Association between red blood cell distribution width and mortality and severity among patients with COVID-19: A systematic review and meta-analysis.

Emerging evidence has underscored the potential usefulness of red blood cell distribution width (RDW) measurement in predicting the mortality and disease severity of COVID-19. This study aimed to assess the association of the plasma RDW levels with adverse prognosis in COVID-19 patients. A comprehensive literature search from inception to September 2020 was performed to harvest original studies reporting RDW on admission and clinical outcomes among patients hospitalized with COVID-19. RDW levels were compared between cases (patients who died or developed more severe symptoms) and controls (patients who survived or developed less severe symptoms). A total of 14,866 subjects from 10 studies were included in the meta-analysis. Higher levels of RDW were associated with adverse outcomes in COVID-19 patients (mean differences = 0.72; 95% CI = 0.47-0.97; I2 = 89.51%). Deceased patients had higher levels of RDW compared to patients who survived (mean differences = 0.93; 95% CI = 0.63-1.23; I2 = 85.58%). Severely ill COVID-19 patients showed higher levels of RDW, as opposed to patients classified to have milder symptoms (mean differences = 0.61; 95% CI = 0.28-0.94; I2 = 82.18%). Elevated RDW levels were associated with adverse outcomes in COVID-19 patients. This finding warrants further research on whether RDW could be utilized as a simple and reliable biomarker for predicting COVID-19 severity and whether RDW is mechanistically linked with COVID-19 pathophysiology.

COVID-19: A double threat to takotsubo cardiomyopathy and spontaneous coronary artery dissection?

Coronavirus disease 2019 (COVID-19) is an ongoing pandemic that has affected millions of individuals worldwide. Prior studies suggest that COVID-19 may be associated with an increased risk for various cardiovascular disorders, such as myocardial injury, arrhythmia, acute coronary syndrome, and venous thromboembolism. Early reports of non-COVID-19 patients have described the concurrence of takotsubo cardiomyopathy (TTC) and spontaneous coronary artery dissection (SCAD). However, the interplay between COVID-19, TTC and SCAD has not been well established. We herein propose two sets of two-hit hypotheses for the development of SCAD and TTC in the context of COVID-19. The first two-hit hypothesis explains the development of SCAD, in which TTC-associated formation of vulnerable coronary substrate serves as the first hit (predisposing factor), and COVID-19-associated inflammation and vascular disruption serves as the second hit (precipitating factor). The second two-hit hypothesis is proposed to explain the development of TTC, in which SCAD-associated formation of vulnerable myocardial substrate serves as the first hit, and COVID-19-associated sympathetic overactivity serves as the second hit. Under this conceptual framework, COVID-19 poses a double threat for the development of SCAD (among patients with underlying TTC) as well as TTC (among patients with underlying SCAD), thereby forming a reciprocal causation. This hypothesis provides a rationale for the joint assessment of TTC and SCAD in COVID-19 patients with pertinent cardiovascular manifestations.

Extended Thromboprophylaxis With Betrixaban or Rivaroxaban for Acutely Ill Hospitalized Medical Patients: Meta-Analysis of Prespecified Subgroups.

BACKGROUND: Betrixaban and rivaroxaban are the direct anticoagulants approved in the United States for extended venous thromboembolism (VTE) prophylaxis among acutely ill medical patients. The efficacy and safety in specific subgroups remain unclear. METHODS: A meta-analysis of 3 randomized trials involving extended thromboprophylaxis with betrixaban or rivaroxaban versus enoxaparin for medically ill patients was performed to compare VTE (composite of asymptomatic proximal and symptomatic deep vein thrombosis, pulmonary embolism, or VTE-related death) and major bleeding in subgroups by baseline D-dimer, age, sex, and major medical illness on hospitalization. Risk difference (RD) was computed with the Mantel-Haenszel method by fitting a fixed-effect model. Heterogeneity of treatment effect across subgroups was examined using the nominal thresholds of P < 0.05 and I2 > 75%. RESULTS: Compared with enoxaparin, extended betrixaban or rivaroxaban reduced VTE (RD = -1.51% [95% CI, -2.32% to -0.69%]; P = 0.0003) without excess major bleeding (RD = 0.12% [-0.05% to 0.29%]; P = 0.16). A significant effect modification was observed in the subgroups by D-dimer (P = 0.004) and age (P = 0.04). Patients with D-dimer >2× upper limit of normal (ULN) experienced a greater VTE reduction (RD = -2.39% [-3.57% to -1.21%]; P < 0.0001) than those with ≤2×ULN (RD = -0.26% [-1.08% to 0.56%]; P = 0.53). Similarly, patients aged ≥75 years had a greater VTE reduction (RD = -2.29% [-3.49% to -1.09%]; P = 0.0002) than those aged <75 years (RD = -0.63% [-1.70% to 0.44%]; P = 0.25). Treatment effect was consistent across the remaining subgroups. CONCLUSIONS: A more favorable efficacy and comparable safety outcome associated with extended betrixaban or rivaroxaban were observed among medical inpatients with D-dimer >2×ULN or aged ≥75 years. D-dimer and advanced age may assist in decision-making on pharmacological thromboprophylaxis for hospitalized medical patients.

Effect of intensive versus standard blood pressure control on major adverse cardiac events and serious adverse events: A bivariate analysis of randomized controlled trials.

BACKGROUND: Intensive blood pressure (BP) lowering may offer protective effects against major adverse cardiac event (MACE) but is also associated with a greater risk of a serious adverse event (SAE). The risk-benefit profile of intensive versus standard BP control has not been comprehensively assessed. METHODS: Four studies were identified from a systematic literature search for randomized controlled trials comparing intensive versus standard BP lowering that reported both MACE and SAE endpoints. A previously described statistical approach was applied to characterize the efficacy-safety tradeoff of BP control. The bivariate outcome was computed to quantitatively assess the net clinical benefit (NCB) of intensive BP lowering as compared to standard treatment, with positive values indicating increased risks and negative values indicating decreased risks. RESULTS: Data from the SPRINT trial demonstrated that intensive strategy was superior in MACE but inferior in SAE, thereby eroding the NCB (bivariate outcome: 0.33% [-0.50% to 1.21%]). Intensive strategy from the SPS3 trial fulfilled non-inferiority in both MACE and SAE but did not reach a favorable NCB (-1.31% [-2.25% to 0.01%]). The ACCORD trial suggested that intensive strategy was non-inferior in MACE but inferior in SAE (-0.19% [-0.79% to 1.37%]). Results from the VALISH trial were inconclusive for SAE but suggested non-inferiority in MACE (-1.19% [-3.24% to 0.68%]). CONCLUSIONS: Compared to the standard blood pressure target, pooled data from randomized controlled trials suggest that intensive strategy did not achieve a net clinical benefit when weighing the benefit of MACE reduction against the risk of SAE under the bivariate framework. ABBREVIATIONS: Blood pressure (BP), diastolic blood pressure (DBP), major adverse cardiac event (MACE), net clinical benefit (NCB), serious adverse event (SAE), systolic blood pressure (SBP).

Dual antithrombotic plus adjunctive antiinflammatory therapy to improve cardiovascular outcome in atrial fibrillation patients with concurrent acute coronary syndrome: A triple-pathway strategy.

The concurrence of atrial fibrillation and acute coronary syndrome poses a conundrum in the antithrombotic management as intensification of anticoagulation or antiplatelet therapy inevitably comes at the price of an increased bleeding risk. Various antithrombotic combinations have been attempted to prevent the recurrent cardiovascular events, however, there has been limited success in effective risk reduction for this high risk population. Given the overarching effect of interleukin 1ß-driven inflammation on the arrhythmogenesis, thrombogenesis, and hypercoagulability, we hypothesize that the triple-pathway strategy (i.e., incorporating antiinflammatory therapy into anticoagulant and antiplatelet therapy) would grant incremental cardiovascular benefits for atrial fibrillation patients with coexisting acute coronary syndrome and stent placement.