Meta-analysis Of Real-world Studies Research Articles

Association between dipeptidyl peptidase-4 inhibitor use and diabetic retinopathy: a systematic review and meta-analysis of real-world studies

BackgroundThe purpose of this review was to examine if dipeptidyl peptidase-4 inhibitor (DPP4i) use affects the risk of diabetic retinopathy (DR).MethodsCohort studies published up to 20th July 2023 in the databases of PubMed, CENTRAL, Embase, Scopus, and Web of Science were searched. The adjusted effect size was pooled to calculate the odds ratio (OR).ResultsSeven studies were included. Meta-analysis showed that the use of DPP4i was not associated with any significant change in the risk of DR (OR: 0.86 95% CI: 0.70, 1.06 I2 = 78%). The pooled analysis also found that DPP4i use was not associated with any significant risk of progression of DR (OR: 0.87 95% CI: 0.47, 1.59 I2 = 86%). The results did not change during sensitivity analysis.ConclusionPresent evidence from a limited number of real-world studies shows that DPP4i may not affect the incidence and progression of DR. There is a need for further studies from different countries using accurate definitions of DR and its progression to validate the current results.

Treatment-free survival after immunotherapy discontinuation in advanced melanoma: A systematic review and meta-analysis of real-world studies.

e21523 Background: Immune checkpoint inhibitors (ICIs) have altered the treatment landscape of advanced melanoma with remarkable improvements in progression-free survival (PFS). Durable responses to ICI cessation have been shown in early clinical trials for ICI usage in melanoma, although the optimal duration of immunotherapy remains unclear. Treatment-free survival (TFS) after immunotherapy cessation for patients with complete response (CR), partial response (PR), and stable disease (SD) has been reported in real-world studies and may help to guide discontinuation of ICI therapy. Methods: A systematic search was conducted using PubMed, Embase, and the Cochrane Library to identify real-world studies reporting TFS after immunotherapy in advanced cutaneous melanoma patients with CR, PR, and SD at 12 and 24 months. Discontinuation due to iRAEs were included. Effect sizes were pooled using a random-effects model using the meta and metafor packages in R after logit transformation. Inter-study heterogeneity was quantified using I2 statistic. Results: Systematic review yielded 34 studies investigating TFS in prospective and retrospective studies. Of these, three retrospective cohort studies reported real-world TFS at 12 and 24 months. Overall, 738 patients with advanced melanoma were included in this meta-analysis, with 384 patients in CR, 278 patients in PR, and 76 patients in SD at time of ICI discontinuation. Mean patient age was 66.4 and 61.9% of patients were male. Pooled 12 and 24-month TFS proportions were higher for patients with CR than PR and for patients with PR than SD. Pooled 24-month TFS was statistically significantly greater in patients with CR compared to SD. I2 statistics showed considerable heterogeneity between studies ( > 80% in CR and PR subgroups). Conclusions: 12 and 24-month TFS after ICI discontinuation was significant for patients with CR and PR to therapy, suggesting the feasibility of ICI discontinuation in patients after therapy response. Pooled 12-month TFS for patients with SD was 66%, although with decline to 36% at 24 months. Limitations of this meta-analysis include a limited number of included studies. Further research is needed to determine the optimal duration of ICI therapy for patients with advanced melanoma depending on best overall therapy response. [Table: see text]

Trilaciclib use for prevention of hematological adverse events in chemotherapy: A meta-analysis of real-world studies and clinical trials.

e24130 Background: Trilaciclib, a cyclin-dependent kinase (CDK)-4 and -6 inhibitor, is the only FDA-approved agent that preemptively protects hematopoietic stem cells from chemotherapy-induced myelosuppression (CIM) without compromising efficacy. It transiently arrests hematopoietic stem cells in the G1 phase, thus temporarily blocking progression through the cell cycle and protecting progenitor cells from cytotoxicity. It has been approved for use in extensive-stage small-cell lung cancer (SCLC). Limited real-world evidence of its efficacy exists owing to its recent approval. We sought to enhance our understanding and evaluate the preventive effect of trilaciclib through a combined meta-analysis of clinical trials and retrospective studies. Methods: A systematic literature search was performed on PubMed, Embase, Cochrane, and Scopus from inception until December 2023. Retrospective cohort studies and randomized-controlled trials with trilaciclib and non-trilaciclib arms were included. The primary outcomes of interest were CIM-related grade ≥3 hematological adverse events, and secondary outcomes included supportive care interventions to remedy CIM. Quantitative meta-analyses were conducted using the random-effects model on STATA v17. Results: The meta-analysis comprised seven studies, including four clinical trials and three real-world retrospective studies, including 6537 patients with extensive SCLC or locally recurrent or metastatic breast cancer. Chemotherapy regimens in SCLC patients included the combination of etoposide/platinum (E/P), E/P/PD-L1 inhibitors, or topotecan, and gemcitabine/carboplatin in patients with breast cancer. The mean age of the patients was 63.28 ± 5.31 years, and 49.21% were males. Administration of trilaciclib led to a reduction in the incidence of febrile neutropenia (2.41% vs. 7.56% OR = 0.35), severe neutropenia (21.76% vs. 41.91% OR = 0.57), anemia (18.02% vs. 32.41% OR = 0.51), and thrombocytopenia (20.06% vs. 31.25% OR = 0.62). Utilization of cytopenia-supportive therapies, including granulocyte colony-stimulating factor use (40.47% vs. 81.01% OR = 0.61) and RBC transfusions (16.66% vs. 18.25% OR = 0.59) were significantly lower in the trilaciclib cohort as compared to control. The overall response rate (mean difference = 1.09,95% CI = 0.74–1.60) and overall survival (OR = -0.02 95% CI = -0.95-0.92) were similar, and progression-free survival was noted to be longer in the trilaciclib group (mean difference = 1.75, 95% CI = 0.75-2.75). Conclusions: Trilaciclib use consistently demonstrated efficacy in reducing CIM, thus lowering cytopenia-related healthcare utilization without compromising treatment efficacy in trials and real-world settings. Its novel mechanism of action offers great promise, and further studies with larger sample sizes on various cancers will corroborate existing evidence.

Drug-coated balloon versus drug-eluting stenting coronary angioplasty for ST-elevation myocardial infarction: a systematic review and meta-analysis of real-world studies

Abstract Funding Acknowledgements None. Introduction In the realm of ST-elevation myocardial infarction (STEMI), drug-eluting stent angioplasty (DES) is a well-established strategy for urgent revascularization. However, several challenges arise when selecting stents for these patients. These challenges include dealing with endothelial oedema and vasospasm during acute thrombotic occlusion. Moreover, there are concerns surrounding DES-related complications. These complications include the need for prolonged anti-platelet therapy, which increases the risk of bleeding, late stent thrombosis, and in-stent restenosis (ISR). In light of these issues, drug-coated balloons (DCB) have emerged as a compelling alternative. Purpose: This study aims to explore the safety and efficacy of DCB compared to conventional DES angioplasty in the management of STEMI. Methods A systematic literature search was conducted across electronic databases (PubMed, EMBASE, Cochrane Library, ClinicalTrials.gov, reference lists of relevant publications, and grey literature sources) for studies published from the inception of DCB up to 31st August 2023. Results Nine eligible studies, consisting of four randomised controlled trials and two retrospective propensity-matched studies, were included. These studies, all single-center, involved a total of 2,122 patients (934 in the DCB versus 1,188 in the DES group) over a median follow-up period of 15 months (ranging from 6 to 36 months). The meta-analysis showed no statistically significant differences between DCB and DES angioplasty in terms of technical success (OR: 1.82, 95% CI: 0.22-15.08, p = 0.58), major adverse cardiovascular events (MACE) (OR: 1.24, 95% CI: 0.60–2.56, p = 0.57), all-cause mortality (OR: 1.20, 95% CI: 0.83–1.75, p = 0.33), cardiac death (OR: 1.40, 95% CI: 0.47-4.17, p = 0.54), cardiovascular-related hospitalization (OR: 0.72, 95% CI: 0.32-1.65, p = 0.44), recurrent myocardial infarction (OR: 0.99, 95% CI:0.34-2.90, p = 0.99), target lesion revascularization (OR: 1.15, 95% CI: 0.56–2.34, p = 0.71), late luminal loss (SMD: -0.25mm, 95% CI: -1.05 to 0.54, p = 0.53), postoperative TIMI flow (OR: 1.16, 95% CI: 0.54-2.50, p = 0.71), fractional flow reserve (MD: 0.012, 95% CI -0.018 to 0.032, p = 0.27), and bleeding risk (7.2% in DCB versus 7.5% in DES). It's noteworthy that 8.2% of patients in the DCB group required bailout stenting due to coronary artery dissection type C, a rate 10 times higher than that in the DES group (p < 0.005). Additionally, DCB angioplasty displayed a statistically significant presence of residual stenosis compared to DES angioplasty (OR: 6.48, 95% CI: 1.13-37.2, p = 0.04). Conclusion DCB angioplasty demonstrates promise but presents unique challenges in STEMI management, particularly in complex scenarios requiring bailout stenting and residual stenosis. The study contributes to the ongoing discussion about the role of DCBs in optimizing STEMI treatment, highlighting their potential benefits and areas of concern.

Glycemic Control, Weight Management, Cardiovascular Safety, and Cost-Effectiveness of Semaglutide for Patients with Type 2 Diabetes Mellitus: A Rapid Review and Meta-analysis of Real-World Studies.

Semaglutide is a high-profile glucose-lowering drug that medical decision-makers have acknowledged in recent years. This rapid review aims to provide evidence-based clinical recommendations for the treatment of type 2 diabetes mellitus (T2DM) with semaglutide. We conducted a rapid review of randomized controlled trial (RCT)-based meta-analyses (MAs) and systematic reviews (SRs) of cost-effectiveness analyses (CEAs) compared to other glucagon-like peptide-1 receptor agonists (GLP-1 RAs) or placebo in patients with T2DM. Prospective cohort real-world studies (RWS) were also retrieved and subjected to MA. Four databases, including PubMed, the Cochrane Library, Embase, and ISPOR, were searched from inception to 5 March 2023. The outcomes of interest were hemoglobin A1c (HbA1c), body weight, major adverse cardiovascular events (MACE), and economic outcomes such as quality-adjusted life-years and total cost. We identified 33 publications: 22 RCT-based MAs, 1 SR of CEAs, and 10 RWS. Evidence showed that semaglutide at usual doses was associated with superior reductions in HbA1c and weight compared to most GLP-1 RAs in patients with T2DM who were drug naive, receiving basal insulin, or using oral hypoglycemic agents, and it was also associated with a lower number of MACE and was more cost-effective. Further, once-weekly semaglutide resulted in a significant reduction in HbA1c levels (-1.1%) and body weight (-4.88kg) in routine clinical practice. This review consolidates the positive current evidence base for prescribing semaglutide to patients with T2DM, but further rigorous studies are still urgently required to develop practice guidelines as innovative drugs become commercially available.

Improvements in Quality of Life and Itch Symptoms with Dupilumab in Patients with Atopic Dermatitis: A Targeted Literature Review and Meta-Analysis of Real-World Studies

Improvements in Quality of Life and Itch Symptoms with Dupilumab in Patients with Atopic Dermatitis: A Targeted Literature Review and Meta-Analysis of Real-World Studies

Safety of Direct Oral Anticoagulants for Gastrointestinal Hemorrhage in Patients With Nonvalvular Atrial Fibrillation: A Systematic Review and Meta-analysis of Real-world Studies.

Since the introduction of Direct Oral Anticoagulants (DOACs), "real-world" studies have investigated their safety profile on gastrointestinal hemorrhage (GIH) when used by patients with Non-Valvular Atrial Fibrillation. We performed a systematic review and meta-analysis to compile and summarize this data after Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. Medline and Embase were systematically searched until April 2021. Observational studies that met predefined inclusion criteria were included and hazard ratios (HRs) with 95% CI were extracted. Subgroup analyses based on DOAC doses, history of chronic kidney disease, stroke, prior exposure to VKA (vitamin K antagonist), age, gender, geographic location of population samples, as well as Leave-One-Out and Low/Moderate Risk of Bias sensitivity analyses were performed. A random effects model was used. A total of 46 studies were included. Apixaban was associated with a reduced risk of GIH compared with Dabigatran (HR: 0.67, 95% CI, 0.56 to 0.81, I2 : 53.28%), Rivaroxaban (HR: 0.56, 95% CI, 0.44 to 0.70, I2 : 79.17%), and VKA (HR: 0.68, 95% CI, 0.60 to 0.78, I2 : 71.93%). Rivaroxaban was associated with increased GIH risk compared with Dabigatran (HR: 1.19, 95% CI, 1.02 to 1.40, I2 : 72.96%) and VKA (HR: 1.16, 95% CI, 1.05 to 1.27, I2 : 81.95%). Dabigatran was associated with similar GIH risk compared with VKA (HR: 1.11, 95% CI, 0.98 to 1.26, I2 : 87.28%). Our study shows that Apixaban was associated with a reduction in GIH risk compared with Dabigatran, Rivaroxaban and VKA, whereas Rivaroxaban was associated with an increase in GIH risk compared with both Dabigatran and VKA.

Venetoclax with Hypomethylating Agents in Newly Diagnosed Acute Myeloid Leukemia: A Systematic Review and Meta-Analysis of Survival Data from Real-World Studies.

In recent years, the association of venetoclax (VEN) with hypomethylating agents (HMAs) significantly improved the outcome of patients with newly diagnosed acute myeloid leukemia (AML) who were unfit for intensive chemotherapy and became the standard of care after the publication of the pivotal RCT VIALE-A. However, it is still not clear to what extent the results observed in the VIALE-A apply to a real-world setting. For this reason, we carried out a systematic review and meta-analysis of real-world studies on newly diagnosed patients with AML, ineligible for intensive induction chemotherapy, receiving first-line VEN+HMA. We then compared their results in term of survival with those from the VIALE-A. Kaplan-Meier curves were extracted from all included studies and individual survival data was reconstructed. We then estimated a pooled survival curve and compared it with the results of the VIALE-A using the log-rank test. We also conducted a secondary analysis including only studies considering VEN plus azacytidine (AZA) as treatment, as this was the schedule originally used in the VIALE-A. Nineteen real-world studies met the inclusion criteria and were included in the systematic review. Most of them reported a worse survival than the VIALE-A. The pooled survival curve was similar to that reported in the VIALE-A during the first three months of treatment but diverged thereafter (p-value = 0.0001). The pooled median survival among the real-world studies was 9.37 months (95%CI 8.81-10.5), substantially lower than that reported in the VIALE-A (14.7 months; 95%CI 11.9-18.7). Results slightly increased when the analysis was restricted to the studies using VEN+AZA as treatment (median survival: 11.5 months; 95%CI 10.2-14.8). Survival of newly diagnosed AML patients treated with VEN+HMAs in a real-world setting seems to be lower than previously reported in the VIALE-A, while the effect of VEN+AZA is more in line with expected results. Future studies are needed to evaluate whether this apparent discrepancy is due to the different characteristics of enrolled patients or to a non-optimal adherence to therapy, and whether alternative regimens can provide better results in terms of safety and effectiveness.

Safety and Immunogenicity of SARS-CoV-2 Vaccines in People Living With HIV: A Systematic Review and Meta-analysis of Real-World Studies

Abstract The safety and immunogenicity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines in people living with HIV (PLWH) in real-world studies remain controversial. Thus, we conducted a comprehensive systematic review and meta-analysis to address this issue. Data search were conducted from PubMed, Web of Science and EMBASE. Adverse events following vaccination, the risk ratio (RR) of SARS-CoV-2–specific IgG seroconversion and the level of anti–SARS-CoV-2 neutralizing antibodies were compared between the PLWH group and a healthy control group. A total of 10,582 PLWH from 22 studies were included. In our analysis, the incidence of local or systemic adverse events after the first SARS-CoV-2 vaccine dose was not statistically different between PLWH and healthy controls. However, there was a statistical difference after the second dose (RR, 0.83; 95% CI, 0.71–0.98). The seroconversion rate of SARS-CoV-2 IgG antibodies in PLWH was significantly lower than that in the healthy control group (RR, 0.94; 95% CI, 0.89–0.98; I 2 = 80%, P < 0.01). The anti–SARS-CoV-2 neutralizing antibody titers in PLWH after full immunization were also significantly lower than those in the healthy control group (RR, 0.91; 95% CI, 0.85–0.98; I 2 = 81%, P < 0.01). The safety and tolerance of COVID-19 vaccines in PLWH are acceptable. However, their immunogenicity may be impaired to a certain extent, characterized by a lower IgG seroconversion rate and neutralizing antibody titers compared with healthy individuals. These findings should provide guidance for optimizing future COVID-19 vaccination strategies among PLWH.

Efficacy and safety of perampanel for epilepsy: a systematic review and meta-analysis of real-world studies.

The aim of the study was to summarize the findings of the studies documenting the efficacy and safety of perampanel when used in children/adolescents or adults, either as add-on therapy or as monotherapy. A systematic search was conducted using PubMed, EMBASE and Scopus. Only studies with a cohort-based approach (either prospective or retrospective) were included. We were interested in real-world studies and therefore, studies with a highly regulated environment, such as randomized controlled trials, were excluded. The primary outcomes of interest were retention rates, response rates and seizure-free rates. Random effects model was used for the analysis. Effect sizes were reported as pooled prevalence along with 95% confidence intervals. A total of 34 studies were included. The retention rates, within 24 months from initiation of treatment as an add-on therapy, ranged between 65% to 77% among children and adolescents. For adults, the retention rate varied between 56 to 77% within 24 months from initiation of treatment. The response rate was around 70% in children/adolescents and 52% in adults at 24 months of follow-up. Around 25% of children and adolescents and 37% of adults were seizure-free at 24 months follow-up period. The proportion of children/adolescents and adults reporting any treatment-related adverse effects was 29% and 41%, respectively. The commonly reported adverse effects were dizziness/drowsiness, somnolence, behavioral problems (irritability, aggression, anxiety, mood changes), postural instability/gait problems, fatigue and weight gain. Perampanel might be an effective anti-epileptic drug in both children/adolescents and adults when used as an adjunct therapy. More data is required to comment on its use as monotherapy. Careful monitoring for psychiatric problems and behavioral disturbances is required, both prior to initiating treatment as well as during the course of management. Studies with long-term follow-up may are needed to confirm the findings of this meta-analysis.

Budget Impact Analysis of the Adjuvanted Quadrivalent Influenza Vaccine in the Elderly in Italy

BACKGROUND: Vaccination is the most effective way to prevent influenza and its complications. The MF59-adjuvanted quadrivalent (aQIV) and the high-dose quadrivalent (QIV-HD) influenza vaccines have been specifically developed to protect subjects aged ≥65 years. The aim of this study was to evaluate the economic consequences associated with the use of aQIV in the elderly population in Italy.METHODS: An Excel-based budget impact model was developed to estimate the costs of aQIV for the prevention of influenza and its complications in elderly subjects, from the perspective of the Italian National Health Service. In the base-case analysis a current scenario (with aQIV) was compared with a past scenario (without aQIV), in which only the standard quadrivalent influenza vaccine (QIV-STD) was available. In the scenario analysis, a current scenario was compared with a future (hypothetical) scenario, in which the market share of aQIV grows. Efficacy (or effectiveness) data of vaccines, in terms of reduction of influenza-related deaths and hospitalizations for influenza/pneumonia, respiratory, and cardiac complications, were obtained from the scientific literature. Relative effectiveness of aQIV and QIV-HD vs. QIV-STD in preventing laboratory-confirmed influenza cases came from two meta-analysis of real-world studies. Epidemiological data and unit costs are collected from Italian published sources.RESULTS: In the base-case analysis the introduction of aQIV e QIV-STD was associated with a reduction of influenza and influenza-like illness – ILI (-93,171) cases, hospitalization for influenza, respiratory and cardiovascular complications (-6,823), and deaths (-1,841) and a consequent saving of € 1.9 million and € 24 million related to events and hospital admissions avoided, respectively. In the scenario analysis, the growth of the market shares of aQIV was associated with 13,602 fewer cases of influenza and ILI, 996 fewer hospitalizations, and an overall saving equal to € 3.8 million.CONCLUSIONS: aQIV reduces the number of cases of influenza and ILI, hospitalizations for influenza and respiratory or cardiac complications, and deaths in the Italian population aged ≥65 years.

Therapeutic vs. prophylactic anticoagulation in COVID-19 patients: a systematic review and meta-analysis of real-world studies.

Coagulopathy, in the form of either venous or arterial thromboembolism, is one of the most severe sequelae of coronavirus disease (COVID-19) and has been associated with poorer outcomes. However, the role of therapeutic anticoagulation (tAC) or prophylactic anticoagulation (pAC) in COVID-19 patients has not been definitely established. Therefore, the aim of this systematic review and meta-analysis was to gather all the available real-world data in the field and to provide a reliable effect size of the effect on mortality of tAC compared to pAC in COVID-19 patients. Real-world studies (RWS) were identified by searching electronic databases from inception to 31st October, 2021. Randomized controlled trials were excluded. Mortality and bleedings were considered as primary and secondary outcomes, respectively. 10 RWS and 5541 patients were included in the analysis. Overall, tAC was associated with lower mortality (HR=0.62, 95% CI: 0.54-0.71). There was asymmetry at the funnel plot suggesting publication bias, that was not confirmed at the Egger test (P=0.07). For the secondary endpoint, there was a non-statistically significant tendency for more bleedings in patients treated with tAC compared to pAC (RR=1.75, 95% CI: 0.81-3.81). Our meta-analysis, based on RWS and adjusted estimates of risk, suggests a survival benefit of tAC over pAC in COVID-19 patients in the real world.

Correction to: Discontinuation and Switchback After Non-Medical Switching from Originator Tumor Necrosis Factor Alpha (TNF) Inhibitors to Biosimilars: A Meta-Analysis of Real-World Studies from 2012 to 2018

Correction to: Discontinuation and Switchback After Non-Medical Switching from Originator Tumor Necrosis Factor Alpha (TNF) Inhibitors to Biosimilars: A Meta-Analysis of Real-World Studies from 2012 to 2018

Discontinuation and Switchback After Non-Medical Switching from Originator Tumor Necrosis Factor Alpha (TNF) Inhibitors to Biosimilars: A Meta-Analysis of Real-World Studies from 2012 to 2018.

IntroductionTo examine the prevalence rates of biosimilar discontinuation and switchback to the originator tumor necrosis factor alpha (TNF) inhibitors following non-medical switch (NMS) in patients.MethodsReal-world studies reporting biosimilar discontinuation and switchback rates following NMS published between January 2012 and August 2018 were identified through a systematic literature review. A meta-analysis estimated the annualized discontinuation and switchback rates. A subsequent meta-analysis assessed annualized incremental discontinuation rate among studies reporting both discontinuation rates in patients who underwent an NMS (switchers) and patients who remained on originators (non-switchers).ResultsA total of 66 publications were identified: 31 in gastroenterology, 32 in rheumatology, and 3 in both. Half of the studies reported switchback rates; only 9 studies reported discontinuation rates for both switchers and non-switchers. Across studies, the mean/range sample size of the NMS patient population was 136/9–1641; mean/range follow-up was 10/3–24 months. Annualized biosimilar discontinuation rate was 21% (95% confidence interval [CI] 18%, 25%). Switchback rate was 14% (95% CI 10%, 17%) among all NMS patients and 62% (95% CI 44%, 80%) among discontinuers. The mean/range sample size of switchers and non-switchers was 344/89–1621 and 768/19–2870, respectively; mean/range follow-up was 11/6–18 and 12/6–8 months, respectively. Annualized incremental biosimilar discontinuation rate was 18% (95% CI 4%, 31%).ConclusionBiosimilar discontinuation was found to be prevalent among patients who underwent an NMS from an originator TNF inhibitor to its biosimilar(s) in the real world. In addition, switchback to the originator TNF inhibitors was common following biosimilar discontinuation. Careful consideration is necessary when switching patients already on an originator TNF inhibitor to its biosimilar(s). Main limitations included the heterogeneity of the studies and the limited comparability of the data.Supplementary InformationThe online version contains supplementary material available at 10.1007/s12325-022-02173-7.

Effectiveness and Safety of Nonvitamin K Oral Anticoagulants Rivaroxaban and Apixaban in Patients with Venous Thromboembolism: A Meta-Analysis of Real-World Studies.

Background Rivaroxaban and apixaban are the most widely used nonvitamin K oral anticoagulants (NOACs) in patients with venous thromboembolism (VTE). This meta-analysis evaluates the effectiveness and safety of both NOACs versus standard of care (SoC) in real-world practice. Methods Real-world evidence (RWE) studies were identified through a systematic literature review conducted between January 2012 and July 2020, using Embase, MEDLINE, and the websites of cardiological, hematological, and oncological associations. Eligible RWE studies recruited adult patients with deep vein thrombosis and/or pulmonary embolism and presented a comparison between rivaroxaban and apixaban versus SoC, consisting either of vitamin K antagonists, heparins, or combinations thereof. Hazard ratios (HRs) for the comparison between NOACs and SoC were extracted from the relevant studies or estimated based on the reported binary data. The between-treatment contrasts were reported as HRs with associated 95% confidence intervals. Results A total of 65 RWE studies were identified and considered relevant for the meta-analysis. Compared with SoC, both rivaroxaban and apixaban were associated with reduced risks of recurrent VTE and a lower rate of major bleeding events. Patients treated with rivaroxaban were at a lower risk of all-cause death compared with those receiving SoC (HR = 0.56 [0.39-0.80]), while evidence for apixaban from the identified studies was insufficient to demonstrate a statistically significant change in mortality (HR = 0.66 [0.30-1.47]). Conclusion This analysis indicates that in real-world practice, rivaroxaban and apixaban are associated with a lower risk of recurrent VTE and major bleeding events compared with SoC. Survival benefit in patients treated with rivaroxaban was also observed.

Non-vitamin K antagonist oral anticoagulants in venous thromboembolism patients: a meta-analysis of real-world studies

BackgroundThe real-world studies on recurrent venous thromboembolism (VTE) and bleeding events of non-vitamin K antagonist oral anticoagulants (NOACs) in VTE patients have reported conflicting findings. Our study aimed to provide the direct comparison evidence of different NOACs for VTE patients in clinical practice settings.MethodsSearch of the medical literature was conducted using PubMed, Web of Science, EMBASE, Clinical Trials.gov, and the Cochrane Library from inception to March 22, 2021. Among the 19,996 citations retrieved, a total of 63,144 patients from 6 studies were analyzed. Clinical outcomes included recurrent VTE, death, and different bleeding events.ResultsAdjusted hazard ratio (HR) analysis suggested that apixaban had significant lower bleeding riskthan rivaroxaban (major, minor and any bleeding: HR = 0.61, 0.56, 0.70; p = 0.008, < 0.0001, 0.006, respectively), but no statistics difference found in recurrent VTE events (HR = 1.02, 95% confidence interval (CI) 0.71–1.47, p = 0.93). There was no significant difference of major bleeding between dabigatran and rivaroxaban (odds ratios (OR) = 0.41, 95% CI 0.09–1.90, p = 0.25), apixaban and dabigatran (OR 0.64, 95% CI 0.15–2.72, p = 0.83). No significant difference was found in the comparison of edoxaban and other NOACs in VTE recurrence, major bleeding and composite outcome.ConclusionsIn the prevention of bleeding events, apixaban was associated with a lower risk than rivaroxaban, but equivalent efficacy for different NOACs in prevention of recurrent VTE. Evidence generated from the meta-analysis based on real-world data can help to guide selection between apixaban and rivaroxaban in routine clinical practice.Trial registration: This systematic review and meta-analysis were conducted and reported according to the Preferred Reporting Items for Systematic Reviews and Meta-analysis and Meta-analysis of Observational Studies in Epidemiology statements and was registered with PROSPERO (CRD42019140553).

Predictors of echocardiographic response to cardiac resynchronization therapy: A systematic review with Meta-Analysis.

At least 30% of the patients do not respond to cardiac resynchronization therapy (CRT). We performed a systematic review and meta-analysis of real-world studies trying to identify predictors of response to CRT. PubMed, Embase and Cochrane Central Register of Controlled Trials (CENTRAL) were searched for observational prospective studies, referring the evaluation of response to CRT, defined as a decrease in left ventricle end-systolic volume (LVESV)≥15% at 6-month follow-up, via two-dimensional echocardiography. A total of 24 studies were included. The meta-analysis showed that female gender (p=0.018), non-ischemic cardiomyopathy (NICM) (p<0.001), left bundle branch morphology (LBBB) (p=0.001), longer QRS (p<0.001) and New York Heart Association (NYHA) class II (p=0.014) appear to favor response to CRT. After ROC analysis and logistic regression procedures, female gender (kappa=0.450; p<0.001), NICM (kappa=0.636; p<0.001), LBBB (kappa=0.935; p<0.001), and NYHA class II (kappa=0.647; p<0.001) were identified as independent predictors of response to CRT, being LBBB the most reliable one (sensitivity=97.24%; specificity=98.86%). Female gender, NICM, LBBB and NYHA class II are baseline variables with an apparent capability to independently predict response to CRT, being LBBB the most reliable one.

Cardiovascular and Renal Effectiveness of GLP-1 Receptor Agonists vs. Other Glucose-Lowering Drugs in Type 2 Diabetes: A Systematic Review and Meta-Analysis of Real-World Studies.

Cardiovascular outcome trials (CVOT) showed that treatment with glucagon-like peptide-1 receptor agonists (GLP-1RA) is associated with significant cardiovascular benefits. However, CVOT are scarcely representative of everyday clinical practice, and real-world studies could provide clinicians with more relatable evidence. Here, literature was thoroughly searched to retrieve real-world studies investigating the cardiovascular and renal outcomes of GLP-1RA vs. other glucose-lowering drugs and carry out relevant meta-analyses thereof. Most real-world studies were conducted in populations at low cardiovascular and renal risk. Of note, real-world studies investigating cardio-renal outcomes of GLP-1RA suggested that initiation of GLP-1RA was associated with a greater benefit on composite cardiovascular outcomes, MACE (major adverse cardiovascular events), all-cause mortality, myocardial infarction, stroke, cardiovascular death, peripheral artery disease, and heart failure compared to other glucose-lowering drugs with the exception of sodium-glucose transporter-2 inhibitors (SGLT-2i). Initiation of SGLT-2i and GLP-1RA yielded similar effects on composite cardiovascular outcomes, MACE, stroke, and myocardial infarction. Conversely, GLP-1RA were less effective on heart failure prevention compared to SGLT-2i. Finally, the few real-world studies addressing renal outcomes suggested a significant benefit of GLP-1RA on estimated glomerular filtration rate (eGFR) reduction and hard renal outcomes vs. active comparators except SGLT-2i. Further real-world evidence is needed to clarify the role of GLP-1RA in cardio-renal protection among available glucose-lowering drugs.

Benefits and Harms of Low-Dose Rivaroxaban in Asian Patients With Atrial Fibrillation: A Systematic Review and Meta-analysis of Real-World Studies

Background: Low-dose prescription of rivaroxaban was common among patients with atrial fibrillation (AF) in Asia. However, the benefits and harms of rivaroxaban at a low dosage in Asian patients with AF remains unclear. Accordingly, we aimed to collect and summarize all available evidence to fill this important knowledge gap. Methods: In this systematic review and meta-analysis, we systematically searched databases of MEDLINE, EMBASE, and Cochrane Library for relevant studies from inception until February 23, 2021. Eligible retrospective nationwide or health insurance database studies or prospective registration studies that reported efficacy (stroke/systemic embolism), safety (major bleeding, intracranial hemorrhage, gastrointestinal bleeding), or other outcomes (myocardial infarction, death) of low-dose rivaroxaban in comparison with warfarin in AF patients were enrolled. Data extraction and study quality assessment were conducted by two authors independently. Low dosing of rivaroxaban (15/10 mg) was defined as the received dose lower than the recommended dose (20 mg) approved in most districts. Hazard ratio (HR) with 95% confidence intervals (95% CIs) was pooled using a random-effect model. Subgroup analyses were conducted according to different dose regimens. Sensitivity analyses were conducted by sequential elimination of each study from the pool. Since potential effect modifiers (patient demographics, differences of each study, and others) may lead to bias in primacy outcomes, we performed a meta-regression analysis to explore the influence of these factors on the primary efficacy and safety outcomes. Results: Totally, 12 studies involving 292,815 Asian patients with AF were included. All studies were detected as low to moderate risk bias. Low-dose rivaroxaban treatment in Asian AF patients was associated with a reduced risk of stroke/systemic embolism (HR: 0.76, 95% CI: 0.70–0.84, I 2: 57.8%), major bleeding (HR: 0.72, 95% CI: 0.62–0.84, I 2: 81.5%), and all-cause death (HR: 0.65, 95% CI: 0.58–0.73, I 2: 81.7%) when compared with warfarin. Furthermore, consistent results were observed among different dose regimens (10/15/20 mg) in all the clinical outcomes (P interaction > 0.05 for each outcome). Meta-regression analysis failed to detect any potential confounding to impact the primacy outcomes. Conclusion: Insights from the present meta-analysis, we found that low-dose rivaroxaban, even at a dosage of 10 mg daily, was associated with a reduced risk of stroke/SE and bleeding than warfarin in Asian AF patients. However, owing to considerable heterogeneity among included studies, further prospective studies are required to confirm these findings.

The Effect of Statin Treatment on Outcomes of Cardioembolic Stroke: A Systematic Review and Meta-Analysis of Real-World Studies.

Several real-world observational studies have investigated the association between statin treatment and outcomes of cardioembolic stroke. However, substantial uncertainties remain about this association. We aimed to perform a systematic review and meta-analysis to determine the effect of statin treatment on the outcomes of cardioembolic stroke. We systematically searched the PubMed and Embase databases for relevant clinical studies. Pooled relative risks (RRs) and 95% confidence intervals (CIs) with a random-effects model were used to assess the outcomes of interest. A total of 18 observational studies published between 2009 and 2020 were included. No randomized clinical trial was found. Compared with non-statin treatment, statin treatment was not associated with a decreased risk of stroke recurrence in patients with cardioembolic stroke [PWCS] (RR, 0.93; 95% CI 0.82-1.06). However, compared with non-statin treatment, statin treatment was associated with a lower risk of all-cause death (RR, 0.59; 95% CI 0.49-0.73) and better functional outcomes (RR, 0.67; 95% CI 0.47-0.97) in PWCS. There was no significant association between statin treatment and major bleeding event risk in PWCS (RR, 0.35; 95% CI 0.06-2.16). Compared with non-statin treatment, statin treatment was not associated with a decreased risk of coronary atherosclerotic disease in PWCS (RR, 1.04; 95% CI 0.96-1.11). Although the use of statins does not enhance the prevention of stroke recurrence in PWCS, statin treatment is associated with improved clinical outcomes in PWCS. Statins play a beneficial role in the treatment of cardioembolic stroke.