转运PCI

Pharmaco-invasive Strategies Ex Ele Da ta, M bott N (PCI ion ( y of regi These ing Hear patie Keywords: I systems of care During acute (STEMI), myoca with time, eventu ization of the in reducing morbidi reducing the ad 4 College of Cardiology (ACC)/American Heart Associa- rred strategy for ithin a door-to- primary PCI in been increasing, n successful in ters.9 The major the strategy chosen for reperfusion in this situation is ad Progress in Cardiovascular Diseases 53 (2010) 188–194 www.onlinepcd.com tion (AHA) and European Society of Cardiology (ESC) guidelines for STEMI if an anticipated delay in performing percutaneous coronary intervention (PCI) occurs.6,7 With subsequent advancements in balloon angioplasty and stenting, PCI has shown to reduce mortality, nonfatal myocardial infarction, recurrent ische- hoc, dependent on complex factors including patient risk stratification, time of day, and availability of cardiologist and PCI facility.10 This leads to inevitable and unaccept- able delays with an inherent increase in mortality.2 Current recommendations for patients undergoing trans- fer from non-PCI hospitals to a PCI facility differ slightly, with a total door-to-balloon treatment goal of 90 minutes in the ACC/AHA and 120 minutes in ESC treatment. In the 1980s, fibrinolytics emerged as the treatment of choice5 and remain part of the American challenge is the treatment of patients with STEMI presenting to a hospital without PCI capability. Often, Statement of Conf ⁎ Address reprint Heart Institution Foun MN 55407-1191. E-mail address: h 0033-0620/$ – see fro doi:10.1016/j.pcad.20 ST-elevation myocardial infarction; Pharmacoinvasive; Primary percutaneous coronary intervention; STEM ST-elevation myocardial infarction rdial damage increases substantially ally reaching a point where revascular- farct-related artery is not beneficial in ty or mortality.1-3 The key factor in verse sequelae of STEMI is prompt mia, and stroke and is now the prefe reperfusion if it can be performed w balloon time of 90 minutes.6-8 Use of STEMI patients in the United States has and the ACC D2B Alliance has bee improving time to treatment at PCI cen © 2010 Elsevier Inc. All rights reserved. patients treated with fibrinolytic therapy. (Pro centers have total door-to-balloon times less than 2 hours. We review the therapeutic options for the STEMI patient with expected delay to PCI focusing on recent pharmacoinvasive trials. Based on these trial results, recent guidelines recommend early transfer and cardiac catheterization for g Cardiovasc Dis 2010;53:188-194) Coronary Intervention in ST- Aaron L. Doonana, Marc C. Newella,b, aUniversity of Minneso bMinneapolis Heart Institute Foundation at Ab Abstract Primary percutaneous coronary intervention patients with ST-elevation myocardial infarct to PCI is a major national focus. The majorit which has stimulated the development of protocols and organized transfer systems. treatment times and clinical outcomes, lead American College of Cardiology/American systems of care. Despite this, less than 15% of lict of Interest: see page 192. requests to Timothy D. Henry, MD, Minneapolis dation, 920 East 28th St., Suite 100, Minneapolis, enry003@umn.edu (T.D. Henry). nt matter © 2010 Elsevier Inc. All rights reserved. 10.09.004 pand Access to Percutaneous vation Myocardial Infarction vid M. Larsonb, Timothy D. Henryb,⁎ inneapolis, MN, USA orthwestern Hospital, Minneapolis, MN, USA ) is the preferred method of reperfusion in STEMI). Therefore, increasing timely access United States hospitals are not PCI capable, onal STEMI programs using standardized regional STEMI systems have improved to a recent class I recommendation in the t Association guidelines to develop STEMI nts transferred from non-PCI hospitals to PCI guidelines.6,7 According to the National Cardiovascular Disease Registry, only 9.9% of patients transferred from a hospital without PCI capability for primary PCI achieve a door-to-balloon time of less than 90 minutes11; and based 188 on the most recent Na- tional Registry of Myo- cardial Infarction data, less than 15% of patient transferred from non- PCI facility are treated in less than 2 hours.12 There continues to be randomized trial (PRAGUE) ev transfer for PCI against fibrin during transport. Mortality was r in the PCI-treated patients; and th death, reinfarction, and stroke w Table 1 Reperfusion options for the patients with expe 1 Full-dose fibrinolytic, a with selective transfer 2 Full-dose fibrinolytic, r aggressive rescue PCI 3 Facilitated or pharmaco 4 Primary PCI (no matte 5 Any of the above depe and the cardiologist on Abbreviations and Acronyms ACC = American College of Cardiology AHA = American Heart Association ESC = European Society of Cardiology A.L. Doonan et al. / Progress in Cardiova ytic therapy.15 The first aluated the strategy of olytics given on-site or educed from 14% to 7% e combined end point of as significantly reduced, cted delays dmission to the non-PCI hospital for rescue PCI outine transfer to PCI hospital with invasive PCI r how long it takes) nding on the PCI facility availale considerable controver- sy regarding the ideal reperfusion strategy for the STEMI patient with an expected delay13 (Table 1). We review these options and discuss how regional systems may increase timely access to PCI. Strategies to treat STEMI in hospitals without PCI capability Full-dose fibrinolytics Full-dose fibrinolytics remain the guideline-recom- mended reperfusion strategy for the patient with expected delay.6,7 By eliminating the need for special equipment and trained personnel, this is often the most expeditious strategy for reperfusion in STEMI in a non-PCI facility. However, 26% to 36% of patients will ultimately fail to reperfuse and will require transfer for rescue PCI.14 Therefore, the current ACC/AHA guidelines recommend early transfer to a PCI center especially for high-risk patients.6 The ESC guidelines are even stronger, with a class I recommendation for all patients receiving fibrino- lytics to undergo transfer and cardiac catheterization within 24 hours.7 In addition, 2% to 3% of fibrinolytic-treated patients will experience an intracranial hemorrhage; and 5% to 10% will have recurrent ischemia or infarction. Transfer for primary PCI Data indicate that transfer for primary PCI is also significantly better than fibrinol PCI = percutaneous coronary intervention STEMI = ST-elevation myocardial infarction call driven mostly by a reduction in reinfarction (10% vs 1%, P b .03).16 The PRAGUE-2 trial found a similar reduction in overall 30-day mortality of transfer for PCI over fibrinolytics (10% vs 6.8%, P = .12); and an analysis based on treatment actually received was statistically significant (10.4% vs 6%, P b .05), as was the subgroup of patients presenting greater than 3 hours from onset of symptoms (15.3% vs 6%, P b .02).17 The only US randomized trial, AIR-PAMI, randomized high-risk patients presenting to hospitals without PCI capability to either on-site fibrinolytics or transfer for primary PCI. The trial was terminated early because of poor enrollment; but there was a trend toward reduced 30-day mortality with transfer for PCI (8.4% vs 12.1%, P = .46), despite a median emergency department to treatment time of 155 minutes.18 The DANAMI-2 trial definitively showed that transfer for PCI reduced the combined end point of death, reinfarction, and disabling stroke over fibrinolytics (13.7% vs 8%, P b .001).19 The median symptom-onset-to- treatment time was 224 minutes, with a median door-to- balloon time of just more than 100 minutes; and the trial demonstrated benefit that persisted at 3 years.20 A contemporary meta-regression analysis confirmed the benefit of transfer for primary PCI over fibrinolysis, showing a reduction in mortality (5.6% vs 6.8%, P = .02), reinfarction (2.1% vs 4.7%, P b .0001), and stroke (0.7% vs 1.7%, P = .0005) in the first 30 days.21 These results indicate that transfer for primary PCI from non- PCI centers has advantages over fibrinolysis similar to patients presenting to a PCI hospital, if performed in a timely manner. Although these trials were encouraging, there were concerns over the ability to translate these European trials in countries with short distances and organized transport systems into successful time-to-treatment in the United States. For instance, the PRAGUE transfer distance (referral hospital to the angioplasty center) ranged from 5 to 74 km; and in DANAMI-2, the mean distance was 35 miles with a maximum of 95 miles. The time from emergency department admission at the transferring hospital to treatment (total door-to-balloon time) in these studies was only 95 to 108 minutes, which is exceptional. In contrast, the median door-to-balloon time in transfer patients in the US National Registry of Myocardial Infarction 3/4 was 180 minutes, with only 4.2% of patients treated within 90 minutes.12 Thus, many believed extending the strategy of transfer for primary PCI to the entire United States would result in unacceptable delays in the majority of patients. The pharmacoinvasive strategy Despite the success of STEMI transfer systems, many areas of the country still have transport distances too long 189scular Diseases 53 (2010) 188–194 to allow timely access to PCI. Facilitated PCI was an appealing strategy to combine the advantages of Table 2 Randomized Controlled Trials Comparing Reperfusion Strategies for STEMI Patients with Expected Delays Study Year Published Trial Design Inclusion Criteria Lytic Patients PCI patients Primary Endpoint Primary Endpoint Results Conclusion PRAGUE16 2000 STKase vs.STKase en route to PCI vs. Transfer for PPCI Chest pain b6 hours, ST elevation or new LBBB 99 (in-hospital) and 100 (during transport) 101 Death, reinfarction, or stroke at 30 days 8% (PCI) vs. 15% (Lytic during transport) vs. 23% (Lytics only), P = b.02 Transfer for PPCI better than lytics during transport and alone PRAGUE-217 2002 STKase vs. Transfer for Primary PCI STEMI, New LBBB, b12 hr of symptoms, b120km from PCI center 421 429 30 Day Mortality 6.8% (PCI) vs. 10% (Lytics), P = .12 (ITT analysis), P b .05 actual therapy Transfer for PPCI probably better than lytics AIR-PAMI18 2002 Lytics vs. Transfer for Primary PCI Pain b12 h with STEMI, new LBBB, plus 1 or more high- risk criteria 66 71 Death, reinfarction, or stroke at 30 days 8.4% (PCI) vs. 13.6% (Lytics), P = .331, P = .028 (secondary analysis) Transfer for PPCI probably better than lytics DANAMI-219 2003 Alteplase vs. Transfer for Primary PCI Pain b12 h with STEMI 782 790 Death, clinical reinfarction, disabling stroke at 30 days 14.2% (lytics) vs. 8.5% (PCI), P b .001 Transfer or PPCI better than lytics SIAM III27 2003 Reteplase + PCI b6 h vs. Delayed PCI (14 days) N18 yrs., Pain b12 h, STEMI, LBBB, Eligible for lytics - 82 (early PCI), 81 (delayed PCI) Death, reinfarction, ischemic events, target lesion revascularization 25.6% (early PCI) vs. 50.6% (delayed PCI), P = .001 Following lytics, early PCI better than delayed PCI CAPITAL AMI28 2005 TNK vs.TNK facilitated PCI Pain ≤6 h, STEMI, high risk feature 84 86 (facilitated PCI) Death, reinfarction, recurrent unstable ischemia, stroke at 6 months 24.4% (lytics alone) vs. 11.6% (lytic facilitated PCI), P = .04 Lytic facilitated PCI is better than lytics alone ASSENT-423,24 2006/2009 Primary PCI vs TNK-facilitated PCI Pain b6 h, STEMI, LBBB with concordant ST elevation 829 (lytics followed by PCI) 838 Death, CHF, shock at 90 days 19% (facilitated PCI) vs. 13% (PCI), P = .0045 Primary PCI better than facilitated PCI FINESSE25,26 2008/2009 Primary PCI vs reteplase/abciximab facilitated PCI vs. abciximab facilitated PCI Pain b6 h, STEMI, eligible for lytics or PCI, estimated time to cath 1-4 h 828 (lytics with abciximab), 818 (abciximab) 806 Death, VF within 48 hours, cardiogenic shock, CHF, ED visit within 90 days 9.8% (lytics/abciximab facilitated PCI) vs. 10.5% (abciximab facilitated PCI) vs. 10.7% (PCI), P = .55 No difference CARESS-IN- AMI29 2008 1/2 dose reteplase with early PCI vs ischemia guided PCI Pain b12 h, ST elevation N 15 mm, new LBBB, previous MI, Killip class ≥ 2, LVEF ≤ 35% 301 299 (early PCI) Death, reinfarction, refractory ischemia at 30 days 4.4% (early PCI) vs. 10.7% (standard), P = .004 Transfer for immediate PCI is better than ischemia guided rescue PCI NORDISTEMI30 2009 TNK with immediate transfer for PCI vs. ischemia guided rescue PCI Age 18–75 yrs., Pain b6 h, STEMI, Expected time delay from first medical contact to PCI N90 min., Receiving thrombolytic treatment with tenecteplase 132 (rescue strategy) 134 (immediate PCI after lytics) Death, reinfarction, stroke, or new ischemia at 12 months 21% (early PCI vs. 27% (ischemia guided) P = .19 No difference between early PCI and rescue stretegy TRANSFER- AMI31 2009 TNK with early PCI vs TNK with ischemia guided rescue PCI ST elevation of ≥2 mm in two anterior leads or ≥1 mm in two inferior leads and: SBP b100 mmHg, HR N100 bpm, Killip class II or III, ST depression of ≥2 mm in the anterior leads, or ST elevation of 1 mm or more in right-sided lead V4 (V4R), indicative of right ventricular involvement 522 (ischemia guided strategy) 537 (early PCI after lytics) Death, reinfarction, recurrent ischemia, new or worsening heart failure, or cardiogenic shock at 30 days 11.0% (early PCI) vs. 17.2% (rescue strategy), P = .004 Transfer for immediate PCI is better than ischemia guided rescue PCI 190 A .L . D oonan et al. / P rogress in C ardiovascular D iseases 53 (2010) 188–194 diova pharmacologic and mechanical revascularization. Unfor- tunately, based primarily on the results of the 2 largest trials, ASSENT-4 and FINESSE, enthusiasm for facilitated PCI waned.22 The ASSENT-4 trial randomized patients to standard-dose tenecteplase followed by PCI vs primary PCI. Despite an improvement in infarct-related artery patency with fibrinolytics, the trial was stopped early because of an increase in in-hospital death in the facilitated arm (6% vs 3.8%, P = .04).23 In retrospect, this trial had a number of shortcomings; 45% of patients were enrolled at PCI centers, less than 5% of patients were enrolled in the United States, patients with long delays were actually excluded, and antiplatelet therapies were not allowed before PCI. Further analysis of the trial, stratified by enrollment site, revealed that the highest mortality cohort was the group presenting to a PCI center randomized to facilitated PCI (8.4%) vs 6.5% in patients presenting to a hospital without PCI capability vs 3.1% in patients randomized in the prehospital settings.24 The authors of the trial noted that few patients actually fit the target population for which facilitated PCI was designed and came to the conclusion that “the ASSENT-4 PCI trial should not be taken as grounds for conclusive rejection of facilitated PCI.”24 The FINESSE trial compared abciximab alone to abciximab plus reteplase vs primary PCI, but was also terminated early because of slow recruitment. Patients assigned to receive abciximab plus reteplase had signifi- cantly greater ST-segment resolution, more TIMI 3 flow, and reduced infarct size. There was, however, no effect on the primary end point of death, ventricular fibrillation, shock, congestive heart failure, and emergency department visits as compared with abciximab alone and primary PCI (9.8% vs 10.5% vs 10.7%, P = .55).25 A post hoc analysis revealed that high-risk patients presenting to hospitals without PCI capability within 4 hours from the onset of symptoms had reduced 1-year mortality with abciximab plus reteplase compared with primary PCI (hazard rate, 0.351; P = .01).26 Recently, there has been a resurgence of interest in the concept of fibrinolysis followed by early revascularization, renamed the pharmacoinvasive strategy.13 How does the pharmacoinvasive approach differ from facilitated PCI? Facilitated PCI trials in general compared the combination of fibrinolysis or IIb/IIIa inhibitors and early PCI with PCI alone. These trials were predominately in PCI hospitals with short delays to PCI. In addition, the majority of trials were done before or prohibited the use of thiopyridines.13 In contrast, the recent pharmacoinvasive trials have compared fibrinolysis followed by early PCI with fibrinolysis alone and an ischemia-guided rescue strategy (standard guideline-recommended therapy). In general, these trials have been conducted in non-PCI hospitals with longer delays to PCI and have used thiopyridines (Table 2). SIAM III enrolled patients in German community hospitals to fibrinolysis followed by transfer for immediate A.L. Doonan et al. / Progress in Car stenting or fibrinolytics with delayed stenting. Stenting performed within 6 hours of symptom onset significantly reduced death, reinfarction, target lesion revascularization, and ischemic events (25.6% vs 50.6%, P = .001) and improved left ventricular function (by ejection fraction) at 6 months (61.5% vs 56.4%, P = .018). In addition, 23.5% of patients assigned to the delayed stenting strategy needed unplanned angiography because of recurrence of ischemia, angina, or hemodynamic instability.27 These results were mimicked in the CAPITAL AMI study in Canada where stenting performed within 3 hours reduced the composite of death, reinfarction, recurrent unstable ischemia, or stroke (11.6% vs 24.4%, P = .04) without an increase in bleeding.28 In the CARESS-IN-AMI trial, mortality, reinfarction, and recurrent ischemia were reduced with transfer for early PCI as compared with a rescue PCI strategy (4.4% vs 10.7%, P = .004).29 Although the primary end point of death, reinfarction, stroke, and new ischemia was not statistically significant, the NORDIS- TEMI trial did show a reduction in death, reinfarction, and stroke with an early invasive approach to PCI after fibrinolysis (6.0% vs 15.9%, P = .01).30 The largest trial to date, TRANSFER-AMI, compared fibrinolytics followed by routine transfer for PCI vs transfer for rescue PCI. Although stopped early because of slow enrollment, early transfer for PCI within 6 hours reduced the composite of death, reinfarction, recurrent ischemia, new or worsening congestive heart failure, or cardiogenic shock within 30 days (11.0% vs 17.2%, P = .004).31 A recent meta-analysis of early routine PCI after fibrinolysis vs standard therapy in patients in STEMI demonstrated a significant reduction in recurrent ischemia and infarction at 30-day follow up with no increase in major bleeding or stroke.32 These results were maintained at 6 to 12 months with significant improvement in reinfarction (odds ratio, 0.64; 95% confidence interval, 0.40-098; P = .01) and the combined death/reinfarction (odds ratio, 0.71; 95% confidence interval, 0.52-0.97; P = .03). These results support early transfer to a PCI center for early angiography and PCI, although the ideal timing and pharmacologic regimen remain to be determined.13,32 Comprehensive regional STEMI systems of care Because of the data supporting transfer for primary PCI and the relative lack of hospitals in the United States with PCI capability, regional STEMI transfer systems have been developed to improve timely access to primary PCI with impressive treatment times and outcomes. In the level I program at the Minneapolis Heart Institute, patients are assigned one of two strategies based on the distance from the PCI center33,34 (Fig 1). Within 60 miles, patients with STEMI are transferred for primary PCI. If presenting between 60 and 210miles, a pharmacoinvasive approach is used. Overall mortality was 4.2% and did not differ between strategies, despite inherently long transfer times.33 191scular Diseases 53 (2010) 188–194 A standardized, comprehensive protocol was developed that included basic forms, treatment algorithms, a