Random-effects Risk Ratio Research Articles

Abstract 4135270: Clinical and Procedural Outcomes after Transcatheter Aortic Valve Replacement vs Surgical Aortic Valve Replacement in Severe Aortic Stenosis: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Introduction: A growing body of evidence from randomized controlled trials (RCTs) has demonstrated the superiority of transcatheter aortic valve replacement (TAVR) over surgical aortic valve replacement (SAVR) irrespective of surgical risk in patients with severe aortic stenosis (SAS). Given the rise in TAVR procedures, analyzing trends in outcomes over time is critical to aid clinical decision-making. Hence, we pooled RCT data for a robust assessment of clinical and procedural outcomes in SAS patients undergoing TAVR and SAVR. Methods: PUBMED and SCOPUS were queried until April 2024. Trials were classified into high and low-risk groups based on surgical risk. The outcomes were analyzed at 30 days (short-term), 1 year (mid-term), and 5 years (long-term). Estimates were calculated as random effects risk ratios (RRs) with 95% confidence intervals (CI). Results: 10 RCTs with a total of 10,252 patients were included. There was no significant association between TAVR and SAVR in reducing all-cause mortality at 30 days (RR: 0.84 [0.64, 1.10]; Figure 1a). While TAVR was associated with a significantly lower all-cause mortality at 1 year (RR: 0.82 [0.68-0.97]; Figure 1b), it was linked with a significantly higher all-cause mortality at 5 years (RR: 1.14 [1.07-1.21]; Figure 1c). Myocardial infarction and stroke were similar in both groups up to 5 years. TAVR was associated with a lower risk of acute kidney injury for up to 1 year and atrial fibrillation for up to 5 years but a higher risk of new permanent pacemaker implantation and aortic valve re-intervention for up to 5 years. In low-risk patients, TAVR showed no significant differences from SAVR for all-cause mortality at 30 days and 5 years, but it was significant at 1 year. In high-surgical-risk patients, all-cause mortality was comparable between TAVR AND SAVR at 30 days and 1 year, with a higher rate observed with TAVR at 5 years. Conclusion: Compared with SAVR, TAVR was superior in reducing all-cause mortality at 1 year in low-risk patients and inferior in reducing all-cause mortality at 5 years in high-risk patients. A thorough evaluation of anatomical, clinical, and procedural factors is crucial to tailor the optimal intervention for each patient.

Efficacy of Anti-VEGF Drugs Based Combination Therapies in Recurrent Glioblastoma: Systematic Review and Meta-Analysis.

Recurrent glioblastoma multiforme (rGBM) has a grim prognosis, with current therapies offering no survival benefit. Several combination therapies involving anti-VEGF agents have been studied with mixed results. A systematic search was performed using five electronic databases: PubMed, Scopus, ISI, Embase, and the Cochrane Library, without language limitations. The primary outcome of interest was progression-free survival (PFS). Secondary outcomes were overall survival (OS), objective response ratio (ORR), and grade ≥ 3 adverse events. Estimates for PFS and OS were calculated as random effects hazard ratio (HR) with 95% confidence intervals (CIs) using the generic inverse variance method. Estimates for ORR and grade ≥ 3 adverse events were calculated using a random-effects risk ratio (RR) with 95% confidence intervals (CIs) using the Mantel-Haenszel method. Thirteen studies met the inclusion criteria and a total of 1994 patients were included in the analysis. There was no statistically significant improvement in PFS (HR 0.84; 95% CI (0.68, 1.03); I2=81%), OS (HR 0.99; 95% CI (0.88, 1.12); I2=0%), and ORR (RR 1.36; 95% CI (0.96, 1.92); I2=61%) in the combination therapy group when compared to the control group. Significantly higher grade ≥ 3 adverse events (RR 1.30; 95% CI (1.14, 1.48); I2=47%) were seen in the combination therapy when compared to the control group. Our analysis showed that the use of combination therapy with anti-VEGF agents did not offer any benefit in PFS, OS, or ORR. In contrast, it had significantly higher grade 3-5 adverse events. Further studies are needed to identify effective therapies in rGBM that can improve survival.

A meta-analysis of the difference in response to trastuzumab-deruxtecan (T-DXd) based on HER2 immunohistochemistry (IHC) in HER2 low metastatic breast cancer (mBC).

e13164 Background: HER2 low BC have an IHC staining of 1+ or 2+ with negative fluorescence in situ hybridization (ISH). Although T-DXd is approved for this, difference in activity between 1+ and 2+ is uncertain. Methods: A systematic search with controlled vocabulary encompassing BC and T-DXd was conducted in PubMed, Embase, Scopus, and Cochrane on November 11 2023 with no search restrictions. 2318 records were identified and duplicates were removed using Mendeley. The remaining 1189 records were imported into Rayyan, and the titles were screened independently by 2 reviewers. 47/75 full texts were relevant, of which 4 [3 clinical trials, 1 retrospective study] were included for analysis. Only studies that provided outcome data for HER2 1+ and 2+ ISH- were included. RevMan was used to analyze the Risk Ratio (RR) and Odds Ratio (OR) with 95% Confidence Interval (CI), derived from Random Effects (RE) model with Mantel-Haenszel (MH) method. Pooled proportions (PP) were determined using OpenMeta. Results: There were a total of 264 patients in 1+ and 204 in 2+ISH-. Median age was 57 years. All studies had pre-treated mBC. T-DXd dose was at least 5.4 mg/kg every 3 weeks. Visual inspection of our funnel plots revealed no bias. PP (3/4 studies) for patients achieving an Objective Response Rate (ORR) [Complete Response (CR)+Partial Response (PR)] was 42.9% (31.6-54.2%) in 1+ and 38% (26.3-49.7%) in 2+. The median Progression free survival (2/4 studies) was 8.6 (1+) and 7.95 (2+) months respectively. RE RR (3/4 studies) for Progressive Disease (PD) showed no difference between 1+ and 2+ [0.93 (0.80, 1.10), p=0.4, I²=0%]. Similarly, RE OR (3/4 studies) for Disease Control Rate (DCR) [CR+PR+Stable disease (SD)] [1.20 (0.78, 1.85), p=0.41, I²=0%], ORR [1.17 (0.58, 2.34), p=0.66, I²=0%], and PR [1.05 (0.52, 2.11), p=0.89, I²=0%] showed no significant difference between 1+ and 2+ (Table). Conclusions: Our results indicate no difference in response to T-DXd between 1+ and 2+, solidifying its role as a treatment option in HER2 low mBC. Limited number and heterogeneity between studies are limitations of our study, which ought to be addressed in future trials through clear subgroup stratification between 1+ and 2+. [Table: see text]

Sex differences in the risk of retinopathy of prematurity: a systematic review, frequentist and Bayesian meta-analysis, and meta-regression.

Retinopathy of prematurity (ROP) is generally considered to be more frequent in males than in females. However, it is not known whether sex differences in ROP affect all degrees of the condition, are global and have changed as neonatology has developed. We aimed to conduct a systematic review and meta-analysis of studies addressing sex differences in the risk of developing ROP. PubMed/MEDLINE and Embase databases were searched. The frequentist, random-effects risk ratio (RR) and 95% confidence interval (CI) were calculated. Bayesian model averaged (BMA) meta-analysis was used to calculate the Bayes factors (BFs). The BF10 is the ratio of the probability of the data under the alternative hypothesis (H1) over the probability of the data under the null hypothesis (H0). We included 205 studies (867,252 infants). Frequentist meta-analysis showed a positive association between male sex and severe ROP (113 studies, RR = 1.14, 95% CI = 1.07-1.22) but no association with any ROP (144 studies, RR = 1.00, 95% CI = 0.96-1.03). BMA showed extreme evidence in favor of H1 for severe ROP (BF10 = 71,174) and strong evidence in favor of H0 for any ROP (BF10 = 0.05). The association between male sex and severe ROP remained stable over time and was present only in cohorts from countries with a high or high-middle sociodemographic index. Our study confirms the presence of a male disadvantage in severe ROP but not in less severe forms of the disease. There are variations in the sex differences in ROP, depending on geographical location and sociodemographic level of the countries.

Abstract 18850: Impact of Intravascular Imaging-Guided versus Coronary Angiography-Guided Percutaneous Coronary Intervention on Adverse Cardiovascular Events: A Systematic Review and Meta-Analysis of Randomized Control Trials

Background: Intravascular imaging (IVI) namely intravascular ultrasound (IVUS) and optical coherence tomography (OCT), presents as a promising imaging modality for drug-eluting stent (DES) implantation compared to the gold-standard conventional two-dimensional angiography. IVI provides detailed information on vessel lumen, lesion length, and degree of calcification. For this purpose, we conducted a meta-analysis by pooling recently conducted randomized control trials (RCTs) to compare IVI with angiography for DES implantation. Hypothesis: IVI is associated with a significant reduction in CV events for DES implantation. Methods: Fourteen RCTs reporting CV outcomes with IVI versus angiography-guided stent implantation in CAD patients undergoing PCI were included in MEDLINE, and Scopus databases (Inception till May 2023). The primary outcome of interest was target-lesion revascularization (TLR). The outcome measures were summary random effects risk ratio (RR) with 95% confidence intervals. Results: A total of 8,946 patients (IVI 4,751 vs. angiography 4,195; mean age 61.7 years) were included. Over a median follow-up of 15 months (12-24.3), IVI was associated with significantly reduced TLR (RR 0.63 [0.49, 0.79]; Figure 1), target vessel revascularization (RR 0.66 [0.53, 0.83]), and major adverse cardiovascular events (MACE) (RR 0.69 [0.58, 0.78]) vs. conventional angiography for PCI. However, no significant difference was observed in all-cause mortality between the two imaging modalities (RR 0.85 [0.63, 1.15]). Meta-regression analysis showed no significant impact of follow-up duration, baseline comorbidities such as hypertension, smoking status, previous myocardial infarction, and stent length on TLR incidence. Conclusion: IVI was associated with improved CV outcomes in terms of reduced TLR, TVR, and MACE incidence when compared with traditional angiography in CAD patients for stent implantation.

Abstract 18242: Mitral Valve Repair vs. Mitral Valve Replacement in Rheumatic Heart Disease Patients: A Systematic Review and Meta-Analysis

Background Mitral valve repair (MVP) is recommended over mitral valve replacement (MVR) for mitral valve disease. However, its benefits in rheumatic heart disease (RHD) patients are unclear. We conducted this meta-analysis to compare perioperative and long-term clinical and safety outcomes of MVP vs. MVR. Methods: MEDLINE, Google Scholar, and Scopus were searched from inception till June 2023 comparing clinical outcomes with MVP vs. MVR in RHD patients. Primary outcomes were early mortality and long-term survival. Secondary outcomes were freedom from reoperation, freedom from valve related adverse events, postoperative infective endocarditis (IE), thromboembolic events (TEE), and hemorrhagic events. The outcome measures were summary random effects risk ratio (RR) and hazard ratios (HR) with 95% confidence intervals. Results: A total of 19 studies with 10,724 RHD patients (3,495 MVP vs. 7,229 MVR; mean age: 38.3 years for MVP vs. 43.5 years for MVR) were included. MVP was associated with significantly lower early mortality (RR 0.62 [0.45, 0.85]; p=0.003), and long-term mortality (HR 0.53 [0.37, 0.76]; p=0.0006). Upon meta-regression analysis, only increasing age was associated with early mortality (Coeff: 0.0194, p=0.037). However, MVP was associated with significantly lower freedom from reoperation at both 5- (RR 0.88 [0.83, 0.93]; p<0.0001) and 10-year (RR 0.90 [0.83, 0.98]; p=0.01) follow-ups. Freedom from valve related adverse events was higher in the MVP group at 10-year follow-up (RR 1.15 [1.06, 1.24]; p=0.0006) with no significant difference at 5-year follow-up (RR 1.03 [0.94, 1.14]; p=0.50). No significant difference was seen for IE (RR 1.03, p=0.91) and hemorrhagic events (RR 0.70, p=0.05). TEE were significantly lower in the MVP group (RR 0.59 [0.44, 0.78]; p=0.0003). Conclusion: In RHD, MVP reduced early- and long-term mortality and achieved greater freedom from valve related adverse events. However, there was a higher risk of reoperation in MVP.

Abstract 18261: Efficacy and Safety of Bempedoic Acid for Prevention of Cardiovascular Events and Diabetes Mellitus: A Systematic Review and Meta-Analysis of Randomized Control Trials

Background: Bempedoic acid (BA) is considered an alternative therapy for hyperlipidemia (HLD) in statin-intolerant patients. Given the positive results from the CLEAR-OUTCOMES trial, we performed a meta-analysis pooling recently conducted randomized control trials (RCTs) to provide a comprehensive clinical evaluation of the safety and efficacy of BA. Hypothesis: Bempedoic acid therapy in HLD patients with statin intolerance may be associated with a significant reduction in LDL-C levels, and CV events. Methods: All RCTs reporting CV outcomes and/or % change in LDL-C from baseline till completion of follow-up duration in HLD patients with statin-intolerance were included in MEDLINE, Google Scholar, and Scopus databases (Inception to April 2023). The outcome measures were summary random effects risk ratio (RR) and mean differences (MD) with 95% confidence intervals. Results: Twelve RCTs were included with 18 510 patients (10,033 BA vs. 8,477 placebo). BA therapy resulted in greater significant % reduction in LDL-C levels post-treatment (mean difference from baseline: 21.73% [-26.94, -16.51], p<0.00001) with no significant impact of the male sex, age, and follow-up duration on LDL-C upon meta-regression analysis. The risk of MACE (RR, 0.86 [0.79, 0.93], p < 0.0004), coronary artery revascularization (RR, 0.81 [0.72, 0.91], p = 0.0005), and myocardial infarction (RR, 0.71 [0.51, 0.99], p= 0.04) were significantly reduced with BA ( Figure 1) . However, no significant reduction in cardiac death (RR, 1.05 [0.89, 1.24], p = 0.56) was observed. A total of 1,019 new-onset DM events (521/6027 with BA; 498/4946 with placebo) were reported, and demonstrated a non-significant lower risk of new-onset or worsening DM (RR 0.83; 95% CI [0.62, 1.13]; P = 0.24) with BA vs. placebo. Conclusion: BA was observed to be safe, efficacious, associated with improved cardiovascular outcomes, and with no effect on new-onset or worsening DM among HLD patients with statin intolerance.

Association of serum uric acid with prognosis in patients with myocardial infarction: an update systematic review and meta-analysis

BackgroundThe prognostic significance of serum uric acid (SUA) in individuals who have experienced myocardial infarction (MI) remains a subject of academic debate. Thus, the aim of this study was to examine the occurrence of immediate and long-term adverse outcomes in individuals with elevated levels of uric acid (UA) following a diagnosis of MI.MethodThis study conducted a literature search from PubMed, Embase, Web of Science, Medline, Cochrane Library, Emcrae, and Scopus to perform a systematic review and meta-analysis of the prognostic impact of MI with a hyper SUA to assess short-term (30-day or in-hospital) and long-term mortality, the incidence of major adverse cardiovascular events (MACE), and its adverse event rate in relation to SUA. The literature search was conducted up until April 2023. A random effects model and risk ratio (RR) were used as epidemiological indicators. For indicators with low disease rates, treatment intensity was reduced and RR was considered equivalent to odds ratio (OR). Hazard Ratio (HR), RR, and OR extracted from the data were simultaneously subjected to multivariable adjustment for confounding factors. In addition, P values for all original hypotheses were extracted and a meta-analysis was conducted. High SUA was defined as SUA levels equal to or greater than 420 μmol/L (7.0 mg/dL) for males and equal to or greater than 357 μmol/L (6.0 mg/dL) for females. The quality of the literature was evaluated using the Newcastle–Ottawa Scale (NOS).ResultsThis comprehensive study included a total of 41 investigations, involving a large sample size of 225,600 individuals who had experienced MI. The findings from the meta-analysis reveal that patients diagnosed with hyperuricemia have significantly increased rates of short-term mortality (RR = 2.14, 95% CI = 1.86, 2.48) and short-term incidence of MACE (RR = 1.94, 95% CI = 1.65–2.11). Furthermore, long-term adverse outcomes, including all-cause mortality (RR = 1.46, 95% CI = 1.40–1.51) and incidence of MACE (RR = 1.43, 95% CI = 1.35–1.52), were also found to be higher in this specific patient population.ConclusionPatients diagnosed with MI and elevated SUA levels exhibit a heightened incidence of MACE during their hospital stay. Furthermore, these individuals also experience elevated rates of in-hospital mortality and mortality within one year of hospitalization. However, it is important to note that further randomized controlled trials are necessary to validate and authenticate these findings.

An Updated Meta-Analysis on Cerebral Embolic Protection in Patients Undergoing Transcatheter Aortic Valve Intervention Stratified by Baseline Surgical Risk and Device Type

BackgroundTranscatheter aortic valve intervention (TAVI) can lead to the embolization of debris. Capturing the debris by cerebral embolic protection (CEP) devices may reduce the risk of stroke. New evidence has allowed us to examine the effects of CEP in patients undergoing TAVI. We aimed to assess the effects of CEP overall and stratified by the device used (SENTINEL or TriGuard) and the surgical risk of the patients. MethodsWe selected randomized controlled trials using electronic databases through September 17, 2022. We estimated random-effects risk ratios (RR) with (95% confidence interval) and calculated absolute risk differences at 30 days across baseline surgical risks derived from the TAVI trials for any stroke (disabling and nondisabling) and all-cause mortality. ResultsAmong 6 trials (n = 3921), CEP vs. control did not reduce any stroke [RR: 0.95 (0.50-1.81)], disabling [RR: 0.75 (0.18-3.16)] or nondisabling [RR: 0.99 (0.65-1.49)] strokes, or all-cause mortality [RR: 1.23 (0.55-2.77)]. However, when analyzed by device, SENTINEL reduced disabling stroke [RR: 0.46 (0.22-0.95)], translating into 6 fewer per 1000 in high-risk, 3 fewer per 1000 in intermediate-risk, and 1 fewer per 1000 in low surgical-risk patients. CEP vs. control did not reduce the risk of any bleeding [RR: 1.03 (0.44-2.40)], major vascular complications [RR: 1.41 (0.57-3.48)], or acute kidney injury [RR: 1.36 (0.57-3.28)]. ConclusionsThis updated meta-analysis showed that SENTINEL CEP might reduce disabling stroke in patients undergoing TAVI. Patients with high and intermediate surgical risks were most likely to derive benefits.

Elevated LDL Triglycerides and Atherosclerotic Risk

BackgroundIt is unclear whether elevated low-density lipoprotein (LDL) triglycerides are associated with an increased risk of atherosclerotic cardiovascular disease (ASCVD). ObjectivesThis study tested the hypothesis that elevated LDL triglycerides are associated with an increased risk of ASCVD and of each ASCVD component individually. MethodsThe study investigators used the Copenhagen General Population Study, which measured LDL triglycerides in 38,081 individuals with a direct automated assay (direct LDL triglycerides) and in another 30,208 individuals with nuclear magnetic resonance (NMR) spectroscopy (NMR LDL triglycerides). Meta-analyses aggregated the present findings with previously reported results. ResultsDuring a median follow-up of 3.0 and 9.2 years, respectively, 872 and 5,766 individuals in the 2 cohorts received a diagnosis of ASCVD. Per 0.1 mmol/L (9 mg/dL) higher direct LDL triglycerides, HRs were 1.26 (95% CI: 1.17-1.35) for ASCVD, 1.27 (95% CI: 1.16-1.39) for ischemic heart disease, 1.28 (95% CI: 1.11-1.48) for myocardial infarction, 1.22 (95% CI: 1.08-1.38) for ischemic stroke, and 1.38 (95% CI: 1.21-1.58) for peripheral artery disease. Corresponding HRs for NMR LDL triglycerides were 1.26 (95% CI: 1.20-1.33), 1.33 (95% CI: 1.25-1.41), 1.41 (95% CI: 1.31-1.52), 1.13 (95% CI: 1.05-1.23), and 1.26 (95% CI: 1.10-1.43), respectively. The foregoing results were not entirely statistically explained by apolipoprotein B levels. In meta-analyses for the highest quartile vs the lowest quartile of LDL triglycerides, random-effects risk ratios were 1.50 (95% CI: 1.35-1.66) for ASCVD (4 studies; 71,526 individuals; 8,576 events), 1.62 (95% CI: 1.37-1.93) for ischemic heart disease (6 studies; 107,538 individuals; 9,734 events), 1.30 (95% CI: 1.13-1.49) for ischemic stroke (4 studies; 78,026 individuals; 4,273 events), and 1.53 (95% CI: 1.29-1.81) for peripheral artery disease (4 studies; 107,511 individuals; 1,848 events). ConclusionsElevated LDL triglycerides were robustly associated with an increased risk of ASCVD and of each ASCVD component individually in 2 prospective cohort studies and in meta-analyses of previous and present studies combined.

Abstract 10553: Staged Percutaneous Coronary Intervention For Chronic Total Occlusion of Non-Infarct Related Artery: A Meta-Analysis

Background: Chronic total occlusion (CTO) of a non-infarct related artery (nIRA) is associated with adverse outcomes following acute myocardial infarction (AMI). The current study aimed to evaluate the impact of successful staged percutaneous coronary intervention (PCI) of nIRA CTO lesions on clinical outcomes. Methods: PubMed, EMBASE, Google Scholar and Scopus databases were queried for studies comparing outcomes between AMI patients who underwent successful staged PCI of nIRA CTO lesions (CTO PCI group) and AMI patients with medical management of nIRA CTO lesions or failed CTO PCI attempt (No CTO PCI group). The primary meta-analysis outcome was major adverse cardiovascular events (MACE). The main summary estimate was the random effects risk ratio (RR) with 95% confidence intervals (CIs). Results: Eleven studies (1 randomized, 10 observational) with 2,788 patients were included. Compared with the No CTO PCI group, the CTO PCI group demonstrated a lower incidence of MACE (Figure A, RR 0.55 [0.46, 0.66], p<0.001), all-cause mortality (Figure B, RR 0.47 [0.33, 0.66], p<0.001), cardiac mortality (Figure C, RR 0.4 [0.28, 0.59], p<0.001), stroke (Figure D, RR 0.38 [0.22, 0.66], p=0.0007) and heart failure (HF) hospitalization (RR 0.61 [0.41, 0.9], p=0.01). There was no significant difference in rates of any repeat revascularization (Figure E, RR 0.98 [0.69, 1.4], p=0.92) or target vessel revascularization (Figure F, RR 0.81 [0.48, 1.37], p=0.43) between the two groups. Conclusion In patients with AMI, staged PCI of nIRA CTO lesions was associated with a significantly lower incidence of MACE, all-cause mortality, cardiac mortality, stroke and HF hospitalization.

Abstract 12706: Stroke Risk and Oral Anticoagulation Use With Extended Cardiac Monitoring for Atrial Fibrillation versus Usual Care: A Systematic Review With Meta-Analysis

INTRODUCTION: Prolonged cardiac monitoring is frequently used to detect atrial fibrillation (AF) in high-risk populations, with the goal of preventing thromboembolic events. We sought to determine the impact of prolonged cardiac monitoring on the incidence of stroke and systemic embolism (SSE) or transient ischemic attack (TIA) METHODS: We performed a systematic review and meta-analysis of randomized trials evaluating prolonged monitoring versus usual care (PROSPERO #CRD42021277611). Studies were identified through CENTRAL, MEDLINE, and Embase. We included studies with ≥100 participants and ≥30 days follow-up. The primary outcome was a composite of SSE/TIA, as reported in the original trials. Secondary outcomes included AF detection, oral anticoagulation (OAC) initiation, and major bleeding. Sensitivity analysis examining the impact of monitoring device, and indication for monitoring were performed. Meta-analyses were performed with R using a random-effects model. RESULTS: From 1411 records, we included 9 RCTs (n = 10,205). Mean age was 70 years, 40% were female, and mean CHADS2 score was 4.0. Studies used implantable cardiac monitors (n = 4), external cardiac monitors (n = 3), or handheld ECG devices (n = 2). Study populations included post-stroke (n = 5), high risk for AF or stroke (n = 2), and post-cardiac surgery (n = 1). Mean follow-up was 16 months (range 3-65). Extended monitoring did not significantly reduce the primary outcome (Figure, random effects risk ratio [RR] 0.87, 95% confidence interval [CI] 0.72-1.06, I2 = 0%) or its individual components. Extended monitoring increased AF detection (RR 4.56, 95% CI 3.01-6.92, I2 = 65%) and OAC usage (RR 2.25, 95% CI 2.01-2.53, I2 = 0%), but did not impact major bleeding (RR 1.23, 95% CI 0.84-1.82, I2 = 0%). CONCLUSION: Prolonged monitoring was associated with increased AF detection and OAC use, without significantly reducing the occurrence of thromboembolic events.

Dual Antiplatelet Therapy in Patients Aged 75 Years and Older with Coronary Artery Disease: A Meta-Analysis and Systematic Review.

Objectives This systematic review and meta-analysis evaluates the safety and efficacy of dual antiplatelet therapy (DAPT) in elderly patients with acute coronary syndrome (ACS). Background The safety and efficacy of DAPT in elderly patients with ACS is not well characterized. Methods We performed a systematic literature review to identify clinical studies that reported safety and efficacy outcomes after DAPT for ACS in elderly patients. The primary outcomes of primary efficacy endpoint rates and bleeding event rates were reported as random effects risk ratio (RR) with 95% confidence interval. No prior ethical approval was required since all data are public. Results Our search yielded 660 potential studies. We included 8 studies reporting on 29,217 patients. There was a higher risk of bleeding event rates in elderly patients treated with prasugrel or ticagrelor when compared to clopidogrel with a risk ratio of 1.17 (95% CI 1.08 to 1.27, p < 0.05). There was no difference in primary efficacy endpoint rates between elderly patients treated with prasugrel or ticagrelor when compared to clopidogrel with a risk ratio of 0.85 (95% CI 0.68 to 1.07, p=0.17). Conclusions This systematic review and meta-analysis suggests that DAPT with prasugrel or ticagrelor compared to clopidogrel is associated with a higher risk of bleeding events in elderly patients with ACS. There was no difference in the primary efficacy endpoints between the two treatment groups.

Colchicine for Secondary Prevention of Coronary Artery Disease: A Meta-Analysis of Randomised Controlled Trials

Colchicine has become prominent as an anti-inflammatory therapy for secondary cardiovascular prevention in patients with coronary artery disease (CAD). This meta-analysis was performed to evaluate the efficacy and safety of colchicine in patients with CAD. Randomised controlled trials (RCTs) that compare major adverse cardiovascular events (MACEs) between patients with CAD randomised to colchicine versus placebo (or no colchicine) were included. Random effect risk ratios (RRs) were calculated for clinical outcomes. A total of 12,071 patients in seven RCTs were included in the meta-analysis. Compared with placebo or no colchicine, colchicine was associated with a significantly lower incidence of MACEs (RR 0.64, 95% CI 0.51-0.80, p<0.01). The reduction in MACEs in the colchicine group was driven by statistically significant reductions in the incidence of myocardial ischaemia (RR 0.74, 95% CI 0.58-0.95, p=0.02), coronary revascularisation (RR 0.61, 95% CI 0.42-0.89, p=0.01), and stroke (RR 0.48, 95% CI 0.28-0.83, p=0.01). However, there was no statistically significant difference for cardiovascular death (RR 0.82, 95% CI 0.55-1.22, p=0.33). All-cause and non-cardiovascular mortality, gastrointestinal events, infection, and cancer were not significantly different between the colchicine and control groups. Colchicine is a reasonably efficacious and safe drug that could be successfully utilised for the secondary prevention of CAD.

Recombinant human thyrotropin (rhTSH)-aided radioiodine treatment for non-toxic multinodular goitre.

Multinodular goitre is common in women. Treatments for non-toxic multinodular goitre include surgery, levothyroxine suppressive therapy, and radioiodine. Radioiodine therapy is the only non-surgical alternative for non-toxic multinodular goitre. However, a high amount of radioiodine is needed to enable the thyroid nodules to adequately take up the radioiodine, because the multinodular goitre takes up a low amount of iodine. Recombinant human thyrotropin (rhTSH) has been used to increase radioiodine uptake and reduce thyroid volume of the multinodular goitre. Whether the improved reduction of the goitre resulting from rhTSH-stimulated radioiodine therapy is beneficial to the person remains controversial. To assess the effects of recombinant human thyrotropin-aided radioiodine treatment for non-toxic multinodular goitre. We searched the CENTRAL, MEDLINE, Scopus as well as ICTRP Search Portal and ClinicalTrials.gov. The date of the last search of all databases was 18 December 2020. We included randomised controlled clinical trials (RCTs) comparing the effects of rhTSH-aided radioiodine treatment compared with radioiodine alone for non-toxic multinodular goitre, with at least 12 months of follow-up. Two review authors independently screened titles and abstracts for relevance. Screening for inclusion, data extraction, and risk of bias assessment were carried out by one review author and checked by a second. Our main outcomes were health-related quality of life (QoL), hypothyroidism, adverse events, thyroid volume, all-cause mortality, and costs. We used a random-effects model to perform meta-analyses, and calculated risk ratios (RRs) for dichotomous outcomes, and mean differences (MDs) for continuous outcomes, using 95% confidence intervals (CIs) for effect estimates. We evaluated the certainty of the evidence using the GRADE approach. We included six RCTs. A total of 197 participants were allocated torhTSh-aided radioiodine therapy, and 124 participants were allocated to radioiodine. A single dose of radioiodine was administered 24 hours after the intramuscular injection of a single dose of rhTSH. The duration of follow-up ranged between 12 and 36 months. Low-certainty evidence from one study, with 85 participants, showed uncertain effects for QoL for either intervention. RhTSH-aided radioiodine increased hypothyroidism compared with radioiodine alone (64/197 participants (32.5%) in the rhTSH-aided radioiodine group versus 15/124 participants (12.1%) in the radioiodine alone group; RR 2.53, 95% CI 1.52 to 4.20; 6 studies, 321 participants; moderate-certainty evidence in favour of radioiodine alone). A total of 118/197 participants (59.9%) in the rhTSH-aided radioiodine group compared with 60/124 participants (48.4%) in the radioiodine alone group experienced adverse events (random-effects RR 1.24, 95% CI 0.94 to 1.63; 6 studies, 321 participants; fixed-effect RR 1.23, 95% CI 1.02 to 1.49 in favour of radioiodine only; low-certainty evidence). RhTSH-aided radioiodine reduced thyroid volume with a MD of 11.9% (95% CI 4.4to 19.4; 6 studies,268participants; moderate-certainty evidence). One study with 28 participants reported one death in the radioiodine alone group (very-low certainty evidence). No study reported on costs. RhTSH-aided radioiodine treatment for non-toxic multinodular goitre, compared to radioiodine alone, probably increased the risk of hypothyroidism but probably led to a greater reduction in thyroid volume. Data on QoL and costs were sparse or missing.

Abstract 9868: Novel Oral Anticoagulants versus Vitamin K Antagonists in Patients with Atrial Fibrillation and Bioprosthetic Valve Replacement: A Systematic Review and Meta-Analysis

Background: Vitamin K antagonists (VKAs) such as warfarin are traditionally prescribed in patients with atrial fibrillation (AF) and bioprosthetic valves (BPVs) to prevent thromboembolic events. However, various studies have proposed novel oral anticoagulants (NOACs) as an effective and safer option to use. Therefore, we conducted a systematic review and meta-analysis to compare their relative efficacy and safety profiles. Methods: Pubmed, Cochrane Central, and Embase were searched up until May 15, 2021 for randomized clinical trials (RCTs) and observational studies determining efficacy and safety of NOACs or VKAs in AF patients who had undergone BPV replacement. Outcomes of interest were: stroke or systemic embolism (SSE), major bleeding, all-cause mortality, and intracranial hemorrhage (ICH). Subgroup analysis by study design (RCT and observational) was performed. Summary estimates were reported as random effects risk ratios (RRs) with 95% confidence intervals (CIs). Results: A total of 12 studies (4 RCTs and 8 observational) with 6436 patients (mean age 72.1 years; 51.4% males) were included in the analysis. In comparison to VKAs, NOACs demonstrated a significant reduction in ICH (RR 0.41 [95% CI 0.25,0.67]; p=0.0003; I 2 = 0%) and major bleeding (RR 0.63 [95% CI 0.53,0.74]; p&lt;0.00001; I 2 = 0%) at a mean duration follow up of 23.8 months. However, no difference was observed in risk of SSE (RR 0.77 [95% CI 0.50,1.19]; p=0.23; I 2 = 53%) and all-cause mortality (RR 0.98 [95% CI 0.78,1.22]; p=0.84; I 2 = 15%). Observational studies and RCTs did not significantly differ across all outcomes in the subgroup analysis. Conclusions: This meta-analysis suggests that NOACs are effective at reducing risk of ICH and major bleeding in AF patients with BPVs in contrast to VKAs. Future large-scale RCTs can aid in corroborating the legitimacy of these results.

Abstract 13979: Meta-Analysis of Efficacy and Safety of Colchicine Therapy in Patients With Acute Coronary Syndrome

Introduction: Colchicine is known to be effective in treatment of inflammatory disorders, however, the effects of colchicine in patients with acute coronary syndrome (ACS) on top of background standard medical therapy remains uncertain. Hypothesis: There is paucity of data about colchicine therapy in patients presenting with acute coronary syndrome which may be associated with significant reduction in cardiovascular events. Methods: Six randomized controlled trials reporting CV outcomes in patients with acute coronary syndrome were included in MEDELINE, EMBASE and CENTRAL database (Inception to May 2021). The outcome measures were the summary random effects risk ratio (RR) with 95% confidence intervals. Results: In 6282 patients presenting with ACS, colchicine therapy did not significantly reduce the risk of all-cause mortality (RR, 1.62 [0.45, 5.88], P=0.87) or CV mortality (RR, 0.98 [0.43, 2.25], P=0.97) or myocardial infarction (MI) (RR, 0.88 [0.69, 1.11], P=0.28). Colchicine therapy had a significant effect on Major adverse cardiovascular events (MACE) (RR, 0.79 [0.64, 0.97], P=0.02), Stroke (RR, 0.33 [0.15, 0.72], P=0.01), and revascularization (RR, 0.46 [0.29, 0.73], P&lt;0.01). In comparison to control, colchicine had significantly higher rate of GI side effects (RR, 1.53 [1.05, 2.23], P=0.03) Conclusions: Colchicine therapy in patients presenting with acute coronary syndrome was associated with significant reduction in MACE, stroke and revascularization at the cost of higher rate of GI side effects.

The use of direct oral anticoagulants for thromboprophylaxis or treatment of cancer-associated venous thromboembolism: a meta-analysis and review of the guidelines

BackgroundVenous thromboembolism (VTE) is a common complication among patients with cancer and is one of the most common causes of increased morbidity and mortality. The use of direct oral anticoagulants (DOACs) for thromboprophylaxis and treatment of cancer-associated venous thromboembolism (CA-VTE) has been evaluated in several randomized clinical trials (RCTs). The aim of this meta-analysis was to assess efficacy and safety of using DOACs for thromboprophylaxis and treatment of CA-VTE and provide a summary for available guidelines’ recommendations.MethodsMEDLINE was searched to identify studies evaluating the use of DOACs for thromboprophylaxis or treatment in patients with cancer. Search was limited to peer-reviewed studies published in English. Studies were excluded if they were not RCTs or subgroup analyses of data derived from RCTs, if they did not report efficacy and safety data on patients with active cancer, or if they were published as an abstract. New VTE or VTE recurrence, and major or clinically relevant non-major bleeding (CRNMB) were used to assess the efficacy and safety, respectively. The Mantel-Haenszel random-effects model risk ratios (RRs) and the corresponding 95% confidence intervals (CIs) were calculated to estimate the pooled treatment effects of DOACs.ResultsFour studies evaluating DOACs use for thromboprophylaxis and four – for treatment of CA-VTE were included. Thromboprophylaxis with DOACs was associated with a significant reduction in the risk of symptomatic VTE (RR = 0.58; 95%CI 0.37,0.91) but with an incremental risk of major bleeding or CRNMB (RR = 1.57; 95%CI 1.10,2.26). CA-VTE treatment with DOACs was linked with a significant reduction in VTE recurrence (RR = 0.62; 95%CI 0.44,0.87) but with an incremental risk of CRNMB (RR = 1.58; 95%CI 1.11,2.24).ConclusionsThe DOACs are associated with a lower risk of symptomatic VTE and VTE recurrence, but the risk of bleeding remains a considerable concern. Clinical decisions should be made by assessing individual patient’s risk of VTE and bleeding.

Lowering Nighttime Blood Pressure With Bedtime Dosing of Antihypertensive Medications: Controversies in Hypertension - Con Side of the Argument.

Lowering Nighttime Blood Pressure With Bedtime Dosing of Antihypertensive Medications: Controversies in Hypertension - Con Side of the Argument.

Direct oral anticoagulants in patients with atrial fibrillation and bioprosthetic valve replacement: A meta-analysis.

This systematic review and meta-analysis compares direct oral anticoagulants (DOACs) versus vitamin K antagonists (VKAs) in patients with atrial fibrillation and bioprosthetic valve replacement or repair (BVR). The optimal anticoagulation therapy for patients with atrial fibrillation and a history of bioprosthetic valve replacement or repair (BVR) is not well understood. We performed a systematic literature review to identify clinical studies that compared anticoagulation therapies for patients with atrial fibrillation and BVR. The primary outcomes of stroke, major bleeding, and mortality were reported as random effects risk ratio (RR) with 95% confidence interval. No prior ethical approval was required since all data is public. Our search yielded 101 potential studies. We included six studies reporting on 1911 patients. There was a lower risk of stroke and major bleeding in patients with atrial fibrillation after BVR treated with DOACs when compared to VKAs with risk ratios of 0.44 (95% CI 0.24-0.82, p < 0.01) and 0.53 (95% CI 0.34-0.83, p < 0.01), respectively. There was no statistically significant difference in mortality between patients with atrial fibrillation after BVR treated with DOACs compared to patients treated with VKAs with a risk ratio of 1.12 (95% CI 0.73-1.74, p=0.60). This systematic review and meta-analysis suggests that DOACs are superior to VKAs with respect to stroke and major bleeding in patients with atrial fibrillation and BVR.