Safety and efficacy of prophylactic anticoagulation versus therapeutic anticoagulation in hospital-admitted COVID-19 patients: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: COVID-19 disease-related coagulopathy and thromboembolic complication, an important aspect of the disease pathophysiology, are frequent and associated with poor outcomes, particularly significant in hospitalized patients. Undoubtedly, anticoagulation forms a cornerstone for the management of hospitalized COVID-19 patients, but the appropriate dosing has been inconclusive and a subject of research. We aim to review existing literature and compare safety and efficacy outcomes of prophylactic and therapeutic dose anticoagulation in such patients. METHODS: We did a systematic review and meta-analysis to compare the efficacy and safety of prophylactic dose anticoagulation when compared with therapeutic dosing in hospitalized COVID-19 patients. We searched PubMed, Google Scholar, EMBASE and COCHRANE databases from 2019 to 2021, without any restriction by language. We screened records, extracted data and assessed the risk of bias in the studies. RCTs that directly compare therapeutic and prophylactic anticoagulants dosing and are not placebo-controlled trials were included. Analyses of data were conducted using the Mantel-Haenszel random-effects model (DerSimonian-Laird analysis). The study is registered with PROSPERO (CRD42021265948). RESULTS: We included three studies in the final quantitative analysis. The incidence of thromboembolic events in therapeutic anticoagulation was lower in comparison with prophylactic anticoagulation in hospitalized COVID-19 patients and reached statistical significance [RR 1·45, 95% CI (1.07, 1.97) I2 -0%], whereas major bleeding as an adverse event was found lower in prophylactic anticoagulation in comparison with therapeutic anticoagulation that was statistically significant [RR 0·42, 95% CI(0.19, 0.93) I2 -0%]. CONCLUSION: Our study shows that therapeutic dose anticoagulation is more effective in preventing thromboembolic events than prophylactic dose but significantly increases the risk of major bleeding as an adverse event. So, the risk-benefit ratio must be considered while using either of them.

Meta-analysis examining phosphodiesterase-5 inhibitors in heart failure with preserved ejection fraction.

Patients with heart failure with preserved ejection fraction have reduced cyclic guanosine 3',5'-monophosphate (cGMP) levels compared to those with reduced ejection fraction. Phosphodiesterase-5 inhibitors may play a cardioprotective role by potentiating the cGMP pathway. To address this question, we conducted a systematic search for randomized trials using the electronic databases of PubMed, Embase, and Google Scholar and used RevMan (version 5.4) for the data analysis. We included 221 subjects in the phosphodiesterase group (mean age 69.2 ± 3.43 years; 58.82% male) and 202 subjects in the control group (mean age 70.4 ± 4.96 years; 53.46% male). The mean follow-up duration was 5.85 ± 3.43 months. The pooled results showed no significant differences in peak oxygen consumption, 6-minute walking distance, mitral annular E/e' ratio, left ventricular ejection fraction, mean pulmonary artery pressure, pulmonary artery systolic pressure, and pulmonary vascular resistance between the phosphodiesterase group and the control group.

IVIG plus Glucocorticoids versus IVIG Alone in Multisystem Inflammatory Syndrome in Children (MIS-C) Associated with COVID-19: A Systematic Review and Meta-Analysis.

Background: There is limited information available regarding the management of multisystem inflammatory syndrome in children (MIS-C) associated with SARS-CoV-2. We performed a systematic review and meta-analysis to evaluate the optimal treatment using IVIG alone versus IVIG plus glucocorticoids. Methods: PubMed, Google Scholar, EMBASE, and Cochrane databases were searched along with other secondary searches. Studies published within the time frame of January 2020 to August 2021 were included. We screened records, extracted data, and assessed the quality of the studies using NOS. Studies that directly compare the two treatment groups were included. Analyses were conducted using the random-effects model (DerSimonian-Laird analysis) if I 2 > 50% and fixed-effects model was used if I 2 < 50%. Results: We included three studies in the final quantitative analysis. The initial therapy with the IVIG plus glucocorticoids group significantly lowered the risk of treatment failure (OR 0.57, 95% CI (0.42, 0.79), I 2 45.36%) and the need for adjunctive immunomodulatory therapy (OR 0.27, 95% CI (0.20, 0.37), I 2 0.0%). The combination therapy showed no significant reduction in occurrence of left ventricular dysfunction (OR 0.79, 95% CI (0.34, 1.87), I 2 58.44%) and the need for inotropic support (OR 0.83, 95% CI (0.35, 1.99), I 2 75.40%). Conclusion: This study supports the use of IVIG with glucocorticoids compared to IVIG alone, as the combination therapy significantly lowered the risk of treatment failure and the need for adjunctive immunomodulatory therapy.

Systematic Review and Meta-Analysis: Can We Compare Direct Oral Anticoagulants to Warfarin in Patients With Atrial Fibrillation and Bio-Prosthetic Valves?

Background There are no clear consensus guidelines on the indications and types of anticoagulation therapies in patients with bio-prosthetic valves either with concomitant atrial fibrillation (AF) or sinus rhythm. In our meta-analysis, we assessed the safety and efficacy of DOACs as compared to the standard treatment with warfarin in patients with AF and bioprosthetic valves. Methods We included randomized controlled trials (RCTs), cohort studies in the English language, and studies reporting patients with valvular heart disease that included bioprosthetic valvular disease. A systematic literature review using Embase, PubMed, and Web of Science was performed using the terms "Direct Acting Oral Anticoagulant," "Oral Anticoagulants," "Non-Vitamin K Antagonist Oral Anticoagulant," "Atrial Fibrillation," "Bioprosthetic Valve" for literature published prior to January 2021. Extraction of data from included studies was carried out independently by three reviewers from Covidence. We assessed the methodical rigor of the included studies using the modified Downs and Black checklist. Results Four RCTs and one observational study (n=1776) were included in our study. A random-effect model using RevMan (version 5.4; The Nordic Cochrane Centre, The Cochrane Collaboration, Copenhagen) was used for data analysis. The pooled data showed that there was a non-significant reduction in the incidence of stroke and systemic embolism in the patients taking DOACs as compared to warfarin (HR 0.69; 95% CI, 0.29, 1.67; I2 = 50%). The incidence of major bleeding was lower in the DOACs group; the difference was statistically significant (HR 0.42; 95% CI, 0.26, 0.67; I2 = 7%). The difference was not statistically significant for all-cause mortality in both groups (HR 1.24; 95% CI, 0.91, 1.67; I2 = 0%). Conclusion Our results showed that there was no difference in the outcomes of stroke and systemic embolism between DOACs and warfarin but there were statistically significantly lower major bleeding events. We conclude that larger clinical trials are needed to assess the true safety and efficacy of DOACs in patients with AF and bioprosthetic valves.

Pharmacotherapies in Heart Failure With Preserved Ejection Fraction: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: Heart failure (HF) with preserved ejection fraction (HFpEF) causes significant cardiovascular morbidity and mortality. It is a growing problem in the developed world, especially, in the aging population. There is a paucity of data on the treatment of patients with HFpEF. We aimed to identify pharmacotherapies that improve peak oxygen consumption (peak VO2), cardiovascular mortality, and HF hospitalizations in patients with HFpEF. METHODS: We conducted a systematic literature search for English studies in PubMed, EMBASE, Cochrane Central Register of Controlled Trials, Web of Science, Scopus, and Google scholar. We searched databases using terms relating to or describing HFpEF, stage C HFpEF, and diastolic HF and included only randomized controlled trials (RCTs). RevMan 5.4 (The Cochrane Collaboration, 2020, London, UK) was used for data analysis, and two independent investigators performed literature retrieval and data-extraction. We used PRISMA guidelines to report the outcomes. We included 14 articles in our systematic review and six studies in meta-analysis. RESULTS: We calculated the pooled mean difference (MD) of peak VO2 between placebo and pharmacotherapies. Our meta-analysis showed that the peak VO2 was comparable between pharmacotherapies and placebo in HFpEF (MD = 0.09, 95% CI: -0.11, 0.30, I2 =28%). Our systematic review highlights that statins and spironolactone use should be further studied in larger RCTs due to their potential beneficial effect on all-cause mortality and hospitalizations, respectively. CONCLUSION: Compared to placebo, none of the pharmacotherapies significantly improved peak VO2 in HFpEF except ivabradine. In our meta-analysis, the pooled improvement in peak VO2 is non-significant. This needs validation with larger studies. We are lacking larger studies on pharmacotherapies that improve peak VO2 in HFpEF. Statin and spironolactone should be further studied in patients with HFpEF as few trials have shown improvement in all-cause mortality and reduction in HF hospitalizations in selected patients, respectively.

Sudden Cardiac Death and Sudden Cardiac Arrest in Patients with Human Immunodeficiency Virus: A Systematic Review.

The importance of this review lies in its study of the risk of sudden cardiac death (SCD) and sudden cardiac arrest (SCA) in people living with the human immunodeficiency virus (PLWH). To the best of our knowledge, this is the first review investigating the effect of the human immunodeficiency virus (HIV) on SCD and SCA. The review's objective was to determine the risk of SCD and SCA in PLWH. To do this, the electronic databases Ovid MEDLINE, EMBASE, Cochrane Central, Scopus, and Google Scholar were systematically searched to identify eligible studies published before January 31, 2021. Reference lists of the included studies were searched for further identification of relevant studies. The search terms included: "Sudden Cardiac Death," "Sudden Cardiac Arrest," "Human Immunodeficiency virus," "HIV," "Acquired immunodeficiency syndrome," and "AIDS." Only observational studies that assessed the association between SCD and SCA in PWLH were selected.  Data were extracted by two independent authors who screened titles, abstracts, and articles to meet the inclusion criterion. Quality assessment was done by using modified Downs and Black checklist. A total of seven studies were included in this review. Five studies revealed a higher incidence of SCD in PLWH, two of which focused on patients with HIV and low left ventricular ejection fraction (LVEF). The other two studies were about the association of HIV and SCA. Studies reported that PLWH had a three- to five-fold higher incidence of SCD as compared to non-HIV patients. HIV patients with low LVEF had a higher incidence of SCD than HIV patients with normal LVEF. PLWH had a higher incidence of SCA and less successful cardiopulmonary resuscitation (CPR) as compared to patients without HIV. After adjusting for various confounders in multiple studies, all the studies reported a higher incidence of SCD in PLWH. To conclude, PLWH is at an increased risk of SCD and SCA. Some risk factors for this include LVEF, viral load (VL), and the cluster of differentiation 4 (CD4) count. There is a paucity of data on the mechanisms involved, although a higher prevalence of cardiac fibrosis and interstitial fibrosis in PLWH may play a role. Because of the general suboptimal quality of the heterogeneous nature of the current evidence, further, rigorous studies are needed to determine the association of increased risk of SCD and SCA in PLWH.