Dipyridamole and vascular healing following stent implantation.

Introduction: Patients undergoing coronary stent implantation incur a 2% annual rate of adverse events, largely driven by in-stent restenosis (ISR) due to neointimal (NI) tissue proliferation, a process in which smooth muscle cell (SMC) biology may play a central role. Dipyridamole (DP) is an approved therapeutic agent with data supporting improved vascular patency rates. Pre-clinical data supports that DP may enact its vasculoprotective effects via adenosine receptor-A2B (ADOR-A2B). We sought to evaluate the efficacy of DP to mitigate ISR in a pre-clinical rabbit stent model. Methods & Results: 24 New Zealand White Rabbits were divided into two cohorts-non-atherosclerosis and atherosclerosis (n = 12/cohort, 6 male and 6 female). Following stent implantation, rabbits were randomized 1:1 to control or oral dipyridamole therapy for 6 weeks followed by optical coherence tomography (OCT) and histology assessment of NI burden and stent strut healing. Compared to control, DP demonstrated a 16.6% relative reduction in NI volume (14.7 ± 0.8% vs. 12.5 ± 0.4%, p = 0.03) and a 36.2% relative increase in optimally healed stent struts (37.8 ± 2.8% vs. 54.6 ± 2.5%, p < 0.0001). Atherosclerosis demonstrated attenuated effect with no difference in NI burden (15.2 ± 1.0% vs. 16.9 ± 0.8%, p = 0.22) and only a 14.2% relative increase in strut healing (68.3 ± 4.1% vs. 78.7 ± 2.5%, p = 0.02). DP treated rabbits had a 44.6% (p = 0.045) relative reduction in NI SMC content. In vitro assessment of DP and coronary artery SMCs yielded dose-dependent reduction in SMC migration and proliferation. Selective small molecule antagonism of ADOR-A2B abrogated the effects of DP on SMC proliferation. DP modulated SMC phenotypic switching with ADOR-A2B siRNA knockdown supporting its role in the observed effects. Conclusion: Dipyridamole reduces NI proliferation and improves stent healing in a preclinical model of stent implantation with conventional antiplatelets. Atherosclerosis attenuates the observed effect. Clinical trials of DP as an adjunctive agent may be warranted to evaluate for clinical efficacy in stent outcomes.

Evaluation of a Rabbit Model of Vascular Stent Healing: Application of Optical Coherence Tomography.

Percutaneous coronary intervention (PCI) is a management strategy for symptomatic obstructive coronary artery disease (CAD). Despite advancements, in-stent restenosis (ISR) still imparts a 1-2% annual rate of repeat revascularization-a focus of ongoing translational research. Optical coherence tomography (OCT) provides high resolution virtual histology of stents. Our study evaluates the use of OCT for virtual histological assessment of stent healing in a rabbit aorta model, enabling complete assessment of intraluminal healing throughout the stent. ISR varies based on intra-stent location, stent length, and stent type in a rabbit model-important considerations for translational experimental design. Atherosclerosis leads to more prominent ISR proliferation independent of stent-related factors. The rabbit stent model mirrors clinical observations, while OCT-based virtual histology demonstrates utility for pre-clinical stent assessment. Pre-clinical models should incorporate clinical and stent factors as feasible to maximize translation to clinical practice.

Rationale and Design of the Rivaroxaban Post-Transradial Access for the Prevention of Radial Artery Occlusion Trial (CAPITAL-RAPTOR).

INTRODUCTION: Transradial access (TRA) has rapidly emerged as the preferred vascular access site for coronary angiography and percutaneous coronary intervention. Radial artery occlusion (RAO) remains as an important complication of TRA as it precludes future ipsilateral transradial procedures. While intraprocedural anticoagulation has been studied extensively, the definitive role of postprocedural anticoagulation has not yet been established. METHODS AND ANALYSIS: The Rivaroxaban Post-Transradial Access for the Prevention of Radial Artery Occlusion trial is a multicentre, prospective, randomised, open-label, blinded-endpoint design study investigating the efficacy and safety of rivaroxaban to reduce the incidence of RAO. Eligible patients will undergo randomisation to receive either rivaroxaban 15 mg once daily for 7 days or to no additional postprocedural anticoagulation. Doppler ultrasound to assess radial artery patency will be performed at 30 days. ETHICS AND DISSEMINATION: The study protocol has been approved by the Ottawa Health Science Network Research Ethics Board (approval number 20180319-01H). The study results will be disseminated via conference presentations and peer-reviewed publications. TRIAL REGISTRATION NUMBER: NCT03630055.

Off-Hours Presentation, Door-to-Balloon Time, and Clinical Outcomes in Patients Referred for Primary Percutaneous Coronary Intervention.

OBJECTIVES: Presentation with ST-segment-elevation myocardial infarction (STEMI) during off-hours may impact timely reperfusion and clinical outcomes. We investigated the association between off-hours presentation, door-to-balloon time, and in-hospital mortality in patients with STEMI referred for primary percutaneous coronary intervention (PCI). METHODS: We included consecutive patients referred for primary PCI at the University of Ottawa Heart Institute between July 2004 and December 2017. The off-hours group included patients presenting on weekends, statutory holidays, or between 18:00 to 07:59 hours on weekdays. The on-hours group included patients presenting between 08:00 and 17:59 hours on weekdays. The primary clinical outcome was the adjusted in-hospital mortality. The primary quality-of-care indicator was door-to-balloon time. RESULTS: A total of 5132 patients were included, with 3152 (61.4%) in the off-hours group and 1980 (38.6%) in the on-hours group. The median door-to-balloon time was longer in the off-hours group compared with the on-hours group (102 minutes vs 77 minutes; P<.001), while the median onset-to-door time was similar (P=.40). There was no difference in the rates of in-hospital mortality (3.5% vs 3.0%; P=.32) or in the adjusted mortality (odds ratio, 1.2; 95% confidence interval, 0.8-1.8; P=.44) between off-hours and on-hours groups. However, door-to-balloon time was an independent predictor of in-hospital mortality (P<.01) and off-hours presentation was an independent predictor of longer door-to-balloon time (P<.001), with an excess of 22.1 minutes. CONCLUSION: Patients treated with primary PCI during off-hours had longer door-to-balloon times. Treatment during off-hours was an independent predictor of longer door-to-balloon time and longer door-to-balloon times were associated with higher mortality.

Association Between the Access Site for Coronary Angiography and Catheter-induced Coronary Artery Dissection.

Background: Catheter-induced coronary artery dissection (CICAD) is a rare complication of coronary angiography. The association between access site and CICAD remains unclear; however, transradial access (TRA) may be associated with a higher incidence of CICAD due to access vessel tortuosity and the mechanical disadvantage of catheters designed for the transfemoral access (TFA) approach. Methods: In this retrospective study, the reports of consecutive left heart catheterizations between April 2007, and December 2021 were reviewed for CICAD. Patients were excluded if the procedural report did not report an arterial access site. Identified CICAD cases were reviewed in detail. Results: There were 142/89,876 (0.16%) identified cases of CICAD. The access site was not associated with an increased risk of CICAD (0.18% with TRA vs 0.15% with TFA; relative risk [RR], 1.18; 95% CI, 0.84-1.65; P = .34) over the entire study period. With respect to TRA-related CICAD, male sex was associated with a decreased risk of dissection (RR, 0.64; 95% CI, 0.41-0.99; P = .04), but ST-elevation myocardial infarction at presentation was associated with an increased risk (RR, 3.01; 95% CI, 1.86-4.85; P < .01). In the TFA-predominant era, TRA was associated with an increased risk of CICAD (0.48% TRA vs 0.11% TFA; RR, 3.42; 95% CI, 2.05-5.69; P < .01)-an association that was not present in the TRA-predominant era. In-hospital mortality in patients with CICAD was 8.5%. Conclusions: CICAD is a rare complication of coronary angiography. Over a 15-year period, we did not demonstrate an association between access site and an increased risk of CICAD. There is substantial mortality associated with CICAD.

Impact of intracoronary assessments on revascularization decisions: A contemporary evaluation.

OBJECTIVES: To investigate the real-world implementation of intracoronary assessment (ICA) techniques and evaluate their impact on clinical decisions regarding the management of coronary artery disease (CAD) in contemporary practice. BACKGROUND: Coronary angiogram is the gold standard used to diagnose vessel stenosis and guide percutaneous coronary intervention (PCI); however, it is limited by its two-dimensional imaging capabilities. ICA techniques like intravascular ultrasound and optical coherence tomography capture the vessel in three-dimensional images. Comparatively, fractional flow reserve provides information on the physiologic significance of coronary stenosis. Both techniques may improve PCI outcomes if they routinely change physician behavior. METHODS: Patients who underwent ICA between August 2015 and March 2020 were included in the study. The primary outcome was the clinical impact of ICA on physician clinical decision making of a stenotic vessel. The secondary outcome was the clinical changes that occurred following ICA. RESULTS: A total of 1135 patients were included in the study. Physiologic assessment (PA) and image assessment (IA) were performed in 61.4% and 38.6% respectively. Management plans were changed in 38.1% and 23.9% of patients who received PA and IA. Over half of the management change resulted in physicians deciding to not intervene on the stenotic vessel. One-year outcome of these decisions showed no significant increase in major adverse cardiac events (hazard ratio [HR], 0.68; 95% confidence interval [CI], 0.40-1.15; p = 0.15) or unplanned revascularization (HR, 0.78; 95% CI, 0.35-1.74; p = 0.55) suggesting reliance on PA/IA data did not increase risk. CONCLUSION: Selected ICA alters physician management of CAD in one-third of patients being evaluated for revascularization-typically leading to fewer interventions. All cause death is numerally lower in patients that received a change in management. However, the 1-year outcome of these altered decisions does not appear to be significantly different.

Impact of atrial fibrillation on the risk of major adverse cardiac events following coronary revascularisation.

OBJECTIVE: Atrial fibrillation (AF) remains a highly prevalent arrhythmia with significant burden on morbidity and mortality. The impact of AF in the revascularised population remains incompletely described. Given the high prevalence of AF in the revascularised population, we sought to evaluate the incidence and prognosis in patients with pre-existing and new-onset AF following revascularisation. METHODS: We used the University of Ottawa Heart Institute Revascularisation Registry to identify patients who underwent revascularisation between August 2015 and March 2020, who were prospectively followed for an average of one year. We conducted a retrospective cohort study analysing the association between AF and clinical outcomes. The primary outcome of interest was 1-year major adverse cardiac events (MACE) defined as a composite of death, myocardial infarction, unplanned revascularisation and cerebrovascular accidents. Moreover, secondary outcomes include the individual components of MACE and bleeding. RESULTS: A total of 6704 patients underwent revascularisation and completed 1-year clinical follow-up. Median time to follow-up was 12.8 (IQR 11.2-15.9) months. One-year MACE occurred in 166 (21.8%) and 683 (11.5%) patients in AF and non-AF groups, respectively (adjusted HR, 1.61; 95% CI 1.29 to 2.01; p<0.0001). AF was independently predictive of 1-year mortality, myocardial infarction, unplanned revascularisation, cerebrovascular accident and bleeding. Within 1 year, 299 (4.5%) episodes of new-onset AF was observed. New-onset AF following revascularisation was also associated with 1-year MACE, mortality, myocardial infarction, cerebrovascular accident and unplanned revascularisation. CONCLUSIONS: Preprocedural and new-onset AF following revascularisation remains highly predictive 1-year MACE. AF should be considered in addition to traditional risk factors for adverse outcomes following revascularisation.

No sex-based difference in cardiogenic shock: A post-hoc analysis of the DOREMI trial.

BACKGROUND: Cardiogenic shock (CS) is associated with significant morbidity and mortality; however, there are limited randomized data evaluating the association between sex and clinical outcomes in patients with CS. Patients with CS enrolled in the DObutamine compaREd with MIlrinone (DOREMI) trial were evaluated in this post-hoc analysis. METHODS: The primary outcome was a composite of all-cause mortality, resuscitated cardiac arrest, cardiac transplant or mechanical circulatory support, non-fatal myocardial infarction, transient ischemic attack or stroke, or initiation of renal replacement therapy. Secondary outcomes included the individual components of the primary outcome. We analyzed the primary and secondary outcomes using unadjusted relative risks and performed adjusted analysis for the primary outcome and all-cause mortality using the covariates mean arterial pressure <70 mmHg at inotrope initiation, age, and acute myocardial infarction CS. RESULTS: Among 192 participants in the DOREMI study, 70 patients (36 %) were female. The primary outcome occurred in 38 female patients (54 %) compared to 61 male patients (50 %) [adjusted relative risk (aRR) 1.23; 95 % CI 0.78-1.95, p = 0.97]. When stratified by inotrope, there was no difference in the primary outcome comparing females to males receiving dobutamine (RR 1.14; 95 % CI 0.79-1.65, p = 0.50) nor milrinone (RR 1.03; 95 % CI 0.68-1.57, p = 0.87). There was no difference in all-cause mortality comparing females to males (aRR 1.51; 95 % CI 0.78-2.94, p = 0.88). Additionally, there were no differences in any secondary outcomes between males and females (p > 0.05 for all endpoints). CONCLUSION: In patients presenting with CS treated with milrinone or dobutamine, no differences in clinical outcomes were observed between males and females.

Significant Valvular Dysfunction and Outcomes in Cardiogenic Shock: Insights From the Randomized DOREMI Trial.

BACKGROUND: Patients with cardiogenic shock (CS) suffer high rates of in-hospital mortality, with little evidence guiding management. The impact of valvular heart disease in patients with CS remains unclear. We therefore conducted a post hoc analysis of the randomized Dobutamine Compared to Milrinone (DOREMI) trial to determine the impact of valvular disease on outcomes in patients with CS. METHODS: We defined significant valvular disease as moderate to severe or greater valvular stenosis or regurgitation and divided participants into a group of those with significant valvular disease and those without. Our primary outcome was all-cause in-hospital mortality. Secondary endpoints included resuscitated cardiac arrest; cardiac transplantation or mechanical circulatory support; nonfatal myocardial infarction; stroke; initiation of renal replacement therapy; as well as changes in renal function, perfusion, and hemodynamics over time. RESULTS: One hundred eighty-nine (98.4%) participants from the DOREMI trial were included in our analysis, and 74 (39.2%) had significant valvular dysfunction. Thirty-six (48.7%) patients with valvular disease died in hospital, compared with 37 (32.2%) in the comparator group (relative risk, 1.5; 95% confidence interval 1.06-2.15; P = 0.02). Patients with aortic stenosis (2.42, 1.56-3.75; P < 0.01) and patients with mitral regurgitation (1.63, 1.1-2.43; P = 0.02) also had increased incidence of in-hospital mortality. There was no significant difference in any secondary outcomes among groups, apart from variances in mean arterial pressure observed in patients with valvular disease (P < 0.01). CONCLUSIONS: Significant valvular dysfunction is associated with increased in-hospital mortality in patients with CS. Randomized clinical trial data are needed to further elucidate the role of transcatheter valvular interventions as a therapeutic target in this population.

Lactate Clearance as a Surrogate for Mortality in Cardiogenic Shock: Insights From the DOREMI Trial.

Background Recent studies have shown improved outcomes in cardiogenic shock through protocols directed toward early identification and initiation of mechanical circulatory support. However, objective therapeutic targets-based on clinical and/or laboratory data-to guide real-time clinical decision making are lacking. Lactate clearance has been suggested as a potential treatment target because of its independent association with mortality. Methods and Results In a post hoc analysis of the DOREMI (Dobutamine Compared to Milrinone in the Treatment of Cardiogenic Shock) trial-a randomized, double-blind, controlled trial comparing milrinone to dobutamine in the treatment of cardiogenic shock-we used prospectively collected lactate data to evaluate lactate clearance as a surrogate marker for in-hospital mortality. In total, 82 (57.7%) patients survived to hospital discharge (survivors). In multivariate logistic regression analysis, complete lactate clearance, percentage lactate clearance, and percentage lactate clearance per hour were independently associated with survival beginning as early as 8 hours after enrollment. Complete lactate clearance was the strongest predictor of survival at all time points, with odds ratios ranging between 2.46 (95% CI, 1.09-5.55; P=0.03) at 8 hours to 5.44 (95% CI, 2.14-13.8; P<0.01) at 24 hours. Conclusions Complete lactate clearance is a strong and independent predictor of in-hospital survival in patients with cardiogenic shock. Together with previously published data, these results further support the validity of lactate clearance as an appropriate surrogate for mortality and as a potential therapeutic target in future cardiogenic shock trials. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT03207165.

Modifiable Risk Factors and Residual Risk Following Coronary Revascularization: Insights From a Regionalized Dedicated Follow-Up Clinic.

OBJECTIVE: To ensure compliance with optimal secondary prevention strategies and document the residual risk of patients following revascularization, we established a postrevascularization clinic for risk-factor optimization at 1 year, with outcomes recorded in a web-based registry. Although coronary revascularization can reduce ischemia, medical treatment of coronary artery disease (CAD) remains the cornerstone of ongoing risk reduction. While standardized referral pathways and protocols for revascularization are prevalent and well studied, post-revascularization care is often less formalized. PATIENTS AND METHODS: The University of Ottawa Heart Institute is a tertiary-care center providing coronary revascularization services. From 2015 to 2019, data were prospectively recorded in the CAPITAL revascularization registry, and patient-level procedural, clinical, and outcome data are collected in the year following revascularization. Major adverse cardiovascular event (MACE) was defined as death, myocardial infarction, unplanned revascularization, or cerebrovascular accident. Kaplan-Meier curves were generated to evaluate time-to-event data for clinical outcomes by risk-factor management, and comparisons were performed using log-rank tests and reported by hazard ratio (HR) and 95% confidence intervals (CIs). RESULTS: A cohort of 4147 patients completed 1-year follow-up after revascularization procedure that included 3462 undergoing percutaneous coronary intervention (PCI), 589 undergoing coronary artery bypass graft (CABG), and 96 undergoing both PCI and CABG. In the year following revascularization (median follow-up 13.3 months-interquartile range [IQR]: 11.9-16.5) 11% of patients experienced MACE, with female patients being disproportionately at risk. Moreover, 47.7% of patients had ≥2 risk factors (diabetes, dyslipidemia, overweight, active smoker) at the time of follow-up, with 45.0% of patients with diabetes failing to achieve target hemoglobin (Hb) A1c, 54.8% of smokers continuing to smoke, and 27.1% of patients failing to achieve guideline-directed lipid targets. CONCLUSION: Patients who have undergone revascularization procedures remain at elevated risk for MACE, and inadequately controlled risk factors are prevalent in follow-up. This highlights the need for aggressive secondary prevention strategies and implementation of programs to optimize postrevascularization care.

Outcomes in Patients Stratified by PRECISE-DAPT Versus DAPT Scores After Percutaneous Coronary Interventions.

The optimal length of dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI) remains debated. Current guidelines recommend individualized treatment with consideration of risk scores. We sought to evaluate the degree of agreement in treatment recommendations and the ability to predict ischemic and bleeding complications of the PRECISE-DAPT (predicting bleeding complications in patients undergoing stent implantation and subsequent dual antiplatelet therapy) and DAPT scores. Consecutive patients receiving 12 months of DAPT were grouped based on score treatment recommendation at the time of PCI: PRECISE-DAPT prolonged or shortened (PRECISE DAPT <25 vs ≥25) and DAPT prolonged or shortened (DAPT ≥2 vs <2). One-year ischemic and bleeding outcomes were compared for each group. In 451 patients, the PRECISE-DAPT and DAPT score recommendations were concordant in 56.7% of patients (Cohen's kappa for agreement of k = 0.139, 95% confidence interval 0.065 to 0.212). There was no difference in composite major adverse cardiovascular and cerebrovascular events between patients with high versus low PRECISE-DAPT or DAPT scores. In patients with a high PRECISE-DAPT score versus a low score, there was an increased incidence of 1-year all-cause mortality (2.13% vs 0%, p = 0.04) and an increase in bleeding (Bleeding Academic Research Consortium ≥3a: 17.0% vs 2.8%; p <0.001; Bleeding Academic Research Consortium 3b/c and 5: 8.5% vs 1.4%; p = 0.001). There were no differences in rates of mortality or bleeding for patients with high versus low DAPT scores. In conclusion, when applied at the baseline, the PRECISE-DAPT and DAPT scores frequently make discordant DAPT duration recommendations. The PRECISE-DAPT, but not the DAPT score, demonstrated associations with all-cause mortality and bleeding in patients prescribed 12 months of DAPT after PCI.

De-escalation of P2Y12 Inhibitor Use After Percutaneous Coronary Intervention and Acute Coronary Syndromes.

BACKGROUND: De-escalation from potent platelet P2Y12 inhibitors to clopidogrel is common. Despite having a clinical rationale, non-bleeding-related de-escalation when a lateral change between potent agents is an option may put patients at increased ischemic risk. We set out to define the scope of P2Y12 inhibitor de-escalation in a large clinical registry and evaluate the potential impact of non-bleeding-related de-escalation on clinical outcomes. METHODS: : A retrospective cohort study was performed on consecutive patients in the Cardiovascular Percutaneous Intervention Trial (CAPITAL) registry to identify those who underwent a switch in therapy within 1 year of percutaneous coronary intervention. The de-escalations were categorized as bleeding-related or non-bleeding-related. The primary outcome was major adverse cardiovascular events, a composite of death, myocardial infarction, and stroke. Secondary outcomes included individual components of major adverse cardiovascular events and a safety endpoint of thrombolysis in myocardial infarction bleeding. RESULTS: Of 1854 patients, 209 (11.3%) underwent de-escalation: 24.9% of cases were bleeding-related, 37.8% were non-bleeding-related, and 37.3% were for unknown reasons. All patients with non-bleeding-related de-escalation were switched from ticagrelor to clopidogrel. The primary outcome occurred in 14 (6.7%) patients, of which 50% underwent non-bleeding-related de-escalation (P = 0.430). Among those with non-bleeding-related de-escalation, 7.6% were hospitalized for myocardial infarction, compared to 1.9% and 3.8% among those with a bleeding-related and unknown rationale, respectively (P = 0.293). CONCLUSIONS: De-escalation, particularly non-bleeding-related de-escalation, of P2Y12 inhibitors is common. A substantial proportion of such de-escalation may be avoidable. Given the potential risk of ischemic complications, strategies should be considered to encourage both the upfront use of potent P2Y12 inhibitors and alternative strategies to de-escalation.

CONTEXTE: La désescalade thérapeutique consistant à passer d'un inhibiteur puissant du récepteur plaquettaire P2Y12 au clopidogrel est pratique courante. En dépit de son fondement clinique, la désescalade non liée aux saignements lorsqu'une substitution d'inhibiteurs puissants est possible peut entraîner une augmentation du risque d'ischémie chez les patients. L'objectif de notre étude était d'analyser, dans un vaste registre clinique, l'amplitude du recours à la désescalade à partir d'un inhibiteur du récepteur P2Y12 et d'évaluer les conséquences possibles de la désescalade non liée aux saignements sur les résultats cliniques. MÉTHODOLOGIE: Une étude de cohorte rétrospective a été effectuée sur une série de patients consécutifs inscrits au registre CAPITAL ( Ca rdiovascular P ercutaneous I ntervention T ri al ) afin de recenser ceux qui avaient fait l'objet d'un changement de traitement au cours de l'année suivant leur intervention coronarienne percutanée. Les désescalades ont été classées en deux catégories selon qu'elles étaient liées ou non liées aux saignements. Le critère d'évaluation principal, soit la survenue d'un événement cardiovasculaire indésirable majeur (ECIM), était un critère composite regroupant le décès, l'infarctus du myocarde et l'accident vasculaire cérébral. Les critères d'évaluation secondaires comprenaient chaque composante individuelle du critère composite et un critère d'évaluation de l'innocuité mesuré par le score TIMI (thrombolyse dans l'infarctus du myocarde) relatif aux saignements. RÉSULTATS: Sur 1854 patients, 209 (11,3 %) avaient fait l'objet d'une désescalade, qui était liée aux saignements dans 24,9 % des cas, non liée aux saignements dans 37,8 % des cas et sans raison indiquée dans 37,3 % des cas. Tous les patients ayant fait l'objet d'une désescalade non liée aux saignements étaient passés du ticagrélor au clopidogrel. Le critère d'évaluation principal a été observé chez 14 (6,7 %) patients, dont 50 % avaient fait l'objet d'une désescalade non liée aux saignements (p = 0,430). Parmi les patients ayant fait l'objet d'une désescalade non liée aux saignements, 7,6 % avaient été hospitalisés pour un infarctus du myocarde, comparativement à 1,9 % et 3,8 % des patients chez qui la désescalade était liée aux saignements ou n'avait pas de raison connue, respectivement (p = 0,293). CONCLUSIONS: La désescalade à partir d'inhibiteurs du récepteur P2Y12, et particulièrement la désescalade non liée aux saignements, est pratique courante, alors qu'elle pourrait être évitée dans une proportion élevée de cas. Compte tenu du risque de complications ischémiques d'une telle pratique, des stratégies devraient être envisagées afin d'encourager à la fois le recours dès le départ à des inhibiteurs puissants du récepteur P2Y12 et l'adoption de stratégies de remplacement de la désescalade.

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.