Combined Abciximab REteplase Stent Study in acute myocardial infarction (CARESS in AMI)

doi:10.1016/j.ahj.2004.03.038

American Heart Journal

Volume 148, Issue 3, September 2004, Pages 378-385

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https://doi.org/10.1016/j.ahj.2004.03.038 Get rights and content

Abstract

Background

Most patients with acute myocardial infarction (AMI) are admitted to hospitals without percutaneous transluminal coronary angioplasty (PTCA) facilities or are initially managed in a prehospital mobile unit. Thrombolysis remains the most readily available reperfusion treatment in those settings, but the optimal subsequent strategy in those patients is unclear. If a mechanical recanalization is likely to be performed in an emergency, it is probably desirable that the patient receives abciximab, the glycoprotein IIb/IIIa antagonist with the strongest evidence of benefit for angioplasty in AMI.

Objective

The aim of this trial is to compare the effects on clinical outcome and cost-effectiveness of 2 strategies after immediate treatment with abciximab and half-dose reteplase for ST-elevation AMI: to manage the patients conservatively (referring them for rescue PTCA only if needed) or to immediately send all patients for emergency coronary angioplasty.

Methods

The Combined Abciximab RE-teplase Stent Study in Acute Myocardial Infarction (CARESS in AMI) is an open, prospective, randomized, multicenter clinical trial conducted in patients with high-risk ST-segment elevation AMI treated within 12 hours from symptom onset in hospitals without PTCA facilities or in a prehospital mobile intensive care unit. Apart from contraindications to thrombolysis, the main exclusion criteria are age ≥75 years and a past history of CABG surgery or a percutaneous coronary intervention procedure involving the infarct-related artery. Enrollment will be performed in hospitals without PTCA facilities or directly in the ambulance if a dedicated system is in place for prehospital diagnosis and treatment of AMI. Patients will receive half-dose reteplase and full-dose abciximab and will subsequently be randomized to conventional medical therapy (with referral for emergency rescue PTCA allowed in selected cases) or emergency angioplasty. The primary end point is the 30-day combined incidence of mortality, reinfarction, and refractory ischemia. In order to obtain a 95% power (2-sided) to detect a 42% reduction in the primary end point, 900 patients are required in each arm of the study. Secondary end points include the 1-year composite end point of mortality, reinfarction, refractory ischemia, and hospital readmission because of heart failure; resource use at 30 days and 1 year; and the incidence of inhospital stroke and bleeding complications in the 2 groups.

Results

Seventy-four patients have been randomized (as of March 10, 2004); results are expected in June 2005.

Conclusion

This study will establish whether angioplasty must be started as soon as possible in all patients who receive combined pharmacologic reperfusion with the glycoprotein IIb/IIIa inhibitor abciximab and half-dose thrombolysis or whether it can be postponed or skipped in patients with signs of successful reperfusion, with obvious organizational advantages.

Section snippets

Patients and centers

In all patients with ST-segment elevation AMI admitted within 12 hours from symptom onset, contraindications will be screened for entry in this study, and the data of patients with AMI who do not meet the inclusion criteria or do not accept to participate in the study will be entered in a dedicated registry. Enrollment into the trial is limited to patients with AMI within 12 hours from symptom onset with an ST-segment elevation ≥1 mm in at least 2 electrocardiographic (ECG) limb leads or ≥2 mm

Results

Enrollment is currently ongoing in 35 peripheral centers, referring to 18 PTCA units in Italy, France, and Poland. On July 13th, 2004, 137 patients were enrolled. Final results (30-day end point) are expected in December 2005.

Discussion

A delay in the initiation of reperfusion treatment may blunt the potential benefit of primary PTCA25, 26, 27 and is likely to occur when the patient is initially admitted to a hospital without PTCA or if the organization of dedicated mobile units allows immediate pharmacologic interventions in the ambulance during transportation. In district hospitals receiving a large population of AMI patients, the alternative can be to start a local primary PTCA program. This solution has been shown to be

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Cited by (39)

Association of initial Thrombolysis in Myocardial Infarction flow grade with mortality among patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention: A National Registry of Myocardial Infarction-5 (NRMI-5) analysis
2011, American Heart Journal
Initial epicardial coronary flow, as assessed by the Thrombolysis in Myocardial Infarction flow grade (TFG), prior to primary percutaneous coronary intervention (pPCI) for ST-segment elevation myocardial infarction (STEMI) has been associated with short- and long-term mortality in randomized clinical trials. This study was designed to determine the relationship between initial TFG and mortality in a large, heterogeneous, real-world population of STEMI patients undergoing pPCI.
The relationship between pre-pPCI TFG among patients undergoing pPCI and in-hospital mortality was evaluated among STEMI patients from 2004 to 2006 in the National Registry of Myocardial Infarction.
Of 8,337 STEMI patients, 6,595 (79.1%) had pre-pPCI TFG 0/1, 1,126 (13.5%) had pre-pPCI TFG 2, and 616 (7.4%) had pre-pPCI TFG 3. TFG 0/1 prior to pPCI was associated with 3.4% in-hospital mortality, whereas TFG 2 (2.0%) and TFG 3 (1.8%) were associated with significantly lower mortality (TFG 0/1 vs TFG 2, P = .013; TFG 0/1 vs TFG 3, P = .035). TFG 0/1 prior to pPCI was also associated with a significant increase in the composite of death, recurrent myocardial infarction, heart failure, and shock (16.1%) when compared with patients presenting with TFG 2 (11.5%; P < .001) and TFG 3 (7.6%; P < .001). The difference in this composite was also significant between patients presenting with TFG 2 and TFG 3 (P = .01).
In a large, heterogeneous group of real-world patients presenting with STEMI, pre-pPCI TFG 0/1 is associated with higher in-hospital mortality and other major adverse cardiovascular events. These results corroborate prior to post hoc analyses from randomized clinical trials and support continued efforts aimed at safely establishing early infarct-related artery patency among patients with STEMI.
Facilitated PCI by combination fibrinolysis or upstream tirofiban in acute ST-segment elevation myocardial infarction: Results of the Alteplase and Tirofiban in Acute Myocardial Infarction (ATAMI) trial
2008, International Journal of Cardiology
Citation Excerpt :
In all studies included 2 to 3 fold higher patency of the infarct-related artery post-fibrinolysis does not translate into lower mortality [3–5]. Nevertheless, due to obvious organisational advantages and significant impact of preprocedural TIMI flow on 1-year mortality in anterior myocardial infarction [6] interest remains in facilitated PCI strategies awaiting results from the FINESSE [7] and the CARESS in AMI trials [8]. In 2002 a pilot study of facilitated PCI using a combination of half-dose alteplase and 10 μg/kg bolus and 0.15 μg/kg/min infusion tirofiban (modified RESTORE regimen) over 24 h could demonstrate high efficacy and high safety in acute ST-segment elevation myocardial infarction with a TIMI 2 or 3 flow of 87%, a 30-day mortality of 2.6% and one minor bleeding complication in a cohort of 39 patients [9].
Direct percutaneous coronary intervention is the generally accepted superior strategy in acute ST-segment myocardial infarction. The concept of facilitating PCI in order to overcome delay by door-to-balloon time or transport is nevertheless of interest. Combination fibrinolysis guarantees higher rates of open infarct-related vessels and reduced reocclusion but without reduction of mortality. After a pilot trial of facilitated PCI by combination fibrinolysis in 39 patients with excellent efficacy and high safety we prospectively randomised 151 patients (96 males, mean age 67.4 ± 8.7 years) to combination fibrinolysis with 50 mg alteplase and tirofiban and 162 patients (103 males, mean age 65.6 ± 9.4 years) to upstream tirofiban before invasive approach including PCI. TIMI 2 or 3 flow of infarct-related vessel before intervention as the primary endpoint and 30-day mortality, bleeding complication and angiographic proven stent thrombosis as secondary endpoints were assessed. 160 matched patients with acute PCI and provisional abciximab served as a control group.
TIMI 2 or 3 flow in the infarct-related vessel could be demonstrated in 87% in the combination fibrinolysis group, in 42% in the upstream tirofiban group (p < 0.0001) and 29% in the control group. 30-day mortality was 0.7% versus 5.5% (p < 0.02) and 6.3% in the control group. No differences could be assessed in severe or moderate (1.3% vs 1.2% vs 1.2%) and mild bleeding complications (2% vs 1.9% vs 2.5%). Stent thrombosis occurred in none of the patients with combination fibrinolysis, in 2 patients (1.5%) in the upstream tirofiban group and in 7 cases (4.4%) in the control group.
Combination fibrinolysis before PCI leads to significantly higher TIMI flow rates of the infarct-related vessel without increase in 30-day mortality or in bleeding complications. This strategy needs to be further investigated in larger trials and could optimise acute myocardial infarction management even without 24-h service of catheter laboratories.
Rationale and design of the Trial of Routine ANgioplasty and Stenting After Fibrinolysis to Enhance Reperfusion in Acute Myocardial Infarction (TRANSFER-AMI)
2008, American Heart Journal
Most patients with ST-elevation myocardial infarction present to hospitals without percutaneous coronary intervention (PCI) facilities and receive fibrinolysis. The role of routine early PCI after fibrinolysis, using stents and contemporary pharmacotherapy, has not been studied in a large adequately powered randomized trial.
To compare a pharmacoinvasive strategy of transfer for routine PCI within 6 hours after fibrinolysis with standard treatment after fibrinolysis (including predefined criteria for rescue PCI and delayed cardiac catheterization for patients who do not require rescue PCI).
A total of 1200 patients with high-risk ST-elevation myocardial infarction presenting to non-PCI centers will be randomized to a pharmacoinvasive strategy (transfer for routine PCI within 6 hours of fibrinolysis) or to standard treatment after fibrinolysis. The primary end point is the 30-day composite of death, reinfarction, recurrent ischemia, heart failure, or shock.
More than 900 patients have been enrolled as of April 2007. An interim safety analysis of the first 536 patients demonstrated no safety concerns. Enrolment is expected to be completed in late 2007.
This study will provide important data on whether routine early PCI within 6 hours after fibrinolysis is safe and superior to the standard treatment of fibrinolysis with rescue PCI or delayed cardiac catheterization.
New Trials and Therapies for Acute Myocardial Infarction
2007, Medical Clinics of North America
Citation Excerpt :
Two ongoing trials are addressing the use of GP IIb/IIIa antagonists in facilitated regimens. The Combined Abciximab Reteplase Stent Study in Acute Myocardial Infarction (CARESS) in 1800 patients who have STEMI is comparing the primary end point of the combined incidence of death, myocardial infarction, or refractory ischemia at 30 days in patients presenting to hospitals without PCI capabilities who are treated with abciximab and half-dose reteplase, with rescue PCI in the case of reperfusion failure, versus referral for facilitated PCI after early administration of abciximab and a half dose of reteplase [26]. GRACIA-3: A Randomized Trial to Evaluate the Role of Paclitaxel Eluting Stent and Tirofiban to Improve the Results of Facilitated PCI in the Treatment of Acute ST-Segment Elevation Myocardial Infarction will determine the efficacy of a paclitaxel-eluting stent compared with conventional bare stent in terms of restenosis [27].
Acute coronary syndromes (ACSs), which include the clinical entities of unstable angina (UA), non–ST-segment elevation myocardial infarction (NSTEMI), and ST-segment elevation myocardial infarction (STEMI), account for more than 1.5 million hospital admissions annually in the United States alone. Approximately 1 million of these admissions are classified as UA/NSTEMI and approximately 500,000 are STEMI. Because of the overwhelming number of studies on ACSs over the past several years, this article focuses on new trials and therapies for treating patients diagnosed with STEMI.
Update and rationale for ongoing acute myocardial infarction trials: Combination therapy, facilitation, and myocardial preservation
2006, American Heart Journal
Citation Excerpt :
It showed no difference between these 2 regimens, suggesting that either therapy was appropriate, but it did not answer the question of whether facilitation is helpful because there was no placebo group. The ongoing 1800-patient CARESS in AMI is comparing half-dose reteplase with abciximab followed by randomization to emergent angioplasty versus conservative care; the primary end point is the combined incidence of death, MI, or refractory ischemia at 30 days.23 The TITAN-TIMI-34 study is a smaller trial of 450 patients comparing early administration of the GP IIb/IIIa inhibitor eptifibatide in the emergency department versus its later administration in the cardiac catheterization laboratory; the primary end point is coronary flow reserve.24
Advancements in the treatment of myocardial infarction such as coronary care units, patient education, improved emergency response systems, and reperfusion therapy have reduced mortality. However, in an effort to further reduce the present rate by improving patency rates and microcirculatory perfusion, by better preserving myocardium, and/or treating shock more effectively, more research is under way to improve strategies now in place and to develop new, more effective ways to treat these patients.
PCI at non-PCI centres: immediate or rescue?
2008, The Lancet

View all citing articles on Scopus

^☆: The CARESS trial is sponsored by the Italian Society of Invasive Cardiology (GISE) and endorsed by the Italian Association of the Hospital Cardiologists (ANMCO). The project is supported by grants provided by Eli Lilly Italia SpA and Biotronik GmbH Germany.

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Trial designCombined Abciximab REteplase Stent Study in acute myocardial infarction (CARESS in AMI)☆

Abstract

Background

Objective

Methods

Results

Conclusion

Section snippets

Patients and centers

Results

Discussion

Lancet

Lancet

J Am Coll Cardiol

J Am Coll Cardiol

Am J Cardiol

J Am Coll Cardiol

J Am Coll Cardiol

Am J Cardiol

J Am Coll Cardiol

Management of acute myocardial infarction in patients presenting with ST segment elevation

Eur Heart J

A comparison of coronary angioplasty with fibrinolytic therapy in acute myocardial infarction

N Engl J Med

Long distance transport for primary angioplasty vs immediate thrombolysis in acute myocardial infarctionfinal results of the randomized national multicentre trial PRAGUE-2

Eur Heart J

Transfer for primary angioplasty versus immediate thrombolysis in acute myocardial infarctiona meta-analysis

Circulation

Multicentre randomized trial comparing transport to primary angioplasty vs immediate thrombolysis vs combined strategy for patients with acute myocardial infarction presenting to a community hospital without a catheterization laboratory

Eur Heart J

Platelet glycoprotein IIb/IIa inhibition with coronary stenting for acute myocardial infarction

N Engl J Med

Trial design
Combined Abciximab REteplase Stent Study in acute myocardial infarction (CARESS in AMI)☆