Immune checkpoint inhibitor-induced cardiotoxicity in patients with lung cancer: a systematic review and meta-analysis.

BACKGROUND: The use of immune checkpoint inhibitors (ICIs) for the treatment of lung cancer may precipitate cardiotoxic events. We aimed to perform a meta-analysis to evaluate the cardiotoxicity associated with ICIs in patients with lung cancer. METHODS: A literature search was conducted across four electronic databases (Cochrane CENTRAL, MEDLINE, OVID EMBASE and Google Scholar) from inception through 31st May 2023. Randomized controlled trials (RCTs) assessing the impact of ICIs on cardiac outcomes in lung cancer patients were considered for inclusion. Risk ratios (RR) with 95% confidence intervals (CIs) were pooled and analysis was performed using a random-effects model. The Grading of Recommendations Assessment, Development and Evaluation approach was followed to assess confidence in the estimates of effect (i.e., the quality of evidence). RESULTS: A total of 30 studies including 16,331 patients, were included in the analysis. Pooled results showed that single ICI (RR: 2.15; 95% CI: 1.13-4.12; p = 0.02; I2 = 0%) or a combination of single ICI plus chemotherapy (RR: 1.38 [1.05-1.82]; p = 0.02) significantly increased the risk of cardiac adverse events when compared with chemotherapy alone. No significant difference was noted when a dual ICI (RR: 0.48 [0.13-1.80]; p = 0.27) was compared with single ICI. In addition, there was no significant association between the use of ICIs and incidence of cardiac failure (RR: 1.11 [0.48-2.58]; p = 0.80), or arrhythmia (RR: 1.87; [0.69-5.08]; p = 0.22). CONCLUSION: Compared with chemotherapy alone, use of a single ICI or a combination of single ICI plus chemotherapy significantly increased the risk of cardiotoxicity. However, employing dual immunotherapy did not result in a significant increase in the risk of cardiotoxicity when compared to the use of a single ICI.

Effectiveness of exercise modalities on breast cancer patient outcomes: a systematic review and meta-analysis.

BACKGROUND: The effects of exercise in patients with breast cancer (BC), has shown some profit, but consistency and magnitude of benefit remains unclear. We aimed to conduct a meta-analysis to assess the benefits of varying types of exercises in patients with BC. METHODS: Literature search was conducted across five electronic databases (MEDLINE, Web of Science, Scopus, Google Scholar and Cochrane) from 1st January 2000 through 19th January 2024. Randomized controlled trials (RCTs) assessing the impact of different types of exercise on outcomes related to fitness and quality of life (QOL) in patients with BC were considered for inclusion. Outcomes of interest included cardiorespiratory fitness (CRF), health-related quality of life (HRQOL), muscle strength, fatigue and physical function. Evaluations were reported as mean differences (MDs) with 95% confidence intervals (CIs) and pooled using random effects model. A p value < 0.05 was considered significant. RESULTS: Thirty-one relevant articles were included in the final analysis. Exercise intervention did not significantly improved the CRF in patients with BC when compared with control according to treadmill ergometer scale (MD: 4.96; 95%Cl [-2.79, 12.70]; P = 0.21), however exercise significantly improved CRF according to cycle ergometer scales (MD 2.07; 95% Cl [1.03, 3.11]; P = 0.0001). Physical function was significantly improved as well in exercise group reported by 6-MWT scale (MD 80.72; 95% Cl [55.67, 105.77]; P < 0.00001). However, exercise did not significantly improve muscle strength assessed using the hand grip dynamometer (MD 0.55; 95% CI [-1.61, 2.71]; P = 0.62), and fatigue assessed using the MFI-20 (MD -0.09; 95% CI [-5.92, 5.74]; P = 0.98) and Revised Piper scales (MD -0.26; 95% CI [-1.06, 0.55] P = 0.53). Interestingly, exercise was found to improve HRQOL when assessed using the FACT-B scale (MD 8.57; 95% CI [4.53, 12.61]; P < 0.0001) but no significant improvements were noted with the EORTIC QLQ-C30 scale (MD 1.98; 95% CI [-1.43, 5.40]; P = 0.25). CONCLUSION: Overall exercise significantly improves the HRQOL, CRF and physical function in patients with BC. HRQOL was improved with all exercise types but the effects on CRF vary with cycle versus treadmill ergometer. Exercise failed to improve fatigue-related symptoms and muscle strength. Large RCTs are required to evaluate the effects of exercise in patients with BC in more detail.

Trans-femoral versus trans-carotid access for transcatheter aortic valve replacement: an updated systematic review and meta-analysis.

Aim: This meta-analysis aims to shed light on any primacy the trans-carotid (TC-TAVR) access may have over the trans-femoral access (TF-TAVR) for those undergoing transcatheter aortic valve replacement (TAVR). Methods: PubMed/MEDLINE and Cochrane Library were searched, from inception to March 2023 retrieving seven adjusted studies with a total of 6609 patients, of which 5048 underwent TF-TAVR while 1561 underwent TC-TAVR. Results: No divergence in risk of mortality, major bleeding or stroke/transient ischemic attack in TC-TAVR when compared with TF-TAVR was found. In TC-TAVR, the risk of vascular complications was low (OR: 0.51, 95% CI: 0.32-0.83, p = 0.003) as compared with TF-TAVR. Conclusion: As of this analysis, the viability of TC-TAVR as first alternative to TF-TAVR is plausible.

Trends in mortality related to kidney failure and diabetes mellitus in the United States: a 1999-2020 analysis.

BACKGROUND: Kidney failure ranks as the tenth leading cause of mortality in the United States (US), frequently arising as a complication associated with diabetes mellitus (DM). METHODS: Trends in DM and kidney failure mortality were assessed using a cross-sectional analysis of death certificates from the Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research (CDC WONDER) database. Crude and age-adjusted mortality rates (AAMR) per 100,000 people and annual percent change (APC) in age-adjusted mortality rate with 95% CI were obtained and measured across different demographic and geographic subgroups. RESULTS: Between 1999 and 2020, a total of 325,515 deaths occurred related to kidney failure and DM. The overall age-adjusted mortality rate showed no significant change between 1999 and 2012, after which it declined until 2015 - 64.8 (95% CI - 75.6 to - 44.8) and has been steadily increasing since. Men had consistently higher age-adjusted mortality rates than women throughout the study duration (overall age-adjusted mortality rate men: 8.1 vs. women: 5.9). Non-Hispanic (NH) Black or African American individuals had the highest overall age-adjusted mortality rate (13.9), followed by non-Hispanic American Indian or Alaskan Native (13.7), Hispanic or Latino (10.3), non-Hispanic Asian or Pacific Islander (6.1), and non-Hispanic White (6.0). Age-adjusted mortality rate also varied by region (overall age-adjusted mortality rate: West:7.5; Midwest: 7.1; South: 6.8; Northeast: 5.8), and non metropolitan areas had higher overall age-adjusted mortality rate (7.5) than small/medium (7.2) and large metropolitan areas (6.4). CONCLUSION: After an initial decline, mortality rose across all the demographic groups from 2015 to 2020, revealing notable disparities in gender, race, and region.

Temporal Trends and Outcomes of Implantable Cardioverter Defibrillators in Heart Failure and Chronic Kidney Disease in the United States.

Chronic kidney disease (CKD) and hemodialysis increase the risk of sudden cardiac death (SCD) in heart failure (HF); however, national trends in utilization and outcomes of implantable cardioverter-defibrillator (ICD) in this population remain unknown. We sought to evaluate the utilization and outcomes of ICD therapy in HF patients with CKD and end-stage renal disease (ESRD) using the National Inpatient Sample from 2009 to 2018. Hospitalizations with a discharge diagnosis of systolic HF and ICD implantation were identified and stratified by stages of kidney disease. A total of 281,219 systolic HF hospitalizations who underwent ICD implantation were included. A significant decrease in inpatient ICD implantation was observed over the past decade (3.7% in 2009 to 1.1% in 2018) regardless of renal impairment. In-hospital mortality was highest in ESRD, followed by CKD compared with patients with no CKD. Length of hospital stay and hospitalization costs were also significantly higher in patients with CKD and ESRD. The overall utilization of inpatient ICD implantation has decreased in systolic HF patients and inpatient ICD placement in CKD is associated with an increased risk of mortality and adverse clinical outcomes. This indicates that patients with renal impairment and HF represent a sicker cohort than the general HF population.

Diagnosis, treatment, and management of pericardial effusion- review.

The hemodynamic stability of the heart and pericardium are maintained by the pericardial fluid of volume ∼10-50 ml. Pericardial effusion is associated with the abnormal accumulation of pericardial fluid in the pericardial cavity. Numerous imaging techniques are utilized to evaluate pericardial effusion including chest X-ray, electrocardiogram, transthoracic echocardiography, computed tomography scan, cardiac magnetic resonance imaging, and pericardiocentesis. Once diagnosed, there are numerous treatment options available for the management of patients with pericardial effusion. These include various invasive and non-invasive strategies such as pericardiocentesis, pericardial window, and sclerosing therapies. In recent times, few studies have been conducted to evaluate the safety and efficacy of each approach in routine clinical practice. In this review, we review the role of different modalities in the diagnosis of pericardial effusion while highlighting existing therapies aimed at the management and treatment of pericardial effusion.

Potential for sodium-glucose cotransporter-2 inhibitors in the management of metabolic syndrome: A systematic review and meta-analysis.

BACKGROUND: Landmark trials have established the benefits of sodium-glucose cotransporter-2 inhibitors (SGLT2-Is) in cardiovascular disease including heart failure with reduced and preserved ejection fraction and renal diseases regardless of the presence of diabetes mellitus. However, studies evaluating the role of SGLT2-Is in metabolic syndrome (MetS) are limited. AIM: This study primarily aimed to evaluate the impact of SGLT2-Is on the components of MetS. METHODS: Two independent reviewers and an experienced librarian searched Medline, Scopus and the Cochrane central from inception to December 9, 2021 to identify placebo controlled randomized controlled trials that evaluated the impact of SGLT2-Is on the components of MetS as an endpoint. Pre- and post-treatment data of each component were obtained. A meta-analysis was performed using the RevMan (version 5.3; Copenhagen: The Nordic Cochrane Center, The Cochrane Collaboration). RESULTS: Treatment with SGLT2-Is resulted in a decrease in fasting plasma glucose (-18.07 mg/dL; 95%CI: -25.32 to -10.82), systolic blood pressure (-1.37 mmHg; 95%CI: -2.08 to -0.65), and waist circumference (-1.28 cm; 95%CI: -1.39 to -1.18) compared to placebo. The impact on high-density lipoprotein cholesterol was similar to placebo (0.01 mg/dL; 95%CI: -0.05 to 0.07). CONCLUSION: SGLT2-Is have a promising role in the management of MetS.

Does individualized guided selection of antiplatelet therapy improve outcomes after percutaneous coronary intervention? A systematic review and meta-analysis.

Background: The potential benefits of individualized guided selection of antiplatelet therapy over standard antiplatelet therapy in improving outcomes in patients undergoing percutaneous coronary intervention (PCI) have not been established. Therefore, we pooled evidence from available clinical trials to assess the effectiveness by comparing the two regimens in patients undergoing PCI. Methods: We queried two electronic databases, MEDLINE and Cochrane CENTRAL, from their inception to April 20, 2021 for published randomized controlled trials in any language that compared guided antiplatelet therapy, using either genetic testing or platelet function testing, versus standard antiplatelet therapy in patients undergoing PCI. The results from trials were presented as risk ratios (RRs) with 95% confidence intervals (CIs) and were pooled using a random-effects model. Results: Eleven eligible studies consisting of 18,465 patients undergoing PCI were included. Pooled results indicated that guided antiplatelet therapy, compared to standard therapy, was associated with a significant reduction in the incidence of MACE [RR 0·78, 95% CI (0·62-0·99), P = 0·04], MI [RR 0·73, 95% CI (0·56-0.96), P = 0·03], ST [RR 0·66, 95% CI (0·47-0.94), P = 0·02], stroke [RR 0·71, 95% CI (0·50-1.00), P = 0·05], and minor bleeding [RR 0·78, 95% CI (0·66-0.91), P = 0·003]. Conclusions: Individualized guided selection of antiplatelet therapy significantly reduced the incidence of MACE, MI, ST, stroke, and minor bleeding in adult patients when compared with standard antiplatelet therapy. Our findings support the implementation of genetic and platelet function testing to select the most beneficial antiplatelet agent.

DOACs or VKAs or LMWH - What is the optimal regimen for cancer-associated venous thromboembolism? A systematic review and meta-analysis.

Background: Clinical guidelines have supported the use of direct anticoagulants (DOACs) for the treatment of cancer-associated venous thromboembolism (Ca-VTE). However, recent trials have reported increased bleeding risks associated with DOACs usage, raising concerns regarding its efficacy. Objectives: The authors conducted a meta-analysis to study the efficacy and safety of DOACs for the treatment of VTE in cancer patients, compared with Low-weight molecular heparin (LMWH) and Vitamin-K antagonists (VKAs). Methods: PubMed, EMBASE, Cochrane Library, Cochrane Central Register of Controlled Trials (CENTRAL) were searched according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines from inception to June 17th, 2021.The primary outcomes studied were VTE recurrence and major bleeding. Results: A total of 8 randomized controlled trials (RCTs) enrolling almost 7000 patients were included. Direct oral anticoagulants significantly reduced VTE Recurrence in cancer patients when compared to patients treated with LMWH or VKAs (Hazard ratio [HR] 0.62, 95% confidence interval [CI] 0.46-0.83; P = 0.002; I2 = 26%). There were no statistically significant differences for major bleeding (HR 0.86, 95% confidence interval [CI] 0.56-1.33; P = 0.50; I2 = 34%), clinically relevant non-major bleeding (HR 1.23, 95% confidence interval [CI] 0.79-1.91; P = 0.35; I2 = 66%), pulmonary embolism (HR 0.71, 95% confidence interval [CI] 0.47-1.06; P = 0.10; I2 = 7%), and all-cause mortality (HR 0.98, 95% confidence interval [CI] 0.86-1.12; P = 0.78; I2 = 1%), between DOACs and LMWH. Conclusion: This analysis shows that DOACs are the optimal regimen to treat Ca-VTE. They have a similar to slightly increased bleeding risk compared with LMWH and are a safer alternative to VKAs.

Efficacy of Sodium-Glucose Cotransporter-2 inhibitors in heart failure patients treated with dual angiotensin receptor blocker-neprilysin inhibitor: An updated meta-analysis.

BACKGROUND: Recent data suggest that the prevalence of heart failure has increased to approximately 23 million people globally. With increasing advancement in pharmacotherapeutics, Sodium-Glucose Cotransporter-2 inhibitors (SGLT2i) have garnered attention among clinicians to treat Heart failure with reduced ejection fraction (HFrEF) in diabetic as well as non-diabetic patients. METHODS: MEDLINE, Scopus, Embase and Cochrane CENTRAL database were searched using relevant keywords and MeSH terms. Studies were considered only if they were randomized in nature and had a sample size >1000 HF patients. RESULTS: Our comprehensive search strategy yielded 864 articles, of which three RCTs met the inclusion criteria with a total population of 9696. Pooled analysis revealed an association between the use of SGLT2i and decreased frequency of primary outcome irrespective of background ARNI use (HR 0.73, 95% CI [0.58-0.93], p = 0.0106; HR 0.73, 95% CI [0.66-0.81], p < 0.0001). CONCLUSION: This meta-analysis provides substantial evidence, to safely use SGLT2i atop ARNI therapy in select HF patients to further improve outcomes.

Effect of iron supplementation in patients with heart failure and iron deficiency: A systematic review and meta-analysis.

BACKGROUND: The effectiveness of oral and intravenous iron supplementation in reducing the risk of mortality and hospitalizations in HF patients with iron deficiency is not well-established. METHODS: A thorough literature search was conducted across 2 electronic databases (Medline and Cochrane Central) from inception through March 2021. RCTs assessing the impact of iron supplementation on clinical outcomes in iron deficient HF patients were considered for inclusion. Primary end-points included all-cause mortality and HF hospitalization. Evaluations were reported as odds ratios (ORs) or risk ratios (RRs) with 95% confidence intervals (CI) and analysis was performed using a random effects model. I2 index was used to assess heterogeneity. RESULTS: From the 2599 articles retrieved from initial search, 10 potentially relevant studies (n = 2187 patients) were included in the final analysis. Both oral (OR: 0.93; 95% CI: 0.08-11.30; p = 0.951) and intravenous (OR: 0.97; 95% CI: 0.73-1.29; p = 0.840) iron supplementation did not significantly reduce all-cause mortality. However, intravenous iron supplementation significantly decreased the rates of overall (OR: 0.52; 95% CI: 0.33-0.81; p = 0.004) and HF (OR: 0.42; 95% CI: 0.22-0.80; p = 0.009) hospitalizations. In addition, intravenous ferric carboxymaltose therapy significantly reduced the time to first HF hospitalization or cardiovascular mortality (RR = 0.70; 95% CI = 0.50-1.00; p = 0.048), but had no effect on time to first cardiovascular death (RR: 0.94; 95% CI: 0.70-1.25; p = 0.655). CONCLUSION: Oral or intravenous iron supplementation did not reduce mortality in iron deficient HF patients. However, intravenous iron supplementation was associated with a significant decrease in overall and HF hospitalizations.

Meta-analysis evaluating the impact of chili-pepper intake on all-cause and cardiovascular mortality: A systematic review.

BACKGROUND: Dietetics today occupy a significant place in the field of research, helping to discover cardiovascular benefits of healthy diets and consumption of organic foods such as fruits, vegetables, legumes, nuts, and whole grains. One of the components of vegetable-based diet is chili pepper (CP) which has been found to affect all-cause mortality. METHODS: MEDLINE, EMBASE, Scopus, EBSCO, and Cochrane (Wiley) Central Register of Controlled Trials were searched from inception till January 9, 2020, identifying all relevant studies using keywords and truncations. Studies were included if (1) they were observational or randomized in nature (2) included patients consuming CP and (3) evaluated direct comparison between regular and rarely/never CP consumption. RESULTS: Our preliminary search yielded 6976 articles. Post exclusion and after full-text screening, four potential observational studies with a population of 570,762. Pooled analysis found reduced all-cause mortality in CP consumers compared to nonconsumers with a risk ratio (RR) of 0.75 [95% CI: 0.64-0.88; p = 0.0004; I 2 = 97%]. The RR for CVD, cancer related and CVA deaths were 0.74 [95% CI: 0.62-0.88; p = 0.0006, I 2 = 66%], 0.77 [95% CI: 0.71-0.84; p = 0.0001; I 2 = 49%] and 0.76 [95% CI: 0.36-1.60; p = 0.47; I2 = 93%], respectively. CONCLUSION: Statistically significant results of our analysis put forward a rationale indicating an association between lower risk of all-cause, cardiovascular and cancer related deaths and CP consumption.

Characteristics of highly cited articles in heart failure: a bibliometric analysis.

Aim: Despite a vast array of research in heart failure (HF), no bibliometric analysis has been conducted for HF. Therefore, we sought to identify in-depth characteristics of 100 most cited publications in HF. Materials & methods: Two independent reviewers searched the Scopus Library Database using a variety of keywords to extract the top 100 articles. Results: Majority (36%) of top 100 cited articles were published between 2001 and 2005. The total number of citations ranged from 6294 to 1003. Females had less than a quarter representation in both first and senior author position. More than three-fourths (86%) of the articles were funded. Conclusion: Our analysis highlights focal areas of research activity in order to guide HF specialists toward impactful research areas.

How well do we represent ourselves: an analysis of cardiology fellowships website content.

Background: The Internet is the primary source of information for prospective cardiology fellowship aspirants. The objective of this study was to evaluate cardiology fellowship programs' online profile. Materials & methods: Two independent reviewers accessed 221 US based cardiology fellowship program websites obtained through Fellowship and Residency Electronic Interactive Database for pre-selected 20 criteria. The update status of websites was assessed using 6-point criteria. Results: Only 25 (11.3%) websites were fully up-to-date; 23 (10.4%) fulfilled 80% of the 20-point criteria and 85 (38.5%) program websites had fewer than 50% of the criteria listed. Conclusion: Most cardiology fellowship program websites lack crucial details. In this technology driven age, efforts should be made to ensure updated websites.

Outcomes Associated with Obesity in Patients Undergoing Left Ventricular Assist Device Implantation: A Systematic Review and Meta-Analysis.

Current data suggest that obesity does not impact survival, but may predispose patients to a higher rate of adverse events during left ventricular assist device (LVAD) support. We performed a systematic review and meta-analysis to assess the effects of obesity on clinical outcomes in LVAD recipients. We searched Medline, Scopus, Cochrane library, and clinicaltrials.gov from inception to February 2019 for studies comparing outcomes in obese (body mass index [BMI]> or ≥30 kg/m) and nonobese (BMI< or ≤30 kg/m) heart failure (HF) patients after LVAD implantation. Our primary endpoint was short-term (≤1 year) and long-term (>1 year) all-cause mortalities. The estimates are presented as random-effects risk ratios (RR) with 95% confidence intervals. In this meta-analysis of 15 observational studies (n = 26,842), obese patients receiving LVAD had significantly decreased 6 months (RR = 0.79 [0.73, 0.86]; p < 0.001, I = 0%) and 1 year all-cause mortality (RR = 0.87 [0.79, 0.97]; p = 0.008, I = 69%) compared with nonobese patients. However, both groups showed no significant difference in all-cause mortality at 2 years (RR = 0.95 [0.87, 1.04]; p = 0.12, I = 55%) or 3 years (RR = 0.84 [0.61, 1.15]; p = 0.28, I = 43%). Obese patients had significantly higher risk of device-related infections (RR = 1.48 [1.25, 1.75]; p < 0.001, I = 37%), right heart failure (RR = 1.41 [1.21, 1.65]; p < 0.001, I = 28%), and pump thrombosis (RR = 1.55 [1.37, 1.76]; p < 0.001, I = 0%) compared with nonobese patients. This meta-analysis suggests that obese patients with HF have short- but not long-term survival benefit after LVAD implantation when compared to nonobese patients, although bias may have impacted these findings.

Comments on "Reporting quality of randomized controlled trial abstracts in the seven highest-ranking anesthesiology journals".

Randomized controlled trials are considered the gold standard in assessing treatment regimens, and since abstracts may be the only part of a paper that a physician reads, accurate reporting of data in abstracts is essential. The CONSORT checklist for abstracts was designed to standardize data reporting; however, for papers submitted to anesthesiology journals, the level of adherence to the CONSORT checklist for abstracts is unknown. Therefore, we commend Janackovic and Puljak for their efforts in determining the adherence of reports of trials in the highest-impact anesthesiology journals between 2014 and 2016. The results of their study are extremely important; however, we believe that that study had some methodological limitations, which we discuss in this manuscript.

Meta-Analysis of the Effect of Preoperative Atrial Fibrillation on Outcomes After Left Ventricular Assist Device Implantation.

The effect of preoperative atrial fibrillation (AF) on clinical outcomes after left ventricular assist device (LVAD) implantation remains uncertain. We sought to conduct a meta-analysis to assess the safety and efficacy of LVAD implantation in AF patients. Medline and Scopus were searched for studies that assessed the effect of preoperative AF on clinical outcomes in patients who underwent LVAD implantation. Outcomes of interest included all-cause mortality, thromboembolic events, and bleeding. Estimates were combined using random effects model to calculate risk ratios (RRs) with 95% confidence intervals. In this meta-analysis of 7 studies including 5,658 patients, preoperative AF was not associated with increased risk of all-cause mortality at 30 days (RR = 0.84 [0.51, 1.37]; p = 0.49; I2 = 0%), 6 months (RR = 1.17 [0.96, 1.14]; p = 0.11; I2 = 21%), 1 year (RR = 1.16 [0.84, 1.60]; p = 0.37; I2 = 53%) and 2 years (RR = 1.14 [0.96, 1.36]; p = 0.12; I2 = 23%). Preoperative AF did not increase the risk of thromboembolism (RR = 0.86 [0.38, 1.92]; p = 0.71; I2 = 26%), pump thrombosis (RR = 1.22 [0.88, 1.68]; p = 0.23; I2 = 49%), stroke (RR = 1.02 [0.87, 1.19]; p = 0.79; I2 = 11%), or major bleeding (RR = 0.86 [0.38, 1.92]; p = 0.71; I2 = 26%) after LVAD implantation. However, AF was associated with significantly increased risk of gastro-intestinal bleeding in patients receiving LVADs (RR = 1.27 [1.05, 1.55]; p = 0.014; I2 = 0%). In conclusion, this meta-analysis reports a significantly increased risk of gastrointestinal (GI) bleeding in LVADs recipients having concomitant AF. However, AF had no significant effect on all-cause mortality, stroke, or thromboembolic events in these patients. Further well-conducted studies are needed to validate these results.

Prasugrel vs. Ticagrelor for Acute Coronary Syndrome Patients Undergoing Percutaneous Coronary Intervention: A Systematic Review and Meta-Analysis.

BACKGROUND: The newer P2Y12 inhibitors have better efficacy than clopidogrel. However, whether ticagrelor or prasugrel have a better comparative safety and efficacy profile, especially in the long-term, remains inconclusive. OBJECTIVE: We compared prasugrel and ticagrelor in patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI). METHODS: MEDLINE and the Cochrane library were queried for randomized controlled trials (RCTs) or observational studies comparing prasugrel with ticagrelor in patients with ACS undergoing PCI. Random-effects pooling was used to calculate odds ratios (ORs) with 95% confidence intervals (CI). Analyses were stratified by duration of follow-up (short term [≤ 3 months] and long term [≥ 1 year]) and study design. RESULTS: In total, 14 studies (six RCTs, eight observational studies), including 40,188 patients, met eligibility criteria. Pooled analysis did not indicate that prasugrel significantly decreased all-cause mortality compared with ticagrelor in the short term (OR 0.49; 95% CI 0.20-1.20; p = 0.11) or long term (OR 0.74; 95% CI 0.48-1.15; p = 0.38). Pooled observational studies showed significantly lower long-term all-cause mortality (OR 0.63; 95% CI 0.43-0.92; p = 0.02) and short-term stent thrombosis (OR 0.46; 95% CI 0.28-0.75; p = 0.002) with prasugrel. No significant difference was observed in the risk of nonfatal myocardial infarction, ischemic stroke, bleeding, or repeat revascularization between the two groups. Results remained similar after stratification according to follow-up and study design. CONCLUSIONS: The present analysis suggests that prasugrel might have a better efficacy profile than ticagrelor in patients with ACS undergoing PCI. However, this advantage was only seen in pooled observational studies and is likely to be affected by selection bias.

Use of Balloon Atrial Septostomy in Patients With Advanced Pulmonary Arterial Hypertension: A Systematic Review and Meta-Analysis.

BACKGROUND: Despite the use and purported benefits of balloon atrial septostomy (BAS), its safety, efficacy, and therapeutic role in the setting of advanced pulmonary arterial hypertension (PAH) are not well defined. OBJECTIVE: The goal of this study was to conduct a systematic review and meta-analysis to better determine the evidence supporting the use of BAS in PAH. METHODS: MEDLINE, Scopus, Cochrane Library, and Clinicaltrials.gov were searched from inception through May 2018 for original studies reporting outcomes with PAH prior to and following BAS. Studies comparing BAS vs other septostomy procedures were excluded. Weighted mean differences and 95% CIs were pooled by using a random effects model. RESULTS: Sixteen studies comprising 204 patients (mean age, 35.8 years; 73.1% women) were included. Meta-analysis revealed significant reductions in right atrial pressure (-2.77 mm Hg [95% CI, -3.50, -2.04]; P < .001) and increases in cardiac index (0.62 L/min/m2 [95% CI, 0.48, 0.75]; P < .001) and left atrial pressure (1.86 mm Hg [95% CI, 1.24, 2.49]; P < .001) following BAS, along with a significant reduction in arterial oxygen saturation (-8.45% [95% CI, -9.93, -6.97]; P < .001). The pooled incidence of procedure-related (48 h), short-term (≤ 30 day), and long-term (> 30 days up to a mean follow-up of 46.5 months) mortality was 4.8% (95% CI, 1.7%, 9.0%), 14.6% (95% CI, 8.6%, 21.5%), and 37.7% (95% CI, 27.9%, 47.9%), respectively. CONCLUSIONS: The present analysis suggests that BAS is relatively safe in advanced PAH, with beneficial hemodynamic effects. The relatively high postprocedural and short-term survival with less impressive long-term survival suggest a bridging role for BAS; its contribution to this change needs to be verified by using a comparator group.

Fragility Index in Cardiovascular Randomized Controlled Trials.

BACKGROUND: Efficacy of an intervention is commonly evaluated using P values, in addition to effect size measures such as absolute risk reduction, relative risk reduction, and numbers needed to treat. However, these measures are not always intuitive to clinicians. The fragility index (FI) is a more intuitive number that can facilitate interpretation but can only be used with binary outcomes. FI is the minimum number of patients who must be moved from the nonevent group to the event group to turn a significant result nonsignificant. In this retrospective analysis, we assessed the robustness of cardiovascular randomized controlled trials (RCTs), which report a positive (statistically significant) primary outcome by using the FI. METHODS AND RESULTS: We searched Medline from 2007 to 2017 to identify cardiovascular RCTs published in 6 high impact journals (The Lancet, New England Journal of Medicine, Journal of the American Medical Association, Circulation, Journal of the American College of Cardiology and European Heart Journal). Only RCTs with sample sizes >500 and a 2-by-2 factorial design or dichotomous primary outcomes were selected. FI was calculated using a defined approach. Among the cohort of 123 RCTs that met inclusion criteria, median FI was 13 (interquartile range, 5-26). In 28 trials (22.8%), FI ranged between 1 and 4. In 37 trials (30.1%), number of patients lost to follow-up was higher than the FI. Pharmaceutical interventions had higher FI compared with other interventions, FI=19 (7-52; P=0.002). Median FI varied according to subspecialty (electrophysiology=2; heart failure=11; interventional cardiology=8; P=0.020) and multiregional RCTs had higher FI=22 (12-53.25; P=0.023). FI did not differ based on risk of bias indicators, funding, or publication year. CONCLUSIONS: Considerable variations in FI were observed among cardiovascular trials, suggesting the need for careful interpretation of results, particularly when number of patients lost to follow-up exceeds FI.