIb/IIIa antagonist, without supplemental use of unfractionated heparin.     

ST segment resolution in patients with tenecteplase-facilitated percutaneous coronary intervention versus tenecteplase alone: Insights from the Combined Angioplasty and Pharmacological Intervention versus Thrombolysis ALone in Acute Myocardial Infarction (CAPITAL AMI) trial

BACKGROUND:

Compared with fibrinolysis alone, fibrinolysis followed by immediate percutaneous coronary intervention (PCI) reduced clinical events in the Combined Angioplasty and Pharmacological Intervention versus Thrombolysis ALone in Acute Myocardial Infarction (CAPITAL AMI) study. It is unclear whether the benefits go beyond achieving epicardial reperfusion.

OBJECTIVES:

To determine the differences in ST segment resolution (STR) among patients treated with tenecteplase (TNK)-facilitated PCI compared with patients treated with TNK alone.

METHODS AND RESULTS:

A formal ST segment analysis was conducted on the 170 patients with ST elevation myocardial infarction in the CAPITAL AMI trial: 86 patients treated with TNK-facilitated PCI were compared with 84 patients who were treated with TNK alone. Epicardial flow measured by percentage with Thrombolysis In Myocardial Infarction (TIMI) 3 flow improved from 52% (pre-PCI) to 89% (post-PCI) in those assigned to facilitated PCI. ST segment resolution was stratified by complete (70% or greater), partial (less than 70% to 30%) or no (less than 30% to 0%) resolution. The baseline mean ST segment elevation was 11.3±7.5 mm in the facilitated PCI patients and 11.8±7.1 mm in patients with TNK alone (P=0.66). Complete STR in the facilitated PCI patients versus the TNK-alone patients was present in 55.6% versus 54.6%, respectively (P=0.58) at 180 min and 62.0% versus 55.3% (P=0.64), respectively at day 1. The mean STR at 180 min and day 1 were similar in patients who experienced death, reinfarction, recurrent unstable ischemia or stroke at six months compared with patients who remained event free: 56.3% versus 64.6% at 180 min (P=0.40); and 67.7% versus 67.6% at day 1 (P=0.99), respectively.

CONCLUSIONS:

TNK-facilitated PCI did not demonstrate differences in ST segment resolution compared with TNK alone, despite improvement in epicardial flow after PCI. Further studies are required to clarify these findings.     

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.     

Relationship of treatment delays and mortality in patients undergoing fibrinolysis and primary percutaneous coronary intervention. The Global Registry of Acute Coronary Events

Objective

Treatment delays may result in different clinical outcomes in patients with ST‐segment elevation myocardial infarction (STEMI) who receive fibrinolytic therapy vs primary percutaneous coronary intervention (PCI). The aim of this analysis was to examine how treatment delays relate to 6‐month mortality in reperfusion‐treated patients enrolled in the Global Registry of Acute Coronary Events (GRACE).

Design

Prospective, observational cohort study.

Setting

106 hospitals in 14 countries.

Patients

3959 patients who presented with STEMI within 6 h of symptom onset and received reperfusion with either a fibrin‐specific fibrinolytic drug or primary PCI.

Main outcome measures

6‐month mortality.

Methods

Multivariable logistic regression was used to assess the relationship between outcomes and treatment delay separately in each cohort, with time modelled with a quadratic term after adjusting for covariates from the GRACE risk score.

Results

A total of 1786 (45.1%) patients received fibrinolytic therapy, and 2173 (54.9%) underwent primary PCI. After multivariable adjustment, longer treatment delays were associated with a higher 6‐month mortality in both fibrinolytic therapy and primary PCI patients (p<0.001 for both cohorts). For patients who received fibrinolytic therapy, 6‐month mortality increased by 0.30% per 10‐min delay in door‐to‐needle time between 30 and 60 min compared with 0.18% per 10‐min delay in door‐to‐balloon time between 90 and 150 min for patients undergoing primary PCI.

Conclusions

Treatment delays in reperfusion therapy are associated with higher 6‐month mortality, but this relationship may be even more critical in patients receiving fibrinolytic therapy.Treatment delays in the delivery of fibrinolytic therapy and primary percutaneous coronary intervention (PCI) are associated with increased rates of mortality in patients with ST‐segment elevation myocardial infarction (STEMI).^1,2 However, there is controversy as to whether treatment delays in primary PCI are less important than those in fibrinolytic therapy, especially when fibrin‐specific agents are utilised.³ This is important because a differential effect of treatment delays on outcomes may influence the selection between these two reperfusion strategies.^3,4,5,6,7 Accordingly, using data from the ongoing, multinational Global Registry of Acute Coronary Events (GRACE), we examined how treatment delays relate to 6‐month mortality in patients with STEMI who received fibrinolytic therapy with a fibrin‐specific agent or primary PCI. GRACE provides an ideal resource for such an investigation because it includes patients who received both types of reperfusion strategies, and the data for each strategy are collected under identical circumstances.     

Safety and effectiveness of enoxaparin following fibrinolytic therapy: Results of the Acute Myocardial Infarction (AMI)-QUEBEC registry

BACKGROUND:

Previous randomized controlled trials and meta-analyses demonstrated the superior efficacy of enoxaparin (ENOX) over unfractionated heparin (UFH) in patients with ST segment elevation myocardial infarction (STEMI). The external validity of randomized controlled trials may be limited by selective inclusion of patients who are younger and healthier than the ‘real-life’ population.

OBJECTIVE:

To evaluate the safety and effectiveness of ENOX compared with UFH in unselected STEMI patients.

METHODS:

The safety and effectiveness of ENOX and UFH were compared in STEMI patients who received fibrinolytic therapy at 17 Quebec hospitals in 2003.

RESULTS:

A total of 498 STEMI patients received systemic anticoagulation, with ENOX and UFH administered in 114 and 384 patients, respectively. There were no differences in baseline characteristics between the two patient groups. The rates of in-hospital major adverse cardiac or cerebral events were 11.4% in the ENOX group compared with 14.0% in the UFH group (P=0.51). In-hospital death or nonfatal reinfarction occurred in 7.9% of patients who received ENOX compared with 9.9% of patients who received UFH (P=0.52). Major bleeding occurred in 4.4% of patients who received ENOX versus 6.0% in patients who received UFH (P=0.51).

INTERPRETATION:

There was no significant difference in the rates of in-hospital adverse events in the ENOX group compared with the UFH group, when used in the real-life context. Larger observational studies may further confirm the safety, effectiveness and optimal duration of the administration of ENOX in unselected STEMI patients treated with fibrinolysis.     

Drip and Ship: A New Strategy for the Treatment of Acute Coronary Syndromes

Glycoprotein (GP) IIb/IIIa inhibitors block the final common pathway of platelet aggregation by preventing fibrinogen from binding to the GP IIb/IIIa platelet receptor. In patients with unstable angina (UA) or a non–Q wave myocardial infarction (NQWMI), including those with UA refractory to medical therapy, these agents decrease the risk of death, myocardial infarction (MI), and recurrent ischemia. Most patients with acute coronary syndromes are managed in hospitals without on-site angioplasty capabilities and often require transfer for an interventional procedure. We propose that GP IIb/IIIa inhibitors can be safely initiated at the referring hospital. We studied 20 patients with UA/NQWMI in whom therapy with a GP IIb/IIIa inhibitor, in addition to standard medical therapy, was initiated prior to transfer for an urgent percutaneous coronary intervention (PCI) (drip and ship). The primary end point was a composite of death, MI, and recurrent ischemia at 30 days. Twelve patients were treated with abciximab, 5 patients were treated with tirofiban, and 3 patients initially treated with tirofiban were converted to abciximab. Procedural success occurred in 33 out of 36 (92%) lesions and 18 out of 20 (90%) patients. At 30 days, 4 out of 20 (20%) patients had recurrent ischemia. The PTCA sites were widely patent in the 3 patients who underwent repeat angiography. The fourth patient had an unsuccessful PCI and was referred for coronary artery bypass surgery. There were no MIs or deaths. Patients who require transfer for an urgent PCI can be managed safely and efficaciously by initiating a GP IIb/IIIa inhibitor, in addition to standard medical therapy, prior to transfer.     

Effectiveness and safety of glycoprotein IIb/IIIa inhibitors and clopidogrel alone and in combination in non-ST-segment elevation myocardial infarction (from the National Registry of Myocardial Infarction-4)

We investigated whether a combination of clopidogrel and glycoprotein (GP) IIb/IIIa inhibitors safely decreases hospital mortality, reinfarction, and major bleeding beyond either therapy alone in patients with non-ST-elevation myocardial infarction (NSTEMI). GP IIb/IIIa inhibitors and clopidogrel, separately, have been shown to decrease adverse outcomes in patients with non-ST-elevation acute coronary syndromes, but the need for combination therapy is uncertain. Multivariate and propensity analyses compared the frequency of death, reinfarction, and major bleeding during hospitalization in 38,691 patients with NSTEMI who were enrolled in the National Registry of Myocardial Infarction 4 from July 2000 to December 2003. Of these, 65% received GP IIb/IIIa inhibitors only, 16.1% clopidogrel only, and 18.8% combination therapy. Among patients who did not undergo percutaneous coronary intervention (PCI), the composite end point of death, reinfarction, and major bleeding was significantly lower with combination therapy than with GP IIb/IIIa inhibitors alone (odds ratio 0.77, 95% confidence interval 0.67 to 0.88). In contrast, this composite end point was significantly higher when combination therapy was employed rather than clopidogrel alone (odds ratio 1.55, 95% confidence interval 1.33 to 1.81). However, among patients who underwent PCI, the composite end point was similar between combination therapy and GP IIb/IIIa inhibitor-only groups (odds ratio 1.01, 95% confidence interval 0.89 to 1.14). Further, there was a strong trend toward a higher composite end point among patients who received combination therapy rather than clopidogrel alone (odds ratio 1.31, 95% confidence interval 0.99 to 1.72). In conclusion, commonly employed strategies using a GP IIb/IIIa inhibitor alone or with the combination of clopidogrel plus GP IIb/IIIa inhibitor in NSTEMI may not be justified in comparison with a simpler strategy of clopidogrel used alone, especially in patients who have not undergone PCI.     

Combination of thrombus aspiration, high-dose statin, adenosine and platelet membrane glycoprotein Ⅱb/Ⅲa receptor antagonist reduce the incidence of no-reflow after primary percutaneous coronary intervention in patients with ST-segment elevation acut

Background No-reflow is associated with an adverse outcome and higher mortality in patients with ST-segment elevation acute my-ocardial infarction (STEMI) who undergo percutaneous coronary intervention (PCI) and is considered a dynamic process characterized by multiple pathogenetic components. The aim of this study was to investigate the effectiveness of a combination therapy for the prevention of no-reflow in patient with acute myocardial infarction (AMI) undergoing primary PCI. Methods A total of 621 patients with STEMI who underwent emergency primary PCI were enrolled in this study. Patients with high risk of no-reflow (no-flow score ≥ 10, by using a no-flow risk prediction model, n = 216) were randomly divided into a controlled group (n = 108) and a combination therapy group (n = 108). Patients in the controlled group received conventional treatment, while patients in combination therapy group received high-dose (80 mg) atorvastatin pre-treatment, intracoronary administration of adenosine (140 μg/min per kilogram) during PCI procedure, platelet membrane glycoprotein Ⅱb/Ⅲa receptor antagonist (tirofiban, 10μg/kg bolus followed by 0.15 μg/kg per minute) and thrombus aspiration. Myocardial contrast echocardiography (MCE; SonoVue^?; Bracco) was performed to assess the myocardial perfusion 72 h after PCI. Major adverse cardiac events (MACE) were followed up for six months. Results Incidence of no-reflow in combination therapy group was 2.8%, which was similar to that in low risk group 2.7% and was significantly lower than that in control group (35.2%, P < 0.01). The myocardial perfusion (A × β) values were higher in combination therapy group than that in control group 72 h after PCI. After 6 months, there were six (6.3%) MACE events (one death, two non-fatal MIs and three revascularizations) in combination therapy group and 12 (13.2%) (four deaths, three non-fatal MIs and five revascularizations, P < 0.05) in control group. Conclusions Combination of thrombus aspiration, high-dose statin pre-treatment, intracoronary administration of adenosine during PCI procedure and platelet membrane glycoprotein Ⅱb/Ⅲa receptor antagonist reduce the incidence of no-reflow after primary PCI in patients with acute myocardial infarction who are at high risk of no-reflow.     

The impact of GP IIb/IIIa inhibitors during primary percutaneous coronary intervention in acute myocardial infarction patients

The use of glycoprotein (GP) IIb/IIIa inhibitors during percutaneous coronary interventions (PCI) in the acute phase of myocardial infarction (AMI) is still a matter of debate. The aim of the present study was to compare the outcomes of patients with acute ST-segment elevation myocardial infarction who underwent primary PCI and were concomitantly treated with GP IIb/IIIa inhibitors with those who were not treated with these drugs. Between January 1996 and November 2003, a total of 418 consecutive patients underwent PCI in the setting of ST-segment elevation AMI. At the operator's discretion, 287 patients were concomitantly treated with GP IIb/IIIa inhibitors and 115 patients were not. Angiographic success and final TIMI 3 flow in the infarct-related artery was achieved more frequently in patients treated with GP IIb/IIIa inhibitors (90% vs. 77%; p=0.001). The in-hospital composite endpoint of death, reinfarction and bleeding complications was significantly better in patients treated with GP IIb/IIIa inhibitors (4% vs. 12%; p=0.005). Furthermore, the adjusted 12-month survival rate was significantly better in these patients (RR: 2.99, CI: 1.29-6.9; p=0.01). Therefore, adjunctive therapy with GP IIbIIIa inhibitors during primary PCI is associated with improved short-term outcomes and one-year survival without an increased risk of bleeding.     

Contemporary management of ST elevation myocardial infarction

Management of acute ST elevation myocardial infarction (MI) has become increasingly complex. Third-generation fibrinolytic agents have provided simpler bolus administration and enhanced arterial patency rates but have not lowered mortality. Prehospital fibrinolysis reduces time to treatment, and studies continue to better define the clinical benefits. Combining glycoprotein (GP) IIb/IIIa inhibitors with reduced-dose fibrinolytic therapy thus far has not reduced mortality; improvements in secondary outcomes such as recurrent infarction have been offset by increases in bleeding complications, particularly in elderly patients. In contrast to fibrinolytic trial results, outcomes are improved in patients who promptly undergo primary percutaneous coronary intervention (PCI). Meta-analyses demonstrate a significant reduction in mortality compared with patients who receive fibrinolytic therapy. Accessibility of primary intervention remains an important limitation, although recent trials suggest superiority of intervention even when hospital transfer is necessary. Conflicting trends include the development of regional centers for interventional treatment of MI as well as the dissemination of limited interventional programs to smaller hospitals. Facilitated PCI, a hybrid of pharmacological reperfusion (typically combination therapy) followed by intervention, may bridge the delay when primary intervention is not immediately available. Optimal therapy for acute MI must be individualized based on both patient characteristics and resource availability.     

The Saudi Project for Assessment of Coronary Events (SPACE) registry: Design and results of a phase I pilot study

OBJECTIVE:

The delay between the availability of clinical evidence and its application to the care of patients with acute coronary syndrome (ACS) in the Kingdom of Saudi Arabia remains undefined. The Saudi Project for Assessment of Coronary Events (SPACE) registry provides a comprehensive view of the current diagnostic and treatment strategies for patients with ACS; thus, the registry may be used to identify opportunities to improve the care of these patients.

METHODS:

Eight hospitals in different regions of Saudi Arabia were involved in the pilot phase of the registry, from December 2005 to July 2006. The study patients included individuals with ST segment elevation myocardial infarction (STEMI), non-STEMI and unstable angina.

RESULTS:

A total of 435 patients (77% men and 80% Saudis) with a mean age of 57.1 years were enrolled. Medical history included previously diagnosed ischemic heart disease (32%), percutaneous coronary intervention (12%), diabetes mellitus (53%), hypertension (48%), current smoking (39%), hyperlipidemia (31%) and family history of premature coronary artery disease (11%). The median door-to-needle time for fibrinolytic therapy received by patients with STEMIs was 90 min. Inhospital medications included acetylsalicylic acid (98%), clopidogrel (73%), angiotensin-converting enzyme inhibitors (74%), beta-blockers (73%), statins (88%), unfractionated heparin (80%), low-molecular weight heparin (22%) and glycoprotein IIb/IIIa inhibitors (9%). The inhospital mortality rate was 5%.

CONCLUSION:

The first nationwide registry of patients with ACS in the Kingdom of Saudi Arabia is presented. In contrast to registries from developed countries, our cohort is characterized by a younger age at presentation and a much higher prevalence of diabetes mellitus. Most patients with STEMIs did not receive fibrinolytic therapy within the time recommended in the American College of Cardiology/American Heart Association guidelines. The results of the present pilot study show potential targets for improvement in care.     

Acute myocardial infarction: Fibrinolytic therapy

Opinion statement Fibrinolytic therapy (also known as thrombolytic therapy) is an established, simple, widely available and cost-effective treatment option for acute myocardial infarction. Adjunctive use of antiplatelet and antithrombin therapies has been shown to reduce reinfarction rates by 30% to 40%. These agents may also improve reperfusion rates and facilitate percutaneous coronary intervention (PCI). Adjunctive use of platelet glycoprotein IIb/IIIa inhibitors and newer antithrombotic agents (eg, low molecular weight heparin, bivalirudin, or pentasaccharide) has not been shown to reduce 30-day mortality rates. Bolus administration of fibrinolytic agents enhances their acceptability for prehospital use, and dose adjustment of antithrombotic therapy may help to reduce the risk of bleeding, particularly in lighter-weight patients and the elderly. There is a need for trials comparing newer fibrinolytic regimens with primary PCI and facilitated PCI. The time from symptom onset to reperfusion is the most important factor affecting patient outcome.     

Glycoprotein IIb/IIIa inhibition in the setting of acute ST-segment elevation myocardial infarction

Glycoprotein (GP) IIb/IIIa inhibitors have been extensively studied in the setting of percutaneous coronary intervention (PCI) and in the management of non-ST-segment elevation acute coronary syndromes. However, the use of GP IIb/IIIa inhibitors is less well established in the setting of acute ST-segment elevation myocardial infarction (MI). Multiple nonrandomized studies suggest that combination therapy with GP IIb/IIIa inhibitors and thrombolytic agents leads to increased rates of TIMI 3 flow. However, two clinical trials involving over 22,000 patients demonstrated that combination therapy is associated with only modest reductions in major adverse cardiac events, does not reduce mortality, and is associated with an increase in bleeding. In the setting of primary PCI, four clinical trials involving over 3,000 patients demonstrated that GP IIb/IIIa inhibition results in a significant decrease in the need for urgent target vessel revascularization but not in reductions of death or recurrent MI. Thus, GP IIb/IIIa inhibition may provide only limited benefits in the setting of acute ST-segment elevation MI.