Effect of Moderate vs Mild Therapeutic Hypothermia on Mortality and Neurologic Outcomes in Comatose Survivors of Out-of-Hospital Cardiac Arrest: The CAPITAL CHILL Randomized Clinical Trial.

Importance: Comatose survivors of out-of-hospital cardiac arrest experience high rates of death and severe neurologic injury. Current guidelines recommend targeted temperature management at 32 °C to 36 °C for 24 hours. However, small studies suggest a potential benefit of targeting lower body temperatures. Objective: To determine whether moderate hypothermia (31 °C), compared with mild hypothermia (34 °C), improves clinical outcomes in comatose survivors of out-of-hospital cardiac arrest. Design, Setting, and Participants: Single-center, double-blind, randomized, clinical superiority trial carried out in a tertiary cardiac care center in eastern Ontario, Canada. A total of 389 patients with out-of-hospital cardiac arrest were enrolled between August 4, 2013, and March 20, 2020, with final follow-up on October 15, 2020. Interventions: Patients were randomly assigned to temperature management with a target body temperature of 31 °C (n = 193) or 34 °C (n = 196) for a period of 24 hours. Main Outcomes and Measures: The primary outcome was all-cause mortality or poor neurologic outcome at 180 days. Neurologic outcome was assessed using the Disability Rating Scale, with poor neurologic outcome defined as a score greater than 5 (range, 0-29, with 29 being the worst outcome [vegetative state]). There were 19 secondary outcomes, including mortality at 180 days and length of stay in the intensive care unit. Results: Among 367 patients included in the primary analysis (mean age, 61 years; 69 women [19%]), 366 (99.7%) completed the trial. The primary outcome occurred in 89 of 184 patients (48.4%) in the 31 °C group and in 83 of 183 patients (45.4%) in the 34 °C group (risk difference, 3.0% [95% CI, 7.2%-13.2%]; relative risk, 1.07 [95% CI, 0.86-1.33]; P = .56). Of the 19 secondary outcomes, 18 were not statistically significant. Mortality at 180 days was 43.5% and 41.0% in patients treated with a target temperature of 31 °C and 34 °C, respectively (P = .63). The median length of stay in the intensive care unit was longer in the 31 °C group (10 vs 7 days; P = .004). Among adverse events in the 31 °C group vs the 34 °C group, deep vein thrombosis occurred in 11.4% vs 10.9% and thrombus in the inferior vena cava occurred in 3.8% and 7.7%, respectively. Conclusions and Relevance: In comatose survivors of out-of-hospital cardiac arrest, a target temperature of 31 °C did not significantly reduce the rate of death or poor neurologic outcome at 180 days compared with a target temperature of 34 °C. However, the study may have been underpowered to detect a clinically important difference. Trial Registration: ClinicalTrials.gov Identifier: NCT02011568.

Acute kidney injury after radial or femoral artery access in ST-segment elevation myocardial infarction: AKI-SAFARI.

BACKGROUND: Acute kidney injury (AKI) complicating primary percutaneous coronary intervention (PCI) is an independent predictor of short- and long-term outcomes in patients presenting with ST-elevation myocardial infarction (STEMI). Prior studies suggest a lower incidence of AKI in patients undergoing PCI through radial artery compared to femoral artery access; however, no randomized clinical trials have specifically investigated this question in patients presenting with STEMI. METHODS: To determine whether radial access (RA) is associated with a reduced frequency of AKI following primary PCI, we performed a substudy of the SAFARI-STEMI trial. The SAFARI-STEMI trial was an open-label, multicenter trial, which randomized patients presenting with STEMI to RA or femoral access (FA), between July 2011 and December 2018. The primary outcome of this post hoc analysis was the incidence of AKI, defined as an absolute (>0.5 mg/dL) or relative (>25%) increase in serum creatinine from baseline. RESULTS: In total 2,285 (99.3%) of the patients enrolled in SAFARI-STEMI were included in the analysis-1,132 RA and 1,153 FA. AKI occurred in 243 (21.5%) RA patients and 226 (19.6%) FA patients (RR: 0.91, 95% CI: 0.78-1.07, P = .27). An absolute increase in serum creatinine >0.5 mg/dL was seen in 49 (4.3%) radial and 52 (4.5%) femoral patients (RR: 1.04, 95% CI: 0.71-1.53, P = .83). AKI was lower in both groups when the KDIGO definition was applied (RA 11.9% vs FA 10.8%; RR: 0.90, 95% CI: 0.72-1.13, P = .38). CONCLUSIONS: Among STEMI patients enrolled in the SAFARI-STEMI trial, there was no association between catheterization access site and AKI, irrespective of the definition applied. These results challenge the independent association between catheterization access site and AKI noted in prior investigations.

Safety and Efficacy of Femoral Access vs Radial Access in ST-Segment Elevation Myocardial Infarction: The SAFARI-STEMI Randomized Clinical Trial.

Importance: Among patients with ST-segment elevation myocardial infarction (STEMI) referred for primary percutaneous coronary intervention (PCI), a survival benefit associated with radial access compared with femoral access remains controversial. Objective: To assess whether there is a survival benefit when radial access is used instead of femoral access among patients with STEMI referred for primary PCI. Design, Setting, and Participants: This multicenter, open-label, randomized clinical trial was conducted at 5 PCI centers in Canada. In total, 2292 patients with STEMI referred for primary PCI were enrolled between July 2011 and December 2018, with a 30-day follow-up. The primary analyses were conducted based on the intention-to-treat population. Interventions: Patients were randomized to radial access (n = 1136) or to femoral access (n = 1156) for PCI. Main Outcomes and Measures: Initially, the primary outcome was bleeding, but this outcome was modified to 30-day all-cause mortality following the recommendation of the granting agency. Secondary outcomes included recurrent myocardial infarction, stroke, and Thrombolysis in Myocardial Infarction-defined major or minor bleeding. Results: Among the 2292 patients enrolled, the mean (SD) age of the patients randomized to radial access was 61.6 (12.3) years and to femoral access was 62.0 (12.1) years, with 883 male patients in the radial access and 901 male patients in the femoral access group. The trial was stopped early following a futility analysis. Primary PCI was performed in 1082 of 1136 patients (95.2%) in the radial access group and 1109 of 1156 patients (95.9%) in the femoral access group. Bivalirudin was administered to 1001 patients (88.1%) in the radial access group and to 1068 patients (92.4%) in the femoral access group, whereas glycoprotein IIb/IIIa inhibitors were administered in only 69 patients (6.1%) in the radial access group and 68 patients (5.9%) in the femoral access group. A vascular closure device was used in 789 patients (68.3%) in the femoral group. The primary outcome, 30-day all-cause mortality, occurred in 17 patients (1.5%) assigned to radial access and in 15 patients (1.3%) assigned to femoral access (relative risk [RR], 1.15; 95% CI, 0.58-2.30; P = .69). There were no significant differences between patients assigned to radial and femoral access in the rates of reinfarction (1.8% vs 1.6%; RR, 1.07; 95% CI, 0.57-2.00; P = .83), stroke (1.0% vs 0.4%; RR, 2.24; 95% CI, 0.78-6.42; P = .12), and bleeding (1.4% vs 2.0%; RR, 0.71; 95% CI, 0.38-1.33; P = .28). Conclusions and Relevance: No significant differences were found for survival or other clinical end points at 30 days after the use of radial access vs femoral access in patients with STEMI referred for primary PCI. However, small absolute differences in end points cannot be definitively refuted given the premature termination of the trial. Trial Registration: ClinicalTrials.gov identifier: NCT01398254.

Early Canadian Multicenter Experience With WATCHMAN for Percutaneous Left Atrial Appendage Closure.

BACKGROUND: There are limited data with WATCHMAN (Boston Scientific Corporation, Natick, MA, USA) for left atrial appendage (LAA) closure in patients with nonvalvular atrial fibrillation (AF) and contraindications to anticoagulation. The purpose of this study was to evaluate the safety and efficacy of WATCHMAN in our early Canadian experience. METHODS: We report our pooled consecutive series of patients who underwent WATCHMAN implantation at four major Canadian centers. Indications for LAA closure were CHADS2 ≥ 1 or CHA2 DS2 -VASc ≥ 2, and contraindication/intolerance to or failure on anticoagulation. Follow-up imaging was typically performed 1-6 months postprocedure. RESULTS: One hundred and six patients underwent LAA closure with WATCHMAN from May 2013 to October 2015. The mean age was 74.8 ± 7.7, mean CHADS2 score was 2.8 ± 1.2, CHA2 DS2 -VASc score was 4.3 ± 1.5, and HASBLED score was 3.2 ± 1.2. Permanent AF was present in 67.9% and paroxysmal AF in 32.1%. Indications for LAA closure were prior bleeding 89.6% (87 major bleeding and 8 minor bleeding), 9.4% were deemed high risk for bleeding, and 0.9% with recurrent strokes on warfarin. Procedural success was 97.2% (103 of 106), with one device embolization (snared percutaneously), one implant failure due to inadequate LAA depth, and one cardiac perforation requiring surgical repair before WATCHMAN implantation. The composite major safety event-rate was 1.9% (1 death and 1 device embolization). Mean hospital stay was 1.8 ± 4.7 days. Antithrombotic therapy postimplant included dual antiplatelet therapy in 76 of 103 (73.8%). Mean follow-up was 210 ± 182 days; there were two transient ischemic attacks, with estimated 66% reduction in thromboembolic events relative to CHADS2 predicted risk. CONCLUSION: In our early Canadian experience, WATCHMAN for LAA closure in patients contraindicated to anticoagulation appeared safe and effective.

Impact of mean arterial pressure on clinical outcomes in comatose survivors of out-of-hospital cardiac arrest: Insights from the University of Ottawa Heart Institute Regional Cardiac Arrest Registry (CAPITAL-CARe).

AIM OF THE STUDY: We sought to assess the relationship between mean arterial pressure (MAP) and clinical outcomes in comatose survivors of out-of-hospital cardiac arrest (OHCA). METHODS: We identified consecutive comatose survivors of OHCA with an initial shockable rhythm treated with targeted temperature management. We examined clinical outcomes in relation to mean MAP (measured hourly) during the first 96h of hospitalization. Co-primary outcomes were the rates of death and severe neurological dysfunction at discharge. RESULTS: In 122 patients meeting inclusion criteria, death occurred in 29 (24%) and severe neurological dysfunction in 39 (32%). Higher mean MAPs were associated with lower odds of death (OR 0.55 per 5mmHg increase; 95%CI 0.38-0.79; p=0.002) and severe neurological dysfunction (OR 0.66 per 5mmHg increase; 95%CI 0.48-0.90; p=0.01). After adjustment for differences in patient, index event, and treatment characteristics, higher mean MAPs remained associated with lower odds of death (OR 0.60 per 5mmHg increase; 95%CI 0.40-0.89; p=0.01) but not severe neurological dysfunction (OR 0.73 per 5mmHg increase; 95%CI 0.51-1.03; p=0.07). The relationship between mean MAP and the odds of death (p-interaction=0.03) and severe neurological dysfunction (p-interaction=0.03) was attenuated by increased patient age. CONCLUSION: In comatose survivors of OHCA treated with target temperature management, a higher mean MAP during the first 96h of admission is associated with increased survival. The association between mean MAP and clinical outcomes appears to be attenuated by increased age.

A randomised study for optimising crossover from ticagrelor to clopidogrel in patients with acute coronary syndrome. The CAPITAL OPTI-CROSS Study.

Ticagrelor has been endorsed by guidelines as the P2Y12 inhibitor of choice in patients with acute coronary syndrome. Clinically, some patients on ticagrelor will require a switch to clopidogrel; however, the optimal strategy and pharmacodynamics effects of switching remain unknown. Patients with an indication to switch were randomly assigned to either a bolus arm (Clopidogrel 600 mg bolus followed by 75 mg daily, n=30) or a no-bolus arm (Clopidogrel 75 mg daily, n=30). Blood samples were collected at baseline, 12, 24, 48, 54, 60 and 72 hours (h) for assessment of platelet reactivity. The primary outcome was P2Y12 reactivity units (PRU) at 72 h. Secondary outcomes included: PRUs at each time point, incidence of high on-treatment platelet reactivity (HPR), major adverse cardiac events (MACE) and TIMI bleeding at 30 days. Serial PRUs increased after switching to clopidogrel in both groups. At 72 h, no difference in PRU was observed (165.8 ± 71.0 vs 184.1 ± 67.7, bolus vs no bolus, respectively, p=0.19). At 48 h the PRUs were significantly lower in the bolus arm (114 ± 73.1 vs 165.1 ± 70.5, respectively; p=0.0076) and at 72 h, there was a significant reduction in incidence of HPR (26.7 % vs 56.7 %, p=0.02). No differences in MACE or TIMI bleeding were observed. Although a bolus strategy was not associated with improved platelet inhibition at 72 h; at 48 h, platelet inhibition was superior with reduced incidence of HPR. Larger studies will be required to determine its clinical significance. Until then, decision for giving a bolus of clopidogrel at the time of a switch may in part be dependent on the indication for switching, especially if there are concerns for bleeding risk.

Safety and Efficacy of a Pharmacoinvasive Strategy in ST-Segment Elevation Myocardial Infarction: A Patient Population Study Comparing a Pharmacoinvasive Strategy With a Primary Percutaneous Coronary Intervention Strategy Within a Regional System.

OBJECTIVES: This study investigated the safety and efficacy of a pharmacoinvasive strategy compared with a primary percutaneous coronary intervention (PCI) strategy for ST-segment elevation myocardial infarction (STEMI) in the context of a real-world system. BACKGROUND: Primary PCI continues to be the optimal reperfusion therapy; however, in areas where PCI centers are not readily available, a pharmacoinvasive strategy has been proposed. METHODS: The University of Ottawa Heart Institute regional STEMI system provides a primary PCI strategy for patients presenting within a 90-km radius from the PCI center, and a pharmacoinvasive strategy for patients outside this limit. We included all confirmed STEMI patients between April 2009 and May 2011. The primary efficacy outcome was a composite of mortality, reinfarction, or stroke and the primary safety outcome was major bleeding. RESULTS: We identified 236 and 980 consecutive patients enrolled in pharmacoinvasive and primary PCI strategies, respectively. The median door-to-needle time was 31 min in the pharmacoinvasive group and the median door-to-balloon time was 95 min in the primary PCI group. In a multivariable model, there was no significant difference in the primary efficacy outcome (odds ratio: 1.54; p = 0.21); however, the propensity for more bleeding with a pharmacoinvasive strategy approached statistical significance (odds ratio: 2.02; p = 0.08). CONCLUSIONS: Within the context of a STEMI system, a pharmacoinvasive strategy was associated with similar rates of the composite of mortality, reinfarction, or stroke as compared with a primary PCI strategy; however, there was a propensity for more bleeding with a pharmacoinvasive strategy.

Ticagrelor in Triple Antithrombotic Therapy: Predictors of Ischemic and Bleeding Complications.

BACKGROUND: Patients on dual antiplatelet therapy following percutaneous coronary intervention often have indications for concurrent oral anticoagulation or triple antithrombotic therapy (TT). Although TT may decrease ischemic complications, it may confer increased bleeding risk. HYPOTHESIS: We hypothesize that the use of ticagrelor in TT is associated with higher risk of complications; accordingly, we sought to determine predictors of complications in patients on TT. METHODS: Patients discharged on TT after percutaneous coronary intervention were followed prospectively for 12 months. The primary endpoint was a composite of ischemic (death, myocardial infarction, stroke) and major bleeding complications or net adverse clinical event (NACE). A major secondary endpoint was BARC (Bleeding Academic Research Consortium) types 2, 3, or 5 bleeding. Outcomes were compared between ticagrelor- and clopidogrel-treated patients. Multivariable analyses were performed to elucidate predictors of complications. RESULTS: Twenty-seven of 152 patients discharged on TT were on ticagrelor. NACE occurred in 52% of patients and BARC 2, 3, or 5 bleeding occurred in 18%. There was no difference in the primary or secondary outcome between ticagrelor vs clopidogrel subgroup. On logistic regressions, use of TT in patients with acute coronary syndrome (P = 0.002) and bridging in with ticagrelor (P = 0.02) were associated with increased NACE. Low estimated glomerular filtration rate was an independent predictor of bleeding (P = 0.03). CONCLUSIONS: The risk of bleeding and ischemic complications among patients on TT is similar between those on ticagrelor and clopidogrel. However, caution with use of bridging anticoagulation should be taken when using ticagrelor.

Safety and Efficacy of Staged Percutaneous Coronary Intervention During Index Admission for ST-Elevation Myocardial Infarction With Multivessel Coronary Disease (Insights from the University of Ottawa Heart Institute STEMI Registry).

The optimal management strategy for patients with ST-elevation myocardial infarction (STEMI) and multivessel disease has not been well established. In the present cohort study, we sought to examine the safety and efficacy of inhospital staged PCI for patients with STEMI and multivessel disease. We identified all patients with STEMI referred for primary PCI who were found to have multivessel disease (stenosis ≥50% in nonculprit vessel) and compared clinical outcomes in relation to the management strategy, staged versus culprit-only PCI, for nonculprit vessel disease. The primary outcome was mortality at 180 days, and secondary outcomes included mortality during the index hospitalization and at 30 days, myocardial infarction, stent thrombosis, stroke, and bleeding. Of the 1,038 patients with STEMI meeting inclusion criteria, 259 (25%) underwent staged PCI and 779 (75%) culprit-only PCI during the index admission. Mortality at 180 days was 0.8% in patients with staged PCI and 5.0% in patients with culprit-only PCI (p = 0.003). The association between staged PCI and reduced mortality persisted after adjusting for baseline differences in patient characteristics and angiographic variables between the 2 cohorts (odds ratio 0.2, 95% confidence interval 0.04 to 0.77, p = 0.02). The rates of inhospital reinfarction in the staged and culprit-only PCI cohorts were 0.8% versus 1.3% (p = 0.50), respectively, stent thrombosis 0.8% versus 1.3% (p = 0.50), and stroke 0.4% versus 1.3% (p = 0.31). There were no inhospital adverse events related to acute occlusion of a nonculprit vessel in either cohort. Staged PCI during index admission is a safe and effective revascularization strategy for patients with STEMI and multivessel disease.

A pharmacodynamic comparison of a personalized strategy for anti-platelet therapy versus ticagrelor in achieving a therapeutic window.

BACKGROUND: A therapeutic window in antiplatelet treatment has been associated with concurrent lowering of bleeding and ischemic risks. Prasugrel and ticagrelor provide potent platelet inhibition, but may increase bleeding. No study has evaluated a personalized therapy with selective use of novel P2Y12 inhibitory agents compared to empiric ticagrelor use. The objective of this study was to compare a personalized anti-platelet therapy strategy to empiric ticagrelor in achieving a therapeutic window. METHODS: Using the CAPITAL registry, we performed a retrospective analysis to evaluate a personalized anti-platelet therapy (PAT) strategy, using a pharmacogenetic approach, and compared it to empiric ticagrelor. In the PAT group, carriers of CYP2C19*2 received prasugrel and non-carriers received clopidogrel. The primary outcome was the proportion of patients within a validated therapeutic window, after a steady state treatment (≥48h) of antiplatelet therapy, as measured by a P2Y12 reaction unit (PRU) >85 and <208. RESULTS: Of 199 patients with platelet function measurements, 150 received PAT, while 49 received ticagrelor. Significantly more patients on PAT achieved the primary outcome (50.0% vs. 4.1%, p<0.0001). This was predominantly driven by an increase in low on-treatment reactivity with ticagrelor (95.9% vs. 37.3%, p<0.0001). Multivariable analysis demonstrated PAT to be the strongest predictor of achieving PRU values within the therapeutic window (odds ratio 20.27; 95% CI: 4.33-94.82, p=0.0001). CONCLUSION: Patients treated with PAT were more likely to achieve a therapeutic window compared to a strategy of ticagrelor. Future prospective evaluation of novel PAT strategies will be required to prove clinical utility.

Prophylactic warfarin therapy after primary percutaneous coronary intervention for anterior ST-segment elevation myocardial infarction.

OBJECTIVES: This study sought to determine the benefits of adding oral anticoagulation therapy in patients with anterior wall ST-segment elevation myocardial infarction (STEMI) patients after primary percutaneous coronary intervention (PCI). BACKGROUND: Guidelines suggest adding oral anticoagulation to dual-antiplatelet therapy in patients with STEMI when left ventricular apical akinesis or dyskinesis is present to prevent thromboembolic complications. The benefits of this triple therapy remain unknown. METHODS: We identified patients with anterior STEMI referred (PCI) between July 2004 and June 2010 with apical akinesis or dyskinesis on transthoracic echocardiography. We compared patients who were prescribed warfarin to patients who were not. We excluded patients with left ventricular thrombus, a separate need for oral anticoagulation, and previous intracranial bleeding. The primary outcome was a composite of net adverse clinical events (NACE) consisting of all-cause mortality, stroke, reinfarction, and major bleeding at 180 days. RESULTS: Among 460 patients who qualified, 131 were discharged on warfarin therapy and 329 without warfarin therapy. Dual-antiplatelet therapy was prescribed for 99.2% of the patients in the warfarin group and for 97.6% of the patients in the no warfarin group (p = 0.46). Compared with patients in the no warfarin group, patients in the warfarin group had higher rates of NACE (14.7% vs. 4.6%, p = 0.001), death (5.4% vs. 1.5%, p = 0.04), stroke (3.1% vs. 0.3%, p = 0.02), and major bleeding (8.5% vs. 1.8%, p < 0.0001). By propensity score analysis, allocation to warfarin therapy was an independent predictor of NACE (odds ratio [OR]: 4.01, 95% confidence interval: 2.15 to 7.50, p < 0.0001). In a separate multivariable analysis, the OR of NACE remained significantly higher compared with patients who were not prescribed warfarin (OR: 3.13, 95% confidence interval: 1.34 to 7.22, p = 0.007). CONCLUSIONS: Our results do not support the addition of warfarin therapy after primary PCI in patients with apical akinesis or dyskinesis.

Granulocyte colony-stimulating factor therapy for stem cell mobilization following anterior wall myocardial infarction: the CAPITAL STEM MI randomized trial.

BACKGROUND: Small studies have yielded divergent results for administration of granulocyte colony-stimulating factor (G-CSF) after acute myocardial infarction. Adequately powered studies involving patients with at least moderate left ventricular dysfunction are lacking. METHODS: Patients with left ventricular ejection fraction less than 45% after anterior-wall myocardial infarction were treated with G-CSF (10 µg/kg daily for 4 days) or placebo. After initial randomization of 86 patients, 41 in the placebo group and 39 in the G-CSF group completed 6-month follow-up and underwent measurement of left ventricular ejection fraction by radionuclide angiography. RESULTS: Baseline and 6-week mean ejection fraction was similar for the G-CSF and placebo groups: 34.8% (95% confidence interval [CI] 32.6%-37.0%) v. 36.4% (95% CI 33.5%-39.2%) at baseline and 39.8% (95% CI 36.2%-43.4%) v. 43.1% (95% CI 39.2%-47.0%) at 6 weeks. However, G-CSF therapy was associated with a lower ejection fraction at 6 months relative to placebo (40.8% [95% CI 37.4%-44.2%] v. 46.0% [95% CI 42.7%-44.3%]). Both groups had improved left ventricular function, but change in left ventricular ejection fraction was lower in patients treated with G-CSF than in those who received placebo (5.7 [95% CI 3.4-8.1] percentage points v. 9.2 [95% CI 6.3-12.1] percentage points). One or more of a composite of several major adverse cardiac events occurred in 8 patients (19%) within each group, with similar rates of target-vessel revascularization. INTERPRETATION: In patients with moderate left ventricular dysfunction following anterior-wall infarction, G-CSF therapy was associated with a lower 6-month left ventricular ejection fraction but no increased risk of major adverse cardiac events. Future studies of G-CSF in patients with left ventricular dysfunction should be monitored closely for safety. TRIAL REGISTRATION: ClinicalTrials.gov, no. NCT00394498.

A comparative pharmacodynamic study of ticagrelor versus clopidogrel and ticagrelor in patients undergoing primary percutaneous coronary intervention: the CAPITAL RELOAD study.

BACKGROUND: In patients undergoing primary percutaneous coronary intervention (PPCI) ticagrelor is superior to clopidogrel in reducing cardiovascular events. This study sought to evaluate the effect of clopidogrel pretreatment on the pharmacodynamics of ticagrelor in patients undergoing PPCI. METHODS: We measured platelet reactivity using the VerifyNow P2Y12 assay at baseline, 1, 2, 4, 6, 12, 24, and 48 hours following ticagrelor bolus in patients previously loaded with clopidogrel (C+T) and in thienopyridine-naive patients (T) referred to our centre for PPCI. RESULTS: In total, 52 consecutive eligible patients with ST-elevation myocardial infarction (STEMI) were enrolled (27 C+T and 25 T). Baseline characteristics and mean baseline platelet reactivity units (PRUs) were similar between the groups. The primary endpoint, the proportion of patients achieving a PRU<208 at 2 hours, was more frequently achieved in the C+T group compared to T treatment (76.0% vs 44.4%, p= 0.026). Notably, C+T therapy resulted in fewer patients with high platelet reactivity at 1 hour (56.0% vs. 14.8%), 4 hours (100.0% vs. 61.5%) and 6 hours (100.0% vs. 64%, p<0.01 for all comparisons). Furthermore, C+T therapy was associated with lower PRU values from 2 to 48 hours. CONCLUSIONS: In patients referred for PPCI, ticagrelor bolus following clopidogrel resulted in more rapid and profound platelet inhibition, demonstrating a positive pharmacodynamic interaction. Further study is needed to determine if this pharmacodynamic effect translates into reduced clinical events.

Percutaneous left atrial appendage closure with the AMPLATZER cardiac plug device in patients with nonvalvular atrial fibrillation and contraindications to anticoagulation therapy.

OBJECTIVES: The aim of this study was to evaluate the results associated with left atrial appendage closure (LAAC) with the AMPLATZER Cardiac Plug (ACP) (St. Jude Medical, Minneapolis, Minnesota) in patients with nonvalvular atrial fibrillation and absolute contraindications to anticoagulation therapy. BACKGROUND: Few data exist on the late outcomes after LAAC in patients with absolute contraindications to warfarin. METHODS: A total of 52 patients with nonvalvular atrial fibrillation underwent LAAC with the ACP device in 7 Canadian centers. Most patients received short-term (1 to 3 months) dual-antiplatelet therapy after the procedure and single-antiplatelet therapy thereafter. A transesophageal echocardiography was performed in 74% of patients at the 6-month follow-up. No patient was lost to follow-up (≥ 12 months in all patients). RESULTS: The mean age and median (interquartile range) CHADS2 score were 74 ± 8 years and 3 (2 to 4), respectively. The procedure was successful in 98.1% of the patients, and the main complications were device embolization (1.9%) and pericardial effusion (1.9%), with no cases of periprocedural stroke. At a mean follow-up of 20 ± 5 months, the rates of death, stroke, systemic embolism, pericardial effusion, and major bleeding were 5.8%, 1.9%, 0%, 1.9%, and 1.9%, respectively. The presence of mild peridevice leak was observed in 16.2% of patients at the 6-month follow-up as evaluated by transesophageal echocardiography. There were no cases of device thrombosis. CONCLUSIONS: In patients with nonvalvular atrial fibrillation at high risk of cardioembolic events and absolute contraindications to anticoagulation, LAAC using the ACP device followed by dual-/single-antiplatelet therapy was associated with a low rate of embolic and bleeding events after a mean follow-up of 20 months. No cases of severe residual leak or device thrombosis were observed at the 6-month follow-up.

The impact of therapeutic hypothermia as adjunctive therapy in a regional primary PCI program.

BACKGROUND: Therapeutic hypothermia (TH) is associated with improved neurologic outcomes in comatose survivors of out-of-hospital cardiac arrest (OHCA). There are currently limited data on the outcomes of patients presenting with resuscitated OHCA in the setting of ST-segment elevation myocardial infarction (STEMI). We conducted a retrospective study to determine the outcomes of patients treated with TH for OHCA in a large regionalized STEMI program. METHODS: Patients referred for primary PCI and TH between July 2004 and April 2011 were identified from the University of Ottawa Heart Institute STEMI database. The primary endpoint was survival to hospital discharge with sufficient neurologic recovery to enable discharge home. RESULTS: Among 2467 consecutive patients referred for primary PCI, we identified 50 patients treated with TH following OHCA. Forty-nine underwent PCI, of which 47 (96%) received a stent. Median door-to-balloon time was 113min (IQR 91-151). Patients with good neurologic recovery were younger, mean 51 ± 9 years versus 64 ± 12, p<0.001, and had higher baseline creatinine clearance, 70 ± 19 mL/min/1.73 m(2) versus 53 ± 23 mL/min/1.73 m(2), p=0.007. The primary endpoint of survival with sufficient neurologic recovery to enable discharge home was reached in 30 patients (60%). Four survivors required levels of assistance that precluded discharge home. CONCLUSIONS: Therapeutic hypothermia in conjunction with primary PCI is associated with a favorable neurologic outcome in the majority of STEMI patients surviving OHCA. Our results suggest that TH is an important adjunctive therapy for STEMI patients suffering OHCA.

Bivalirudin for primary percutaneous coronary interventions: outcome assessment in the Ottawa STEMI registry.

BACKGROUND: Data from randomized trials has demonstrated the superiority of bivalirudin to glycoprotein IIb/IIIa inhibitors plus heparin in patients undergoing primary percutaneous coronary intervention. Real-world performance of bivalirudin in primary percutaneous coronary intervention and the benefit of bivalirudin over heparin remain unknown in an era of routine dual antiplatelet therapy. METHODS AND RESULTS: From July 2004 to December 2010, 2317 consecutive patients were indexed in the University of Ottawa Heart Institute ST-segment-elevation myocardial infarction registry. During this period 748 patients received bivalirudin, 699 patients received glycoprotein IIb/IIIa inhibitors, and 676 patients received unfractionated heparin alone. The primary outcome was the rate of noncoronary artery bypass graft related thrombolysis in myocardial infarction major bleeding. Bivalirudin significantly reduced the primary outcome compared with heparin plus glycoprotein IIb/IIIa inhibitors (2.7% versus 7.3%, adjusted OR 2.96, 95% CI: 1.61-5.45, P<0.001) and the composite end point of death, stroke, reinfarction and major bleed (OR 1.66, 95% CI: 1.12-2.45, P=0.01). Compared with heparin alone, a reduction in major bleeds (OR 1.21, 95% CI: 0.60-2.44, P=0.59) or the composite end point (1.05, 95% CI: 0.68-1.63, P=0.83) with bivalirudin could not be demonstrated. Notably, major bleeding was associated with a 5-fold increase in the risk of mortality both in-hospital (3.5% versus 20.6%) and out to 180 days (5.6% versus 25.8%). CONCLUSIONS: Bivalirudin use compared with glycoprotein IIb/IIIa inhibitors plus heparin as an antithrombotic strategy in primary percutaneous coronary intervention results in less major bleeding in contemporary practice. A benefit of bivalirudin over heparin could not be established with this registry and requires additional investigations to either confirm or refute.

Reduction in mortality as a result of direct transport from the field to a receiving center for primary percutaneous coronary intervention.

OBJECTIVES: This study sought to determine whether mortality complicating ST-segment elevation myocardial infarction (STEMI) was impacted by the design of transport systems. BACKGROUND: It is recommended that regions develop systems to facilitate rapid transfer of STEMI patients to centers equipped to perform primary percutaneous coronary intervention (PCI), yet the impact on mortality from the design of such systems remains unknown. METHODS: Within the framework of a citywide system where all STEMI patients are referred for primary PCI, we compared patients referred directly from the field to a PCI center to patients transported beforehand from the field to a non-PCI-capable hospital. The primary outcome was all-cause mortality at 180 days. RESULTS: A total of 1,389 consecutive patients with STEMI were assessed by the emergency medical services (EMS) and referred for primary PCI: 822 (59.2%) were referred directly from the field to a PCI center, and 567 (40.8%) were transported to a non-PCI-capable hospital first. Death at 180 days occurred in 5.0% of patients transferred directly from the field, and in 11.5% of patients transported from the field to a non-PCI-capable hospital (p < 0.0001. After adjusting for baseline characteristics in a multivariable logistic regression model, mortality remained lower among patients referred directly from the field to the PCI center (odds ratio: 0.52, 95% confidence interval: 0.31 to 0.88, p = 0.01). Similar results were obtained by using propensity score methods for adjustment. CONCLUSIONS: A STEMI system allowing EMS to transport patients directly to a primary PCI center was associated with a significant reduction in mortality. Our results support the concept of STEMI systems that include pre-hospital referral by EMS.

Transradial versus transfemoral artery approach for coronary angiography and percutaneous coronary intervention in the extremely obese.

OBJECTIVES: This study sought to evaluate the safety and efficacy of transradial versus transfemoral access for coronary angiography and percutaneous coronary intervention in patients with a body mass index ≥ 40 kg/m(2). BACKGROUND: Coronary angiography is most commonly performed via femoral artery access; however, the optimal approach in extremely obese (EO) patients remains unclear. METHODS: Between January 2007 and August 2010, a cohort of consecutive EO patients who underwent coronary angiography was identified in our center's registry of angiography and percutaneous coronary intervention procedures. Of 21,103 procedures, 564 (2.7%) were performed in unique EO patients: 203 (36%) via the transradial approach; and 361 (64%) via the transfemoral approach. RESULTS: The primary outcome, a combined endpoint of major bleeding, access site complications, and nonaccess site complications, occurred in 7.5% of the transfemoral group and 2.0% of the transradial group (odds ratio [OR]: 0.30, 95% confidence interval [CI]: 0.10 to 0.88, p = 0.029), an endpoint driven by reductions in major bleeding (3.3% vs. 0.0%, OR: 0.12, 95% CI: 0 to 0.71, p = 0.015), as well as access site injuries (4.7% vs. 0.0%, OR: 0.08, 95% CI: 0 to 0.48, p = 0.002). There were no differences in nonaccess site complications (1.7% vs. 2.0%, OR: 1.50, 95% CI: 0.41 to 5.55), but transradial access procedures were associated with an increase in procedure time and patient radiation dose (p < 0.05). CONCLUSIONS: Transfemoral access for coronary angiography and percutaneous coronary intervention was associated with more bleeding and access site complications when compared with a transradial approach. Important reductions in procedural associated morbidity may be possible with a transradial approach in EO patients.