Comparison of Thrombotic Complications in Critically Ill Patients between COVID-19 and Mers-COV

Background: Several observational studies have reported the rate of thrombotic events in patients infected with coronavirus disease 2019 (COVID-19), with conflicting results 1. The conflicting results could be partially explained by different population critically ill vs non critically ill, different definition of thrombotic events, follow up period was variable, and different prophylaxis that were used. Middle east respiratory syndrome (MERS-COV) is another coronavirus had been initially reported in Saudi Arabia in 2012. A genome scan has shown a 50% similarity between COVID-19 and MERS-COV 2.A common features of covid-19 and MERS-COV including transmissibility, and MERS-COV clinical presentation have been identified 3. However, data about thrombotic complications in patients with MERS-COV are limited. The aim of this study was to compare the rate of thrombotic events between patients with COVID-19 and MERS-COV. Methods: Patients : We included all confirmed COVID-19 patients who were admitted to intensive care unit (ICU) in 3 major hospitals in Saudi Arabia between February and July 2020. We included all confirmed cases of MERS-COV who were admitted to ICU from these centers between March to May 2014. Patients were excluded if they were transferred in or out from one of these three hospital to another hospitals. Data were collected retrospectively from the first day of admission until discharge or death. Outcome: The primary outcome was the rate of venous thromboembolism (VTE). The secondary outcomes were the rate of arterial events, the rate of composite events (venous and arterial) and the rate of bleeding. VTE included all symptomatic or incidentally diagnosed cases of pulmonary embolism (PE), deep vein thrombosis (DVT) and thrombosis in unusual sites (cerebral, mesenteric, portal, splenic, hepatic, and renal veins). All VTEs were confirmed radiographically by appropriate imaging. Screening for VTE in asymptomatic patients was not performed. If more than on type of VTE occurred in the same patient, it was considered one event. Arterial events included cerebrovascular accidents (CVAs), mesenteric ischemia, and limb ischemia and were confirmed by the appropriate imaging modality. Myocardial infarction (MI) was diagnosed based on the suspicion of the attending physician using clinical criteria as well as biomarker elevations or electrocardiographic changes. Composite events were defined as any VTE or arterial event. Bleeding events were classified as major and nonmajor based on the definition of international society of thrombosis and hemostasis (ISTH) 4. Informed consent was waived. Statistical analysis: Characteristics and outcomes were compared between COVID-19 and MERS-COV groups using chi-square test, fisher exact test or t-test. The rates of thrombosis and bleeding are summarized as proportions, with the corresponding 95 % confidence intervals (CI). A P-value less than 0.05 was considered significant. Statistical analyses were performed using SAS version 9.4 (SAS Institute, Cary, NC, USA) Result: After exclusion, 234 COVID-19 and 58 MERS-COV patients were included. The majority of patients with COVID-19 (98%, n=230) and more than (67% ,n =39 ) of those with MERS-COV group received pharmacological prophylaxis. The most frequently prescribed regimen in both groups was enoxaparin (40 mg twice per day). Over a median length of stay in the COVID-19 group of 22 days, the rate of VTE 9.8%(CI; 6.6-14.3) and was 3.4%(CI; 0.95-11.7) in the MESR-COV group over median length of stay of 10 days. The rate of arterial events were 5.9 % (CI;3.6-9.7) and 8.6% (CI;3.7-18.6) in COVID-19 and MERS-COV respectively. Table 1 and 2. Conclusions: To our knowledge, this is the first study compared thrombotic risk between COVID-19 and MERS-COV. We found a similar rate of composite thrombotic events (venous and arterial ) between COVID-19 and MERS-COV with higher rate of venous thrombosis in COVID-19 and higher rate arterial thrombosis in MERS-COV. This may indicate that not only COVID-19 is a prothrombotic disease, but MERS-COV may have similar risk of thrombotic complication . These result needs to be confirmed in a larger studies. References 1- Al-Samkari, H, 2020. Blood, 136(4), Pp.489-500. 2- Lu, R, 2020. The Lancet, 395(10224), Pp.565-574. 3- Petrosillo, N, 2020. Clinical Microbiology And Infection, 26(6), Pp.729-734. 4- Schulman, S, 2005. Journal Of Thrombosis And Haemostasis, 3(4), Pp.692-694. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

Risk Stratifying and Prognostic Analysis of Subclinical Cardiac Implantable Electronic Devices Infection: Insight From Traditional Bacterial Culture

Background Subclinical infection of cardiac implantable electronic devices (CIEDs) is a common condition and increases the risk of clinical infection. However, there are limited studies focused on risk stratifying and prognostic analysis of subclinical CIED infection. Methods and Results Data from 418 consecutive patients undergoing CIED replacement or upgrade between January 2011 and December 2019 were used in the analysis. Among the patients included, 50 (12.0%) were detected as positive by bacterial culture of pocket tissues. The most frequently isolated bacteria were coagulase‐negative staphylococci (76.9%). Compared with the noninfection group, more patients in the subclinical infection group were taking immunosuppressive agents, received electrode replacement, or received CIED upgrade and temporary pacing. Patients in the subclinical infection group had a higher PADIT (Prevention of Arrhythmia Device Infection Trial) score. Univariable and multivariable logistic regression analysis found that use of immunosuppressive agents (odds ratio [OR], 6.95 [95% CI, 1.44–33.51]; P =0.02) and electrode replacement or CIED upgrade (OR, 6.73 [95% CI, 2.23–20.38]; P =0.001) were significantly associated with subclinical CIED infection. Meanwhile, compared with the low‐risk group, patients in the intermediate/high‐risk group had a higher risk of subclinical CIED infection (OR, 3.43 [95% CI, 1.58–7.41]; P =0.002). After a median follow‐up time of 36.5 months, the end points between the subclinical infection group and noninfection group were as follows: composite events (58.0% versus 41.8%, P =0.03), rehospitalization (54.0% versus 32.1%, P =0.002), cardiovascular rehospitalization (32.0% versus 13.9%, P =0.001), CIED infection (2.0% versus 0.5%, P =0.32), all‐cause mortality (28.0% versus 21.5%, P =0.30), and cardiovascular mortality (10.0% versus 7.6%, P =0.57). Conclusions Subclinical CIED infection was a common phenomenon. The PADIT score had significant value for stratifying patients at high risk of subclinical CIED infection. Subclinical CIED infection was associated with increased risks of composite events, rehospitalization, and cardiovascular rehospitalization.

Dual versus single antiplatelet therapy for secondary prevention in ischaemic stroke or transient ischaemic attack: A retrospective cohort study using real-world data

Objective: This study aimed to assess effectiveness and safety outcomes of antiplatelet therapy for secondary prevention among patients with ischaemic stroke or transient ischaemic attack (TIA) in Malaysia. Method: Patients with a first ischaemic stroke/TIA between 2014 and 2017 were identified from stroke registry and data was linked with other data sources for information on antiplatelet exposure and outcome events. Exposure was defined as antiplatelet therapy at discharge from the index stroke hospitalisation and categorised into single antiplatelet therapy (SAPT) and dual antiplatelet therapy (DAPT) groups. Primary outcome was composite events of stroke, myocardial infarction, and all-cause death at up to one year after the index stroke in an intention-to-treat analysis. Results: Of 4434 patients included in the analysis, 6.7% were treated with DAPT and 93.3% were in SAPT group. During the 1-year follow-up, composite events occurred in 5.7% of patients in DAPT group and in 12.3% of SAPT (p<0.001). The rates of individual events were lower in DAPT group compared to SAPT: recurrent stroke (3.4% versus 4.8%), myocardial infarction (0.7% versus 1.9%), and all-cause death (1.7% versus 6.0%). Bleeding occurred in 1.3% of the DAPT group versus 1.6% of the SAPT. Multivariable-adjusted Cox regression analysis showed that rates of composite outcome was lower in the DAPT group compared to SAPT (HR 0.53, 95%CI 0.32, 0.86). Conclusion: In patients with ischaemic stroke/TIA, treatment with DAPT following the index stroke was associated with reduced risk of the composite events of stroke, myocardial infarction, and death. There appears to be similar risk of bleeding with DAPT versus SAPT.

Secondary prevention medication persistence and prognosis of acute ischaemic stroke or transient ischaemic attack

IntroductionThe risk of disability and mortality is high among recurrent stroke, which highlights the importance of secondary prevention measures. We aim to evaluate medication persistence for secondary prevention and the prognosis of acute ischaemic stroke or transient ischaemic attack (TIA) in China.MethodsPatients with acute ischaemic stroke or TIA from the China National Stroke Registry II were divided into 3 groups based on the percentage of persistence in secondary prevention medication classes from discharge to 3 months after onset (level I: persistence=0%, level II: 0%<persistence<100%, level III: persistence=100%). The primary outcome was recurrent stroke. The secondary outcomes included composite events (stroke, myocardial infarction or death from cardiovascular cause), all-cause death and disability (modified Rankin Scale score=3–5) from 3 months to 1 year after onset. Recurrent stroke, composite events and all-cause death were performed using Cox regression model, and disability was identified through logistic regression model using the generalised estimating equation method.Results18 344 patients with acute ischaemic stroke or TIA were included, 315 (1.7%) of whom experienced recurrent strokes. Compared with level I, the adjusted HR of recurrent stroke for level II was 0.41 (95% CI 0.31 to 0.54) and level III 0.37 (0.28 to 0.48); composite events for level II 0.41 (0.32 to 0.53) and level III 0.38 (0.30 to 0.49); all-cause death for level II 0.28 (0.23 to 0.35) and level III 0.20 (0.16–0.24). Compared with level I, the adjusted OR of disability for level II was 0.89 (0.77 to 1.03) and level III 0.82 (0.72 to 0.93).ConclusionsPersistence in secondary prevention medications, especially in all classes of medications prescribed by the physician, was associated with lower hazard of recurrent stroke, composite events, all-cause death and lower odds of disability in patients with acute ischaemic stroke or TIA.

Urine albumin dipstick independently predicts cardiovascular and renal outcomes among rural Thai population: a 14-year retrospective cohort study

Background Albuminuria is an established risk marker for both cardiovascular and renal outcomes. In this study, we expected to use portable and inexpensive test strips to detect urine albumin level for risk stratification in cardiovascular and renal outcomes among rural Thai community. Objective To evaluate the relationship between urine albumin dipstick and cardiovascular and renal complications in rural Thai population. Methods We conducted a retrospective study in 635 rural Thai adults who tested urine albuminuria by using commercial urine albumin dipstick and the Micral-albumin test II strips at baseline. The subjects were divided into normoalbuminuria (albumin < 20 mg/L), microalbuminuria (albumin 20–200 mg/L), or macroalbuminuria (Urine dipstick at least 1+ or albumin > 200 mg/L). We collected data on the incidences of primary composite outcomes including cardiovascular or renal morbidity and mortality. Incident density and cox regression were analyzed to evaluate the association between albuminuria status and primary composite outcome. Results During an average 14-year follow-up, 102 primary composite events occurred including 59 (13.1%), 32 (20.6%) and 11 (39.3%) among 452, 155, and 28 subjects with normoalbuminuria, microalbuminuria, and macroalbuminuria, respectively. Incident densities of primary composite outcome were elevated continually according to the degree of albuminuria (9.36, 17.11 and 38.12 per 1000 person-years). Compared with the subjects without albuminuria, subjects with microalbuminuria and macroalbuminuria at baseline had higher risk for primary composite outcome in univariate model. After multivariate analysis was performed, the effect of macroalbuminuria was only persisted with 3.13-fold risk (adjusted HR 3.13; 95% CI 1.40–6.96, P= 0.005). Conclusion Albuminuria from semi-quantitative methods is an important factor predicting cardiovascular and renal risk among subjects in Thai rural population. Our findings support to also incorporating urine albumin dipstick into assessments of cardiovascular risk in the general population.

Comparative effectiveness of erenumab versus oral preventive medications among migraine patients: A US claims database study

Background: Erenumab, a fully human monoclonal antibody targeting the calcitonin gene-related peptide pathway, was developed specifically for preventive treatment of migraine. Objective: To compare the real-world effectiveness of erenumab and non-specific oral migraine preventive medication (OMPM) on acute medication usage and healthcare resource utilization (HCRU) among migraine patients. Methods: This retrospective US claims analysis included patients (≥18 years) diagnosed with migraine who initiated erenumab (May 01, 2018 and September 30, 2019) or OMPM (May 01, 2016 and October 31, 2017). Cohorts were matched 1:1 using the propensity score (PS) method with stratification. Acute medication usage, HCRU, and a composite endpoint of 1) outpatient visit with a migraine diagnosis and associated acute medication claim, 2) hospital admission with a primary migraine diagnosis, or 3) emergency room visit with a primary migraine diagnosis were assessed 6 months post-treatment initiation. Results: Following PS matching, both cohorts included 2,343 patients. At 6 months, erenumab was associated with significantly less acute medication usage versus OMPM, including number of types of acute medications used, number of claims per person, and proportion of patients using acute medication. HCRU and number of composite events were also significantly lower among erenumab users. Conclusion: Erenumab is more effective than OMPM at reducing acute medication usage and HCRU among migraine patients. Trial registration: N/A.

Towards clinical data-driven eligibility criteria optimization for interventional COVID-19 clinical trials

Objective This research aims to evaluate the impact of eligibility criteria on recruitment and observable clinical outcomes of COVID-19 clinical trials using electronic health record (EHR) data. Materials and Methods On June 18, 2020, we identified frequently used eligibility criteria from all the interventional COVID-19 trials in ClinicalTrials.gov (n = 288), including age, pregnancy, oxygen saturation, alanine/aspartate aminotransferase, platelets, and estimated glomerular filtration rate. We applied the frequently used criteria to the EHR data of COVID-19 patients in Columbia University Irving Medical Center (CUIMC) (March 2020–June 2020) and evaluated their impact on patient accrual and the occurrence of a composite endpoint of mechanical ventilation, tracheostomy, and in-hospital death. Results There were 3251 patients diagnosed with COVID-19 from the CUIMC EHR included in the analysis. The median follow-up period was 10 days (interquartile range 4–28 days). The composite events occurred in 18.1% (n = 587) of the COVID-19 cohort during the follow-up. In a hypothetical trial with common eligibility criteria, 33.6% (690/2051) were eligible among patients with evaluable data and 22.2% (153/690) had the composite event. Discussion By adjusting the thresholds of common eligibility criteria based on the characteristics of COVID-19 patients, we could observe more composite events from fewer patients. Conclusions This research demonstrated the potential of using the EHR data of COVID-19 patients to inform the selection of eligibility criteria and their thresholds, supporting data-driven optimization of participant selection towards improved statistical power of COVID-19 trials.

Sex differences in clinical characteristics and long-term outcomes in patients with vasospastic angina: results from the VA-Korea registry, a prospective multi-center cohort

Background Sex differences in clinical characteristics and prognosis of vasospastic angina (VA) have not been well elucidated. This study was performed to investigate sex-specific characteristics and predictors for long-term clinical outcomes in patients with VA. Methods We analyzed 1838 patients (55 years and 62% male) who were diagnosed with definite (n = 680) or intermediate (n = 1212) VA in ergonovine provocation test from a nation-wide VA registry. The primary study end-point was composite events including cardiac death, acute coronary syndrome, ventricular tachycardia or fibrillation, and atrioventricular block during clinical follow-up. Results Male patients were younger, and there were more smokers and alcohol drinkers in male patients than in female patients. During the median follow-up period of 760 days (interquartile range, 336–1105 days), there were 73 cases (3.97%) of composite events. There was no sex difference in the occurrence of composite events (log-rank p = 0.649). Concomitant significant (≥ 50%) organic coronary stenosis was associated with worse clinical outcomes in both male (hazard ration [HR], 1.97; 95% confidence interval [CI], 1.01–3.85; p = 0.047) and female (HR, 3.26; 95% CI, 1.07–9.89; p = 0.037) patients. Obesity (body mass index ≥ 25 kg/m2) was associated with better prognosis in female VA patients (HR, 0.22; 95% CI, 0.07–0.68; p = 0.008). Even when only patients with definite diagnosis of VA were considered, there was no significant sex difference in clinical outcomes (log-rank p = 0.876). Conclusions In VA patients, there were several different clinical characteristics according to sex; however, long-term clinical outcome was similar between sexes. Significant organic coronary stenosis in both sexes and low body mass index (< 25 kg/m2) in females were associated with worse prognosis in VA patients.

High Rate of Bleeding and Arterial Thrombosis in COVID-19: Saudi Multicenter Study

Background: Coronavirus disease 2019 (COVID-19) is a global pandemic with a substantial impact on mortality, the health system and the economy8,9. Several observational studies reported the rate of venous and arterial thrombotic events in patients infected with COVID-19, with conflicting results . The aim of this multicentre study was to estimate the rate of thrombotic and bleeding events in hospitalized patients diagnosed with COVID-19 in Saudi Arabia. Method: multicenter study of 636 hospitalized patients with COVID-19.Result: Twelve patients were diagnosed with VTE 1.89% (95% CI, 1.18–3). The rate in the non-ICU group was 0.19% (95% CI, 0.04–0.84) compared to 10.38% (95% CI, 6.45–16.27) in the ICU group. Fourteen patients were diagnosed with an arterial event with an overall rate of 2.20% (95% CI, 1.43–3.38). The rate in the non-ICU group was 0.94% (95% CI, 0.46–0.1.93) and 8.49% (95% CI, 5.01–14.04) in the ICU group. The overall composite events rate was 2.99% (95% CI, 2.06–4.31). The composite events rate in the non-ICU group was 0.94% (95% CI, 0.46–0.1.93) and 13.21% (95% CI, 8.7–19.54) in the ICU group. Eleven patients developed bleeding with an overall rate of 1.73% (95% CI, 1.06–2.81). The bleeding rate in the non-ICU group was 0.19% (95% CI, 0.04–0.84), and 9.43% (95% CI, 5.72–15.16) in the ICU group. Of the selected risk factors, the only risk factor that predicted VTE and the composite outcome, was the baseline D-dimer. (OR 1.31, 95% CI, 1.084-1.573, p=0.005) and composite events (OR 1.32, 95% CI, 1.126-1.555, p=0.0007).Conclusion: Of 636 adults with COVID-19, the rate of VTE was similar to the rate of hospitalized patients with a similar degree of critical illness. In contrast to the risk of VTE, we found a high rate of arterial and bleeding complications in patients admitted to ICU. An elevated D-dimer at baseline could predict a thrombotic complication in the COVID-19 patients, which may assist in the identification of these patients. Given the high rate of bleeding, the current study suggests that the intensification of anticoagulation in COVID-19 patients beyond the standard of care, should be pursued with caution and is best evaluated in a randomised controlled study.