Milrinone as Compared with Dobutamine in the Treatment of Cardiogenic Shock.

BACKGROUND: Cardiogenic shock is associated with substantial morbidity and mortality. Although inotropic support is a mainstay of medical therapy for cardiogenic shock, little evidence exists to guide the selection of inotropic agents in clinical practice. METHODS: We randomly assigned patients with cardiogenic shock to receive milrinone or dobutamine in a double-blind fashion. The primary outcome was a composite of in-hospital death from any cause, resuscitated cardiac arrest, receipt of a cardiac transplant or mechanical circulatory support, nonfatal myocardial infarction, transient ischemic attack or stroke diagnosed by a neurologist, or initiation of renal replacement therapy. Secondary outcomes included the individual components of the primary composite outcome. RESULTS: A total of 192 participants (96 in each group) were enrolled. The treatment groups did not differ significantly with respect to the primary outcome; a primary outcome event occurred in 47 participants (49%) in the milrinone group and in 52 participants (54%) in the dobutamine group (relative risk, 0.90; 95% confidence interval [CI], 0.69 to 1.19; P = 0.47). There were also no significant differences between the groups with respect to secondary outcomes, including in-hospital death (37% and 43% of the participants, respectively; relative risk, 0.85; 95% CI, 0.60 to 1.21), resuscitated cardiac arrest (7% and 9%; hazard ratio, 0.78; 95% CI, 0.29 to 2.07), receipt of mechanical circulatory support (12% and 15%; hazard ratio, 0.78; 95% CI, 0.36 to 1.71), or initiation of renal replacement therapy (22% and 17%; hazard ratio, 1.39; 95% CI, 0.73 to 2.67). CONCLUSIONS: In patients with cardiogenic shock, no significant difference between milrinone and dobutamine was found with respect to the primary composite outcome or important secondary outcomes. (Funded by the Innovation Fund of the Alternative Funding Plan for the Academic Health Sciences Centres of Ontario; ClinicalTrials.gov number, NCT03207165.).

Routine invasive management early after fibrinolysis: relationship between baseline risk and treatment effects in a pooled patient-level analysis of 7 randomized controlled trials.

BACKGROUND: The efficacy of a routine invasive strategy early after fibrinolysis in relation to baseline risk status is unclear. We sought to characterize the interaction between patient risk and treatment with routine invasive strategy early after fibrinolysis for ST-segment elevation myocardial infarction. METHODS: We pooled 2,974 patients from 7 randomized trials of fibrinolysis-treated patients with ST-segment elevation myocardial infarction comparing a routine early invasive strategy with a standard approach of percutaneous coronary intervention (PCI) guided by recurrent ischemia or need for rescue. Cox proportional hazards regression was used to examine the interaction between baseline patient risk classified by Thrombolysis in Myocardial Infarction risk score (low/intermediate: ≤ 5 [n = 2,697] vs high: > 5 [n = 277]) and treatment with routine early invasive strategy. RESULTS: Time to PCI after fibrinolysis was longer among patients randomized to standard treatment compared with routine early invasive strategy in the low/intermediate-risk strata (median 11.4 vs 3.5 hours), but was only marginally different between the 2 groups in the high-risk strata (median 4.1 vs 3.5 hours). There was a significant interaction between treatment assignment and risk status for the composite of 30-day death or reinfarction (P = .01). Compared with standard treatment, routine early invasive strategy was associated with lower 30-day death/reinfarction in the low/intermediate-risk stratum (7.5% vs 4.0%, P < .001), but not in the high-risk stratum (14.9% vs 19.6%, P = .45). CONCLUSIONS: Although clearly beneficial among the larger subgroup of patients at low/intermediate risk, the benefit of a routine early invasive strategy was not evident in the smaller subgroup of higher-risk patients in the context of an increased requirement for urgent PCI in the comparative standard treatment arm.

Canadian Cardiovascular Society/Canadian Cardiovascular Critical Care Society/Canadian Association of Interventional Cardiology Clinical Practice Update on Optimal Post Cardiac Arrest and Refractory Cardiac Arrest Patient Care.

Survival to hospital discharge among patients with out-of-hospital cardiac arrest (OHCA) is low and important regional differences in treatment practices and survival have been described. Since the 2017 publication of the Canadian Cardiovascular Society's position statement on OHCA care, multiple randomized controlled trials have helped to better define optimal post cardiac arrest care. This working group provides updated guidance on the timing of cardiac catheterization in patients with ST-elevation and without ST-segment elevation, on a revised temperature control strategy targeting normothermia instead of hypothermia, blood pressure, oxygenation, and ventilation parameters, and on the treatment of rhythmic and periodic electroencephalography patterns in patients with a resuscitated OHCA. In addition, prehospital trials have helped craft new expert opinions on antiarrhythmic strategies (amiodarone or lidocaine) and outline the potential role for double sequential defibrillation in patients with refractory cardiac arrest when equipment and training is available. Finally, we advocate for regionalized OHCA care systems with admissions to a hospital capable of integrating their post OHCA care with comprehensive on-site cardiovascular services and provide guidance on the potential role of extracorporeal cardiopulmonary resuscitation in patients with refractory cardiac arrest. We believe that knowledge translation through national harmonization and adoption of contemporary best practices has the potential to improve survival and functional outcomes in the OHCA population.

Point-of-care genetic testing for personalisation of antiplatelet treatment (RAPID GENE): a prospective, randomised, proof-of-concept trial.

BACKGROUND: Prospective assessment of pharmacogenetic strategies has been limited by an inability to undertake bedside genetic testing. The CYP2C19*2 allele is a common genetic variant associated with increased rates of major adverse events in individuals given clopidogrel after percutaneous coronary intervention (PCI). We used a novel point-of-care genetic test to identify carriers of the CYP2C19*2 allele and aimed to assess a pharmacogenetic approach to dual antiplatelet treatment after PCI. METHODS: Between Aug 26, 2010, and July 7, 2011, 200 patients were enrolled into our prospective, randomised, proof-of-concept study. Patients undergoing PCI for acute coronary syndrome or stable angina were randomly assigned to rapid point-of-care genotyping or to standard treatment. Individuals in the rapid genotyping group were screened for the CYP2C19*2 allele. Carriers were given 10 mg prasugrel daily, and non-carriers and patients in the standard treatment group were given 75 mg clopidogrel daily. The primary endpoint was the proportion of CYP2C19*2 carriers with high on-treatment platelet reactivity (P2Y12 reactivity unit [PRU] value of more than 234) after 1 week of dual antiplatelet treatment, which is a marker associated with increased adverse cardiovascular events. Interventional cardiologists and data analysts were masked to genetic status and treatment. Patients were not masked to treatment allocation. All analyses were by intention to treat. This study is registered with ClinicalTrials.gov, NCT01184300. FINDINGS: After randomisation, 187 patients completed follow-up (91 rapid genotyping group, 96 standard treatment). 23 individuals in each group carried at least one CYP2C19*2 allele. None of the 23 carriers in the rapid genotyping group had a PRU value of more than 234 at day 7, compared with seven (30%) given standard treatment (p=0·0092). The point-of-care genetic test had a sensitivity of 100% (95% CI 92·3-100) and a specificity of 99·3% (96·3-100). INTERPRETATION: Point-of-care genetic testing after PCI can be done effectively at the bedside and treatment of identified CYP2C19*2 carriers with prasugrel can reduce high on-treatment platelet reactivity. FUNDING: Spartan Biosciences.

Neuroprognostication in the Post Cardiac Arrest Patient: A Canadian Cardiovascular Society Position Statement.

Cardiac arrest (CA) is associated with a low rate of survival with favourable neurologic recovery. The most common mechanism of death after successful resuscitation from CA is withdrawal of life-sustaining measures on the basis of perceived poor neurologic prognosis due to underlying hypoxic-ischemic brain injury. Neuroprognostication is an important component of the care pathway for CA patients admitted to hospital but is complex, challenging, and often guided by limited evidence. Using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system to evaluate the evidence underlying factors or diagnostic modalities available to determine prognosis, recommendations were generated in the following domains: (1) circumstances immediately after CA; (2) focused neurologic exam; (3) myoclonus and seizures; (4) serum biomarkers; (5) neuroimaging; (6) neurophysiologic testing; and (7) multimodal neuroprognostication. This position statement aims to serve as a practical guide to enhance in-hospital care of CA patients and emphasizes the adoption of a systematic, multimodal approach to neuroprognostication. It also highlights evidence gaps.

Coronary Flow Reserve, Inflammation, and Myocardial Strain: The CIRT-CFR Trial.

Inflammation is a key determinant of cardiovascular outcomes, but its role in heart failure is uncertain. In patients with cardiometabolic disease enrolled in the prospective, multicenter ancillary study of CIRT (Cardiovascular Inflammation Reduction Trial), CIRT-CFR (Coronary Flow Reserve to Assess Cardiovascular Inflammation), impaired coronary flow reserve was independently associated with increased inflammation and myocardial strain despite well-controlled lipid, glycemic, and hemodynamic profiles. Inflammation modified the relationship between CFR and myocardial strain, disrupting the association between cardiac blood flow and function. Future studies are needed to investigate whether an early inflammation-mediated reduction in CFR capturing microvascular ischemia may lead to heart failure in patients with cardiometabolic disease. (Cardiovascular Inflammation Reduction Trial [CIRT]; NCT01594333; Coronary Flow Reserve to Assess Cardiovascular Inflammation [CIRT-CFR]; NCT02786134).

Antithrombotic therapies in Canadian atrial fibrillation patients with concomitant coronary artery disease: Insights from the CONNECT AF + PCI-II program.

BACKGROUND: Selecting the appropriate antithrombotic regimen for patients with atrial fibrillation (AF) who have undergone percutaneous coronary intervention (PCI) or have had medically managed acute coronary syndrome (ACS) remains complex. This multi-centre observational study evaluated patterns of antithrombotic therapies utilized among Canadian patients with AF post-PCI or ACS. METHODS AND RESULTS: By retrospective chart audit, 611 non-valvular AF patients [median (interquartile range) age 76 (69-83) years, CHADS2 score 2 (1-3)] who underwent PCI or had medically managed ACS between August 2018 and December 2020 were identified by 68 cardiologists across eight provinces in Canada. Overall, triple antithrombotic therapy [TAT: combined oral anticoagulation (OAC) and dual antiplatelet therapy (DAPT)] was the most common initial antithrombotic strategy, with use in 53.8 % of patients, followed by dual pathway therapy (32.7 % received OAC and a P2Y12 inhibitor, and 4.1 % received OAC and aspirin) and DAPT (9.3 %). Median duration of TAT was 30 (7, 30) days. Compared to the previous CONNECT AF + PCI-I program, there was an increased use of dual pathway therapy relative to TAT over time (P-value <.0001). DOACs (direct oral anticoagulants) represented 90.3 % of all OACs used overall, with apixaban being the most utilized (50.5 %). Proton pump inhibitors were used in 57.0 % of all patients, and 70.1 % of patients on ASA. Planned antithrombotic therapies at 1 year were: 76.2 % OAC monotherapy, 8.3 % OAC + ASA, 7.9 % OAC + P2Y12 inhibitor, 4.3 % DAPT, 1.3 % ASA alone, and <1 % triple therapy. CONCLUSION: In accordance with recent Canadian Cardiovascular Society guideline recommendations, we observed an increased use of dual pathway therapy relative to TAT over time in both AF patients post-PCI (elective and emergent) and in those with medically managed ACS. Additionally, DOACs have become the prevailing form of anticoagulation across all antithrombotic regimens. Our findings suggest that Canadian physicians are integrating evidence-based approaches to optimally manage the bleeding and thrombotic risks of AF patients post-PCI and/or ACS.

Aspirin plus clopidogrel versus aspirin alone after coronary artery bypass grafting: the clopidogrel after surgery for coronary artery disease (CASCADE) Trial.

BACKGROUND: clopidogrel inhibits intimal hyperplasia in animal studies and therefore may reduce saphenous vein graft (SVG) intimal hyperplasia after coronary artery bypass grafting. The Clopidogrel After Surgery for Coronary Artery DiseasE (CASCADE) study was undertaken to evaluate whether the addition of clopidogrel to aspirin inhibits SVG disease after coronary artery bypass grafting, as assessed at 1 year by intravascular ultrasound. METHODS AND RESULTS: in this double-blind phase II trial, 113 patients undergoing coronary artery bypass grafting with SVGs were randomized to receive aspirin 162 mg plus clopidogrel 75 mg daily or aspirin 162 mg plus placebo daily for 1 year. The primary outcome was SVG intimal hyperplasia (mean intimal area) as determined by intravascular ultrasound at 1 year. Secondary outcomes were graft patency, major adverse cardiovascular events, and major bleeding. One-year intravascular ultrasound and coronary angiography were performed in 92 patients (81.4%). At 1 year, SVG intimal area did not differ significantly between the 2 groups (4.1 ± 2.0 versus 4.5 ± 2.1 mm(2), aspirin-clopidogrel versus aspirin-placebo, P=0.44). Overall 1-year graft patency was 95.2% in the aspirin-clopidogrel group compared with 95.5% in the aspirin-placebo group (P=0.90), and SVG patency was 94.3% in the aspirin-clopidogrel group versus 93.2% in the aspirin-placebo group (P=0.69). Freedom from major adverse cardiovascular events at 1 year was 92.9 ± 3.4% in the aspirin-clopidogrel group and 91.1 ± 3.8% in the aspirin-placebo group (P=0.76). The incidence of major bleeding at 1 year was similar for the 2 groups (1.8% versus 0%, aspirin-clopidogrel versus aspirin-placebo, P=0.50). CONCLUSIONS: compared with aspirin monotherapy, the combination of aspirin plus clopidogrel did not significantly reduce the process of SVG intimal hyperplasia 1 year after coronary artery bypass grafting.

A citywide protocol for primary PCI in ST-segment elevation myocardial infarction.

BACKGROUND: If primary percutaneous coronary intervention (PCI) is performed promptly, the procedure is superior to fibrinolysis in restoring flow to the infarct-related artery in patients with ST-segment elevation myocardial infarction. The benchmark for a timely PCI intervention has become a door-to-balloon time of less than 90 minutes. Whether regional strategies can be developed to achieve this goal is uncertain. METHODS: We developed an integrated-metropolitan-area approach in which all patients with ST-segment elevation myocardial infarction were referred to a specialized center for primary PCI. We sought to determine whether there was a difference in door-to-balloon times between patients who were referred directly from the field by paramedics trained in the interpretation of electrocardiograms and patients who were referred by emergency department physicians. RESULTS: Between May 1, 2005, and April 30, 2006, a total of 344 consecutive patients with ST-segment elevation myocardial infarction were referred for primary PCI: 135 directly from the field and 209 from emergency departments. Primary PCI was performed in 93.6% of patients. The median door-to-balloon time was shorter in patients referred from the field (69 minutes; interquartile range, 43 to 87) than in patients needing interhospital transfer (123 minutes; interquartile range, 101 to 153; P<0.001). Door-to-balloon times of less than 90 minutes were achieved in 79.7% of patients who were transferred from the field and in 11.9% of those transferred from emergency departments (P<0.001). CONCLUSIONS: Guideline door-to-balloon-times were more often achieved when trained paramedics independently triaged and transported patients directly to a designated primary PCI center than when patients were referred from emergency departments.

Early routine percutaneous coronary intervention after fibrinolysis vs. standard therapy in ST-segment elevation myocardial infarction: a meta-analysis.

AIMS: Multiple trials in patients with ST-segment elevation myocardial infarction (STEMI) compared early routine percutaneous coronary intervention (PCI) after successful fibrinolysis vs. standard therapy limiting PCI only to patients without evidence of reperfusion (rescue PCI). These trials suggest that all patients receiving fibrinolysis should receive mechanical revascularization within 24 h from initial hospitalization. However, individual trials could not demonstrate a significant reduction in 'hard' endpoints such as death and reinfarction. We performed a meta-analysis of randomized controlled trials to define the benefits of early PCI after fibrinolysis over standard therapy on clinical and safety endpoints in STEMI. METHODS AND RESULTS: We identified seven eligible trials, enrolling a total of 2961 patients. No difference was found in the incidence of death at 30 days between the two strategies. Early PCI after successful fibrinolysis reduced the rate of reinfarction (OR: 0.55, 95% CI: 0.36-0.82; P = 0.003), the combined endpoint death/reinfarction (OR: 0.65, 95% CI: 0.49-0.88; P = 0.004) and recurrent ischaemia (OR: 0.25, 95% CI: 0.13-0.49; P < 0.001) at 30-day follow-up. These advantages were achieved without a significant increase in major bleeding (OR: 0.93, 96% CI: 0.67-1.34; P = 0.70) or stroke (OR: 0.63, 95% CI: 0.31-1.26; P = 0.21). The benefits of a routine invasive strategy over standard therapy were maintained at 6-12 months, with persistent significant reduction in the endpoints reinfarction (OR: 0.64, 95% CI: 0.40-0.98; P = 0.01) and combined death/reinfarction (OR: 0.71, 95% CI: 0.52-0.97; P = 0.03). CONCLUSION: Early routine PCI after fibrinolysis in STEMI patients significantly reduced reinfarction and recurrent ischaemia at 1 month, with no significant increase in adverse bleeding events compared to standard therapy. Benefits of early PCI persist at 6-12 month follow-up.

A Shifting Paradigm: The Role of Focused Cardiac Ultrasound in Bedside Patient Assessment.

Transthoracic echocardiography is the standard of care in anatomic and functional cardiovascular assessment; however, focused cardiac ultrasound (FoCUS) performed with portable ultrasound equipment is increasingly being used as an adjunct to comprehensive history and physical examination. FoCUS assessments, unlike formal echocardiography, are intended to assist physicians in answering explicit clinical questions with a narrow differential diagnosis in real time. Over the past decade, a growing body of literature has repeatedly shown the value that FoCUS adds to clinical evaluation. Specifically, FoCUS improves point-of-care diagnostic accuracy, which in turn modifies treatment plans, decreases time to diagnosis, and reduces resource utilization. Although less robust, there is also evidence showing improvement in clinical outcomes. Based on this evidence, clinicians, training programs, and clinical societies have embraced FoCUS as a tool to complement bedside patient evaluation. Herein, we review the evidence for FoCUS in clinical practice, specifically evaluating the diagnostic accuracy, the impact on clinical decision-making, and the effect on clinical outcomes.

Early Observations During the COVID-19 Pandemic in Cardiac Catheterization Procedures for ST-Elevation Myocardial Infarction Across Ontario.

BACKGROUND: In response to the COVID-19 pandemic, Ontario issued a declaration of emergency, implementing public health interventions on March 16, 2020. METHODS: We compared cardiac catheterization procedures for ST-elevation myocardial infarction (STEMI) between January 1 and May 10, 2020 to the same time frame in 2019. RESULTS: From March 16 to May 10, 2020, after implementation of provincial directives, STEMI cases significantly decreased by up to 25%. The proportion of patients who achieved guideline targets for first medical contact balloon for primary percutaneous coronary intervention (PCI) decreased substantially to 28% (median, 101 minutes) for patients who presented directly to a PCI site and to 37% (median, 149 minutes) for patients transferred from a non-PCI site, compared with 2019. CONCLUSIONS: STEMI cases across Ontario have been substantially affected during the COVID-19 pandemic.

INTRODUCTION: En réponse à la pandémie de COVID-19, l'Ontario a déclaré l'état d'urgence et mis en place des interventions de santé publique le 16 mars 2020. MÉTHODES: Nous avons comparé les procédures de cathétérisme cardiaque lors d'infarctus du myocarde avec sus-décalage du segment ST (STEMI) du 1er janvier au 10 mai 2020 à la même période en 2019. RÉSULTATS: Du 16 mars au 10 mai 2020, après la mise en place des directives provinciales, les cas de STEMI ont connu une diminution significative pouvant atteindre jusqu'à 25 %. La proportion de patients qui ont atteint les objectifs prévus aux lignes directrices entre le premier contact médical et le ballonnet de l'intervention coronarienne percutanée (IPC) a connu une diminution considérable de 28 % (médiane, 101 minutes) pour ceux qui se présentaient directement dans un site d'IPC et de 37 % (médiane, 149 minutes) pour ceux qui étaient dirigés vers un site non-ICP, et ce, en comparaison à 2019. CONCLUSIONS: La pandémie de COVID-19 a considérablement nui aux cas de STEMI de l'Ontario.

Periprocedural Bivalirudin Versus Unfractionated Heparin During Percutaneous Coronary Intervention Following Fibrinolysis for ST-Segment Elevation Myocardial Infarction.

BACKGROUND: A pharmacoinvasive strategy for ST-segment elevation myocardial infarction (STEMI) management combines the use of fibrinolysis with the routine transfer to coronary angiography, with percutaneous coronary intervention (PCI) if needed. This method reduces the risk of major adverse cardiovascular event (MACE) compared with fibrinolysis alone; however, it is associated with higher bleeding risk. We sought to assess the bivalirudin compared with unfractionated heparin (UFH) used during PCI as part of a pharmacoinvasive strategy. METHODS: We identified consecutive patients referred to the University of Ottawa Heart Institute between April 2009 and May 2011 as part of a pharmacoinvasive strategy for STEMI. The primary efficacy outcome was MACE, defined as a composite of death, reinfarction, or stroke during index hospitalization. The primary safety outcome was TIMI bleeding. RESULTS: We identified 200 patients meeting inclusion criteria: 123 patients (61.5%) in the bivalirudin group and 77 patients (37.5%) in the UFH group. Median fibrinolysis to balloon time was 324 minutes in the bivalirudin group and 226 minutes in the UFH group (P<.001). Initial TIMI grade 3 flow was higher in the bivalirudin group vs the UFH group, but there was no difference in the rates post PCI. MACE rates were 4.9% vs 7.8% (P=.40) and TIMI bleeding rates were 7.3% vs 11.7% (P=.29) in patients treated with bivalirudin vs UFH, respectively. CONCLUSION: The periprocedural use of bivalirudin vs UFH was associated with similar rates of MACE and bleeding. Given the expense of bivalirudin and lack of demonstrable clinical superiority, UFH remains the first-line periprocedural anticoagulant in a pharmacoinvasive strategy.

Hyperglycaemia in comatose survivors of out-of-hospital cardiac arrest.

BACKGROUND: The optimal blood glucose target during the early hospitalisation of comatose survivors of out-of-hospital cardiac arrest (OHCA) has not been established. METHODS: In a retrospective cohort study, we examined clinical outcomes in relation to mean blood glucose during the first 96 hours of hospital admission in comatose survivors of OHCA with an initial shockable rhythm. Mean blood glucose was assessed as a continuous (primary analysis) and categorical variable: <6 mmol/L, 6 to <8 mmol/L and ⩾8 mmol/L. Co-primary outcomes were the rates of death during the index hospitalisation and severe neurological dysfunction at discharge. We used multivariable logistic regression analyses to adjust for baseline differences in patient and index event characteristics. RESULTS: Among 122 eligible patients, death and severe neurological dysfunction occurred in 29 (24%) and 40 (33%) patients, respectively. Higher mean blood glucose levels during the first 96 hours of admission were associated with increased odds of death (odds ratio (OR): 1.50; 95% confidence interval (CI): 1.17-1.92; p = 0.001) and severe neurological dysfunction (OR: 1.42; 95% CI: 1.11-1.80; p = 0.004). The associations between mean blood glucose and the odds of death (OR: 1.35; 95% CI: 1.04-1.76; p = 0.02) and severe neurological dysfunction (OR: 1.28; 95% CI: 1.00-1.64; p = 0.05) persisted after adjusting for age, time from cardiac arrest to return of spontaneous circulation (ROSC) and vasoactive agent use. There was no interaction between age, time from cardiac arrest to ROSC or a history of diabetes mellitus and the relationship between mean blood glucose and co-primary outcomes. CONCLUSIONS: In comatose survivors of OHCA with initial shockable rhythms, higher mean blood glucose levels during the first 96 hours of admission are associated with increased rates of death and severe neurological dysfunction.

Optimal mean arterial pressure in comatose survivors of out-of-hospital cardiac arrest: An analysis of area below blood pressure thresholds.

AIM OF THE STUDY: To determine the optimal mean arterial pressure (MAP) during the early-to-intermediate phase care of comatose survivors of out-of-hospital cardiac arrest (OHCA). METHODS: We identified consecutive comatose survivors of OHCA with an initial shockable rhythm. Using blood pressure-over-time plots, we calculated the area below pre-specified MAP thresholds (ABT; mmHg*hours) during the first 96 h of admission. We used incremental MAP thresholds ranging between 65 and 85 mmHg. Logistic regression analyses were used to examine the association between ABT and clinical outcomes for each MAP threshold and to adjust for age, duration of cardiac arrest, and bystander CPR. The primary outcome was severe neurological dysfunction as defined by a cerebral performance category (CPC) ≥3. RESULTS: We identified 122 consecutive OHCA patients meeting inclusion criteria. The rate of the primary outcome was 33%. There was a significant association between ABT and the rate of the primary outcome when MAP thresholds of 60 (p = 0.01), 65 (p < 0.01), 70 (p < 0.01), 75 (p < 0.01), and 80 mmHg (p < 0.01) were used. This association was lost once a MAP threshold of 85 mmHg was reached (p = 0.63). In the adjusted analysis, the association between ABT and the primary outcome was no longer present when the MAP threshold reached 75 mmHg. CONCLUSIONS: In comatose survivors of OHCA with an initial shockable rhythm, higher ABT is associated with increased rates of severe neurological dysfunction when MAP thresholds <75 mmHg are used. The current findings support the hypothesis that higher MAP targets (≥75 mmHg) may be indicated in this patient population.

Marital status and outcomes after myocardial infarction: Observations from the Canadian Observational Antiplatelet Study (COAPT).

While divorced or living alone, patients with stable cardiovascular disease are at increased risk for adverse cardiovascular events. The importance of marital status following a myocardial infarction (MI) is less clear. We hypothesized that marital status may affect cardiovascular outcomes following MI. We analyzed outcomes among patients with MI who underwent percutaneous coronary intervention from the Canadian Observational Antiplatelet Study (COAPT). Marital status was categorized into 3 groups: married/common-law patients living together; never married; and divorced, separated, or widowed patients. Patients were followed for 15 months and our primary outcome was the occurrence of a major adverse cardiovascular event (MACE), defined as a composite of mortality, repeat acute MI, stroke, or urgent coronary revascularization. Multivariable logistic regression models were performed, with married/common-law patients living together considered the reference group. Among 2100 patients included in analyses, 1519 (72.3%) were married/common-law patients living together, 358 (17.1%) were separated/divorced/widowed, and 223 (10.6%) patients were never married. Dual antiplatelet therapy use after 15 months was similar across groups (75.4%, 77.8%, and 73.6%, respectively). The risk of MACE after 15 months was similar among married patients living together (12.7%; referent) compared with patients who were never married (13.9%; adjusted odds ratio: 1.09, 95% confidence interval: 0.58-2.07, P = 0.79) and patients separated/divorced/widowed (14.3%; adjusted odds ratio: 0.71, 95% confidence interval: 0.40-1.25, P = 0.23). Similarly, the risk of individual endpoints, including mortality, was similar across the 3 groups. Among patients stabilized following an MI, we found no association between marital status and 15-month outcomes.

Preliminary experience with intravenous P2Y12 platelet receptor inhibition as an adjunct to reduced-dose alteplase during acute myocardial infarction: results of the Safety, Tolerability and Effect on Patency in Acute Myocardial Infarction (STEP-AMI) angiographic trial.

BACKGROUND: Fibrinolytic therapy for acute myocardial infarction (AMI) results in normal flow in only about half of patients. Adjunctive treatment with potent antiplatelet and antithrombin agents increases arterial patency but is associated with excessive bleeding. Cangrelor (formerly AR-C69931MX) is a rapidly acting, specific antagonist of platelet aggregation via binding to the adenosine diphosphate P2Y12 receptor subtype. The aim of this study was to assess the safety and coronary artery patency of cangrelor as an adjunct to alteplase (tissue plasminogen activator [t-PA]). METHODS: Patients with AMI received aspirin, heparin, and an intravenous infusion of either cangrelor alone, full-dose t-PA alone, or 1 of 3 doses of cangrelor along with half-dose t-PA. The primary end point was Thrombolysis in Myocardial Infarction (TIMI) grade 3 flow at 60 minutes. Secondary end points included TIMI frame count, TIMI myocardial perfusion grade, extent of ST-segment resolution, composite clinical events, and bleeding. RESULTS: Ninety-two of planned 180 patients were enrolled. The combination of cangrelor and half-dose t-PA resulted in similar 60-minute patency as full-dose t-PA alone (55% vs 50%, P = not significant) and greater patency than with cangrelor alone (55% vs 18%, P < .05). The percentage of patients achieving >70% ST-segment resolution at 60 minutes tended to be greater with combination therapy than with either cangrelor or t-PA alone (28% vs 13%, P = .13 and 28% vs 14%, P = .30, respectively). Bleeding and adverse clinical events were comparable among the groups. CONCLUSION: This first experience with the intravenous P2Y12 receptor inhibitor, cangrelor, suggests the potential of this compound as an adjunct to fibrinolysis during treatment of AMI.

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.