Effectiveness and Safety of Enoxaparin Versus Unfractionated Heparin as Thromboprophylaxis in Hospitalized COVID-19 Patients: Real-World Evidence.

BACKGROUND: Coronavirus 2019 (COVID-19) patients are at risk of thrombosis. Literature that compares the effectiveness of enoxaparin to unfractionated heparin (UFH) in COVID-19 patients is scarce. OBJECTIVE: We aimed to evaluate the effectiveness and safety of enoxaparin compared with UFH when used at their standard/intermediate dosing in COVID-19 patients. METHODS: This was a retrospective study conducted at a large COVID-19 center located in Eastern Province, Saudi Arabia. Confirmed COVID-19 cases (≥18 years old) admitted between January and December 2020 were randomly screened for inclusion. Exclusion criteria were patients receiving therapeutic anticoagulation, on chronic anticoagulation, had active bleeding, a platelet count <25 × 109/L, or an incomplete electronic file. The primary endpoint was the occurrence of any thrombotic event (pulmonary embolism, deep venous thrombosis, stroke, or myocardial infarction) or mortality. Secondary endpoints were major or minor bleeding. We applied inverse propensity score weighting (IPTW) with survival analysis to analyze the primary endpoint. Logistic regression was used for the secondary endpoint. RESULTS: A total of 980 patients were included (enoxaparin, n = 470 and UFH, n = 510) with a mean age (±SD) of 47.7 (± 12.3) for the enoxaparin arm and 52 (±13.9) for the UFH arm. There was a statistically significant difference in the primary endpoint with an adjusted hazard ratio (aHR) of 0.46 (95%CI: 0.22 to 0.96, P = 0.039) in favor of the enoxaparin arm. There was no statistically significant difference in major or minor bleeding rates between the two arms. CONCLUSION AND RELEVANCE: When compared with UFH, enoxaparin was associated with a significant reduction in thrombotic events or mortality among COVID-19 patients. The results need confirmation from randomized controlled trials.

Cost-effectiveness of Favipiravir in moderately to severely ill COVID-19 patients in the real-world setting of Saudi arabian pandemic referral hospitals.

Purpose: We aimed to evaluate the cost effectiveness of Favipiravir treatment versus standard of care (SC) in moderately to severely ill COVID-19 patients from the Saudi healthcare payer perspective. Methods: We used the patient-level simulation method to simulate a cohort of 415 patients with moderate to severe COVID-19 disease who were admitted to two Saudi COVID-19 referral hospitals: 220 patients on Favipiravir and 195 patients on SC. We estimated the incremental cost-effectiveness ratio (ICER) of Favipiravir versus SC in terms of the probability to be discharged alive from hospital and the mean time in days to discharge one patient alive. The model was performed twice: first, using unweighted, and second, using weighted clinical and economic data. Weighting using the inverse weight probability method was performed to achieve balance in baseline characteristics. Results: In the unweighted model, base case (probabilistic) ICER estimates favored Favipiravir at savings of Saudi Riyal (SAR)1,611,511 (SAR1,998,948) per 1% increase in the probability of being discharged alive. As to mean time to discharging one patient alive, ICERs favored Favipiravir at savings of SAR11,498 (SAR11,125). Similar results were observed in the weighted model with savings using Favipiravir of SAR1,514,893 (SAR2,453,551) per 1% increase in the probability of being discharged alive, and savings of SAR11,989 (SAR11,277) for each day a patient is discharged alive. Conclusion: From the payer perspective, the addition of Favipiravir in moderately to severely ill COVID-19 patients was cost-savings over SC. Favipiravir was associated with a higher probability of discharging patients alive and lower daily spending on hospitalization than SC.

A comparison of three thromboprophylaxis regimens in critically ill COVID-19 patients: An analysis of real-world data.

Introduction: Thrombotic complications of coronavirus disease 2019 (COVID-19) have received considerable attention. Although numerous conflicting findings have compared escalated thromboprophylaxis doses with a standard dose to prevent thrombosis, there is a paucity of literature comparing clinical outcomes in three different anticoagulation dosing regimens. Thus, we investigated the effectiveness and safety profiles of standard, intermediate, and high-anti-coagulation dosing strategies in COVID-19 critically ill patients. Methodology: This retrospective multicenter cohort study of intensive care unit (ICU) patients from the period of April 2020 to August 2021 in four Saudi Arabian centers. Inclusion criteria were age ≥ 18 years, diagnosis with severe or critical COVID-19 infection, and receiving prophylactic anticoagulant dose within 24-48 h of ICU admission. The primary endpoint was a composite of thrombotic events, with mortality rate and minor or major bleeding serving as secondary endpoints. We applied survival analyses with a matching weights procedure to control for confounding variables in the three arms. Results: A total of 811 patient records were reviewed, with 551 (standard-dose = 192, intermediate-dose = 180, and high-dose = 179) included in the analysis. After using weights matching, we found that the standard-dose group was not associated with an increase in the composite thrombotic events endpoint when compared to the intermediate-dose group {19.8 vs. 25%; adjusted hazard ratio (aHR) =1.46, [95% confidence of interval (CI), 0.94-2.26]} or when compared to high-dose group [19.8 vs. 24%; aHR = 1.22 (95% CI, 0.88-1.72)]. Also, there were no statistically significant differences in overall in-hospital mortality between the standard-dose and the intermediate-dose group [51 vs. 53.4%; aHR = 1.4 (95% CI, 0.88-2.33)] or standard-dose and high-dose group [51 vs. 61.1%; aHR = 1.3 (95% CI, 0.83-2.20)]. Moreover, the risk of major bleeding was comparable in all three groups [standard vs. intermediate: 4.8 vs. 2.8%; aHR = 0.8 (95% CI, 0.23-2.74); standard vs. high: 4.8 vs. 9%; aHR = 2.1 (95% CI, 0.79-5.80)]. However, intermediate-dose and high-dose were both associated with an increase in minor bleeding incidence with aHR = 2.9 (95% CI, 1.26-6.80) and aHR = 3.9 (95% CI, 1.73-8.76), respectively. Conclusion: Among COVID-19 patients admitted to the ICU, the three dosing regimens did not significantly affect the composite of thrombotic events and mortality. Compared with the standard-dose regimen, intermediate and high-dosing thromboprophylaxis were associated with a higher risk of minor but not major bleeding. Thus, these data recommend a standard dose as the preferred regimen.

Characteristics of mechanically ventilated COVID-19 patients in the Al-Ahsa Region of Saudi Arabia: a retrospective study with survival analysis.

BACKGROUND: About 5-10% of coronavirus disease 2019 (COVID-19) infected patients require critical care hospitalization and a variety of respiratory support, including invasive mechanical ventilation. Several nationwide studies from Saudi Arabia have identified common comorbidities but none were focused on mechanically ventilated patients in the Al-Ahsa region of Saudi Arabia. OBJECTIVES: Identify characteristics and risk factors for mortality in mechanically ventilated COVID-19 patients. DESIGN: Retrospective chart review SETTING: Two general hospitals in the Al-Ahsa region of Saudi Arabia PATIENTS AND METHODS: We included mechanically ventilated COVID-19 patients (>18 years old) admitted between 1 May and 30 November 2020, in two major general hospitals in the Al-Ahsa region, Saudi Arabia. Descriptive statistics were used to characterize patients. A multivariable Cox proportional hazards (CPH) model was used exploratively to identify hazard ratios (HR) of predictors of mortality. MAIN OUTCOME MEASURES: Patient characteristics, mortality rate, extubation rate, the need for re-intubation and clinical complications during hospitalization. SAMPLE SIZE AND CHARACTERISTICS: 154 mechanically ventilated COVID-19 patients with median (interquartile range) age of 60 (22) years; 65.6% male. RESULTS: Common comorbidities were diabetes (72.2%), hypertension (67%), cardiovascular disease (14.9%) and chronic kidney disease (CKD) (14.3%). In the multivariable CPH model, age >60 years old (HR=1.83, 95% CI 1.2-2.7, P=.002), CKD (1.61, 95% CI 0.9-2.6, P=.062), insulin use (HR=0.65, 95% CI 0.35-.08, P<.001), and use of loop diuretics (HR=0.51, 95% CI 0.4, P=.037) were major predictors of mortality. CONCLUSION: Common diseases in mechanically ventilated COVID-19 patients from the Al-Ahsa region were diabetes, hypertension, other cardiovascular diseases, and CKD in this exploratory analysis. LIMITATIONS: Retrospective, weak CPH model performance. CONFLICTS OF INTEREST: None.

Tocilizumab effectiveness in mechanically ventilated COVID-19 patients (T-MVC-19 Study): a multicenter real-world evidence.

BACKGROUND: This study aimed to evaluate the effectiveness of tocilizumab in mechanically ventilated patients with coronavirus disease 2019 (COVID-19). RESEARCH DESIGN AND METHODS: This retrospective multicenter study included adults (≥18 years) diagnosed with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by real-time polymerase chain reaction (RT-PCR) from nasopharyngeal swab, and requiring invasive mechanical ventilation during admission. Survival analyses with inverse propensity score treatment weighting (IPTW) and propensity score matching (PSM) were conducted. To account for immortal bias, we used Cox proportional modeling with time-dependent covariance. Competing risk analysis was performed for the extubation endpoint. RESULTS: A total of 556 (tocilizumab = 193, control = 363) patients were included. Males constituted the majority of the participants (69.2% in tocilizumab arm,74.1% in control arm). Tocilizumab was not associated with a reduction in mortality with hazard ratio [(HR) = 0.82,95% confidence interval (95%CI): 0.62-1.10] in the Inverse propensity score weighting (IPTW) analysis and (HR = 0.86,95% CI: 0.64-1.16) in the PSM analysis. However, tocilizumab was associated with an increased rate of extubation (33.6%) compared to the control arm (11.9%); subdistributional hazards (SHR) = 3.1, 95% CI: 1.86-5.16). CONCLUSIONS: Although tocilizumab was not found to be effective in reducing mortality, extubation rate while on mechanical ventilation was higher among tocilizumab treated group.

Severity of COVID-19 infection in ACEI/ARB users in specialty hospitals: A retrospective cohort study.

BACKGROUND: The uncertainty about COVID-19 outcomes in angiotensin-converting enzyme inhibitors (ACEI)/angiotensin receptor blockers (ARB) users continues with contradictory findings. This study aimed to determine the effect of ACEI/ARB use in patients with severe COVID-19. METHODS: This retrospective cohort study was done in two Saudi public specialty hospitals designated as COVID-19 referral facilities. We included 354 patients with a confirmed diagnosis of COVID-19 between April and June 2020, of which 146 were ACEI/ARB users and 208 were non-ACEI/ARB users. Controlling for confounders, we conducted multivariate logistic regression and sensitivity analyses using propensity score matching (PSM) and Inverse propensity score weighting (IPSW) for high-risk patient subsets. RESULTS: Compared to non-ACEI/ARB users, ACEI/ARB users had an eight-fold higher risk of developing critical or severe COVID-19 (OR = 8.25, 95%CI = 3.32-20.53); a nearly 7-fold higher risk of intensive care unit (ICU) admission (OR = 6.76, 95%CI = 2.88-15.89) and a nearly 5-fold higher risk of requiring noninvasive ventilation (OR = 4.77,95%CI = 2.15-10.55). Patients with diabetes, hypertension, and/or renal disease had a five-fold higher risk of severe COVID-19 disease (OR = 5.40,95%CI = 2.0-14.54]. These results were confirmed in the PSM and IPSW analyses. CONCLUSION: In general, but especially among patients with hypertension, diabetes, and/or renal disease, ACEI/ARB use is associated with a significantly higher risk of severe or critical COVID-19 disease, and ICU care.

Proposed guidance on cost-avoidance studies in pharmacy practice.

PURPOSE: Cost-avoidance studies of pharmacist interventions are common and often the first type of study conducted by investigators to quantify the economic impact of clinical pharmacy services. The purpose of this primer is to provide guidance for conducting cost-avoidance studies pertaining to clinical pharmacy practice. SUMMARY: Cost-avoidance studies represent a paradigm conceptually different from traditional pharmacoeconomic analysis. A cost-avoidance study reports on cost savings from a given intervention, where the savings is estimated based on a counterfactual scenario. Investigators need to determine what specifically would have happened to the patient if the intervention did not occur. This assessment can be fundamentally flawed, depending on underlying assumptions regarding the pharmacists' action and the patient trajectory. It requires careful identification of the potential consequence of nonaction, as well as probability and cost assessment. Given the uncertainty of assumptions, sensitivity analyses should be performed. A step-by-step methodology, formula for calculations, and best practice guidance is provided. CONCLUSIONS: Cost-avoidance studies focused on pharmacist interventions should be considered low-level evidence. These studies are acceptable to provide pilot data for the planning of future clinical trials. The guidance provided in this article should be followed to improve the quality and validity of such investigations.

Effectiveness and safety of favipiravir compared to supportive care in moderately to critically ill COVID-19 patients: a retrospective study with propensity score matching sensitivity analysis.

INTRODUCTION: Favipiravir is a repurposed drug to treat coronavirus 2019 (COVID-19). Due to a lack of available real-world data, we assessed its effectiveness and safety in moderately to critically ill COVID-19 patients. METHODS: This retrospective study was conducted in two public/specialty hospitals in Saudi Arabia. We included patients ≥18 years) admitted April-August 2020 with confirmed SARS-CoV-2 diagnosed by real-time polymerase chain reaction (RT-PCR) from nasopharyngeal swab. Patients received either favipiravir (1800 mg or 1600 mg twice daily loading dose, followed by 800 mg or 600 mg twice daily) or supportive-care treatment. Patients were excluded if they were outside the study period, classified as having a mild form of the disease per WHO criteria, or had an incomplete patient file. Kaplan-Meier (KM) models were used to estimate median time to discharge. Discharge ratios, progression to mechanical ventilation, and mortality outcomes were estimated across the severity spectrum using Cox proportional-hazards models. As a sensitivity analysis, we performed propensity score-matching (PSM) analysis. RESULTS: Overall, median time to discharge was 10 days (95%CI = 9-10) in the favipiravir arm versus 15 days (95%CI = 14-16) in the supportive-care arm. The accelerated discharge benefit was seen across the COVID-19 spectrum of severity. The adjusted discharge ratio was 1.96 (95%CI = 1.56-2.46). Progression to mechanical ventilation was slower with favipiravir (HRadj = 0.10, 95%CI = 0.04-0.29). There was no significant effect on mortality (HRadj = 1.56, 95%CI = 0.73-3.36). There was a statistically non-significant trend toward worse outcomes in the critical category (HRadj = 2.80, 95%CI = 0.99-7.89). Age was an independent risk factor for mortality in mechanically ventilated patients. PSM analyses confirmed these findings. CONCLUSION: Favipiravir was associated with clinical benefits, including accelerated discharge rate and less progression to mechanical ventilation; however, no overall mortality benefits were seen across the severity spectrum.

Mortality, Severity, and Hospital Admission among COVID-19 Patients with ACEI/ARB Use: A Meta-Analysis Stratifying Countries Based on Response to the First Wave of the Pandemic.

BACKGROUND: The use of angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) is controversial for treating COVID-19 patients. We aimed to estimate pooled risks of mortality, disease severity, and hospitalization associated with ACEI/ARB use and stratify them by country and country clusters. METHODS: We conducted a search in various databases through 4 July 2020 and then applied random-effects models to estimate pooled risks (ORp) across stratifications by country cluster. Clusters were chosen to reflect outbreak times (China followed by Korea/Italy, others subsequently) and mobility restrictions (China and Denmark/France/Spain with stricter lockdowns than the UK/US). RESULTS: Overall analysis showed no increase in mortality; however, a statistical increase in mortality was seen in the US/UK cluster with ORp = 1.28 [95% CI = 1.04; 1.56] and a decrease in China with ORp = 0.65 [95% CI = 0.43; 0.96] and France with OR = 0.31 [95% CI = 0.14; 0.69]. Severity and hospitalization were not statistically significant in the analysis; however, several associations were seen in specific countries but not in country clusters. CONCLUSION: The country-cluster meta-analysis provided a reasonable explanation for COVID-19 mortality among ACEI/ARB users. The analysis did not explain differences in severity and suggested the involvement of other factors. Hospitalization findings among ACEI/ARB users may be considered informative as they may have been subjected to clinical decisions and hospital-bed availability.