The coronavirus disease 2019 (COVID-19) can result in a hyperinflammatory state, leading to acute respiratory distress syndrome (ARDS), myocardial injury, and thrombotic complications, among other ...sequelae. Statins, which are known to have anti-inflammatory and antithrombotic properties, have been studied in the setting of other viral infections, but their benefit has not been assessed in COVID-19. This is a retrospective analysis of patients admitted with COVID-19 from February 1
through May 12
, 2020 with study period ending on June 11
, 2020. Antecedent statin use was assessed using medication information available in the electronic medical record. We constructed a multivariable logistic regression model to predict the propensity of receiving statins, adjusting for baseline sociodemographic and clinical characteristics, and outpatient medications. The primary endpoint includes in-hospital mortality within 30 days. A total of 2626 patients were admitted during the study period, of whom 951 (36.2%) were antecedent statin users. Among 1296 patients (648 statin users, 648 non-statin users) identified with 1:1 propensity-score matching, statin use is significantly associated with lower odds of the primary endpoint in the propensity-matched cohort (OR 0.47, 95% CI 0.36-0.62, p < 0.001). We conclude that antecedent statin use in patients hospitalized with COVID-19 is associated with lower inpatient mortality.
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.
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
Objectives This study evaluated data from 3 federally funded trials that focused on optimal medical therapy to determine if formalized attempts at risk factor control within clinical trials are ...effective in achieving guideline-driven treatment goals for diabetic patients with coronary artery disease (CAD). Background Despite clear evidence of benefit for CAD secondary prevention, the level of risk factor control in clinical practice has been disappointing. Methods We obtained data from the COURAGE (Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation) diabetes subgroup, (n = 766 of 2,287), the BARI 2D (Bypass Angioplasty Revascularization Investigation 2 Diabetes) trial (n = 2,368), and the FREEDOM (Comparison of Two Treatments for Multivessel Coronary Artery Disease in Individuals With Diabetes) trial (n = 1,900) to evaluate the proportion of patients achieving guideline-based, protocol-driven treatment targets for systolic blood pressure, low-density lipoprotein cholesterol, smoking cessation, and hemoglobin A1c. The primary outcome measure was the proportion of diabetic CAD patients meeting all 4 pre-specified targets at 1 year after enrollment. Results The pooled data include 5,034 diabetic patients. The percentages of patients achieving the 1-year low-density lipoprotein cholesterol targets compared with baseline increased from 55% to 77% in COURAGE, from 59% to 75% in BARI 2D, and from 34% to 42% in FREEDOM. Although similar improved trends were seen for systolic blood pressure, glycemic control, and smoking cessation, only 18% of the COURAGE diabetes subgroup, 23% of BARI 2D patients, and 8% of FREEDOM patients met all 4 pre-specified treatment targets at 1 year of follow-up. Conclusions A significant proportion of diabetic CAD patients fail to achieve pre-specified targets for 4 major modifiable cardiovascular risk factors in clinical trials. We conclude that fundamentally new thinking is needed to explore approaches to achieve optimal secondary prevention treatment goals. (Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation; NCT00007657 ) (Bypass Angioplasty Revascularization Investigation 2 Diabetes BARI 2D; NCT00006305 ) (Comparison of Two Treatments for Multivessel Coronary Artery Disease in Individuals With Diabetes FREEDOM; NCT00086450 )
The optimal treatment strategy of patients with pulmonary embolism (PE) (especially those with intermediate risk) continues to evolve and remains controversial.
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.
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).
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.
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.
AbstractObjectiveTo assess the effect of statin treatment versus placebo on clinical outcomes in patients with covid-19 admitted to the intensive care unit (ICU).DesignINSPIRATION/INSPIRATION-S was a ...multicenter, randomized controlled trial with a 2×2 factorial design. Results for the anticoagulation randomization have been reported previously. Results for the double blind randomization to atorvastatin versus placebo are reported here.Setting11 hospitals in Iran.ParticipantsAdults aged ≥18 years with covid-19 admitted to the ICU.InterventionAtorvastatin 20 mg orally once daily versus placebo, to be continued for 30 days from randomization irrespective of hospital discharge status.Main outcome measuresThe primary efficacy outcome was a composite of venous or arterial thrombosis, treatment with extracorporeal membrane oxygenation, or all cause mortality within 30 days from randomization. Prespecified safety outcomes included increase in liver enzyme levels more than three times the upper limit of normal and clinically diagnosed myopathy. A clinical events committee blinded to treatment assignment adjudicated the efficacy and safety outcomes.ResultsOf 605 patients randomized between 29 July 2020 and 4 April 2021 for statin randomization in the INSPIRATION-S trial, 343 were co-randomized to intermediate dose versus standard dose prophylactic anticoagulation with heparin based regimens, whereas 262 were randomized after completion of the anticoagulation study. 587 of the 605 participants were included in the primary analysis of INSPIRATION-S, reported here: 290 were assigned to atorvastatin and 297 to placebo (median age 57 years (interquartile range 45-68 years); 256 (44%) women). The primary outcome occurred in 95 (33%) patients assigned to atorvastatin and 108 (36%) assigned to placebo (odds ratio 0.84, 95% confidence interval 0.58 to 1.21). Death occurred in 90 (31%) patients in the atorvastatin group and 103 (35%) in the placebo group (odds ratio 0.84, 95% confidence interval 0.58 to 1.22). Rates for venous thromboembolism were 2% (n=6) in the atorvastatin group and 3% (n=9) in the placebo group (odds ratio 0.71, 95% confidence interval 0.24 to 2.06). Myopathy was not clinically diagnosed in either group. Liver enzyme levels were increased in five (2%) patients assigned to atorvastatin and six (2%) assigned to placebo (odds ratio 0.85, 95% confidence interval 0.25 to 2.81).ConclusionsIn adults with covid-19 admitted to the ICU, atorvastatin was not associated with a significant reduction in the composite of venous or arterial thrombosis, treatment with extracorporeal membrane oxygenation, or all cause mortality compared with placebo. Treatment was, however, found to be safe. As the overall event rates were lower than expected, a clinically important treatment effect cannot be excluded.Trial registrationClinicalTrials.gov NCT04486508.
Abstract
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.
Contemporary care patterns/outcomes in high-risk pulmonary embolism (PE) patients are unknown.
This study sought to characterize the management of high-risk PE patients and identify factors ...associated with poor outcomes.
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.
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.
In the largest analysis of high-risk PE patients to date, mortality rates were high with the worst outcomes among patients with hemodynamic collapse.
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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.
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.
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.
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