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.     

Meta-Analysis of Efficacy and Safety of Proton Pump Inhibitors with Dual Antiplatelet Therapy for Coronary Artery Disease

BackgroundThere is inconsistency in the literature regarding the clinical effects of proton pump inhibitors (PPI) when added to dual antiplatelet therapy (DAPT) in subjects with coronary artery disease (CAD). We performed meta-analysis stratified by study design to explore these differences.Methods and results39 studies [4 randomized controlled trials (RCTs) and 35 observational studies) were selected using MEDLINE, EMBASE and CENTRAL (Inception-January 2018). In 221,204 patients (PPI = 77,731 patients, no PPI =143,473 patients), RCTs restricted analysis showed that PPI did not increase the risk of all-cause mortality (Risk Ratio (RR): 1.35, 95% Confidence Interval (CI), 0.56–3.23, P = 0.50, I² = 0), cardiovascular mortality (RR: 0.94, 95% CI, 0.25–3.54, P = 0.92, I² = 56), myocardial infarction (MI) (RR: 0.97, 95% CI, 0.62–1.51, P = 0.88, I² = 0) or stroke (RR: 1.11, 95% CI, 0.25–5.04, P = 0.89, I² = 26). However, PPI significantly reduced the risk of gastrointestinal (GI) bleeding (RR: 0.32, 95% CI, 0.20–0.52, P < 0.001, I² = 0). Conversely, analysis of observational studies showed that PPI significantly increased the risk of all-cause mortality (RR: 1.25, 95% CI, 1.11–1.41, P < 0.001, I² = 82), cardiovascular mortality (RR: 1.25, 95% CI, 1.03–1.52, P = 0.02, I² = 71), MI (RR: 1.30, 95% CI, 1.16–1.47, P < 0.001, I² = 82) and stroke (RR: 1.60, 95% CI, 1.43–1.78, P < 0.001, I² = 0), without reducing GI bleeding (RR: 0.74, 95% CI, 0.45–1.22, P = 0.24, I² = 79).ConclusionMeta-analysis of RCTs endorsed the use of PPI with DAPT for reducing GI bleeding without worsening cardiovascular outcomes. These findings oppose the negative observational data regarding effects of PPI with DAPT.     

Statins and risk of thromboembolism: A meta-regression to disentangle the efficacy-to-effectiveness gap using observational and trial evidence

Background and aimsMeta-analyses of randomised controlled trials (RCTs) and observational studies indicate a lower risk of venous thromboembolism (VTE) associated with statin treatment. We aimed to compare the effect of statin therapy in these two settings and to identify and quantify potential factors to explain statin efficacy and effectiveness.Methods and resultsWe electronically searched on December 11th, 2018, articles reporting on first VTE events in RCTs (statin vs placebo) and in observational studies (participants exposed vs non-exposed to statin). We performed Knapp-Hartung random-effect meta-analyses to calculate pooled relative risks (RRs) of VTE events associated with statin treatment, separately for RCTs and observational studies; and estimated the ratio of the relative risk (RRR) comparing RCTs and observational studies using meta-regressions, progressively adjusted for study-level characteristics. Twenty-one RCTs (115,107 participants; 959 events) and 8 observational studies (2,898,096 participants; 19,671 events) were included. Pooled RRs for RCTs and observational studies were 0.82 (95% confidence interval (CI): 0.67–1.00; I² 19.2%) and 0.60 (95% CI: 0.42–0.86; I² 86.3%), respectively. In meta-regressions, the unadjusted RRR indicated a nonsignificant 23% smaller benefit in RCTs (RRR 0.77; 95% CI: 0.52–1.13); accounting for age, sex, geographical region, and duration of follow-up, there was a sensible change of the RRR which resulted 0.30 (95% CI: 0.13–0.68).ConclusionDifferences in the characteristics between patients included in RCTs and those in observational studies may account for the differential effect of statins in preventing VTE in the two settings.     

Immune checkpoint inhibitors in neoadjuvant therapy of non-small cell lung cancer: a systematic review and meta-analysis

BackgroundOur objective was to explore the safety and feasibility of immune checkpoint inhibitors (ICIs) in the neoadjuvant treatment of non-small cell lung cancer (NSCLC).MethodsEmbase, PubMed and Web of Science were systematically searched from 1^st January 2018 to 1^st August 2021 for studies with data on the treatment-related adverse reactions (TRAE), immune-related adverse events (irAE), perioperative information, major pathological response (MPR), pathologic complete remission (pCR) and objective response rate (ORR). The QUADAS-2 tool was used to assess the quality of the studies, then the data were transformed for meta-analysis. Review Manager 5.3 (Cochrane) was used for statistical analyses with a P value of <0.05 considered significant.ResultsThirteen studies with 358 patients were included in this meta-analysis, of which, 218 patients received ICI and chemotherapy-containing regimens and 140 patients received neoadjuvant ICIs only. The 157 (72.0%) patients who received combined neoadjuvant therapy showed a higher incidence of TRAEs, while only 37 (26.4%) patients who received neoadjuvant ICIs experienced TRAEs. Grade 3 or higher irAEs were observed in 92 (25.7%) patients, of which, 81 patients belonged to the neoadjuvant immunochemotherapy subgroup. The surgical resection rate was between 38.5–100%, with only two patients experiencing a delay in surgery. Complication rates were between 3.6–100% in the 8 studies that reported postoperative complications, with more postoperative complications [35 (18.9%)] identified in the neoadjuvant immunochemotherapy subgroup. Of which 176 patients achieved MPR, 126 received ICI and chemotherapy combined neoadjuvant therapy. Seventy-one of 95 patients who had achieved pCR had undergone ICI and chemotherapy. Compared with the neoadjuvant immunotherapy group, patients undergoing ICI and chemotherapy achieved more radiological response [118 (54.1%)] than patients undergoing ICIs [25 (17.9%)] only. The odds ratio (OR) value of the MPR/pCR/ORR rate in the neoadjuvant immunochemotherapy group was higher [OR =0.55/0.32/0.39, 95% confidence interval (CI): 0.44–0.66/0.22–0.44/0.26–0.53, P=0.0004/0.14/<0.0001] after transformation.DiscussionNeoadjuvant immunotherapy shows lower toxicity and fewer perioperative complications. ICI combined chemotherapy can achieve more pathological relief and clinical benefits in the neoadjuvant treatment of NSCLC but is associated with increased irAE and perioperative complications. However, the small sample size limits the reliability of the research.     

Transcatheter Aortic Valve Replacement in Low-Risk Patients: A Meta-Analysis of Randomized Controlled Trials

IntroductionTranscatheter aortic valve replacement (TAVR) has become the standard treatment option for patients with symptomatic severe aortic stenosis (AS) with high surgical risk and a reasonable option for intermediate surgical risk as an alternative to surgical aortic valve replacement (SAVR). The role of TAVR in lower risk patients is less established but has been the focus of recent randomized controlled trials (RCTs). We performed a meta-analysis of RCTs to assess TAVR outcomes among low surgical risk patients.Methods and resultsSystematic search of RCTs was done using PubMed, EMBASE, and Cochrane Library databases. Statistical analysis was performed with RevMan v5.3 software using a random effects model to report risk ratio (RR) with 95% confidence interval (CI). A total of three RCTs including 2698 patients (1375 TAVR and 1323 SAVR) were analyzed. Compared to SAVR, TAVR was not associated with all-cause mortality [RR 0.86 (95% CI 0.61–1.19); P = 0.36; I² = 8%] or stroke [RR 0.82 (0.48–1.43); P = 0.49; I² = 42%]. However, TAVR was significantly associated with lower risk of acute kidney injury [RR 0.27 (0.13–0.54); P = 0.0002; I² = 0%], new-onset atrial fibrillation [RR 0.26 (0.18–0.39); P < 0.00001; I² = 80%], and life-threatening or disabling bleeding [RR 0.35 (0.22–0.55); P < 0.00001; I² = 57%], but a higher risk of moderate-severe paravalvular leak [RR 4.40 (1.22–15.86); P = 0.02; I² = 26%] and permanent pacemaker insertion [RR 2.73 (1.41–5.28); P = 0.003; I² = 83%].ConclusionsThere is no difference in all-cause mortality or stroke between TAVR and SAVR, but TAVR is associated with lower risk of other perioperative complications except for moderate-severe paravalvular leak and the need for permanent pacemaker implantation.     

Risk of herpes zoster associated with biological therapies for psoriasis and psoriatic arthritis: A systematic review and meta-analysis

Background:Biological therapy is effective for the treatment of psoriasis and psoriatic arthritis; however, adverse effects related to immunosuppression, such as viral infections, have been reported. Amongst these infections, herpes zoster (HZ) is common.Objective:To evaluate the risk of HZ in psoriasis and psoriatic arthritis patients treated with biological therapy.Data sources:A comprehensive literature search of PubMed, Embase, and Web of Science was performed using certain keywords until October 9, 2020. Nine studies were included after a detailed assessment.Study eligibility criteria:The eligibility criteria included randomized controlled trials (RCTs) and observational studies of patients with psoriasis or psoriatic arthritis treated with biological therapies; compared with non-biological therapies, non-biological systemic therapies, or controls; with the incidence of HZ reported in case and control groups. The Cochrane risk of bias tool and Newcastle-Ottawa scale were used to assess the quality of the RCTs and observational studies, respectively. Data were extracted from 9 eligible studies and then analyzed using Stata software (Version 12.0).Results:The risk of HZ in biological therapies was higher than that in non-biological (odds ratios [OR]: 1.48; 95% confidence interval [CI]: 1.18–1.86; I² = 0%) and non-biological systemic (OR: 1.32; 95% CI: 1.02–1.71; I² = 0%) therapies. Furthermore, the risk of HZ associated with tumor necrosis factor-α inhibitors increased significantly (OR: 1.50; 95% CI: 1.11–2.02; I² = 0%). Notably, infliximab (OR: 2.43; 95% CI: 1.31–4.50; I² = 0%) and etanercept (OR: 1.65; 95% CI: 1.07–2.56; I² = 0%) increased the risk of HZ, while adalimumab (OR: 1.21; 95% CI: 0.64–2.30; I² = 0%), ustekinumab (OR: 2.20; 95% CI: 0.89–5.44; I² = 0%), alefacept (OR: 1.46; 95% CI: 0.20–10.47; I² = 0%), and efalizumab (OR: 1.58; 95% CI: 0.22–11.34; I² = 0%) did not.Limitations:Few RCTs have reported HZ incidents; thus, our results require confirmation via large-scale RCTs.Conclusions and implications of key findings:Biological therapies, especially tumor necrosis factor-α inhibitors, may lead to the risk of HZ in psoriasis and psoriatic arthritis patients. Amongst these agents, infliximab and etanercept have been shown to significantly increase the risk of HZ. Additionally, younger age and female sex may be risk factors.Systematic review registration number:INPLASY202110027.     

Aspirin in the primary prevention of cardiovascular disease on diabetic patients: Systematic review and meta-analysis

AimsThe publication of new trials brought additional data to the controversial topic of aspirin use in diabetic patients for primary prevention. Therefore, we aimed to systematically review all randomized controlled trials evaluating the clinical impact of aspirin in this setting.MethodsWe searched for randomized controlled trials (RCTs) evaluating the impact of aspirin in patients with diabetes in primary prevention, in MEDLINE, EMBASE, CENTRAL (November/2018). The primary outcomes were all-cause mortality and the composite outcome of major adverse cardiovascular events (MACE). A meta-analysis was performed deriving risk ratios (RR) and 95% confidence intervals (CI).ResultsAll-cause mortality was not significantly reduced with RR 0.96 (95% CI 0.90–1.03; 7RCT; 27,595 patients). Regarding MACE, there was an 8% risk reduction (RR 0.92, 95% CI 0.84-0.999; I² = 0%; 8RCT; 29,814 patients). The risks of major bleeding (RR 1.30, 95% CI 1.10–1.53; 2RCTs, 18,019 patients), and major GI bleeding (RR 1.39, 95% CI 1.08–1.80; 2RCTs, 18,019 patients) were significantly increased.The risks of cardiovascular mortality, myocardial infarction, stroke and amputation were not significantly different from control arm.ConclusionsAspirin use among diabetic patients in primary prevention appears was associated with increased risk of major bleeding, a modest decrease of MACE and lack of mortality benefit.     

Effectiveness and safety of NER1006 versus standard bowel preparations: A meta-analysis of randomized phase-3 clinical trials

BackgroundA 1 L PEG-based preparation for colonoscopy (NER1006) has been recently developed.AimsWe conducted a meta-analysis of randomized controlled trials (RCTs) to explore the effectiveness and safety of NER1006 versus traditional preparations.MethodsPubMed/Medline and Embase were systematically searched through January 2020 for phase-3 RCTs comparing NER1006 versus standard preparations.ResultsThree RCTs (1879 participants) met the inclusion criteria and were included. The analysis showed a higher cleansing success for NER1006 compared standard preparations (OR=1.28; 95% CI 1.00–1.62; p = 0.047, I²=0%) as well as a greater high-quality cleansing of the right colon (OR=2.13; 95% CI 1.16–3.94; p = 0.015, I²=76.0%) when assessed by the Harefield Cleansing Scale (HCS).The pooled estimate of the NER1006 effect on ADR showed a higher, although not significant, ADR of the right colon (OR=1.19; 95% CI 0.73–1.92; p = 0.485, I²=53%). When considering the impact of NER1006 on mild to moderate treatment-emergent adverse events (TEAEs), we observed a significant pooled estimate of TEAEs (OR=2.31; 95% CI 1.82–2.94; p<0.001, I²=0%).ConclusionsWhen compared to traditional preparations, NER1006 showed a better overall cleansing of the colon as well as a greater high-quality cleansing of the right colon, with comparable ADR. A higher incidence of mild to moderate TEAEs was observed for NER1006, in the absence of serious adverse events.     

Pharmacist- and Nurse-Led Medical Optimization in Heart Failure: A Systematic Review and Meta-Analysis

BackgroundTraditional approaches to guideline-directed medical therapy (GDMT) management often lead to delayed initiation and titration of therapies in patients with heart failure. This study sought to characterize alternative models of care involving nonphysician provider-led GDMT interventions and their associations with therapy use and clinical outcomes.MethodsWe performed a systematic review and meta-analysis of randomized controlled trials (RCTs) and observational studies comparing nonphysician provider-led GDMT initiation and/or uptitration interventions vs usual physician care (PROSPERO ID: CRD42022334661). We queried PubMed, Embase, the Cochrane Library, and the World Health Organization International Clinical Trial Registry Platform for peer-reviewed studies from database inception to July 31, 2022. In the meta-analysis, we used RCT data only and leveraged random-effects models to estimate pooled outcomes. Primary outcomes were GDMT initiation and titration to target dosages by therapeutic class. Secondary outcomes included all-cause mortality and HF hospitalizations.ResultsWe reviewed 33 studies, of which 17 (52%) were randomized controlled trials with median follow-ups of 6 months; 14 (82%) trials evaluated nurse interventions, and the remainder assessed pharmacists’ interventions. The primary analysis pooled data from 16 RCTs, which enrolled 5268 patients. Pooled risk ratios (RR) for renin-angiotensin system inhibitor (RASI) and beta-blocker initiation were 2.09 (95% CI 1.05–4.16; I² = 68%) and 1.91 (95% CI1.35-2.70; I² = 37%), respectively. Outcomes were similar for uptitration of RASI (RR 1.99, 95% CI 1.24-3.20; I² = 77%) and beta-blocker (RR 2.22, 95% CI 1.29–3.83; I² = 66%). No association was found with mineralocorticoid receptor antagonist initiation (RR 1.01, 95% CI 0.47–2.19). There were lower rates of mortality (RR 0.82, 95% CI 0.67–1.04; I² = 12%) and hospitalization due to HF (RR 0.80, 95% CI 0.63–1.01; I² = 25%) across intervention arms, but these differences were small and not statistically significant. Prediction intervals were wide due to moderate-to-high heterogeneity across trial populations and interventions. Subgroup analyses by provider type did not show significant effect modification.ConclusionsPharmacist- and nurse-led interventions for GDMT initiation and/or uptitration improved guideline concordance. Further research evaluating newer therapies and titration strategies integrated with pharmacist- and/or nurse-based care may be valuable.     

Male circumcision for the prevention of heterosexually acquired HIV infection: a meta-analysis of randomized trials involving 11,050 men

Objectives

Observational studies and a small collection of randomized controlled trials (RCTs) suggest that male circumcision may significantly reduce HIV transmission between sero‐discordant contacts. The Joint United Nations Programme on HIV/AIDS (UNAIDS) and World Health Organization have recently announced recommendations to scale up male circumcision in countries with generalized epidemics and low levels of male circumcision. However, no meta‐analysis has been conducted to determine the effectiveness of this intervention.

Methods

We conducted a systematic review of medical literature, and included any RCTs assessing male circumcision to prevent heterosexually acquired HIV infection among males. We used the DerSimonian–Laird random effects method to pool study outcomes. We calculated the relative risk (RR), risk difference, number needed to treat (NNT) and I², all with 95% confidence intervals (CIs).

Results

We identified three RCTs that met our inclusion criteria, involving a total of 11 050 men. The pooled RR was 0.44 (95% CI 0.33–0.60, P<0.0001, I²=0%, 95% CI 0–35%). The risk difference was 0.014 (95% CI 0.07–0.21), yielding a NNT of 72 (95% CI 50–143).

Conclusions

Male circumcision is an effective strategy for reducing new male HIV infections. Its impact on a population level will require consistently safe sexual practices to maintain the protective benefit.     

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.     

Effect of new glucose-lowering drugs on stroke in patients with type 2 diabetes: A systematic review and Meta-analysis

AimsPeople with diabetes tend to face a higher risk of stroke. Randomized controlled trials (RCTs) have demonstrated the different outcomes of new glucose-lowering drugs marketed in recent years on cardiovascular outcome events. The effects of glucagon-like peptide-1 (GLP-1) agonists, sodium-glucose cotransporter-2 (SGLT-2) inhibitors, and dipeptidyl peptidase-4 (DPP-4) inhibitors on stroke risk were evaluated in published RCTs.MethodsA search of Embase, Cochrane Library, and PubMed databases identified studies with stroke as an outcome event up to 3 December 2021. Risk ratios for stroke outcomes were analyzed using a fixed-effects model. I² was used to assess the heterogeneity of the study.Results19 RCTs with 155,027 participants with type 2 diabetes were identified. Pooled analysis showed that compared to placebo, GLP-1 agonists reduced non-fatal stroke by 15 % (RR = 0.85, 95%CI 0.77–0.94, P = 0.002, I² = 0 %) and total stroke (RR = 0.84, 95%CI 0.77–0.93, P = 0.000, I² = 0 %) by 16 %. SGLT-2 inhibitors and DPP-4 inhibitors were not significantly associated with lower stroke risk.ConclusionsThis meta-analysis indicates that GLP-1 agonists have potential benefits for stroke. However, further studies are needed if GLP-1 agonists are to be used to reduce the risk of stroke in patients with type 2 diabetes. More research is also needed to investigate the effects of new glucose-lowering drugs on different stroke subtypes.Systematic review registrationThis protocol was registered on the International Prospective Register of Systematic Reviews (https://www.crd.york.ac.uk/PROSPERO/; registration number: CRD42022326382).     

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.     

The effectiveness of pistachio on glycemic control and insulin sensitivity in patients with type 2 diabetes,prediabetes and metabolic syndrome: A systematic review and meta-analysis

Background and aimsPistachio nuts have been considered to improve dysglycemia. However, there are controversial results. This systematic review and meta-analysis carried out to evaluate the effects of pistachio nuts on glycemic control and insulin sensitivity in patients with type 2 diabetes mellitus (T2DM), prediabetes, and metabolic syndrome.MethodsMedline/PubMed, ProQuest, Web of Knowledge, Scopus, Cochrane library, and ScienceDirect were systematically searched to find randomized controlled trials (RCTs). Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) checklist was used to conduct the study.ResultsSix RCTs were included in the review. Treatment with pistachio nuts exerted a significant reduction in fasting blood glucose (FBG) level (OR = 1.7, 95% CI; 1.2–2.4, P = 0.002, I² = 0.0%, P = 0.731) and homeostasis model assessment of insulin resistance (HOMA-IR) index (OR = 1.5, 95% CI; 1.0–2.4, P = 0.043, I² = 0.0%, P = 0.617), but no significant improvement was observed in regard to hemoglobin A1c (HbA1c) level (OR = 1.4, 95% CI; 0.9–2.1 P = 0.089, I² = 0.0%, P = 0.957) and fasting plasma insulin (FPI) level (OR = 1.3, 95% CI; 0.9–1.9, P = 0.133, I² = 0.0%, P = 0.776).ConclusionsPistachio nuts might cause a significant reduction in FBG and HOMA-IR, although HbA1c and FPI might not significantly improve in patients suffering from or at risk of T2DM.     

SGLT2 inhibitors and cardiovascular outcomes in heart failure with mildly reduced and preserved ejection fraction: A systematic review and meta-analysis

AimTo provide a pooled effect of sodium-glucose cotransporter-2 inhibitors (SGLT2i) on cardiovascular outcomes in patients with heart failure with preserved ejection fraction (HFpEF: ≥50%) or/and mildly reduced EF (HFmrEF: 41–49%) regardless of baseline diabetes.MethodsWe systemically searched PubMed/MEDLINE, Embase, Web of Science databases and clinical trial registries using appropriate keywords till August 28, 2022, to identify randomized controlled trials (RCTs) or post-hoc analysis of RCTs, reporting cardiovascular death (CVD) and/or urgent visits/hospitalization for heart failure(HHF) in patients with HFmrEF/HFpEF receiving SGLTi vs. placebo. Hazard ratios (HR) with 95% confidence intervals (CI) for outcomes were pooled together using generic inverse variance method with fixed-effects model.ResultsWe identified six RCTs, pooling data retrieved from 15,769 patients with HFmrEF/HFpEF. Pooled analysis showed that compared to placebo, SGLT2i use was significantly associated with improved CVD/HHF outcomes in HFmrEF/HFpEF (pooled HR 0.80, 95% CI: 0.74, 0.86, p < 0.001, I² = 0%). When separately analyzed, benefits of SGLT2i remained significant across HFpEF (N = 8891, HR 0.79, 95% CI: 0.71, 0.87, p < 0.001, I² = 0%) and HFmrEF (N = 4555, HR 0.77, 95% CI: 0.67, 0.89, p < 0.001, I² = 40%). Consistent benefits were observed also in HFmrEF/HFpEF subgroup without baseline diabetes (N = 6507, HR 0.80, 95% CI: 0.70, 0.91, p < 0.001, I² = 0%). Sensitivity analysis including the DELIVER and EMPEROR-Preserved trials found a trend towards significant beneficial effects on CV deaths with no heterogeneity (HR 0.90, 95% CI: 0.79, 1.02, p = 0.08, I² = 0%).ConclusionsThis meta-analysis established the place of SGLT2i as a foundational therapy among patients with HF with preserved and mildly reduced EF regardless of diabetes.     

The effect of PCSK9 inhibitors on brain stroke prevention: A systematic review and meta-analysis

Background and aimsAlthough proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors have been shown to improve cardiovascular outcomes, their effects on brain stroke risk are unclear. The present meta-analysis aimed to evaluate the effects of PCSK9 inhibitors on brain stroke prevention.Methods and resultsWe searched PubMed, Embase, Cochrane Library, Web of Science, and ClinicalTrials.gov for research published until December 30, 2020, to find randomized controlled trials (RCTs) of PCSK9 inhibitors for brain stroke prevention. Relative risk (RR) and 95% confidence intervals (CIs) were used to represent the outcomes. Seven RCTs with 57,440 participants, including 29,850 patients treated with PCSK9 inhibitors and 27,590 control participants, were included. PCSK9 inhibitors were associated with significant reductions in total brain stroke risk (RR, 0.77; 95% CI, 0.67–0.88; P < 0.001) and ischemic brain stroke risk (RR, 0.76; 95% CI, 0.66, 0.89; P < 0.001) in comparison with the control group. There was no significant difference in cardiovascular mortality (RR, 0.95; 95% CI, 0.84–1.07; P = 0.382) and the risk of hemorrhagic brain stroke (RR, 1.00; 95% CI, 0.66–1.51; P = 0.999) between patients treated with PCSK9 inhibitors and controls. PCSK9 inhibitors did not significantly increase the incidence of neurocognitive adverse events (RR, 1.02; 95% CI, 0.81–1.29; P = 0.85). Moreover, subgroup analysis showed no difference in cognitive function disorder risks among different PCSK9 inhibitors and treatment times.ConclusionsPCSK9 inhibitors significantly reduced the risk of total brain stroke and ischemic brain stroke without increasing the risk of brain hemorrhage and neurocognitive impairment.     

Revascularization strategies in cardiogenic shock complicating acute myocardial infarction: A systematic review and meta-analysis

BackgroundThe optimal revascularization strategy in patients with multi-vessel disease (MVD) presenting with acute myocardial infarction (AMI) and cardiogenic shock (CS) remains unclear.ObjectiveTo investigate the comparative differences between culprit-only revascularization (COR) versus instant multi-vessel revascularization (IMVR) in AMI and CS.Methods13 studies were selected using MEDLINE, EMBASE and the CENTRAL (Inception - 31 November2017). Outcomes were assessed at short-term (in-hospital or ≤30 days duration) and long-term duration (≥6 months). Estimates were reported as random effects relative risk (RR) with 95% confidence interval (CI).ResultsIn analysis of 7311 patients, COR significantly reduced the relative risk of short-term all-cause mortality (RR: 0.87; 95% CI, 0.77–0.97; p = 0.01, I² = 50%) and renal failure (RR: 0.75; 95% CI, 0.61–0.94; p = 0.01, I² = 7%) compared with IMVR. There were no significant differences between both the strategies in terms of reinfarction (RR: 1.25; 95% CI, 0.59–2.63; p = 0.56, I² = 0%), major bleeding (RR: 0.88; 95% CI, 0.75–1.04; p = 0.14, I² = 0%) and stroke (RR: 0.77; 95% CI, 0.50–1.17; p = 0.22, I² = 0%) at short term duration. Similarly, no significant differences were observed between both groups regarding all-cause mortality (RR; 1.01; 95% CI, 0.85–1.20; p = 0.93, I² = 61%) and reinfarction (RR: 0.71; 95% CI, 0.34–1.47; p = 0.35, I² = 26%) at long term duration.ConclusionIn MVD patients presenting with AMI and CS, IMVR was comparable to COR in terms of all-cause mortality at long term follow up duration. These results are predominantly derived from observational data and more randomized controlled trials are required to validate this impression.     

Tobacco smoking and the risk of pancreatitis: A systematic review and meta-analysis of prospective studies

BackgroundTobacco smoking has been associated with increased risk of pancreatitis in several studies, however, not all studies have found an association and it is unclear whether there is a dose-response relationship between increasing amount of tobacco smoked and pancreatitis risk. We conducted a systematic review and meta-analysis of prospective studies on tobacco smoking and pancreatitis to clarify the association.MethodsPubMed and Embase databases were searched for relevant studies up to April 13th^, 2019. Prospective studies that reported adjusted relative risk (RR) estimates and 95% confidence intervals (CIs) for the association between tobacco smoking and pancreatitis were included and summary RRs were calculated using a random effects model.ResultsTen prospective studies were included. The summary RR for acute pancreatitis was 1.49 (95% CI: 1.29–1.72, I² = 68%, n = 7) for current smokers, 1.24 (95% CI: 1.15–1.34, I² = 0%, n = 7) for former smokers, and 1.39 (95% CI: 1.25–1.54, I² = 69%, n = 7) for ever smokers compared to never smokers. Similar results were observed for chronic pancreatitis and acute/chronic pancreatitis combined. The summary RR per 10 cigarettes per day was 1.30 (95% CI: 1.18–1.42, I² = 42%, n = 3) and per 10 pack-years in current smokers was 1.13 (95% CI: 1.08–1.17, I² = 14%, n = 4) for acute pancreatitis and results were similar for chronic pancreatitis and acute/chronic pancreatitis combined.ConclusionsThese results suggest that tobacco smoking increases the risk of acute and chronic pancreatitis and acute and chronic pancreatitis combined and that there is a dose-response relationship between increasing number of cigarettes and pack-years and pancreatitis risk.     

Dipeptidyl peptidase-4 inhibitors and risk of arthralgia: A systematic review and meta-analysis

BackgroundThe US Food and Drug Administration has warned that treatment with dipeptidyl peptidase (DPP)-4 inhibitors may promote serious arthralgia. However, the clinical evidence for this is relatively lacking.ObjectiveFor this reason, a systematic review and meta-analysis of randomized controlled trials (RCTs) were carried out to determine the relationship between DPP-4 inhibitors and risk of arthralgia, and also to investigate any potential risk factors.MethodsAn extensive electronic search for RCTs comparing DPP-4 inhibitors with any comparators was performed up to July 2016. Outcomes of interest were overall and serious arthralgia. Summary risk ratios (RRs) with 95% confidence intervals (CIs) were calculated.ResultsA total of 67 RCTs (involving 79,110 patients) was ultimately included. Pooled results showed that DPP-4 inhibitors were associated with a slightly but significantly increased risk of overall arthralgia (RR: 1.13, 95% CI: 1.04–1.22; P = 0.003) and a non-significant increased risk of serious arthralgia (RR: 1.44, 95% CI: 0.83–2.51; P = 0.20). Also, subgroup analyses showed that add-on/combination therapy and longer diabetes duration (> 5 years) were possible factors associated with the increased risk of overall arthralgia.ConclusionThese findings suggest that DPP-4 inhibitors can increase the risk of arthralgia. Thus, the benefits of glycaemic control must be weighed against the risk of arthralgia when prescribing DPP-4 inhibitors. Further studies are now needed to identify and confirm these risk factors.     

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.