Ticagrelor alone vs. ticagrelor plus aspirin following percutaneous coronary intervention in patients with non-ST-segment elevation acute coronary syndromes: TWILIGHT-ACS.

AIMS: The aim of this study was to determine the effect of ticagrelor monotherapy on clinically relevant bleeding and major ischaemic events in relation to clinical presentation with and without non-ST elevation acute coronary syndromes (NSTE-ACS) among patients undergoing percutaneous coronary intervention (PCI) with drug-eluting stents (DES). METHODS AND RESULTS: We conducted a pre-specified subgroup analysis of The Ticagrelor With Aspirin or Alone in High Risk Patients After Coronary Intervention (TWILIGHT) trial, which enrolled 9006 patients with high-risk features undergoing PCI with DES. After 3 months of dual antiplatelet therapy (DAPT) with ticagrelor plus aspirin, 7119 adherent and event-free patients were randomized in a double-blind manner to ticagrelor plus placebo versus ticagrelor plus aspirin for 12 months. The primary outcome was Bleeding Academic Research Consortium (BARC) type 2, 3, or 5 bleeding while the composite of all-cause death, myocardial infarction (MI), or stroke was the key secondary outcome. Among patients with NSTE-ACS (n = 4614), ticagrelor monotherapy reduced BARC 2, 3, or 5 bleeding by 53% [3.6% vs. 7.6%; hazard ratio (HR) 0.47; 95% confidence interval (CI) 0.36-0.61; P < 0.001) and in stable patients (n = 2503) by 24% (4.8% vs. 6.2%; HR 0.76; 95% CI 0.54-1.06; P = 0.11; nominal Pint = 0.03). Rates of all-cause death, MI, or stroke among those with (4.3% vs. 4.4%; HR 0.97; 95% CI 0.74-1.28; P = 0.84) and without (3.1% vs. 3.2%; HR 0.96; 95% CI 0.61-1.49; P = 0.85) NSTE-ACS were similar between treatment arms irrespective of clinical presentation (Pint = 0.96). CONCLUSION: Among patients with or without NSTE-ACS who have completed an initial 3-month course of DAPT following PCI with DES, ticagrelor monotherapy reduced clinically meaningful bleeding events without increasing ischaemic risk as compared with ticagrelor plus aspirin. The benefits of ticagrelor monotherapy with respect to bleeding events were more pronounced in patients with NSTE-ACS. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT02270242.

Incidence, timing, and type of first and recurrent ischemic events in patients with and without peripheral artery disease after an acute coronary syndrome.

BACKGROUND: Patients with peripheral artery disease (PAD) are known to have an increased risk of ischemic cardiovascular events. However, the influence of concomitant PAD on first and subsequent recurrent ischemic events after an acute coronary syndrome (ACS) remains poorly characterized. METHODS: We analyzed the combined data set from 4 randomized trials (PLATO, APPRAISE-2, TRA-CER, and TRILOGY ACS) in ACS for a follow-up length of 1 year. Using multivariable regression, we examined the association between PAD and major adverse cardiovascular events, a composite of cardiovascular death, myocardial infarction, and stroke. Among patients with a nonfatal first event, we evaluated the incidence and type of a second recurrent event. RESULTS: A total of 4,098 of 48,094 (8.5%) post-ACS patients had a history of PAD. The unadjusted frequency of major adverse cardiovascular events was 2-fold higher in patients with PAD (14.3% vs 7.5%) over a median (25th-75th) follow-up of 353 (223-365) days with an adjusted hazard ratio of 1.63 (95% CI: 1.48-1.78; P < .001). The frequency of recurrent ischemic events among those patients with a first, nonfatal event was higher among those with PAD (40.0% vs 27.7%). The relative frequency of each event type (cardiovascular death, noncardiovascular death, myocardial infarction, or stroke) within first and subsequent ischemic events was similar regardless of PAD status at baseline. CONCLUSIONS: Patients with PAD have a significantly higher risk of first and recurrent ischemic events in the post-ACS setting. These findings highlight the opportunity for improved treatments in patients with PAD who experience an ACS.

Differential occurrence, profile, and impact of first recurrent cardiovascular events after an acute coronary syndrome.

OBJECTIVE: Acute coronary syndrome (ACS) trials typically use a composite primary outcome (myocardial infarction [MI], stroke, or cardiovascular death), but differential patient characteristics, timing, and consequences associated with individual component end points as first events have not been well studied. We compared patient characteristics and prognostic significance associated with first cardiovascular events in the post-ACS setting for initially stabilized patients. METHODS: We combined patient-level data from 4 trials of post-ACS antithrombotic therapies (PLATO, APPRAISE-2, TRACER, and TRILOGY ACS) to characterize the timing of and characteristics associated with first cardiovascular events (MI, stroke, or cardiovascular death). Landmark analysis at 7 days after index ACS presentation was used to focus on spontaneous, postdischarge events that were not confounded by in-hospital procedural complications. Using a competing risk framework, we tested for differential associations between prespecified covariates and the occurrence of nonfatal stroke vs MI as the first event, and we examined subsequent events after the first nonfatal event. RESULTS: Among 46,694 patients with a median follow-up of 358 (25th, 75th percentiles 262, 486) days, a first ischemic event occurred in 4,307 patients (9.2%) as follows: MI in 5.8% (n = 2,690), stroke in 1.0% (n = 477), and cardiovascular death in 2.4% (n = 1,140). Older age, prior stroke/transient ischemic attack, prior atrial fibrillation, and higher diastolic blood pressure were associated with a significantly greater risk of stroke vs MI, whereas prior percutaneous coronary intervention was associated with a greater risk of MI vs stroke. Second events occurred in 32% of those with a first nonfatal stroke at a median of 13 (3, 59) days after the first event and in 32% of those with a first nonfatal MI at a median of 35 (5, 137) days after the first event. The most common second event was a recurrent MI among those with MI as the first event and cardiovascular death among those with stroke as the first event. CONCLUSIONS: Approximately 9% of patients experienced a first cardiovascular event in the post-ACS setting during a median follow-up of 1 year. Although the profile and prognostic implications of stroke vs MI as the first nonfatal event differ substantially, approximately one-third of these patients experienced a second event, typically soon after the first event. These findings have implications for improving post-ACS care and influencing the design of future cardiovascular trials.

A randomized trial to compare the safety of rivaroxaban vs aspirin in addition to either clopidogrel or ticagrelor in acute coronary syndrome: The design of the GEMINI-ACS-1 phase II study.

Dual antiplatelet therapy (DAPT), the combination of aspirin and a P2Y12 inhibitor, given for 12 months remains the standard of care after presentation with acute coronary syndrome (ACS) because it has been shown to be associated with a significant reduction in ischemic events compared with aspirin monotherapy. The factor Xa inhibitor rivaroxaban was shown to be associated with a significant reduction in the composite of cardiovascular death, myocardial infarction, and stroke, and resulted in a nominal reduction in cardiovascular death, when added to background DAPT in the ATLAS ACS 2-TIMI 51 trial; however, there was excessive bleeding with this "triple-therapy" approach. The combination of rivaroxaban with P2Y12 inhibition in a "dual-pathway" approach may be an effective therapeutic regimen for the treatment of ACS, given the known importance of P2Y12 inhibition after stenting and intriguing data that the combination of an anticoagulant with clopidogrel after stenting in patients with atrial fibrillation appears an attractive option to this patient population. GEMINI-ACS-1 is a prospective, randomized, double-dummy, double-blind, active-controlled trial that will assess the safety of dual antithrombotic therapy (rivaroxaban [2.5 mg twice daily] + P2Y12 inhibitor) as compared with DAPT (aspirin [100 mg] + P2Y12 inhibitor) within 10 days of an ACS event in 3,000 patients. Patients will be randomized in a 1:1 ratio stratified by intended P2Y12 inhibitor use (clopidogrel 75 mg daily or ticagrelor 90 mg twice daily), with 1500 patients expected in each P2Y12 inhibitor strata. The primary end point is Thrombolysis in Myocardial Infarction clinically significant bleeding (major, minor, or requiring medical attention). The exploratory efficacy determination will be a composite of cardiovascular death, myocardial infarction, ischemic stroke, and stent thrombosis. GEMINI-ACS-1 will assess the safety and feasibility of dual antithrombotic therapy with rivaroxaban and a P2Y12 inhibitor compared with conventional DAPT for the treatment for patients with recent ACS.

A critical reappraisal of aspirin for secondary prevention in patients with ischemic heart disease.

Aspirin was established more than a quarter century ago as an evidence-based therapy to reduce recurrent cardiovascular events in patients with coronary artery disease based on limited data by contemporary standards. Indeed it is unclear how regulatory agencies would define the optimal dose or duration of aspirin therapy if assessed in the current era. Subsequent clinical investigation has focused on the addition of antithrombotic agents on top of baseline aspirin therapy in the acute and chronic setting to reduce patient's risk of further ischemic events, at the cost of increased bleeding complications. The current armamentarium of potent and predictable antiplatelet and antithrombotic agents has ushered in a new era where clinicians and scientists are contemplating withdrawal of previously established agents to minimize bleeding risk while sustaining efficacy; indeed, subtraction may lead to the next advance in the treatment of acute and chronic ischemic vascular disease.

Pooled analysis of adverse event collection from 4 acute coronary syndrome trials.

BACKGROUND: Adverse event collection in randomized clinical trials establishes drug safety. Although costly and regulated, it is rarely studied. METHODS: Adverse event data from 4 clinical trials (APPRAISE-2, PLATO, TRACER, TRILOGY ACS) comprising 48,118 participants with acute coronary syndromes were pooled to compare patterns and determinants of reporting. Events were classified as serious (SAE) or nonserious (AE) from hospital discharge to 1 year; study end points were excluded. RESULTS: In total, 84,901 events were reported. Of those, 12,266 (14.4%) were SAEs and 72,635 (85.6%) were AEs. Of all participants, 7,823 (16.3%) had SAEs, 18,124 (37.7%) had only AEs, and 22,171 (46.1%) had neither. Nonserious adverse events were distributed across system organ classes: general disorders (11%), infection (10%), gastrointestinal (10%), respiratory (9%), cardiovascular (8.4%), and other (35%). Serious adverse events had a higher proportion of cardiovascular causes (14.0%). Event reporting was highest after hospital discharge, decreasing rapidly during the following 3 months. In a Cox proportional hazards model, chronic obstructive pulmonary disease (hazard ratio 1.58, 95% CI 1.44-1.74), heart failure (1.55, 1.40-1.70), older age, and female sex were independent predictors of more SAEs, whereas enrollment in Eastern Europe (0.63, 0.58-0.69) or Asia (0.84, 0.75-0.94) were independent predictors of fewer SAEs. CONCLUSIONS: Half of all participants reported adverse events in the year after acute coronary syndrome; most were AEs and occurred within 3 months. The high volume of events, as well as the variation in SAE reporting by characteristics and enrollment region, indicates that efforts to refine event collection in large trials are warranted.

Long-term outcomes for women versus men with unstable angina/non-ST-segment elevation myocardial infarction managed medically without revascularization: insights from the TaRgeted platelet Inhibition to cLarify the Optimal strateGy to medicallY manage Acute Coronary Syndromes trial.

BACKGROUND: Women with acute coronary syndromes (ACS) are less likely to undergo invasive revascularization than men, but sex-specific differences in long-term outcomes and platelet reactivity among medically managed ACS patients remain uncertain. We examined sex-specific differences in long-term ischemic and bleeding outcomes and platelet reactivity for medically managed ACS patients randomized to prasugrel versus clopidogrel plus aspirin. METHODS: Data from 9,326 patients enrolled in TRILOGY ACS were analyzed to determine differences in long-term ischemic and bleeding outcomes between women (n = 3,650 [39%]) and men (n = 5,676 [61%]) randomized to prasugrel 10 mg/d (5 mg/d for patients ≥75 years and/or <60 kg) versus clopidogrel 75 mg/d. Sex-specific differences in 30-day platelet reactivity were analyzed in 2,564 (27%) patients participating in a platelet function substudy. RESULTS: Compared with men, women were older, weighed less, were less likely to have prior myocardial infarction or revascularization, and had lower baseline creatinine clearance and hemoglobin level values. Rates of the composite of cardiovascular death/myocardial infarction/stroke (20.2% vs 19.1%; P = .56), all-cause mortality (12.2% vs 11.7%; P = .88), and Global Use of Strategies to Open Occluded Arteries severe/life-threatening/moderate bleeding (3.8% vs 2.8%; P = .74) through 30 months were similar in women versus men. After adjustment, women had significantly lower risk for ischemic outcomes and all-cause mortality. There were no sex-specific, treatment-related differences in 30-day platelet reactivity. CONCLUSIONS: Long-term ischemic and bleeding outcomes in medically managed ACS patients were similar for women versus men, as was treatment-related platelet reactivity. Women had a higher baseline risk profile and, after adjustment, significantly lower risk of the primary composite end point and all-cause death through 30 months.

Antiplatelet and anticoagulation agents in acute coronary syndromes: what is the current status and what does the future hold?

Mortality and morbidity in acute coronary syndromes (ACSs), caused principally by plaque erosion or rupture leading to thrombus formation and myocardial ischemia, have been reduced by a combination of antithrombotic agents (antiplatelet drugs and anticoagulants) and early revascularization. Aspirin is the foundation antiplatelet agent. New P2Y12 receptor inhibitors (prasugrel and ticagrelor) have clear benefits compared with clopidogrel for dual antiplatelet therapy, and cangrelor or vorapaxar, a thrombin receptor inhibitor, may be of value in specific settings. Anticoagulation uses 1 of 4 choices: bivalirudin, unfractionated heparin, enoxaparin, and fondaparinux. Moreover, some patients (such as those who have chronic atrial fibrillation) require triple therapy with aspirin, clopidogrel, plus an anticoagulant, frequently a vitamin K antagonist. New oral anticoagulants have been shown to be at least as effective as vitamin K antagonists in atrial fibrillation and led to fewer bleeding complications. Finally, the combination of aspirin, clopidogrel, and low-dose rivaroxaban has recently been approved by the European Medicines Agency (but not the Food and Drug Administration) for secondary prevention after ACS. Several strategies have been developed to balance the potential benefit of antithrombotic therapy against the risk of bleeding complications, for example, radial access in coronary angiography or restricted use of combination therapy, and others are under investigation, such as discontinuation of aspirin. This overview summarizes the current status of antithrombotic therapy in ACS and describes strategies currently explored to optimize its benefit/risk ratio.

A multicenter, randomized, controlled study of mechanical left ventricular unloading with counterpulsation to reduce infarct size prepercutaneous coronary intervention for acute myocardial infarction: rationale and design of the Counterpulsation Reduces Infarct Size Acute Myocardial Infarction trial.

BACKGROUND: Despite advances in care processes to improve reperfusion in patients with acute myocardial infarction (AMI), the short-term and 1-year mortality remains high, in part, because of reperfusion injury, microvascular obstruction, and infarct expansion. Intraaortic balloon counterpulsation (IABC) is an adjunct to revascularization and has reduced microvascular obstruction and infarct size in animal models of AMI. METHODS: CRISP AMI is a multicenter randomized trial that aims to determine if IABC initiated before percutaneous coronary intervention (PCI) for reperfusion compared with routine PCI in patients with anterior ST-segment elevation AMI reduces infarct size as measured by cardiac magnetic resonance imaging. Patients are randomly assigned to receive IABC initiated before primary PCI and continued for at least 12 hours or routine PCI with standard-of-care medical therapy in both groups. The primary efficacy end point is infarct size measured by cardiac magnetic resonance imaging at 3 to 5 days post-PCI. The secondary clinical end point is the composite of major adverse clinical events including death, reinfarction, and heart failure at 6 months. According to sample size calculation, 300 patients will be randomized at 50 sites across 10 countries. CONCLUSION: The CRISP AMI study will determine if IABC before reperfusion in patients with anterior AMI reduces infarct size.

Risk score to predict serious bleeding in stable outpatients with or at risk of atherothrombosis.

AIMS: To develop a risk score to quantify bleeding risk in outpatients with or at risk of atherothrombosis. METHODS AND RESULTS: We studied patients in the REACH Registry, a cohort of 68 236 patients with/at risk of atherothrombosis. The outcome of interest was serious bleeding (non-fatal haemorrhagic stroke or bleeding leading to hospitalization and transfusion) over 2 years. Risk factors for bleeding were assessed using modified regression analysis. Multiple potential scoring systems based on the least complex models were constructed. Competing scores were compared on their discriminative ability via logistic regression. The score was validated externally using the CHARISMA population. From a final cohort of 56 616 patients, 804 (1.42%, 95% confidence interval 1.32-1.52) experienced serious bleeding between baseline and 2 years. A nine-item bleeding risk score (0-23 points) was constructed (age, peripheral arterial disease, congestive heart failure, diabetes, hypertension, smoking, antiplatelets, oral anticoagulants, hypercholesterolaemia). Observed incidence of bleeding at 2 years was: 0.46% (score < or = 6); 0.95% (7-8); 1.25% (9-10); 2.76% (> or = 11). The score's discriminative performance was consistent in CHARISMA and REACH (c-statistics 0.64 and 0.68, respectively); calibration in the CHARISMA population was very good (modified Hosmer-Lemeshow c(2) = 4.74; P = 0.69). CONCLUSION: Bleeding risk increased substantially with a score >10. This score can assist clinicians in predicting the risk of serious bleeding and making decisions on antithrombotic therapy in outpatients.

Patterns and prognostic implications of low high-density lipoprotein levels in patients with non-ST-segment elevation acute coronary syndromes.

AIMS: The patterns and prognostic significance of low high-density lipoprotein (HDL) cholesterol levels have not been well characterized. We sought to determine the prevalence and prognostic significance of low HDL cholesterol levels in patients with non-ST-segment elevation acute coronary syndromes (NSTE ACS). METHODS AND RESULTS: We evaluated HDL levels among NSTE ACS patients [ischaemic ECG (electrocardiogram) changes and/or positive cardiac markers] from the CRUSADE [Can Rapid Stratification of Unstable Angina Patients Suppress Adverse Outcomes with Early Implementation of the ACC(American College of Cardiology)/AHA(American Heart Association) Guidelines] initiative treated at 555 US hospitals from January 2001 through June 2006. Clinical and angiographic characteristics, treatments, and in-hospital outcomes were analysed by categories of HDL levels measured during hospitalization. Among 93 263 NSTE ACS patients with HDL measurements, 16 854 (18.1%) had very low HDL levels (10-29 mg/dL), 32 185 (34.5%) had low HDL levels (30-39 mg/dL), 35 875 (38.5%) had normal HDL levels (40-59 mg/dL), and 8349 (9.0%) had high HDL levels (60-100 mg/dL). Patients with very low HDL levels were younger, more often male, and more commonly obese and diabetic. Patients with very low HDL levels had the greatest risk of multi-vessel coronary disease on angiography and in-hospital mortality compared with patients with normal and high HDL levels. CONCLUSION: Almost one-fifth of patients with NSTE ACS have very low HDL levels--a finding that adds incrementally to a greater burden of atherosclerosis and a higher risk of mortality. Consequently, strategies for mitigating the adverse prognosis associated with very low HDL levels warrant further exploration in patients with ACS.

Percutaneous coronary intervention outcomes in patients with stable coronary disease and left ventricular systolic dysfunction.

AIMS: We sought to better understand the role of percutaneous coronary intervention (PCI) in patients with stable coronary artery disease (CAD) and moderate or severe left ventricular systolic dysfunction. METHODS AND RESULTS: Using data from the Duke Databank for Cardiovascular Disease, we analysed patients who underwent coronary angiography at Duke University Medical Center (1995-2012) that had stable CAD amenable to PCI and left ventricular ejection fraction ≤35%. Patients with acute coronary syndrome or Canadian Cardiovascular Society class III or IV angina were excluded. We used propensity-matched Cox proportional hazards to evaluate the association of PCI with mortality and hospitalizations. Of 901 patients, 259 were treated with PCI and 642 with medical therapy. PCI propensity scores created from 24 variables were used to assemble a matched cohort of 444 patients (222 pairs) receiving PCI or medical therapy alone. Over a median follow-up of 7 years, 128 (58%) PCI and 125 (56%) medical therapy alone patients died [hazard ratio 0.87 (95% confidence interval 0.68, 1.10)]; there was also no difference in the rate of a composite endpoint of all-cause mortality or cardiovascular hospitalization [hazard ratio 1.18 (95% confidence interval 0.96, 1.44)] between the two groups. CONCLUSIONS: In this well-profiled, propensity-matched cohort of patients with stable CAD amenable to PCI and moderate or severe left ventricular systolic dysfunction, the addition of PCI to medical therapy did not improve long-term mortality, or the composite of mortality or cardiovascular hospitalization. The impact of PCI on other outcomes in these high-risk patients requires further study.

Outcomes Among Patients Transferred for Revascularization With Impella for Acute Myocardial Infarction With Cardiogenic Shock from the cVAD Registry.

The outcomes for patients transferred with cardiogenic shock and later treated with revascularization and Impella support have not previously been studied. To evaluate these outcomes, patients in cardiogenic shock were recruited from the catheter-based ventricular assist device registry, a prospective registry enrolling patients who underwent percutaneous coronary intervention with hemodynamic support using Impella 2.5 or CP. Analysis was performed on subgroups of patients who were characterized as those directly admitted to a tertiary care hospital (direct), or those transferred from an outside hospital (transfer). Patients who were transferred with acute myocardial infarction with cardiogenic shock (AMICS) more often presented in shock were in shock longer than 24 hours, and were more likely to be on intra-aortic balloon pump but were less likely to sustain cardiac arrest. The number of pressors, EF, diseased, and treated vessels were similar between the 2 groups. Despite baseline differences, the mortality was similar in the transfer versus direct patients (47.0% vs 53.5% p = 0.19). In a multivariate model, the factors independently associated with 30-day mortality in AMICS treated with revascularization and Impella support were cardiopulmonary resuscitation (CPR) (p <0.01), age (p <0.01), and ST-segment elevation myocardial infarction (STEMI) (p = 0.02). Whether the patient was transferred or directly admittedly with AMICS was not an independent predictor of death. In conclusion, these findings suggest that considerations should be given to transfer patients with AMICS to allow them to be treated in a contemporary manner.

Relationship Between Optimism and Outcomes in Patients With Chronic Angina Pectoris.

Greater optimism regarding recovery from chronic illness is associated with improved quality of life and clinical outcomes. We performed a post-hoc analysis on the association between optimism and outcomes in Ranolazine in Patients with Incomplete Revascularization after Percutaneous Coronary Intervention (RIVER-PCI), a randomized trial in patients with chronic angina pectoris who had incomplete revascularization following percutaneous coronary intervention. At baseline, patients answered how much they agreed with the phrase, "I am optimistic about my future and returning to a normal lifestyle." We evaluated the association between baseline optimism and time to ischemia-driven hospitalization or revascularization using a Cox model, and the association between baseline optimism and change in frequency of angina pectoris using a mixed measures model. Of 2,389 patients, 782 (33.2%) were very optimistic ("strongly agree"), 1,000 (42.4%) were optimistic ("agree"), 451 (19.1%) were neutral ("undecided"), and 123 (5.2%) were not optimistic ("disagree" or "strongly disagree"). Very optimistic patients had a lower prevalence of co-morbidities and less severe angina at baseline than less optimistic patients. The rate of ischemia-driven revascularization or hospitalization was higher in neutral and not optimistic patients compared with very optimistic patients; this finding persisted after adjustment for co-morbidities and baseline angina frequency (hazard ratio 1.42, 95% confidence interval 1.14 to 1.77 for neutral vs very optimistic; hazard ratio 1.38, 95% confidence interval 0.98 to 1.94 for not optimistic vs very optimistic). Neutral and not optimistic patients also had less improvement in angina than very optimistic patients. In conclusion, in patients with angina, those with more self-reported optimism had better health status outcomes. Whether structured interventions targeting optimism improve outcomes in these patients warrants further study.

Importance of total ischemic time and preprocedural infarct-related artery blood flow in predicting infarct size in patients with anterior wall myocardial infarction (from the CRISP-AMI Trial).

The goal of this study was to characterize determinants of infarct size in the multicenter randomized Counterpulsation to Reduce Infarct Size Pre-PCI Acute Myocardial Infarction (CRISP-AMI) trial. Contemporary determinants of infarct size in patients presenting with acute anterior myocardial infarction without shock and undergoing percutaneous revascularization have been incompletely characterized. In CRISP-AMI, 337 patients with acute anterior ST segment elevation myocardial infarction but without cardiogenic shock at 30 sites in 9 countries were randomized to initiation of intra-aortic balloon counterpulsation before primary percutaneous coronary intervention versus standard of care. The primary outcome was infarct size as measured by cardiac magnetic resonance imaging 3 to 5 days after percutaneous coronary intervention. Of 337 randomized patients, complete periprocedural and infarct size data were available in 250 patients (74%). After a comparison of baseline characteristics to ensure no significant differences, patients with missing data were excluded. Using multiple linear regression of 23 variables, time from symptom onset to first device (ß = 0.022, p = 0.047) and preprocedural Thrombolysis In Myocardial Infarction flow 0/1 (ß = 15.28, p <0.001) were independent predictors of infarct size. Infarct size increased by 0.43% per 30 minutes in early reperfusion and by 0.63% every 30 minutes in late reperfusion. In conclusion, in patients with acute anterior ST elevation myocardial infraction without cardiogenic shock, total ischemic time and preprocedural Thrombolysis In Myocardial Infarction flow 0/1 were associated with increased infarct size as determined by cardiac magnetic resonance imaging. These findings underscore the importance of systems of care aimed at reducing total ischemic time to open infarct arteries.