Fibrinolysis or primary PCI in ST-segment elevation myocardial infarction.

BACKGROUND: It is not known whether prehospital fibrinolysis, coupled with timely coronary angiography, provides a clinical outcome similar to that with primary percutaneous coronary intervention (PCI) early after acute ST-segment elevation myocardial infarction (STEMI). METHODS: Among 1892 patients with STEMI who presented within 3 hours after symptom onset and who were unable to undergo primary PCI within 1 hour, patients were randomly assigned to undergo either primary PCI or fibrinolytic therapy with bolus tenecteplase (amended to half dose in patients ≥75 years of age), clopidogrel, and enoxaparin before transport to a PCI-capable hospital. Emergency coronary angiography was performed if fibrinolysis failed; otherwise, angiography was performed 6 to 24 hours after randomization. The primary end point was a composite of death, shock, congestive heart failure, or reinfarction up to 30 days. RESULTS: The primary end point occurred in 116 of 939 patients (12.4%) in the fibrinolysis group and in 135 of 943 patients (14.3%) in the primary PCI group (relative risk in the fibrinolysis group, 0.86; 95% confidence interval, 0.68 to 1.09; P=0.21). Emergency angiography was required in 36.3% of patients in the fibrinolysis group, whereas the remainder of patients underwent angiography at a median of 17 hours after randomization. More intracranial hemorrhages occurred in the fibrinolysis group than in the primary PCI group (1.0% vs. 0.2%, P=0.04; after protocol amendment, 0.5% vs. 0.3%, P=0.45). The rates of nonintracranial bleeding were similar in the two groups. CONCLUSIONS: Prehospital fibrinolysis with timely coronary angiography resulted in effective reperfusion in patients with early STEMI who could not undergo primary PCI within 1 hour after the first medical contact. However, fibrinolysis was associated with a slightly increased risk of intracranial bleeding. (Funded by Boehringer Ingelheim; ClinicalTrials.gov number, NCT00623623.).

Practice patterns and clinical outcomes among non-ST-segment elevation acute coronary syndrome (NSTE-ACS) patients presenting to primary and tertiary hospitals: insights from the EARLY glycoprotein IIb/IIIa inhibition in NSTE-ACS (EARLY-ACS) trial.

OBJECTIVES: We evaluated patients at tertiary [both percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) capable] and primary hospitals in the EARLY-ACS trial. BACKGROUND: Early invasive management is recommended for high-risk non-ST-segment elevation acute coronary syndromes. METHODS: We evaluated outcomes in 9,204 patients presenting to: tertiary sites, primary sites with transfer to tertiary sites ("transferred") and those who remained at primary sites ("non-transfer"). RESULTS: There were 348 tertiary (n = 7,455 patients) and 89 primary hospitals [n = 1,749 patients (729 transferred; 1,020 non-transfer)]. Significant delays occurred in time from symptom onset to angiography (49 hr), PCI (53h), and CABG (178 hr) for transferred patients (P < 0.001). Non-transfer patients had less 30-day death/myocardial infarction [9.4% vs. 11.7% (tertiary); adjusted odds ratio (OR): 0.78 (0.62-0.97), P = 0.026]; transferred (14.0%) and tertiary patients were similar [adjusted OR: 1.23 (0.98-1.53), P = 0.074]. Non-transfer patients had lower 1-year mortality [4.3% vs. 6.3% (tertiary); adjusted hazard ratio (HR): 0.64 (0.47-0.87), P = 0.005]: there was no difference between transferred and tertiary patients [5.2% vs. 6.3%; adjusted HR: 0.80 (0.58-1.12), P = 0.202]. Despite similar rates of catheterization, GUSTO severe/moderate bleeding within 120 hr was less in non-transfer [3.1% vs. 6.7% (tertiary); adjusted OR: 0.47 (0.32-0.68), P < 0.001], whereas transferred (6.1%) and tertiary patients were similar [adjusted OR: 0.94 (0.68-1.30), P = 0.693]. There was no difference in non-CABG bleeding. CONCLUSIONS: Timely angiography and revascularization were often not achieved in transferred patients. Non-transferred patients presenting to primary sites had the lowest event rates and the best long-term survival.

Non-invasive risk stratification for sudden cardiac death by heart rate turbulence and microvolt T-wave alternans in patients after myocardial infarction.

AIMS: To evaluate the predictive value of heart rate turbulence (HRT) and microvolt T-wave alternans (mTWA) for sudden cardiac death (SCD) in patients after myocardial infarction (MI). METHODS AND RESULTS: We studied 111 patients with MI in the previous 60 days (median, 27 [9;84] months) before inclusion (84 men, mean age 64.1 ± 10.5 years, mean left ventricular ejection fraction 46.6 ± 12.2%). Heart rate turbulence and mTWA were evaluated using 24 h ambulatory electrocardiogram monitoring. The primary endpoint was SCD, and the secondary endpoint was all-cause mortality and non-sudden death from cardiovascular causes. During follow-up of 12 months, 15 SCD and 8 non-sudden cardiovascular deaths (including five fatal MI and three fatal strokes) occurred. Non-survivors had significantly higher mTWA values (83 [74;165] vs. 79 [78;94] mcV, P= 0.002), absolute turbulence onset (TO) values (0 [-0.005;0.01] vs. -0.01 [-0.013;-0.004], P= 0.004), and significantly lower absolute turbulence slope (TS) values (3.34 [2.10;4.83], vs. 3.82 [4.48;7.27], P< 0.001) compared with survivors. In patients with SCD, mTWA, and TO were significantly higher (92 [72;213] vs. 74 [65;86] mcV, P= 0.004 and 0 [-0.001;0.01] vs. -0.01 [-0.03;0.01], P= 0.007, respectively) and TS values were significantly lower (2.14 [1.10;4.56] vs. 4.41 [2.1;7.18], P= 0.005) than in patients with non-sudden death. All parameters were significantly worse in non-survivors than in survivors. We defined cut-off values for increased risk of SCD: for TO = -0.005, relative risk (RR) was 12.4 [95% confidence interval (CI) 2.6-38.2, P< 0.001; positive predictive value (PPV) 28.3%, negative predictive value (NPV) 96.9%], and for mTWA > 53.5 mcV at 100 b.p.m., RR was 5.01 (95% CI 1.5-17.0, P= 0.005; PPV 24.4%, NPV 93.9%). Notably, mTWA > 18.5 mcV at 05.00 AM significantly increased all-cause mortality [RR 7.5 (95% CI 1.4-38.7), P= 0.01; PPV 19.6%, NPV 90.8%]. CONCLUSION: In patients who died from cardiovascular causes, mTWA, and TO values were significantly higher and TS values were significantly lower than in survivors, and the subgroup with SCD was characterized by significantly increased mTWA and TO values and decreased TS values. mTWA > 53.5 mcV at 100 b.p.m. was an independent significant predictor of SCD and increased risk of SCD by five-fold.

Aborted myocardial infarction in ST-elevation myocardial infarction: insights from the STrategic Reperfusion Early After Myocardial infarction trial.

BACKGROUND: We evaluated the prespecified endpoint, aborted myocardial infarction (AbMI), according to the use of a pharmacoinvasive (PI) strategy versus primary percutaneous coronary intervention (PCI) in 1754 patients randomised within 3 h of symptom onset in the STrategic Reperfusion Early After Myocardial infarction (STREAM) trial. METHODS: Based on sequential ECG's and biomarkers, AbMI was defined as ST-elevation resolution ≥50% (90 min posttenecteplase (TNK) in the PI arm or 30 min postprimary PCI) with minimal biomarker rise. RESULTS: In the PI arm 11.1% (n=99) had AbMI versus 6.9% (n=59) in primary PCI arm (p<0.01). In a multivariable model, AbMI patients overall had less baseline ΣST-deviation, fewer baseline Q-waves and shorter total ischaemic times. PI AbMI patients had faster time to TNK (90 vs 100 min, p=0.015): total ischaemic time was 100 min longer in primary PCI AbMI patients and no difference in ischaemic time existed between AbMI and non-AbMI patients within this group. Although no significant interaction between treatment and AbMI on the composite endpoint of death/shock/congestive heart failure/recurrent MI occurred (p=0.292), PI AbMI patients had a lower incidence in this endpoint than non-AbMI patients (5.1 vs 12%, p=0.038); this was not evident in primary PCI patients. Forty-five patients (ie, 2.5%) had masquerading MI with minimal biomarker elevation and no evolution in baseline ST-elevation. CONCLUSIONS: A PI strategy of early fibrinolysis more frequently aborts MI than primary PCI. Such PI patients had more favourable outcomes as compared with non-AbMIs. Diligent review of ECG evolution in STEMI distinguishes AbMI from infarct masquerade. ClinicalTrials.gov ID: NCT00623623.

Perceived risk of ischemic and bleeding events in acute coronary syndromes.

BACKGROUND: Acute coronary syndrome registries report the use of incomplete guideline therapies, especially among the highest risk patients. Whether this treatment gap results from misperceptions of risk by physicians is uncertain. METHODS AND RESULTS: The Perceived Risk of Ischemic and Bleeding Events in Acute Coronary Syndrome Patients (PREDICT) study was a prospective acute coronary syndrome registry in Australia, China, India, and Russia, involving 58 hospitals between May 2009 and February 2011. In-hospital care and events up to 6 months were assessed. At least 2 clinicians involved in patient care estimated the untreated risk and change in risk with each therapy. Physician risk assessment and objective risk measures (eg, Global Registry of Acute Coronary Events [GRACE] score) for death, death/myocardial infarction, and bleeding events were compared using the c statistic and integrated discrimination improvement. In total, 1542 patients and 4230 patient-specific physician estimates were obtained. Of responding clinicians, 81.9% were cardiovascular specialists (years of practice: mean [SD], 11.5 [7.7] years). The median physician-perceived risk of 6-month death was 25% (interquartile range, 14%-35%). The GRACE score was superior to physician estimation (c statistic: GRACE score, 0.812 [95% confidence interval, 0.772-0.851] versus physician, 0.652 [95% confidence interval, 0.596-0.708]; P<0.0001). The GRACE score added to clinician intuition improved discrimination (integrated discrimination improvement, 0.0632 [SE, 0.012]; P<0.0001). Invasive management correlated with physician-estimated risk but not with GRACE risk. Among patients not at high risk by physician estimation, increased risk by GRACE score was associated with higher mortality (3.7% versus 0.8%; P<0.001). CONCLUSIONS: Objective risk assessment provides superior risk discrimination when compared with physician-estimated risk. Whether systematic use of objective risk stratification improves clinical outcomes should be studied in appropriately designed clinical trials.