Preparation of small bowel capsule endoscopy (SBCE) with simethicone: A meta-analysis

BackgroundIt is disputed about optimal bowel preparation for small bowel capsule endoscopy (SBCE). This meta-analysis aimed to investigate the role of simethicone in intestinal preparation for SBCE.MethodsWe searched four databases (PubMed, web of science, Embase, and Scopus databases) for relevant studies. Studies evaluating the effect of simethicone as an adjunct to SBCE bowel preparation were included. The random-effects model was applied to calculate the risk estimates. Primary outcomes include the degree of gas bubbles and small bowel visualization quality (SBVQ). Secondary outcomes include diagnostic yield (DY), gastric transit time (GTT), small bowel transit time (SBTT), and completion rate (CR).ResultsA total of 10 studies were included (8 RCTs, 1 prospective, and 1 retrospective study). Compared with the control group, the simethicone group showed significant improvements in the degree of gas bubbling (RR = 2.05, 95%CI:1.56-2.71, P < 0.001, I² = 62%) and SBVQ (RR = 1.41, 95%CI: 1.20-1.65, P < 0.001, I² = 16%). Subgroup analysis showed that the SBVQ of simethicone group was better than fasting (RR = 2.62, 95% CI:1.49–4.59, P < 0.001, I² = 0%), mannitol (RR = 1.35, 95% CI: 1.14-1.59, P < 0.001, I² = 0%) and PEG group (RR = 1.32, 95%CI:1.06-1.65, P = 0.01, I² = 0%). No significant associations were found for DY, GTT, SBTT, and CR.ConclusionsSimethicone for bowel preparation is useful to improve visualization and reduce the gas bubbling of SBCE.     

Impact of semaglutide on biochemical and radiologic measures of metabolic-dysfunction associated fatty liver disease across the spectrum of glycaemia: A meta-analysis

Background and aimsNo meta-analysis has analysed efficacy and safety of semaglutide in metabolic-dysfunction associated fatty-liver disease (MAFLD).MethodsElectronic databases were searched for RCTs involving people with MAFLD and/or type-2 diabetes (T2DM) receiving semaglutide. Primary outcome was to evaluate changes in alanine aminotransferase (ALT). Secondary outcomes were to evaluate alterations in other measures of NAFLD, glycaemia, lipids and adverse-events.ResultsData from 4 RCTs (2115 patients) was analysed. A greater lowering with injectable semaglutide 0.4mg/0.5 mg once weekly was seen with regards to ALT [MD -3.89U/L (95%CI: ?5.41 to ?2.36); P < 0.01; I² = 0%; 2050 patients], liver stiffness (fibroscan®) [MD -3.19 kPa (95%CI: ?3.26 to ?3.12); P < 0.01; 162 patients], steatosis [MD -13.40 dB/m (95%CI: 20.56 to ?6.24); P < 0.01; 162 patients], triglycerides [MD -21.43 mg/dl (95% CI: 41.63 to ?1.23); P = 0.04; I² = 99%; 2050 patients], total cholesterol [MD -5.53 mg/dl (95% CI: ?8.45 to ?2.61); P < 0.01; I² = 0%; 1888 patients], LDL-cholesterol [MD -3.55 mg/dl (95% CI: ?5.87 to ?1.23); P < 0.01; I² = 0%; 1888 patients], percent-weight [MD -8.99% (95%CI: ?14.64 to ?3.34); P = 0.002; I² = 100%; 2115 patient] and HbA1c [MD -0.77% (95%CI: 1.10 to ?0.45); P = 0.002; I² = 100%; 2115 patients]. Number of patients inadequate to comment on histopathologic measures of MAFLD. Occurrence of treatment-emergent adverse-events [RR 2.31 (95% CI: 0.76–7.06); P = 0.14; I² = 82%] and severe adverse events [RR 1.07 (95%CI: 0.69–1.65); P = 0.77; I² = 33%] were comparable. Adverse-events leading to trial discontinuation [RR 2.37 (95% CI: 1.33–4.22); P = 0.003; I² = 24%], diarrhea [RR 2.05 (95%CI: 1.17–3.60); P = 0.01; I² = 66%], nausea [RR 4.98 (95%CI: 3.23–7.67); P < 0.001; I² = 0%] and vomiting [RR 3.90 (95%CI: 1.75–8.68); P < 0.01; I² = 54%] were higher with semaglutide.ConclusionThis meta-analysis provides reassuring data on efficacy of low dose semaglutide injections in improving ALT and certain radiologic features in MAFLD. Current conclusions are limited by small number of patients evaluated. Urgent need remains for larger studies focussing on liver biopsy.     

Microalbuminuria and mortality in individuals with coronary heart disease: A meta-analysis of a prospective study

AimMicroalbuminuria has been elevated as an outcome predictor in cardiovascular medicine. However, due to the small number of studies investigating the association of microalbuminuria and mortality in the coronary heart disease (CHD) population, the prognosis value of microalbuminuria in CHD remains under debate. The objective of this meta-analysis was to investigate the relationship between microalbuminuria and mortality in individuals with CHD.MethodA comprehensive literature search was performed using Pubmed, EuroPMC, Science Direct, and Google Scholar from 2000 to September 2022. Only prospective studies investigating microalbuminuria and mortality in CHD patients were selected. The pooled effect estimate was reported as risk ratio (RR).Results5176 patients from eight prospective observational studies were included in this meta-analysis. Individuals with CHD have a greater overall risk of all-cause mortality (ACM) [rR = 2.07 (95% CI = 1.70–2.44); p = 0.0003; I² = 0.0%] as well as cardiovascular mortality (CVM) [rR = 3.23 (95% CI = 2.06–4.39), p < 0.0001; I² = 0.0%]. Subgroup analysis based on follow-up duration and a subset of CHD patients were similarly associated with an increased risk of ACM.ConclusionThis meta-analysis indicates that microalbuminuria is associated with a higher risk of mortality in individuals with CHD. Microalbuminuria can serve as a predictor of poor outcomes in CHD patients.     

Efficacy and safety of novel dual glucokinase activator dorzagliatin in type-2 diabetes A meta-analysis

Background & aimsGlucokinase has a critical role in regulating glucose homeostasis in humans, and has been a target for diabetes drug development since 1990s. Dorzagliatin is a novel allosteric dual glucokinase activator targeting both pancreatic and hepatic glucokinase. No meta-analysis has analysed the efficacy and safety of dorzagliatin in type-2 diabetes (T2DM). We undertook this meta-analysis to address this knowledge-gap.MethodsElectronic databases were searched for RCTs involving T2DM patients receiving dorzagliatin in intervention arm, and placebo/active comparator in control arm. Primary outcome was to evaluate changes in HbA1c. Secondary outcomes were to evaluate alterations in blood glucose parameters, lipids, insulin-resistance and adverse events.ResultsFrom initially screened 17 articles, data from 3 RCTs (1333 patients) was analysed. Over 12–24 weeks use, dorzagliatin had significantly higher lowering of HbA1c [MD -0.66% (95%CI: ?0.74 to ?0.59); P < 0.01; I² = 99%], fasting glucose [MD -32.03 mg/dl (95%CI: 45.12 to ?18.94); P < 0.01; I² = 100%], 2-h post-prandial glucose [MD -43.49 mg/dl (95%CI: ?46.26 to ?40.72); P < 0.01; I² = 90%] along with greater number of patients achieving HbA1c<7% [OR 6.01 (95% CI: 2.50–14.46); P < 0.01; I² = 83%], as compared to placebo. Dorzagliatin was associated with significant elevation of triglycerides [MD 0.43 mmol/L (95%CI:0.30–0.56); P < 0.01; I² = 0%], greater occurrence of hyperlipidaemia [RR 1.52 (95% CI:1.05–2.18); P = 0.03; I² = 0%], and increase in body-weight [MD 0.40 kg (95%CI:0.06–0.75); P = 0.03; I² = 0%], compared to placebo. The occurrence of total-adverse-events [RR 1.43 (95%CI:1.11–1.83); P < 0.01; I² = 0%] but not severe adverse-events [RR 0.92 (95%CI:0.54–1.57); P = 0.76; I² = 0%] was significantly higher with dorzagliatin.ConclusionDorzagliatin has good glycaemic efficacy and well tolerated over 6-months use. Mild increase in body-weight, serum triglycerides and overall adverse events remain issues of concern warranting further evaluation in longer clinical trials with active controls.     

Efficacy and safety of long-acting growth hormone in adult growth hormone deficiency: A systematic review and meta-analysis

Background & aimsNo meta-analysis has analysed efficacy and safety of long-acting growth hormone (GH) therapy in adult GH deficiency. We undertook this meta-analysis to address this gap in knowledgeMethodsElectronic databases were searched for RCTs involving adult GH deficiency patients receiving weekly long-acting GH as compared to daily GH/placebo controls. Primary outcome was to evaluate changes in body-composition parameters. Secondary outcomes were to evaluate alterations in glycaemia and adverse-events.ResultsData from 5 studies involving 648 patients were analysed (4 studies having daily GH as active controls; 1 study having placebo as passive controls). Over 24–34 weeks clinical use, patients receiving long-acting GH had comparable change in lean mass [MD-0.28 kg (95%CI: 0.94 – 0.38); P = 0.41; I² = 29% (low heterogeneity)] and fat mass [MD-0.10 kg (95%CI: 1.97–1.78); P = 0.92; I² = 77%(considerable heterogeneity)] as compared to daily GH injections. Long-acting GH use was associated with significantly lower visceral adipose tissue [MD-1.75 cm²(95%CI: 2.14 to ?1.35); P < 0.01; I² = 0% (low heterogeneity)] and higher gynoid fat-mass [MD 0.14 kg(95%CI:0.02–0.26); P = 0.03] compared to daily GH injections. Total adverse events [Risk ratio (RR) 1.65 (95% CI: 0.83–3.29); P = 0.15; I² = 68%] and severe adverse events [RR 0.60 (95% CI: 0.30–1.19); P = 0.14; I² = 0%] were not significantly different in long-acting GH group compared to controls. Occurrence of headache, arthralgia, nasopharyngitis, new onset diabetes, anti-GH antibodies were comparable among groups. Long-acting GH users had significantly higher treatment adherence compared to controls [OR 4.80 (95%CI:3.58–6.02); P < 0.01; I² = 0%].ConclusionLong-acting GH has comparable beneficial impact on body composition parameters in adult GH deficiency, is well tolerated without any increased adverse events.     

Efficacy and safety of novel thiazolidinedione lobeglitazone for managing type-2 diabetes a meta-analysis

Background and aimsNo meta-analysis has analysed the safety and efficacy of lobeglitazone in type-2 diabetes (T2DM). We undertook this meta-analysis to address this knowledge-gap.MethodsElectronic databases were searched for RCTs involving type-2 diabetes patients receiving lobeglitazone in intervention arm, and placebo/active comparator in control arm. Primary outcome was to evaluate changes in HbA1c. Secondary outcomes were to evaluate alterations in glucose, lipids and adverse events.ResultsFrom initially screened 65 articles, data from 4 RCTs (828 patients) which fulfilled all criteria was analysed. Over 24 weeks, when compared to sitagliptin 100 mg/d and half maximal pioglitazone dose (15 mg/d), lobeglitazone 0.5 mg/day had comparable impact on HbA1c [MD 0.03% (95%CI: 0.11–0.17); P = 0.65; I² = 0%], fasting glucose [MD 1.47 mg/dl (95%CI: 4.66–7.60); P = 0.64; I² = 0%], triglycerides [MD-9.96 mg/dl (95%CI: 43.55–23.62); P = 0.56; I² = 81%], LDL-cholesterol [MD0.74 mg/dl (95%CI: 4.60–6.09); P = 0.79; I² = 0%] and HDL-cholesterol [MD1.55 mg/dl (95%CI: 3.72–6.82); P = 0.56]. Occurrence of treatment-emergent adverse events (AEs) [RR 1.07 (95% CI:0.78–1.47); P = 0.67; I² = 0%] and severe AEs [RR 1.05(95%CI: 0.42–2.65); P = 0.91; I² = 0%] were similar. Edema and weight gain were significantly higher with lobeglitazone compared to controls [RR 2.58 (95%CI: 1.08–6.17); P = 0.03; I² = 0%]. Lobeglitazone 0.5 mg/d compared to half-maximal pioglitazone (15 mg/d), had similar edema and weight gain [RR 1.65 95% CI: 0.78–1.47)]. BMD percent changes at neck of femur was comparable in both groups [MD 0.07% (95%CI: 0.19–0.33); P = 0.60; I² = 91%]. Low dose lobeglitazone (0.25 mg/d) was inferior to high dose lobeglitazone (0.5 mg/d) with regards to glycaemic efficacy with advantage of lower weight gain and edema.ConclusionThe current evidence makes lobeglitazone unlikely to replace pioglitazone as the preferred thiazolidinedione in T2DM.     

Non-traditional lipid profiles and the risk of stroke: A systematic review and meta-analysis

AimsAn increasing number of studies on non-traditional lipid profiles have been investigated in recent years. However, the associations between non-traditional lipid profiles and the risk of stroke remained inconsistent. Therefore, this meta-analysis aimed to evaluate the associations between non-traditional lipid profiles and the risk of stroke and clarify the dose–response relations.Data synthesisWe performed a systematic literature search in PubMed, Embase, and Web of Science databases until 1 November 2022 for relevant studies. Relative risks and 95% confidence intervals were pooled by random-effects or fixed-effects models. A total of 26 full-text studies with 676678 participants and 18057 stroke cases were eligible for the final study. We found a positive association between the risk of stroke and total cholesterol to high-density lipoprotein cholesterol (TC/HDL-C) ratio (RR = 1.19,95%CI = 1.00–1.40, I² = 74.6%), triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) ratio (RR = 1.24,95%CI = 1.10–1.41, I² = 62.8%) or low-density lipoprotein cholesterol to high-density lipoprotein cholesterol (LDL-C/HDL-C) ratio (RR = 1.24, 95%CI = 1.11–1.39, I² = 49.4%). When focusing on the stroke subtype, a more significant association was observed between the risk of ischemic stroke and four non-traditional lipid profiles. In dose–response analysis, we found a linear association between TC/HDL-C ratio and the risk of stroke (RR = 1.16,95%CI = 1.07–1.26).ConclusionsElevated non-traditional lipid profiles were associated with an increased risk of ischemic stroke. The linear association showed the risk of stroke increased by 16% when the pooled RR of TC/HDL-C ratio per 1-unit increased.Registration number in prosperoCRD42022321251.     

Prasugrel vs Ticagrelor for DAPT in Patients with ACS Undergoing PCI: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

IntroductionDual antiplatelet therapy (DAPT) with a P2Y12 inhibitor added to aspirin is considered the standard of care for patients with acute coronary syndrome (ACS) undergoing percutaneous intervention (PCI). Prasugrel and ticagrelor are commonly used P2Y12 inhibitors, and a few head-to-head randomized control trials (RCTs) have been performed. We performed a systematic review and meta-analysis of these RCTs to compare the efficacy and adverse effects between these two agents when used in patients with ACS undergoing PCI.MethodsWe searched PubMed/MEDLINE and Cochrane library for RCTs comparing prasugrel to ticagrelor in ACS. The primary endpoint was major adverse cardiovascular events (MACE). Secondary outcomes were all-cause mortality, cardiovascular mortality, myocardial infarction (MI), stent thrombosis, major bleeding, and all bleeding event. Estimates were calculated as random effects risk ratios (RRs) with 95% confidence intervals (CI).ResultsSix trials with 6807 patients were included. There were no significant difference of MACE (RR 0.93; 95% CI [0.72–1.20]; p = 0.59; I² = 26%), all-cause mortality (RR 0.92; 95% CI [0.73–1.17]; p = 0.51; I² = 0%), cardiovascular mortality (RR 0.99; 95% CI [0.75–1.31]; p = 0.96; I² = 0%), MI (RR 0.87; 95% CI [0.60–1.27]; p = 0.48; I² = 27%), stent thrombosis (RR 0.64; 95% CI [0.39–1.04]; p = 0.07; I² = 0%), major bleeding (RR 0.94; 95% CI [0.70–1.26]; p = 0.68; I² = 6%), and all bleeding event (RR 0.92; 95% CI [0.77–1.09]; p = 0.32; I² = 0%) for prasugrel compared with ticagrelor.ConclusionThere are no significant difference of MACE, all-cause mortality, cardiovascular mortality, MI, stent thrombosis, and bleeding between prasugrel and ticagrelor when added to aspirin among patients with ACS undergoing PCI.     

Hyperlipasemia in absence of acute pancreatitis is associated with elevated D-dimer and adverse outcomes in COVID 19 disease

BackgroundCoronavirus SARS-CoV-2 affects multiple organs. Studies have reported mild elevations of lipase levels of unclear significance. Our study aims to determine the outcomes in patients with COVID-19 and hyperlipasemia, and whether correlation with D-dimer levels explains the effect on outcomes.MethodsCase-control study from two large tertiary care health systems, of patients with COVID-19 disease admitted between March 1 and May 1, 2020 who had lipase levels recorded. Data analyzed to study primary outcomes of mortality, length of stay (LOS) and intensive care utilization in hyperlipasemia patients, and correlation with D-dimer and outcomes.Results992 out of 5597 COVID-19 patients had lipase levels, of which 429 (43%) had hyperlipasemia. 152 (15%) patients had a lipase > 3x ULN, with clinical pancreatitis in 2 patients. Hyperlipasemia had a higher mortality than normal lipase patients (32% vs. 23%, OR = 1.6,95%CI = 1.2–2.1, P = 0.002). In subgroup analysis, hyperlipasemia patients had significantly worse LOS (11vs.15 days, P = 0.01), ICU admission rates (44% vs. 66%,OR = 2.5,95%CI = 1.3–5.0,P = 0.008), ICU LOS (12vs.19 days,P = 0.01), mechanical ventilation rates (34% vs. 55%,OR = 2.4,95%CI = 1.3–4.8,P = 0.01), and durations of mechanical ventilation (14 vs. 21 days, P = 0.008). Hyperlipasemia patients were more likely to have a D-dimer value in the highest two quartiles, and had increased mortality (59% vs. 15%,OR = 7.2,95%CI = 4.5–11,P < 0.001) and LOS (10vs.7 days,P < 0.001) compared to those with normal lipase and lower D-dimer levels.ConclusionThere is high prevalence of hyperlipasemia without clinical pancreatitis in COVID-19 disease. Hyperlipasemia was associated with higher mortality and ICU utilization, possibly explained by elevated D-dimer.     

Cardiac Radiation Dose,Cardiac Disease,and Mortality in Patients With Lung Cancer

BackgroundRadiotherapy-associated cardiac toxicity studies in patients with locally advanced non–small cell lung cancer (NSCLC) have been limited by small sample size and nonvalidated cardiac endpoints.ObjectivesThe purpose of this analysis was to ascertain whether cardiac radiation dose is a predictor of major adverse cardiac events (MACE) and all-cause mortality (ACM).MethodsThis retrospective analysis included 748 consecutive locally advanced NSCLC patients treated with thoracic radiotherapy. Fine and Gray and Cox regressions were used to identify predictors for MACE and ACM, adjusting for lung cancer and cardiovascular prognostic factors, including pre-existing coronary heart disease (CHD).ResultsAfter a median follow-up of 20.4 months, 77 patients developed ≥1 MACE (2-year cumulative incidence, 5.8%; 95% confidence interval [CI]: 4.3% to 7.7%), and 533 died. Mean radiation dose delivered to the heart (mean heart dose) was associated with a significantly increased risk of MACE (adjusted hazard ratio [HR]: 1.05/Gy; 95% CI: 1.02 to 1.08/Gy; p < 0.001) and ACM (adjusted HR: 1.02/Gy; 95% CI: 1.00 to 1.03/Gy; p = 0.007). Mean heart dose (≥10 Gy vs. <10 Gy) was associated with a significantly increased risk of ACM in CHD-negative patients (178 vs. 118 deaths; HR: 1.34; 95% CI: 1.06 to 1.69; p = 0.014) with 2-year estimates of 52.2% (95% CI: 46.1% to 58.5%) versus 40.0% (95% CI: 33.5% to 47.4%); but not among CHD-positive patients (112 vs. 82 deaths; HR: 0.94; 95% CI: 0.70 to 1.25; p = 0.66) with 2-year estimates of 54.6% (95% CI: 46.8% to 62.7%) versus 50.8% (95% CI: 41.5% to 60.9%), respectively (p for interaction = 0.028).ConclusionsDespite the competing risk of cancer-specific death in locally advanced NSCLC patients, cardiac radiation dose exposure is a modifiable cardiac risk factor for MACE and ACM, supporting the need for early recognition and treatment of cardiovascular events and more stringent avoidance of high cardiac radiotherapy dose.     

Radial vs. Femoral Access for Percutaneous Coronary Artery Intervention in Patients With ST-Elevation Myocardial Infarction

BackgroundWe aimed to compare the safety and efficacy of transradial vs transfemoral access for coronary angiography and intervention in patients presenting with ST-segment elevation myocardial infarction (STEMI) without cardiogenic shock.MethodsPubMed, Embase and Cochrane Central were searched for randomized controlled trials (RCTs) comparing outcomes of STEMI patients who underwent transradial angiography (TRA) compared to transfemoral angiography (TFA). Our outcomes of interest were major adverse cardiac events (MACE), all-cause mortality, severe bleeding, access site bleeding, myocardial infarction, stroke, and major vascular complications. Summary statistics are reported as odds ratios (OR) with 95% confidence intervals (CI).ResultsIn a pooled analysis of 17 RCTs with 12,118 randomized patients, the use of transradial compared to transfemoral approach in STEMI patients without cardiogenic shock was associated with a significant reduction in MACE [OR 0.85 (95% CI 0.73–0.99; p = 0.04; NNT = 111; I² = 0%)] and all-cause mortality [OR 0.71 (95% CI 0.57–0.88; p < 0.01; NNT = 111; I² = 0%)]. Severe bleeding [OR 0.57 (95% CI 0.44–0.74; p < 0.01; NNT = 77; I² = 0%)], access-site bleeding [OR 0.39 (95% CI 0.26–0.59; p < 0.01; NNT = 67; I² = 24%)], and major vascular complications [OR of 0.31 (95% CI 0.17–0.55; p < 0.01; NNT = 125; I² = 0%)] were lower in TRA compared to TFA. There was no difference in stroke (0.6% vs 0.5%) or recurrent myocardial infarction (2.01% vs 2.02%) between the two approaches.ConclusionsFor coronary intervention in STEMI patients without cardiogenic shock, there is a clear mortality benefit with the TRA over TFA. Further studies are needed to see if this mortality benefit persists over the long-term.     

Safety of coffee consumption after myocardial infarction: A systematic review and meta-analysis

Background and aimsThis systematic review aims to evaluate the impact of coffee consumption in patients with previous myocardial infarction (MI), in relation to all-cause and cardiovascular mortality, as well as other major cardiovascular events (MACE) such as stroke, heart failure, recurrent MI and sudden death.Methods and resultsMEDLINE, Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science Core Collection, SciELO Citation Database, Current Contents Connect®, KCI Korean Journal Database, African Index Medicus, and LILACS were searched for longitudinal studies evaluating the impact of coffee consumption in patients with previous myocardial infarction. We performed a random-effects meta-analysis to estimate the pooled hazard ratios (HR) with 95% confidence intervals (CI). The statistical heterogeneity was measured by I². A dose–response analysis was also conducted.Six prospective cohort studies were included in the primary meta-analysis. Consumption of coffee was associated with lower risk of cardiovascular mortality (HR = 0.70; 95% CI 0.54–0.91, I² = 0%; 2 studies) and was not associated with an increased risk of all-cause mortality (HR = 0.85; 95% CI 0.63–1.13; I² = 50%; 3 studies), recurrent MI (HR = 0.99; 95% CI 0.80–1.22; I² = 0%; 3 studies), stroke (HR = 0.97; 95% CI 0.63–1.49; I² = 39%; 2 studies) and MACE (HR = 0.96; 95% CI 0.86–1.07; I² = 0%; 2 studies). A significant non-linear inverse dose–response association was found for coffee consumption and all-cause mortality.ConclusionsConsumption of coffee was not associated with an increased risk of all-cause mortality and cardiovascular events in patients with previous myocardial infarction.     

Efficacy and safety of novel sodium glucose cotransporter-2 inhibitor remogliflozin in the management of type 2 diabetes mellitus: A systematic review and meta-analysis

Background and aimsNo meta-analysis has analysed efficacy and safety of remogliflozin. We undertook this meta-analysis to address this gap in knowledgeMethodsElectronic databases were searched for RCTs involving diabetes patients receiving remogliflozin as compared to controls. Primary outcome was to evaluate changes in HbA1c. Secondary outcomes were to evaluate alterations in glycaemia, lipids and adverse events.ResultsData from 3 RCTs involving 535 patients was analysed [2 having pioglitazone and 1 having dapagliflozin as active comparator]. Over 12–24 weeks use, Hba1c [mean difference (MD) −0.13% (95% CI: 0.35 – 0.09%); P = 0.24; I² = 99%] and fasting glucose [MD 3.67 mg/dl (95% CI: 0.53 – 7.88 mg/dl); P = 0.09; I² = 52%]. reduction with remogliflozin was not significantly different from controls. Remogliflozin was inferior to dapagliflozin with regards to reduction in post-prandial glucose [MD+12.17 mg/dl (95%CI:10.79–13.55 mg/dl); P < 0.001].Remogliflozin use was associated with a significantly greater decline in body weight [MD -2.79 kg (95% CI: 3.07 to −2.51 kg); P < 0.001; I² = 30%]. Total adverse events [Risk ratio (RR) 1.21 (95% CI: 0.62–2.64); P = 0.58; I² = 59%] were comparable among groups.ConclusionRemogliflozin had HbA1c and fasting glucose reduction comparable to pioglitazone and dapagliflozin. The paradox with regard to post-prandial glucose reduction needs further evaluation. The current analysis is limited by considerable data heterogeneity and low certainty of evidence for most primary and secondary outcomes. There remains urgent need for high quality RCTs evaluating long-term outcomes with remogliflozin.     

Impact of obesity on adverse in-hospital outcomes in patients undergoing percutaneous mitral valve edge-to-edge repair using MitraClip® procedure - Results from the German nationwide inpatient sample

Background and aimThe number of percutaneous edge-to-edge mitral regurgitation (MR) valve repairs with MitraClip® implantations increased exponentially in recent years. Studies have suggested an obesity survival paradox in patients with cardiovascular diseases. We investigated the influence of obesity on adverse in-hospital outcomes in patients with MitraClip® implantation.Methods and resultsWe analyzed data on characteristics of patients and in-hospital outcomes for all percutaneous mitral valve repairs using the edge-to-edge MitraClip®-technique in Germany 2011–2015 stratified for obesity vs. normal-weight/over-weight.The nationwide inpatient sample comprised 13,563 inpatients undergoing MitraClip® implantations. Among them, 1017 (7.5%) patients were coded with obesity. Obese patients were younger (75 vs.77 years,P < 0.001), more often female (45.4% vs.39.5%,P < 0.001), had more often heart failure (87.1% vs.79.2%,P < 0.001) and renal insufficiency (67.0% vs.56.4%,P < 0.001). Obese and non-obese patients were comparable regarding major adverse cardiac and cerebrovascular events (MACCE) and in-hospital death. The combined endpoint of cardio-pulmonary resuscitation (CPR), mechanical ventilation and death was more often reached in non-obese than in obese patients with a trend towards significance (20.6%vs.18.2%,P = 0.066). Obesity was an independent predictor of reduced events regarding the combined endpoint of CPR, mechanical ventilation and death (OR 0.75, 95%CI 0.64–0.89,P < 0.001), but not for reduced in-hospital mortality (P = 0.355) or reduced MACCE rate (P = 0.108). Obesity class III was associated with an elevated risk for pulmonary embolism (OR 5.66, 95%CI 1.35–23.77,P = 0.018).ConclusionsWe observed an obesity paradox regarding the combined endpoint of CPR, mechanical ventilation and in-hospital death in patients undergoing MitraClip® implantation, but our results failed to confirm an impact of obesity on in-hospital survival or MACCE.     

Safety and efficacy of once weekly dipeptidyl-peptidase-4 inhibitor trelagliptin in type-2 diabetes: A meta-analysis

Background & aimsPooled systematic analysis of safety and efficacy data of trelagliptin in type-2 diabetes (T2DM) is lacking. We undertook this meta-analysis to address this issue.MethodsElectronic databases were searched for RCTs involving people with T2DM receiving trelagliptin in study arm, and placebo/active comparator in control arm. Primary outcome was to evaluate changes in HbA1c. Secondary outcomes were to evaluate alterations in pre and post-meal glucose levels, glycaemic targets, lipid parameters and adverse events.ResultsFrom initially screened 63 articles, data from 6 RCTs involving 981 patients was analysed [3 in active control group (ACG) defined as having alogliptin, sitagliptin, linagliptin, teneligliptin, anagliptin or vildagliptin as active comparator; 2 in passive control group (PCG) defined as having placebo as controls; 1 study had both ACG and PCG]. HbA1c reduction by trelagliptin was comparable to ACG [MD 0.06% (95% CI: ?0.03 – 0.16); P = 0.20; I² = 0%], but superior to PCG [MD -0.54% (95% CI: ?0.64 to ?0.44); P < 0.01; I² = 22%]. Fasting blood glucose lowering with trelagliptin was inferior to ACG [MD +6.98 mg/dl (95%CI: 2.55–11.42); P = 0.002; I² = 0%], but superior to PCG [MD -6.11 mg/dl (95%CI: ?12.00 to ?0.23); P = 0.04; I² = 54%]. Glycated albumin lowering was similar to ACG [MD 0.03% (95%CI: ?0.47 – 0.53); P = 0.92; I² = 0%], but superior to PCG [MD -2.31% (95% CI: ?2.86 to ?1.76); P < 0.01; I² = 0%]. Treatment-emergent adverse events [Risk ratio (RR) 1.18 (95%CI:0.63–2.21); P = 0.59; I² = 19%] and severe adverse events [RR 1.75 (95%CI: 0.90–3.40); P = 0.10; I² = 0%] were comparable among groups.ConclusionOnce weekly trelagliptin has good glycaemic efficacy and well tolerated in people with T2DM.     

Complete Revascularization in Patients With STEMI and Multi-Vessel Disease: A Meta-Analysis of Randomized Controlled Trials

BackgroundPercutaneous coronary intervention (PCI) is the treatment of choice for ST-elevation myocardial infarction (STEMI). However, efficacy of complete vs culprit only revascularization in patients with STEMI and multivessel disease remains unclear.MethodsWe searched PubMed/MEDLINE, and Cochrane library. The primary endpoint was major adverse cardiovascular events (MACE). Secondary outcomes were all-cause mortality, cardiovascular mortality, myocardial infarction (MI), repeat revascularization, stroke, major bleeding, and contrast induced nephropathy. Estimates were calculated as random effects hazard ratios (HRs) with 95% confidence intervals (CI).ResultsTwelve trials with 7592 patients were included. There was a significantly lower risk of MACE [HR 0.61; 95% CI (0.43–0.60); p = 0.0009; I² = 72%], cardiovascular mortality [HR 0.74; 95% CI (0.56–0.99); p = 0.04; I² = 2%], and repeat revascularization [HR 0.43; 95% CI (0.31–0.59); p < 0.00001; I² = 67%] in patients treated with complete compared with culprit-only revascularization. There was no statistically significant difference in MI [HR 0.77; 95% CI (0.52–1.12); p = 0.17; I² = 49%], all-cause mortality [HR 0.86; 95% CI (0.65–1.13); p = 0.28; I² = 14%], heart failure [HR 0.82 95% CI (0.51–1.32); p = 0.42; I² = 26%], major bleeding [HR 1.07; 95% CI (0.66–1.75); p = 0.78; I² = 25%], stroke [HR 0.67; 95% CI (0.24–1.89); p = 0.45; I² = 54%], or contrast induced nephropathy, although higher contrast volumes were used in the complete revascularization group [HR 1.22; 95% CI (0.78–1.92); p = 0.39; I² = 0%].ConclusionComplete revascularization was associated with a significantly lower risk of MACE, cardiovascular mortality, and repeat revascularization compared with culprit-only revascularization. These results suggest complete revascularization with PCI following STEMI and multivessel disease should be considered.     

Novel predictors and adverse long-term outcomes of No-reflow phenomenon in patients with acute ST elevation myocardial infarction undergoing primary percutaneous coronary intervention

ObjectivesThe no-reflow phenomenon occurs in 25% of patients with ST elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI), and may be associated with adverse outcomes. The aim of our study was to detect novel predictors of no-reflow phenomenon and the resulting adverse long term outcomes.MethodsWe enrolled 400 STEMI patients undergoing primary PCI; 228 patients had TIMI flow 3 after PCI (57%) and the remaining 172 patients had TIMI flow <3 (43%). Fibrinogen to albumin ratio (FAR), high sensitive C-reactive protein to albumin ratio (CAR), and atherogenic index of plasma (AIP) were calculated. Long term mortality and morbidity during 6 months follow up were recorded. These data were compared among both groups.ResultsIn multivariate regression analysis, old age (OR = 1.115, 95% CI: 1.032–1.205, P = 0.006), higher troponin level >5.6 ng/mL (OR = 1.040, 95% CI: 1.001–1.080, P = 0.04), diabetes mellitus (OR = 4.401, 95% CI: 1.081–17.923, P = 0.04) and heavy thrombus burden (OR = 16.915, 95% CI: 5.055–56.602, P < 0.001) could be considered as predictors for the development of no-reflow. Interestingly, CAR >0.21, FAR >11.56, and AIP >0.52 could be considered as novel powerful independent predictors (OR = 3.357, 95% CI: 2.288–4.927, P < 0.001, OR = 4.187, 95% CI: 2.761–6.349, P < 0.001, OR = 16.794, 95% CI: 1.018–277.01, P = 0.04, respectively). Higher long term mortality (P < 0.001) and heart failure (P < 0.001) was also strongly related to incidence of no-reflow.ConclusionNo-reflow could be attributed to novel predictors as CAR, FAR, and AIP. This phenomenon was associated with long term adverse events as higher mortality and pump failure.     

Gender differences in the impact of metabolic syndrome components on mortality in older people: A systematic review and meta-analysis

Background and aimsThe influence of metabolic syndrome (MetS) on mortality may be influenced by age- and gender-related changes affecting the impact of individual MetS components. We investigated gender differences in the association between MetS components and mortality in community-dwelling older adults.Methods and resultsProspective studies were identified through a systematic literature review up to June 2019. Random-effect meta-analyses were run to estimate the pooled relative risk (RR) and 95% confidence intervals (95% CI) of all-cause and cardiovascular (CV) mortality associated with the presence of MetS components (abdominal obesity, high triglycerides, low HDL cholesterol, high fasting glycemia, and high blood pressure) in older men and women. Meta-analyses considering all-cause (103,859 individuals, 48,830 men, 55,029 women; 10 studies) and CV mortality (94,965 individuals, 44,699 men, 50,266 women; 8 studies) did not reveal any significant association for abdominal obesity and high triglycerides in either gender. Low HDL was associated with increased all-cause (RR = 1.16, 95% CI: 1.02–1.32) and CV mortality (RR = 1.34, 95% CI: 1.03–1.74) among women, while weaker results were found for men. High fasting glycemia was associated with higher all-cause mortality in older women (RR = 1.35, 95% CI: 1.22–1.50) more than in older men (RR = 1.21, 95% CI: 1.13–1.30), and CV mortality only in the former (RR = 1.36, 95% CI: 1.04–1.78). Elevated blood pressure was associated with increased all-cause mortality (RR = 1.16, 95% CI: 1.03–1.32) and showed marginal significant results for CV death only among women.ConclusionsThe impact of MetS components on mortality in older people present some gender differences, with low HDL cholesterol, hyperglycemia, and elevated blood pressure being more strongly associated to all-cause and CV mortality in women.     

Short- and long-term cardiovascular outcomes in insulin-treated versus non-insulin-treated diabetes mellitus patients after percutaneous coronary intervention: A systematic review and meta-analysis

AimsThis study aims to assess differences in severity of short-term (<1 year) and long-term (≥1 year) adverse CV outcomes after PCI in insulin-treated vs. non-insulin-treated diabetes mellitus (DM) patients.MethodsA systematic search on Pubmed and Embase led to the incorporation of 29 studies that compared post-percutaneous coronary interventional outcomes in insulin-treated and non-insulin-treated diabetes mellitus. Diabetes mellitus (type 2) was defined as fasting blood glucose (FBG) level of >7.0 mmol/L or with an oral glucose tolerance test (OGTT) level of >11.1 mmol/L at least on two separate occasions. Adverse CV outcomes were assessed in insulin-treated and non-insulin-treated DM after the PCI procedure considered for the analyses were mortality, MACE, TLR, TVR, MI, stent thrombosis, target lesion failure (TLF), and need for-post PCI CABG. Data were pooled and analyzed using Review Manager 5.3, and risk ratios (RR) with respective 95% confidence intervals (CI) were calculated.The statistical analyses were carried out by Review Manager v.5.3, and the data were pooled using a random-effects model. Risk ratios (RRs) with 95% confidence intervals (CI) were reported along with forest plots. The chi-square test was performed to assess for differences between the subgroups. Heterogeneity across studies was evaluated using Higgins I² statistics. Visual inspection of the funnel plot and Begg's regression test were used to assess publication bias.ResultsA total of 40,527 patients (11742 in the Insulin-treated diabetes mellitus group and 28785 in the non-insulin-treated DM group) who underwent PCI were included. The pooled analysis of short-term follow up outcomes preceding PCI demonstrated a significantly higher risk of mortality (RR = 1.75 [1.24,2.47]; p = 0.002), MI (RR = 1.81[1.14,2.87]; p = 0.01], stent thrombosis (RR = 1.63[1.13, 2.35]; p = 0.009) and target lesion revascularization (TLR) (RR = 1.29[1.02,1.63]; p = 0.03) in insulin-treated DM patients. Similarly, analysis of long-term follow-up studies depicted a significantly higher risk mortality (RR = 1.55 [1.22, 1.97]; p = 0.0003), MI (RR = 1.63 [1.35, 1.97]; p=<0.00001), MACE (R = 1.47 [1.31, 1.65]; p=<0.00001), stent thrombosis (RR = 1.54 [1.19,1.99]; p = 0.001), TLR (RR = 1.40 [1.18, 1.66]; p = 0.0001), target vessel revascularization (TVR) (RR = 1.35 [1.11, 1.64]; p = 0.003) in insulin-treated DM group after PCI versus non-insulin-treated DM patients.ConclusionDespite a tremendous technical success rate of multi-vessel stenting, people living with diabetes who were being treated with insulin had higher long-term, and short-term mortality rates, MI, TLR, TVR, and stroke compared to people living with diabetes who were being treated with means other than insulin and are more prone to detrimental cardiovascular outcomes.     

Efficacy and safety of saroglitazar in managing hypertriglyceridemia in type-2 diabetes: A meta-analysis

Background and aimsSaroglitazar is commonly used in India for managing hypertriglyceridemia in diabetes. This meta-analysis evaluated the efficacy and safety of saroglitazar in hypertriglyceridemia.MethodsElectronic databases were searched for RCTs involving diabetes patients receiving saroglitazar in intervention arm, and placebo/lipid/diabetes medication in the control arm. Primary outcome was to evaluate change in serum triglyceride and HbA1c. Secondary outcomes were to evaluate changes in other lipid parameters, glycaemia and adverse effects. Analysis for lipid and glycaemic parameters were done separately for controls receiving anti-lipid medications (statins/fibrates) [active control group (ACG)] and those receiving placebo/diabetes medications [passive control group (PCG)].ResultsFollowing 12 weeks therapy, individuals receiving saroglitazar had significantly lower triglycerides when compared to PCG [MD -71.67 mg/dl (95% CI: −123.67 to −19.66 mg/dl); P < 0.01; I² = 91% (considerable heterogeneity); low certainty of evidence (LCE)], but not ACG [MD -37.38 mg/dl (95% CI: −84.55–9.79 mg/dl; P = 0.12; I² = 98% (considerable heterogeneity); LCE]. Individuals receiving saroglitazar had significantly lower fasting glucose when compared to PCG [MD -24.61 mg/dl (95% CI: −44.13 to −5.09 mg/dl); P = 0.01; I² = 65% (moderate heterogeneity); LCE], but not ACG [MD -13.5 mg/dl (95% CI: −33.1–6.10 mg/dl; P = 0.18; I² = 98% (considerable heterogeneity); LCE]. HbA1c, total cholesterol, LDL-C, apolipoprotein-B and HDL-C were not significantly different among study groups. Creatinine was significantly higher in patients receiving saroglitazar as compared to controls [MD 0.12 mg/dl (95% CI: 0.04–0.21 mg/dl); P < 0.01; I² = 29% (low heterogeneity); high certainty of evidence].ConclusionThis meta-analysis reinforces the excellent triglyceride lowering of saroglitazar, but highlights significant increase in creatinine.