University of Texas Health Science Center and Memorial Hermann

Heart and Vascular Institute, Houston, Texas.

Am J Cardiol 2014;113:60e63

Introduction

• Extensive investigations of treatment strategies for patients with STEMIs have led to many improvements in care.

• Yet optimal treatment strategies for patients aged ≥75 years with STEMIs are much less clear, and many knowledge gaps remain.

• Age ≥75 years is an independent predictor of 30-day mortality in STEMI.

• Although this higher mortality risk generally would dictate more aggressive treatments, recent data have shown, for example, that <1/2 of patients aged ≥80 years with STEMIs are treated with any reperfusion therapies at all.

• Field evaluation for STEMI using 12-lead electrocardiograms obtained on the scene by EMS personnel and transmitted for overreadby emergency center physicians.

• Eligible patients with STEMIs receive pre hospital, reduced-dose fibrinolytic agents along with aspirin, clopidogrel, and heparin and are transported to our STEMI center for urgent percutaneous coronary intervention (PCI). This is termed the FAST-PCI strategy.

• Patients with STEMIs evaluated by EMS units not equipped with fibrinolytic kits, and those who are not eligible for fibrinolysis, receive aspirin, clopidogrel, and heparin followed by transport for urgent PCI (the primary PCI [PPCI] strategy.

• The purpose of this retrospective study was to examine differences in outcomes for patients aged ≥75 years treated in this coordinated STEMI system of care according to FAST-PCI or PPCI strategy.

Methods

• The prehospital evaluation and treatment protocol

• Field evaluation of STEMI using 12-lead electrocardiograms obtained and transmitted by EMS personnel, with overread by emergency department physicians.

• Eligible patients with STEMIs are given reduced dose reteplase (10 U intravenously), aspirin (325 mg orally), clopidogrel (600 mg orally), and heparin (60 U/kg, up to 4,000 U intravenously).

• Patients with STEMIs who are not eligible for fibrinolysis receive aspirin, clopidogrel, and heparin at the same dosages.

• Glycoprotein IIb/IIIa inhibitors are used according to local practices or at the discretion of the treating physician.

• From March 2006 to February 2013- 1,303 patients with STEMIs

• Of these, 214 (16.4%) were ≥75 years of age and formed the basis of this study.

• In the subset of 214 patients aged ≥75 years, the FAST-PCI strategy was used in 120 (56%) and PPCI in 94 (44%).

• Analyzed demographics, clinical features, laboratory data, angiographic data, and outcomes of the 2 strategies.

• The primary end point comparison was 30-day mortality.

• Secondary end points included stroke, reinfarction, and major bleeding.

• A composite end point of mortality, stroke, reinfarction, or major bleeding was also analyzed.

• Ischemic time was defined as the time from pain onset to first device activation (first balloon inflation or thrombus aspiration).

• Stroke was defined as the development of new neurologic deficit not present on initial screening examination, neurologist diagnosis of stroke, or new intracranial bleeding diagnosed by CT or MRI.

• Reinfarction was defined as new significant Q waves in 2 contiguous leads different from the initial STEMI, reelevation of creatinekinase-MB to normal or higher (or by another 50%, if already normal or higher), and reelevation of creatine kinase-MB to >3 or >5 times the upper limit of normal after angioplasty or surgery, respectively.

• Major bleeding was defined as bleeding resulting in hemodynamic instability requiring intervention and assessed using Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries (GUSTO) trial criteria.

• Patients were followed up for events after hospital discharge by telephone call, outpatient visit, or both at 30 days after the index STEMI.

Results

Discussion

• Our main finding is that FAST-PCI decreased 30-day mortality compared with PPCI in patients aged ≥75 years with STEMIs treated within a coordinated STEMI system of care.

• There were no apparent bleeding, stroke, or reinfarction penalties.

• These results are similar to what we found previously for in-hospital outcomes in the overall STEMI population including all ages.

• The combination of prehospital reduced-dose fibrinolysis followed by urgent PCI offers potential benefits of smaller infarct size and lower mortality compared with PPCI alone.

• The likely mechanism is shortened time to initial treatment and thus earlier infarct artery patency, ultimately reducing ischemic times.

• Because ischemic time is a better measure of infarct size and mortality, minimization of this ischemic time is the supreme goal of coordinated STEMI systems of care

• The population ≥75 years in age has not been studied as extensively as others with acute coronary syndromes.

• Fibrinolytic agents are administered only cautiously because intracranial hemorrhage and nonhemorrhagic strokes are possible complications of treatment, especially in those with certain risk factors such as uncontrolled hypertension, low body weight, and female gender.

• This concern has led to the belief that PPCI may offer advantages over full-dose intravenous fibrinolysis in elderly patients.

• Unfortunately, the 2 largest trials testing this hypothesis, the Primary Angioplasty Versus Thrombolytic Therapy for Acute Myocardial Infarction in the Elderly (Senior PAMI) trial (481 patients) and the Tratamiento del Infarto Agudo de Miocardio en Ancianos (TRIANA) trial (266 patients) were terminated early because of slow enrollment.

• Although neither trial demonstrated superiority of PPCI over full-dose intravenous fibrinolysis with the enrollment numbers obtained, numerically, the results seemed to favor PPCI.

• A pooled analysis of available randomized patients aged >75 years with STEMIs (n ¼ 834) included within the TRIANA report indicated only a nonsignificant reduction in mortality for PPCI over full-dose intravenous fibrinolysis(10.7% vs 13.8%, odds ratio 0.74, 95% confidence interval, 0.49 to 1.13, p ¼ 0.16).

• However, this pooled analysis did suggest a benefit of PPCI over full-dose fibrinolysis for the larger composite end point of mortality, reinfarction, and disabling stroke (14.9% vs 21.5%, odds ratio 0.64, 95% confidence interval 0.45 to 0.91, p ¼ 0.013).

• More recently, the Strategic Reperfusion Early After Myocardial Infarction (STREAM) study, which included 255 patients aged ≥75 years from a total of 1,892 patients, initially compared prehospital full-dose fibrinolysis with PPCI in patients with STEMIs.

• At an interim safety analysis, intracranial hemorrhage rates were noted to be higher in the full-dose fibrinolysis group (1.0% vs 0.2%, p ¼ 0.04).

• A protocol change was then adopted to use only half-dose fibrinolysis in patients aged ≥75 years, and after that, the intracranial hemorrhage rates were equivalent (0.5% vs 0.3%, p ¼ 0.45).

• There were no cases of intracranial hemorrhage in patients aged ≥75 years (0 of 97 patients) after the protocol change, compared with 3 cases of intracranial hemorrhage in 37 patients in this age group before the change.

• The primary composite end point of death, shock, congestive heart failure, or reinfarction at 30 days was equivalent in the 2 groups (all ages), 12.4% for prehospital fibrinolysis and 14.3% for PPCI (p ¼ 0.21).

• The total ischemic time was shorter in the prehospital fibrinolysis group compared with the PPCI group (median 100 vs 178 minutes, p <0.001).

• However, in STREAM, this ischemic time was measured from the onset of symptoms until the initiation of therapy.

• For the prehospital fibrinolysis group it was administration of the agent that was used as the initiation measure, and first device activation was used for the PPCI group.

• In our study, we used time from symptom onset to first device activation as the ischemic time measure in the 2 groups so as to have consistent comparisons.

• The frequency of completely occluded arteries at angiography before PCI in STREAM was lower for prehospital fibrinolysis compared with PPCI (16.0% vs 59.5%, p <0.001).

• We noted comparable differences, and this again suggests that 1 mechanism of benefit to prehospital reduced-dose fibrinolysis is earlier patency of the infarct artery.

limitations

• Patients were not assigned randomly to treatment strategy but rather were assigned on the basis of eligibility, EMS vehicle status (equipped or not), and sequential timing (because of the nature of fibrinolytic supply interruption). This might have led to selection bias.

• Only simple comparative analyses were performed, because the group sizes were too small to permit more sophisticated comparisons.

• Nevertheless, the same operators and the same system were at work for the 2 groups, reducing the impact of such differences.

• Adverse event rates were low in the 2 groups examined, although numerically, there were more strokes and more major bleeding events in the FAST-PCI than in the PPCI group.

• With larger sample sizes, these differences may or may not have become significant.

• It is also unknown but likely that aggressive adherence to bleeding avoidance strategies, including the use of a radial artery approach, would have reduced the frequency of bleeding events in the 2 groups, thus making it even more difficult to compare small values.

• In general, enrolling large numbers of patients aged ≥75 years with STEMIs in randomized controlled trials is difficult because of the presence of many high-risk features.

• Registry analyses and meta-analyses of smaller studies may be the only way to obtain data on this population.

Conclusion

• For patients aged ≥75 years with STEMIs, a FAST-PCI strategy in a coordinated system of care was associated with reduced 30-day mortality, earlier infarct artery patency, and lower incidence of cardiogenic shock at arrival compared with PPCI, without apparent bleeding, stroke, or reinfarctionpenalties.

• Larger studies and clinical trials if possible are needed to further investigate this approach.