Presence and Relevance of Myocardial Bridge in LAD-PCI of CTO and Non-CTO Lesions.

BACKGROUND: Intravascular ultrasound (IVUS) studies show that one-quarter of left anterior descending (LAD) arteries have a myocardial bridge. An MB may be associated with stent failure when the stent extends into the MB. OBJECTIVES: The aim of this study was to investigate: 1) the association between an MB and chronic total occlusion (CTO) in any LAD lesions; and 2) the association between an MB and subsequent clinical outcomes after percutaneous coronary intervention in LAD CTOs. METHODS: A total of 3,342 LAD lesions with IVUS-guided percutaneous coronary intervention (280 CTO and 3,062 non-CTO lesions) were included. The primary outcome was target lesion failure (cardiac death, target vessel myocardial infarction, definite stent thrombosis, and ischemic-driven target lesion revascularization). RESULTS: An MB by IVUS was significantly more prevalent in LAD CTOs than LAD non-CTOs (40.4% [113/280] vs 25.8% [789/3,062]; P < 0.0001). The discrepancy in CTO length between angiography and IVUS was greater in 113 LAD CTOs with an MB than 167 LAD CTOs without an MB (6.0 [Q1, Q3: 0.1, 12.2] mm vs 0.2 [Q1, Q3: -1.4, 8.4] mm; P < 0.0001). Overall, 48.7% (55/113) of LAD CTOs had a stent that extended into an MB after which target lesion failure was significantly higher compared to a stent that did not extend into an MB (26.3% vs 0%; P = 0.0004) or compared to an LAD CTO without an MB (26.3% vs 9.6%; P = 0.02). CONCLUSIONS: An MB was more common in LAD CTO than non-CTO LAD lesions. If present, approximately one-half of LAD CTOs had a stent extending into an MB that, in turn, was associated with worse outcomes.

Ostial right coronary artery lesion morphology and outcomes after treatment with drug-eluting stents.

BACKGROUND: Outcomes after percutaneous coronary intervention (PCI) for de novo ostial right coronary artery (RCA) lesions are poor. AIMS: We used intravascular ultrasound (IVUS) to clarify the morphological patterns of de novo ostial RCA lesions and their associated clinical outcome. METHODS: Among 5,102 RCA IVUS studies, 170 de novo ostial RCA stenoses (within 3 mm from the aorto-ostium) were identified. These were classified as 1) isolated ostial lesions (no disease extending beyond 10 mm from the ostium and without a calcified nodule [CN]); 2) ostial CN, typically with diffuse disease (disease extending beyond 10 mm); and 3) ostial lesions with diffuse disease but without a CN. The primary outcome was target lesion failure (TLF: cardiac death, target vessel myocardial infarction, definite stent thrombosis, and ischaemia-driven target lesion revascularisation). RESULTS: The prevalence of an isolated ostial lesion was 11.8% (n=20), 47.6% (n=81) were ostial CN, and 40.6% (n=69) were ostial lesions with diffuse disease. Compared to ostial lesions with diffuse disease, isolated lesions were more common in women (75.0% vs 42.0%; p=0.01), and CN were associated with older age (median [first, third quartile] 76 [70, 83] vs 69 [63, 81] years old; p=0.002). The Kaplan-Meier rate of TLF at 2 years was significantly higher in patients with CN (21.6%) compared to diffuse lesions (8.2%) (p=0.04), and patients with isolated lesions had no events. A multivariable Cox proportional hazard model revealed that CN were significantly associated with TLF (hazard ratio 6.63, 95% confidence interval: 1.28-34.3; p=0.02). CONCLUSIONS: Ostial RCA lesions have specific morphologies - detectable by IVUS - that may be associated with long-term clinical outcomes.

Impact of Interventricular Interaction on Ventricular Function: Insights From Right Ventricular Pressure-Volume Analysis.

BACKGROUND: Interventricular interactions may be responsible for the decline in ventricular performance observed in various disease states that primarily affect the contralateral ventricle. OBJECTIVES: This study sought to quantify the impact of such interactions on right ventricular (RV) size and function using clinically stable individuals with left ventricular assist devices (LVADs) as a model for assessing RV hemodynamics while LV loading conditions were acutely manipulated by changing device speed during hemodynamic optimization studies (ie, ramp tests). METHODS: The investigators recorded RV pressure-volume loops with a conductance catheter at various speeds during ramp tests in 20 clinically stable HeartMate3 recipients. RESULTS: With faster LVAD speeds and greater LV unloading, indexed RV end-diastolic volume increased (72.28 ± 15.07 mL at low speed vs 75.95 ± 16.90 at high speed; P = 0.04) whereas indexed end-systolic volumes remained neutral. This resulted in larger RV stroke volumes and shallower end-diastolic pressure-volume relationships. Concurrently, RV end-systolic pressure decreased (31.58 ± 9.75 mL at low speed vs 29.58 ± 9.41 mL at high speed; P = 0.02), but contractility, as measured by end-systolic elastance, did not change significantly. The reduction in RV end-systolic pressure was associated with a reduction in effective arterial elastance from 0.65 ± 0.43 mm Hg/mL at low speed to 0.54 ± 0.33 mm Hg/mL at high speed (P = 0.02). CONCLUSIONS: Interventricular interactions resulted in improved RV compliance, diminished afterload, and did not reduce RV contractility. These data challenge the prevailing view that interventricular interactions compromise RV function, which has important implications for the understanding of RV-LV interactions in various disease states, including post-LVAD RV dysfunction.

Contemporary Management and Outcomes of Patients With High-Risk Pulmonary Embolism.

BACKGROUND: Contemporary care patterns/outcomes in high-risk pulmonary embolism (PE) patients are unknown. OBJECTIVES: This study sought to characterize the management of high-risk PE patients and identify factors associated with poor outcomes. METHODS: A retrospective analysis of the PERT (Pulmonary Embolism Response Team) Consortium Registry was performed. Patients presenting with intermediate-risk PE, high-risk PE, and catastrophic PE (those with hemodynamic collapse) were identified. Patient characteristics were compared with chi-square testing for categorical covariates and Student's t-test for continuous covariates. Multivariable logistic regression was used to assess associations between clinical characteristics and outcomes in the high-risk population. RESULTS: Of 5,790 registry patients, 2,976 presented with intermediate-risk PE and 1,442 with high-risk PE. High-risk PE patients were more frequently treated with advanced therapies than intermediate-risk PE patients (41.9% vs 30.2%; P < 0.001). In-hospital mortality (20.6% vs 3.7%; P < 0.001) and major bleeding (10.5% vs. 3.5%; P < 0.001) were more common in high-risk PE. Multivariable regression analysis demonstrated vasopressor use (OR: 4.56; 95% CI: 3.27-6.38; P < 0.01), extracorporeal membrane oxygenation use (OR: 2.86; 95% CI: 1.12-7.30; P = 0.03), identified clot-in-transit (OR: 2.26; 95% CI: 1.13-4.52; P = 0.02), and malignancy (OR: = 1.70; 95% CI: 1.13-2.56; P = 0.01) as factors associated with in-hospital mortality. Catastrophic PE patients (n = 197 [13.7% of high-risk PE patients]) had higher in-hospital mortality (42.1% vs 17.2%; P < 0.001) than those presenting with noncatastrophic high-risk PE. Extracorporeal membrane oxygenation (13.3% vs. 4.8% P < 0.001) and systemic thrombolysis (25% vs 11.3%; P < 0.001) were used more commonly in catastrophic PE. CONCLUSIONS: In the largest analysis of high-risk PE patients to date, mortality rates were high with the worst outcomes among patients with hemodynamic collapse.

Patient-Reported Outcomes in Venous Thromboembolism: A Systematic Review of the Literature, Current Challenges, and Ways Forward.

BACKGROUND: Venous thromboembolism (VTE) affects >1.2 million Americans annually. Although the clinical outcomes and economic burdens of VTE have been well described, the impact of VTE on patients' health status has yet to be summarized. This systematic review summarizes how patient-reported outcome measures (PROMs) have been used in VTE to date. METHODS AND RESULTS: PubMed/MEDLINE was queried for literature published through March 2023 using PROMs in a population of patients with VTE. Studies were excluded if the reference was an editorial, review, or case report, or if the study included patients with conditions other than VTE. Qualitative analyses were performed. After screening and exclusion, 136 references were identified; 5 described PROM development, 20 focused on PROM validation, and 111 used PROMs in outcomes research. The most used generic PROMs were the 36-item Short-Form Health Survey and EuroQol 5-dimensional questionnaire, and the most common disease-specific PROMs were the Venous Insufficiency Epidemiological and Economic Study-Quality of Life/Symptoms and the Pulmonary Embolism Quality of Life Questionnaire. PROMs were used to quantify the changes in health status after diagnosis, characterize the trajectory of subsequent improvement, and identify drivers of continued impairments in health status like postthrombotic syndrome and postpulmonary embolism syndrome. PROMs were also used to investigate the impact of novel treatment modalities on quality of life. CONCLUSIONS: This review demonstrates the many benefits of PROM use, including quantifying changes in health status with treatment, capturing patients' experiences with the treatment itself, and identifying complications of VTE. Incorporating PROMs into VTE care will be an essential component of evaluating the effectiveness of novel therapies and should lead to improved shared decision-making for patients with VTE.

Percutaneous Transluminal Angioplasty for Infrapopliteal Chronic Limb-Threatening Ischemia: A Systematic Review and Meta-analysis of Primary Patency and Binary Restenosis Rates.

PURPOSE: Percutaneous transluminal angioplasty (PTA) remains the mainstay of endovascular therapy for infrapopliteal chronic limb-threatening ischemia (CLTI), but outcomes have not been well characterized using high-quality data. The aim of this meta-analysis was to provide an updated benchmark for rates of primary patency and binary restenosis after PTA using prospectively collected, predominantly core-lab adjudicated randomized controlled trial (RCT) data. MATERIALS AND METHODS: MEDLINE, EMBASE, Cochrane Central, and ClinicalTrials.gov were queried for RCTs published through November 2022 using PTA as a control arm and including patients with infrapopliteal CLTI. Studies were excluded if >25% of patients had intermittent claudication, other vessels were included, or primary patency or binary restenosis were not outcomes. Outcomes were analyzed using random effects models. This analysis was publicly registered (PROSPERO ID#394543). No funding was utilized. RESULTS: Seventeen RCTs were included (1048 patients, 1279 lesions). Pooled primary patency rates using data from 6 RCTs were 68% at 6 months (95% confidence interval [CI]=45%-84%) and 66% at 12 months (95% CI=51%-79%). Pooled binary restenosis rates using data from 11 RCTs were 54% at 6 months (95% CI=33%-73%) and 60% at 9 to 12 months (95% CI=39%-78%). Significant heterogeneity was present in all outcomes (I2>50%, p<0.0001). Publication bias was not observed (Egger's p>0.1). CONCLUSIONS: This meta-analysis provides estimates for binary restenosis and primary patency following PTA utilizing prospectively collected, predominantly core-lab adjudicated data. Results demonstrate 1-year primary patency rates that are 10% to 20% higher than what has been historically used in power calculations. These new estimates will help facilitate more accurate power analysis for future RCTs. CLINICAL IMPACT: Rates of primary patency and binary restenosis after percutaneous transluminal angioplasty (PTA) have not been well-described using high-quality data, and investigators have been utilizing estimates of 40% to 50% and 45% to 65%, respectively, when performing power calculations for trials. This meta-analysis demonstrates using high-quality, prospectively collected, and predominantly core-lab adjudicated randomized controlled trial data that actual rates of primary patency are closer to 60% up to 1 year following PTA and provides the first meta-analysis estimate of binary restenosis rates up to 1 year after PTA. These estimates will help facilitate more accurate power calculations for future RCTs in this space.

Efficacy and Safety of Anticoagulation, Catheter-Directed Thrombolysis, or Systemic Thrombolysis in Acute Pulmonary Embolism.

BACKGROUND: The optimal treatment strategy of patients with pulmonary embolism (PE) (especially those with intermediate risk) continues to evolve and remains controversial. OBJECTIVES: This study sought to compare the efficacy and safety of anticoagulation (AC) alone, catheter-directed thrombolysis (CDT), and systemic thrombolysis (ST) in patients with acute PE. METHODS: PubMed and EMBASE were searched for randomized controlled trials or observational studies which compared outcomes of AC alone, CDT, and ST in acute PE. Efficacy outcome was all-cause mortality. Safety outcomes were major bleeding and intracranial hemorrhage (ICH). RESULTS: We identified 45 studies (17 randomized controlled trials, 2 prospective nonrandomized trials, and 26 retrospective observational trials), which included 81,705 patients. When compared with AC alone, CDT had lower mortality (OR: 0.55; 95% CI: 0.39-0.80) but higher major bleeding (OR: 1.84; 95% CI: 1.10-3.08) and numerically higher ICH (OR: 1.51; 95% CI: 0.75-3.04). ST was associated with no difference in mortality but higher major bleeding (OR: 2.16; 95% CI: 1.38-3.38) and ICH (OR: 2.26; 95% CI: 1.14-4.48) when compared with AC alone. The risk of mortality (OR: 2.05; 95% CI: 1.46-2.89) and ICH (OR: 1.50; 95% CI: 1.13-1.99) was higher with ST when compared with CDT. Findings were similar when analysis was restricted to trials of intermediate risk PE. CONCLUSIONS: In patients with acute PE, when compared with AC alone, CDT was associated with a lower mortality but higher risk of bleeding. Moreover, CDT had an enhanced safety profile when compared with ST.

Gender Disparities in Presentation, Management, and Outcomes of Acute Pulmonary Embolism.

Pulmonary embolism (PE) is the third most common cause of cardiovascular death; however, gender disparities in PE remain understudied. All PE cases at a single institution between January 2013 and June 2019 were retrospectively reviewed. The clinical presentation, treatment modalities, and outcomes were compared between men and women using univariate and multivariate analyses adjusting for differences in baseline characteristics. A total of 1,345 patients were diagnosed with acute PE, of whom 56.3% were women (n = 757). Women had a significantly higher mean body mass index (29.4 vs 28.4) and a higher frequency of hypertension (53% vs 46%) and hormone use (6.6% vs 0%; all p <0.02). Men had a higher frequency of smoking (45% vs 33%, p <0.0001). Women had significantly lower PE severity index classifications (p = 0.0009). The rates of intensive care unit admission, vasopressor requirements, extracorporeal membrane oxygenation cannulation, and mechanical ventilation were similar between the genders. There was no significant difference in the treatment modality used between the genders. Although the risk factors and PE severity index class differed between the genders, there was no significant difference in resource utilization or treatment modality. Gender was also not a significant predictor of in-hospital mortality, moderate or severe bleeding, increased length of stay, or readmission in the study population.

Mechanisms and treatment outcomes of ostial right coronary artery in-stent restenosis.

BACKGROUND: Despite a high rate of in-stent restenosis (ISR) after stenting the right coronary artery (RCA) ostium, the mechanism of ostial RCA ISR is not well understood. AIMS: We aimed to clarify the cause of ostial RCA ISR using intravascular ultrasound (IVUS). METHODS: Overall, 139 ostial RCA ISR lesions were identified with IVUS, pre-revascularisation. Primary ISR mechanisms were classified as follows: 1) neointimal hyperplasia (NIH); 2) neoatherosclerosis; 3) ostium not covered by the stent; 4) stent fracture or deformation; 5) stent underexpansion (old minimum stent area <4.0 mm2 or stent expansion <50%); or 6) a protruding calcified nodule. RESULTS: The median duration from prior stenting was 1.2 (first quartile 0.6, third quartile 3.1) years. The primary mechanisms of ISR were NIH in 25% (n=35) of lesions, neoatherosclerosis in 22% (n=30), uncovered ostium in 6% (n=9) (biological cause 53%, n=74), stent fracture or deformation in 25% (n=35), underexpansion in 11% (n=15), and protruding calcified nodules in 11% (n=15) (mechanical cause 47%, n=65). Including secondary mechanisms, 51% (n=71) of ostial RCA ISRs had stent fractures that were associated with greater hinge motion of the ostial-aorta angle during the cardiac cycle. The Kaplan-Meier rate of target lesion failure at 1 year was 11.5%. When the mechanically caused ISRs were treated without new stents, they suffered a higher subsequent event rate (41.4%) compared with non-mechanical causes or mechanical causes treated without restenting (7.8%, unadjusted hazard ratio 6.44, 95% confidence interval: 2.33-17.78; p<0.0001). CONCLUSIONS: Half of the ostial RCA ISRs were due to mechanical causes. Subsequent event rates were high, especially in mechanically caused ISRs treated without the implantation of a new stent.

Association between Hispanic or Latino ethnicity and pulmonary embolism severity, management, and in-hospital outcomes.

BACKGROUND: Hispanic and Latino patients are under-represented in existing healthcare disparities research in pulmonary embolism (PE). The goal of this study was to determine if differences in PE severity, treatment modality, or in-hospital outcomes exist for Hispanic or Latino patients with PE. METHODS: All PE cases from 2013 to 2019 at a single institution were reviewed. Clinical characteristics, imaging findings, intervention types, and in-hospital and 30-day outcomes were collected. Two cohorts were created based on patients' self-reported ethnicity. Outcomes were compared using univariate and multivariate analysis. RESULTS: A total of 1265 patients were identified with confirmed PE; 474 (37%) identified as Hispanic or Latino. Hispanic or Latino patients presented with high-risk PE significantly less often (19% vs 25%, p = 0.03). On univariate analysis, Hispanic or Latino patients had lower rates of PE-specific intervention (15% vs 19%, p = 0.03) and similar rates of inpatient mortality (6.8% vs 7.5%, p = 0.64). On ordinal regression analysis, Hispanic or Latino ethnicity was associated with lower PE severity (OR 0.69, 95% CI 0.54-0.89, p = 0.003). In subgroup analyses of intermediate and high-risk PEs, ethnicity was not a significant predictor of receipt of PE-specific intervention or in-hospital mortality. CONCLUSIONS: At this institution, Hispanic or Latino patients were less likely to present with high-risk PE but had similar rates of inpatient mortality. Future research is needed to identify if disparities in in-hospital care are driving perceived differences in PE severity and what addressable systematic factors are driving higher-than-expected in-hospital mortality for Hispanic or Latino patients.

Atorvastatin versus Placebo in ICU Patients with COVID-19: Ninety-day Results of the INSPIRATION-S Trial.

BACKGROUND: In the INSPIRATION-S trial, atorvastatin versus placebo was associated with a nonsignificant 16% reduction in 30-day composite of venous/arterial thrombosis or death in intensive care unit (ICU) patients with COVID-19. Thrombo-inflammatory response in coronavirus disease 2019 (COVID-19) may last beyond the first 30 days. METHODS: This article reports the effects of atorvastatin 20 mg daily versus placebo on 90-day clinical and functional outcomes from INSPIRATION-S, a double-blind multicenter randomized trial of adult ICU patients with COVID-19. The main outcome for this prespecified study was a composite of adjudicated venous/arterial thrombosis, treatment with extracorporeal membrane oxygenation (ECMO), or all-cause mortality. Functional status was assessed with the Post-COVID-19 Functional Scale. RESULTS: In the primary analysis, 587 patients were included (age: 57 [Q1-Q3: 45-68] years; 44% women). By 90-day follow-up, the main outcome occurred in 96 (33.1%) patients assigned to atorvastatin and 113 (38.0%) assigned to placebo (hazard ratio [HR]: 0.80, 95% confidence interval [CI]: 0.60-1.05, p = 0.11). Atorvastatin in patients who presented within 7 days of symptom onset was associated with reduced 90-day hazard for the main outcome (HR: 0.60, 95% CI: 0.42-0.86, p interaction = 0.02). Atorvastatin use was associated with improved 90-day functional status, although the upper bound CI crossed 1.0 (ORordinal: 0.64, 95% CI: 0.41-1.01, p = 0.05). CONCLUSION: Atorvastatin 20 mg compared with placebo did not significantly reduce the 90-day composite of death, treatment with ECMO, or venous/arterial thrombosis. However, the point estimates do not exclude a potential clinically meaningful treatment effect, especially among patients who presented within 7 days of symptom onset (NCT04486508).

Call for Formalized Pathways in Vascular Medicine Training: JACC Review Topic of the Week.

The burden of vascular diseases and complexity of their management have been growing. Vascular medicine specialists may help to bridge gaps in care, especially as part of multidisciplinary teams. However, there is a limited number of vascular medicine specialists because of constraints in training. Despite established pathways for training in vascular medicine, there are obstacles that restrict completion of training in dedicated programs. A key factor is lack of funding as a result of inadequate recognition by key national accrediting and credentialing organizations. A concerted effort is required to overcome the obstacles to expand vascular medicine training programs and ultimately the pool of vascular medicine specialists. Well-trained vascular medicine specialists will be well positioned to ease the burden of vascular disease and optimize patient outcomes.

Sex Differences in Peripheral Artery Disease.

Peripheral artery disease (PAD) is a prevalent condition that confers substantial morbidity and mortality and remains underdiagnosed as well as undertreated in the overall population. Although PAD prevalence is similar or higher in women compared with men, associations of traditional and nontraditional risk factors with PAD and clinical manifestations of PAD differ by sex and may contribute to delayed or lack of diagnosis in women. Such sex-based differences in the manifestation of PAD may arise from sexual dimorphism in the vascular substrate in health as well as sex variation in the responses to vascular stressors. Despite the availability of proven therapies for improving symptoms and reducing risk of ischemic cardiovascular and limb events among patients with diagnosed PAD, important sex differences in treatment and outcomes have been observed. We provide an overview of current knowledge regarding sex differences in the epidemiology, pathophysiology, clinical presentation, and management of PAD.

Intermediate-Dose versus Standard-Dose Prophylactic Anticoagulation in Patients with COVID-19 Admitted to the Intensive Care Unit: 90-Day Results from the INSPIRATION Randomized Trial.

BACKGROUND: Thrombotic complications are considered among the main extrapulmonary manifestations of coronavirus disease 2019 (COVID-19). The optimal type and duration of prophylactic antithrombotic therapy in these patients remain unknown. METHODS: This article reports the final (90-day) results of the Intermediate versus Standard-dose Prophylactic anticoagulation In cRitically-ill pATIents with COVID-19: An opeN label randomized controlled trial (INSPIRATION) study. Patients with COVID-19 admitted to intensive care were randomized to intermediate-dose versus standard-dose prophylactic anticoagulation for 30 days, irrespective of hospital discharge status. The primary efficacy outcome was a composite of adjudicated venous or arterial thrombosis, treatment with extracorporeal membrane oxygenation (ECMO), or all-cause death. The main safety outcome was major bleeding. RESULTS: Of 600 randomized patients, 562 entered the modified intention-to-treat analysis (median age [Q1, Q3]: 62 [50, 71] years; 237 [42.2%] women), of whom 336 (59.8%) survived to hospital discharge. The primary outcome occurred in 132 (47.8%) of patients assigned to intermediate dose and 130 (45.4%) patients assigned to standard-dose prophylactic anticoagulation (hazard ratio [HR]: 1.21, 95% confidence interval [CI]: 0.95-1.55, p = 0.11). Findings were similar for other efficacy outcomes, and in the landmark analysis from days 31 to 90 (HR: 1.59, 95% CI: 0.45-5.06). There were 7 (2.5%) major bleeding events in the intermediate-dose group (including 3 fatal events) and 4 (1.4%) major bleeding events in the standard-dose group (none fatal) (HR: 1.82, 95% CI: 0.53-6.24). CONCLUSION: Intermediate-dose compared with standard-dose prophylactic anticoagulation did not reduce a composite of death, treatment with ECMO, or venous or arterial thrombosis at 90-day follow-up.

The "Lollipop" During Catheter-Directed Thrombectomy: 2 Case Examples.

Intraprocedural embolization has been described as a potential complication of catheter thrombectomy for acute pulmonary embolism and may be under-recognized. We describe 2 case examples of "Lollipopping" during thrombectomy, which may be a mechanism of intraprocedural embolization and describe our treatment approach. (Level of Difficulty: Advanced.).

Iatrogenic Arteriovenous Fistula Following Femoral Access Precipitating High-Output Heart Failure.

Iatrogenic complications may manifest in a variety of ways. We present the case of an 86-year-old woman who underwent a percutaneous coronary intervention with a drug-eluting stent for non-ST-segment elevation myocardial infarction followed by leadless pacemaker placement through a femoral approach. Her post-procedure course was complicated by new onset high-output heart failure secondary to iatrogenic arteriovenous fistula formation, requiring covered stent placement. (Level of Difficulty: Advanced.).

Pulmonary Embolism Response Team utilization during the COVID-19 pandemic.

Coronavirus disease 2019 (COVID-19) may predispose patients to venous thromboembolism (VTE). Limited data are available on the utilization of the Pulmonary Embolism Response Team (PERT) in the setting of the COVID-19 global pandemic. We performed a single-center study to evaluate treatment, mortality, and bleeding outcomes in patients who received PERT consultations in March and April 2020, compared to historical controls from the same period in 2019. Clinical data were abstracted from the electronic medical record. The primary study endpoints were inpatient mortality and GUSTO moderate-to-severe bleeding. The frequency of PERT utilization was nearly threefold higher during March and April 2020 (n = 74) compared to the same period in 2019 (n = 26). During the COVID-19 pandemic, there was significantly less PERT-guided invasive treatment (5.5% vs 23.1%, p = 0.02) with a numerical but not statistically significant trend toward an increase in the use of systemic fibrinolytic therapy (13.5% vs 3.9%, p = 0.3). There were nonsignificant trends toward higher in-hospital mortality or moderate-to-severe bleeding in patients receiving PERT consultations during the COVID-19 period compared to historical controls (mortality 14.9% vs 3.9%, p = 0.18 and moderate-to-severe bleeding 35.1% vs 19.2%, p = 0.13). In conclusion, PERT utilization was nearly threefold higher during the COVID-19 pandemic than during the historical control period. Among patients evaluated by PERT, in-hospital mortality or moderate-to-severe bleeding were not significantly different, despite being numerically higher, while invasive therapy was utilized less frequently during the COVID-19 pandemic.

Effect of Intermediate-Dose vs Standard-Dose Prophylactic Anticoagulation on Thrombotic Events, Extracorporeal Membrane Oxygenation Treatment, or Mortality Among Patients With COVID-19 Admitted to the Intensive Care Unit: The INSPIRATION Randomized Clinical Trial.

Importance: Thrombotic events are commonly reported in critically ill patients with COVID-19. Limited data exist to guide the intensity of antithrombotic prophylaxis. Objective: To evaluate the effects of intermediate-dose vs standard-dose prophylactic anticoagulation among patients with COVID-19 admitted to the intensive care unit (ICU). Design, Setting, and Participants: Multicenter randomized trial with a 2 × 2 factorial design performed in 10 academic centers in Iran comparing intermediate-dose vs standard-dose prophylactic anticoagulation (first hypothesis) and statin therapy vs matching placebo (second hypothesis; not reported in this article) among adult patients admitted to the ICU with COVID-19. Patients were recruited between July 29, 2020, and November 19, 2020. The final follow-up date for the 30-day primary outcome was December 19, 2020. Interventions: Intermediate-dose (enoxaparin, 1 mg/kg daily) (n = 276) vs standard prophylactic anticoagulation (enoxaparin, 40 mg daily) (n = 286), with modification according to body weight and creatinine clearance. The assigned treatments were planned to be continued until completion of 30-day follow-up. Main Outcomes and Measures: The primary efficacy outcome was a composite of venous or arterial thrombosis, treatment with extracorporeal membrane oxygenation, or mortality within 30 days, assessed in randomized patients who met the eligibility criteria and received at least 1 dose of the assigned treatment. Prespecified safety outcomes included major bleeding according to the Bleeding Academic Research Consortium (type 3 or 5 definition), powered for noninferiority (a noninferiority margin of 1.8 based on odds ratio), and severe thrombocytopenia (platelet count <20 ×103/µL). All outcomes were blindly adjudicated. Results: Among 600 randomized patients, 562 (93.7%) were included in the primary analysis (median [interquartile range] age, 62 [50-71] years; 237 [42.2%] women). The primary efficacy outcome occurred in 126 patients (45.7%) in the intermediate-dose group and 126 patients (44.1%) in the standard-dose prophylaxis group (absolute risk difference, 1.5% [95% CI, -6.6% to 9.8%]; odds ratio, 1.06 [95% CI, 0.76-1.48]; P = .70). Major bleeding occurred in 7 patients (2.5%) in the intermediate-dose group and 4 patients (1.4%) in the standard-dose prophylaxis group (risk difference, 1.1% [1-sided 97.5% CI, -∞ to 3.4%]; odds ratio, 1.83 [1-sided 97.5% CI, 0.00-5.93]), not meeting the noninferiority criteria (P for noninferiority >.99). Severe thrombocytopenia occurred only in patients assigned to the intermediate-dose group (6 vs 0 patients; risk difference, 2.2% [95% CI, 0.4%-3.8%]; P = .01). Conclusions and Relevance: Among patients admitted to the ICU with COVID-19, intermediate-dose prophylactic anticoagulation, compared with standard-dose prophylactic anticoagulation, did not result in a significant difference in the primary outcome of a composite of adjudicated venous or arterial thrombosis, treatment with extracorporeal membrane oxygenation, or mortality within 30 days. These results do not support the routine empirical use of intermediate-dose prophylactic anticoagulation in unselected patients admitted to the ICU with COVID-19. Trial Registration: ClinicalTrials.gov Identifier: NCT04486508.