Effects of pioglitazone on cardiovascular events and all-cause mortality in patients with type 2 diabetes: A meta-analysis of randomized controlled trials

AimIn 2019, the Italian Society of Diabetology and the Italian Association of Clinical Diabetologists nominated an expert panel to develop guidelines for drug treatment of type 2 diabetes. After identifying the effects of glucose-lowering agents on major adverse cardiovascular events (MACEs), all-cause mortality, and hospitalization for heart failure (HHF) as critical outcomes, the experts decided to perform a systematic review and meta-analysis on the effect of pioglitazone with this respect.Data synthesisA MEDLINE database search was performed to identify RCTs, up to June 1st, 2021, with duration≥52 weeks, in which pioglitazone was compared with either placebo or active comparators. The principal endpoints were MACE and HHF (restricted for RCT reporting MACEs within their outcomes), all-cause mortality (irrespective of the inclusion of MACEs among the pre-specified outcomes). Mantel-Haenszel odds ratio (MH–OR) with 95% Confidence Interval (95% CI) was calculated for all the endpoints considered.Eight RCTs were included in the analysis for MACEs and HF (5048 and 5117 patients in the pioglitazone and control group, respectively), and 24 in that for all-cause mortality (10,682 and 9674 patients). Pioglitazone neither significantly increased nor reduced the risk of MACE, all-cause mortality, and HHF in comparison with placebo/active comparators (MH–OR: 0.90, 95% CI 0.78–1.03, 0.91, 95% CI 0.77, 1.09, and 1.16, 95% CI 0.73, 1.83, respectively). Pioglitazone was associated with a significant reduction of MACE in patients with prior cardiovascular events (MH–OR 0.84, 95% CI 0.72–0.99).ConclusionsThis meta-analysis showed no significant effects of pioglitazone on incident MACE, all-cause mortality, and HHF.     

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.     

Blood fibrinogen level as a biomarker of adverse outcomes in patients with coronary artery disease: A systematic review and meta-analysis

Background:The association between elevated fibrinogen level and adverse outcomes in patients with coronary artery disease (CAD) remains conflicting. This systematic review and meta-analysis aims to evaluate the association between fibrinogen level and adverse outcomes in CAD patients.Methods:Relevant studies were identified by searching PubMed, Web of Science, and Embase databases from their inception to September 30, 2021. Observational studies that investigated the association of blood fibrinogen level with cardiovascular death, all-cause mortality, and major adverse cardiovascular events were eligible.Results:A total of 20,395 CAD patients from 15 articles (13 studies) were included. Comparison with the highest and the lowest fibrinogen level indicated that elevated fibrinogen level was associated with higher risk of cardiovascular death (risk ratio [RR] 2.24; 95% confidence interval [CI] 1.69–2.98), all-cause mortality (RR 1.88; 95% CI 1.50–2.36), and major adverse cardiovascular events (RR 1.46; 95% CI 1.18–1.81).Conclusion:Elevated fibrinogen level is significantly associated with an increased risk of cardiovascular and all-cause mortality in patients with CAD. Baseline fibrinogen level can serve as a promising biomarker for risk stratification of CAD.     

Effects of insulin on cardiovascular events and all-cause mortality in patients with type 2 diabetes: A meta-analysis of randomized controlled trials

AimIn 2019, the Italian Society of Diabetology and the Italian Association of Clinical Diabetologists nominated an expert panel to develop guidelines for drug treatment of type 2 diabetes. This expert panel, after identifying the effects of glucose-lowering agents on major adverse cardiovascular events (MACEs), all-cause mortality, and hospitalization for heart failure (HHF) as critical outcomes, decided to perform a systematic review and meta-analysis on the effect of insulin with this respect.Data synthesisA MEDLINE database search was performed to identify all RCTs, up to June 1st, 2021, with duration≥52 weeks, in which insulin was compared with either placebo or active comparators. The principal endpoints were MACE and HHF (restricted for RCT reporting MACEs within their outcomes), all-cause mortality (irrespective of the inclusion of MACEs among the pre-specified outcomes). Mantel-Haenszel odds ratio (MH-OR) with 95% Confidence Interval (95% CI) was calculated for all the endpoints considered.Six RCTs (enrolling 8091 patients and 10,139 in the insulin and control group, respectively) were included in the analysis for MACEs and HF, and 18 in that for all-cause mortality (9760 and 11,694 patients in the insulin and control group, respectively). Treatment with insulin neither significantly increased nor reduced the risk of MACE, all-cause mortality, and HHF in comparison with placebo/active comparators (MH-OR: 1.09, 95% CI 0.97–1.23; 0.99, 95% CI 0.91, 1.08; and 0.90, 95% CI 0.78, 1.04, respectively).ConclusionsThis meta-analysis showed no significant effects of insulin on incident MACE, all-cause mortality, and HHF.     

High triglyceride-glucose index is associated with adverse cardiovascular outcomes in patients with acute myocardial infarction

Background and aimsTriglyceride glucose (TyG) index is considered a new surrogate marker of insulin resistance that associated with the development of vascular disease. The aim of this study was to evaluate the prognostic value of TyG index in patients with acute myocardial infarction (AMI).Methods and resultsA total of 3181 patients with AMI were included in the analysis. Patients were stratified into 2 groups according to their TyG index levels: the TyG index <8.88 group and the TyG index ≥8.88 group. The incidence of major adverse cardiovascular events (MACEs) during a median of 33.3-month follow-up were recorded. Multivariable Cox regression models revealed that the TyG index was positively associated with all-cause death [HR (95% CI): 1.51 (1.10,2.06), p = 0.010], cardiac death [HR (95% CI): 1.68 (1.19,2.38), p = 0.004], revascularization [HR (95% CI): 1.50 (1.16,1.94), p = 0.002], cardiac rehospitalization [HR (95% CI): 1.25 (1.05,1.49), p = 0.012], and composite MACEs [HR (95% CI): 1.19 (1.01,1.41), p = 0.046] in patients with AMI. The independent predictive effect of TyG index on composite MACEs was mainly reflected in the subgroups of male gender and smoker. The area under the curve (AUC) of the TyG index predicting the occurrence of MACEs in AMI patients was 0.602 [95% CI 0.580,0.623; p < 0.001].ConclusionHigh TyG index levels appeared to be associated with an increased risk of MACEs in patients with AMI. The TyG index might be a valid predictor of cardiovascular outcomes of patients with AMI.Trial registrationRetrospectively registered.     

Screening for occult cancer in idiopathic venous thromboembolism — Systemic review and meta-analysis

BackgroundIdiopathic venous thromboembolism (VTE) may be associated with an occult malignancy. Early detection of cancer might be translated to a better prognosis for these patients. However, the efficacy of extensive screening for cancer in patients with idiopathic VTE is controversial.Materials and methodsSystemic review and meta-analysis of all available prospective trials comparing extensive to limited screening for occult malignancies in patients with idiopathic VTE.Primary outcome: all-cause mortality. Secondary outcomes: cancer related mortality, early cancer diagnosis, cancer diagnosis at the end of follow up and cancer diagnosis at an early stage. Risk ratios (RR) with 95% confidence intervals (CIs) were estimated and pooled.ResultsThe study included five trials and 2287 patients. Extensive screening did not affect all-cause mortality at the end of follow up [RR 0.86 (95% CI 0.58–1.27)] or cancer-related mortality [RR 0.93 (95% CI 0.54–1.58)]. Yet, it yielded more diagnoses of cancer [RR 2.17 (95% CI 1.42–3.32)]. Rates of cancer diagnosis at an early stage did not differ statistically between the two groups [RR 1.49 (95% CI 0.86–2.56)]. However, analysis of the randomized controlled trials alone showed a tendency towards early stage cancer at diagnosis in extensive screening group in, with results almost statistically significant [RR 2.14 (95% CI 0.98–4.67), p = 0.06].ConclusionsExtensive screening for malignancy after idiopathic VTE does not affect mortality rates. Yet, it yields more cancer diagnoses shortly after the VTE event. Further research is needed to determine whether extensive screening might be proper for specific high risk populations.     

Baseline serum uric acid level as a predictor of cardiovascular disease related mortality and all-cause mortality: A meta-analysis of prospective studies

Objective

Serum uric acid (SUA) levels have been used to predict cardiovascular and all-cause mortality event, but the data have yielded conflicting results. We investigated whether SUA was an independent predictor for cardiovascular or all-cause mortality with prospective studies by meta-analysis.

Methods

Pubmed and Embase were searched without language restrictions for publications available till April 2013. Only prospective studies on cardiovascular or all-cause mortality related to SUA levels were included. Pooled adjust relative risk (RR) and corresponding 95% confidence intervals (CI) were calculated separately for the highest vs. lowest category or the lowest vs. middle category.

Results

For the highest SUA, eleven studies with 172,123 participants were identified and analyzed. Elevated SUA increased risk of all-cause mortality (RR 1.24; 95% CI 1.09–1.42) and cardiovascular mortality (RR 1.37; 95% CI 1.19–1.57). Subgroup analyses showed that elevated SUA significantly increase the risk of all-cause mortality among men (RR 1.23; 95% CI 1.08–1.42), but not in women (RR 1.05; 95% CI 0.79–1.39). Risk of cardiovascular mortality appeared to be more pronounced among women (RR 1.35; 95% CI 1.06–1.72). The association between extremely low SUA and mortality was reported in three studies; we did not perform a pooled analysis because of high degree of heterogeneity in these studies.

Conclusions

Baseline SUA level is an independent predictor for future cardiovascular mortality. Elevated SUA appears to significantly increase the risk of all-cause mortality in men, but not in women. Whether low SUA levels are predictors of mortality is still inconclusive.     

Body mass index and colorectal cancer prognosis: a systematic review and meta-analysis

Colorectal cancer is one of the most common cancers worldwide. However, it is unclear what influence body mass index (BMI) has on colorectal cancer prognosis. We conducted a systematic review and meta-analysis of observational studies to examine the association of BMI with colorectal cancer outcomes. We searched MEDLINE and EMBASE databases from inception to February 2015 and references of identified articles. We selected observational studies that reported all-cause mortality, colorectal cancer-specific mortality, recurrence and disease-free survival according to BMI category. Random-effects meta-analyses were conducted to combine estimates. We included 18 observational studies. Obese patients had an increased risk of all-cause mortality [relative risk (RR) 1.14; 95 % confidence interval (CI) 1.07–1.21], cancer-specific mortality (RR 1.14; 95 % CI 1.05–1.24), recurrence (RR 1.07; 95 % CI 1.02–1.13) and worse disease-free survival (RR 1.07; 95 % CI 1.01–1.13). Underweight patients also had an increased risk of all-cause mortality (RR 1.43; 95 % CI 1.26–1.62), cancer-specific mortality (RR 1.50; 95 % CI 1.20–1.87), recurrence (RR 1.13; 95 % CI 1.05–1.21) and worse disease-free survival (RR 1.27; 95 % CI 1.13–1.43). Overweight patients had no increased risk for any of the outcomes studied. Both obese and underweight patients with colorectal cancer have an increased risk of all-cause mortality, cancer-specific mortality, disease recurrence and worse disease-free survival compared to normal weight patients.     

Silent myocardial ischemia detected by single photon emission computed tomography (SPECT) and risk of cardiac events among asymptomatic patients with type 2 diabetes: A meta-analysis of prospective studies

ObjectiveTo assess the value of detecting silent myocardial ischemia (SMI) by single photon emission computed tomography (SPECT) in predicting risk of cardiac events among patients with type 2 diabetes mellitus (T2DM) who do not have overt cardiac symptoms.Materials and MethodsElectronic databases (PubMed, Cochrane Library, EMBASE, and others) and original article references were systematically searched through February 1, 2013. A fixed-effects model was applied to pooled data to estimate relative risks (RR) and 95% confidence intervals (CI).ResultsTen prospective studies with follow-up ranging from 1 to 6 years were identified. Among the total of 1360 asymptomatic patients with T2DM screened by SPECT, the cumulative prevalence rate of SMI was 26.1%. Patients with SMI were at increased risk of experiencing endpoints relative to patients without SMI: RR (95% CI) for cardiac death, 4.60 (1.78–11.84); non-fatal cardiac events, 3.48 (2.30–5.28); total cardiac events, 3.48 (2.59–4.68); and all-cause mortality, 2.20(1.14–4.25). The risk of cardiac death and non-fatal cardiac events increased with increasing severity of SPECT-detected abnormalities.ConclusionsSMI detected by SPECT is associated with increased risk of cardiac death, all-cause mortality, and non-fatal cardiac events in T2DM patients without overt cardiac symptoms. Advanced intervention procedures including intensive drug management should be implemented to reduce the risk of cardiac events for SMI-positive T2DM patients.     

Effect of insulin secretagogues on major cardiovascular events and all-cause mortality: A meta-analysis of randomized controlled trials

Background and aimIn 2019, the Italian Society of Diabetology and the Italian Association of Clinical Diabetologists nominated an expert panel to develop guidelines for drug treatment of type 2 diabetes. This expert panel, after identifying the effects of glucose-lowering agents on major adverse cardiovascular events (MACEs) and all-cause mortality as critical outcomes, decided to perform a systematic review and meta-analysis on the effect of insulin secretagogues (sulfonylureas and glinides) with this respect.Methods and resultsA MEDLINE database search was performed to identify all RCTs, up to January 1st, 2020, with duration≥52 weeks, in which insulin secretagogues (glibenclamide, gliclazide, glimepiride, glipizide, chlorpropamide, repaglinide, nateglinide) were compared with either placebo or active comparators. The principal endpoints were MACE (restricted for RCT reporting MACEs within their outcomes) and all-cause mortality (irrespective of the inclusion of MACEs among the pre-specified outcomes). Mantel-Haenszel odds ratio (MH–OR) with 95% Confidence Interval (95% CI) was calculated for all the endpoints considered. Fourteen RCTs were included in the analysis for MACEs (919 in insulin secretagogues and 1,087 in control group). Insulin secretagogues were not significantly associated with an increased risk of MACEs in comparison with controls (MH–OR 1.08 [95% CI 0.96, 1.22], p = 0.20). When considering the 48 RCTs fulfilling criteria for inclusion in the analysis on all-cause mortality, insulin secretagogues were associated with a significantly increased risk of all-cause mortality (MH–OR 1.11 [1.00, 1.23], p = 0.04).ConclusionsThis meta-analysis suggests that insulin secretagogues are associated with an increased risk of all-cause mortality when compared with placebo or other anti-hyperglycaemic drugs.     

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.     

Valor Prognóstico dos Níveis Plasmáticos de NT-proBNP em Pacientes Hospitalizados com Mais de 80 Anos de Idade em um Hospital em Pequim,China

BackgroundDespite growing evidence that N-terminal pro-brain natriuretic peptide (NT-proBNP) has an important prognostic value in older adults, there is limited data on its prognostic predictive value.ObjectivesThe aim of this study is to evaluate the clinical significance of NT-proBNP in hospitalized patients older than 80 years of age in Beijing, China.MethodsThis prospective, observational study was conducted in 724 very elderly patients in a geriatric ward (age ≥80 years, range, 80100 years, mean, 86.6 3.0 years). Multivariate linear regression analysis was used to screen for factors independently associated with NT-proBNP, and the Cox proportional hazard regression model was used to screen for relationships between NT-proBNP levels and major endpoints. The major endpoints assessed were all-cause death and MACEs. P values < 0.05 were considered statistically significant.ResultsThe prevalence rates of coronary heart disease, hypertension, and diabetes mellitus were 81.4%, 75.1%, and 41.2%, respectively. The mean NT-proBNP level was 770 ± 818 pg/mL. Using multivariate linear regression analyses, correlations were found between plasma NT-proBNP and body mass index, atrial fibrillation, estimated glomerular filtration rate, left atrial diameter, left ventricular ejection fraction, use of betablocker, levels of hemoglobin, plasma albumin, triglycerides, serum creatinine, and blood urea nitrogen. The risk of all-cause death (HR, 1.63; 95% CI, 1.0052.642; P = 0.04) and major adverse cardiovascular events (MACE; HR, 1.77; 95% CI, 1.2893.531; P = 0.04) in the group with the highest NT-proBNP level was significantly higher than that in the group with the lowest level, according to Cox regression models after adjusting for multiple factors. As expected, echocardiography parameters adjusted the prognostic value of NT-proBNP in the model.ConclusionsNT-proBNP was identified as an independent predictor of all-cause death and MACE in hospitalized patients older than 80 years of age.     

The prognostic nutritional index might predict clinical outcomes in patients with idiopathic dilated cardiomyopathy

Background and aimsThe prognostic nutritional index (PNI) had been associated with adverse outcomes in numerous clinical conditions. However, its influence on idiopathic dilated cardiomyopathy (DCM) was not determined. This aim of this study was to determine the predictive ability of PNI in patients with idiopathic DCM.Methods and resultsA total of 1021 consecutive patients with idiopathic DCM were retrospectively included and divided into three groups based on admission PNI tertiles: <41.7 (n = 339), 41.7–47.3 (n = 342), >47.3 (n = 340). The association of PNI with in-hospital major adverse clinical events (MACEs) and death during follow-up was evaluated. In-hospital mortality (2.9% vs. 1.5% vs. 0.0%, respectively; p = 0.006) and MACEs (13.6% vs. 6.7% vs. 3.5%, respectively; p < 0.001) decreased from the lowest to the highest PNI tertile. The optimal cut-off value of PNI to predict in-hospital MACEs was 44.0 (area under the curve: 0.689; 95% confidence interval [CI]: 0.626–0.753; p < 0.001). Multivariate analysis showed that a PNI≤44.0 was an independent risk factor of in-hospital MACEs (odd ratio: 2.86; 95% CI: 1.64–4.98; p < 0.001) and all-cause mortality at a median follow-up of 27 months (hazard ratio: 1.67; 95% CI: 1.11–2.49; p = 0.013). In addition, patients with a PNI≤44.0 had a lower cumulative survival rate during follow-up (log-rank: 35.62; p < 0.001).ConclusionThe PNI was an independent risk factor for in-hospital MACEs and all-cause mortality at a median follow-up of 27 months in patients with idiopathic DCM; hence, it may be considered a tool for risk assessment.     

Multivessel Versus Culprit-Only Revascularization in STEMI and Multivessel Coronary Artery Disease: Meta-Analysis of Randomized Trials

ObjectivesThe goal of this systematic review and meta-analysis was to provide a comprehensive evaluation of contemporary randomized trials addressing the efficacy and safety of multivessel versus culprit vessel–only percutaneous coronary intervention (PCI) among patients presenting with ST-segment elevation myocardial infarction and multivessel coronary artery disease.BackgroundMultivessel coronary artery disease is present in about one-half of patients with ST-segment elevation myocardial infarction. Randomized controlled trials comparing multivessel and culprit vessel–only PCI produced conflicting results regarding the benefits of a multivessel PCI strategy.MethodsA comprehensive search for published randomized controlled trials comparing multivessel PCI with culprit vessel–only PCI was conducted on ClinicalTrials.gov, PubMed, Web of Science, EBSCO Services, the Cochrane Central Register of Controlled Trials, Google Scholar, and scientific conference sessions from inception to September 15, 2019. A meta-analysis was performed using a random-effects model to calculate the risk ratio (RR) and 95% confidence interval (CI). Primary efficacy outcomes were all-cause mortality and reinfarction.ResultsTen randomized controlled trials were included, representing 7,030 patients: 3,426 underwent multivessel PCI and 3,604 received culprit vessel–only PCI. Compared with culprit vessel–only PCI, multivessel PCI was associated with no significant difference in all-cause mortality (RR: 0.85; 95% CI: 0.68 to 1.05) and lower risk for reinfarction (RR: 0.69; 95% CI: 0.50 to 0.95), cardiovascular mortality (RR: 0.71; 95% CI: 0.50 to 1.00), and repeat revascularization (RR: 0.34; 95% CI: 0.25 to 0.44). Major bleeding (RR: 0.92; 95% CI: 0.50 to 1.67), stroke (RR: 1.15; 95% CI: 0.65 to 2.01), and contrast-induced nephropathy (RR: 1.25; 95% CI: 0.80 to 1.95) were not significantly different between the 2 groups.ConclusionsMultivessel PCI was associated with a lower risk for reinfarction, without any difference in all-cause mortality, compared with culprit vessel–only PCI in patients with ST-segment elevation myocardial infarction.     

Platelet reactivity-adjusted antiplatelet therapy in patients with percutaneous coronary intervention: a meta-analysis of randomized controlled trials

Numerous number of evidences show that high on-treatment platelet reactivity is a well-known risk factor for adverse events in patients after percutaneous coronary intervention (PCI). Controversial situations still exist regarding the effectiveness of tailoring antiplatelet therapy according to platelet function monitoring. The PubMed, Embase, and Cochrane Central databases were searched for randomized trials comparing platelet reactivity-adjusted antiplatelet therapy with conventional antiplatelet therapy in patients undergoing PCI. The primary end point was all-cause mortality, major adverse cardiac events (MACE) including cardiovascular (CV) death, nonfatal myocardial infarction (MI), definite/probable stent thrombosis (ST), revascularization, and stroke or transient ischemic attack (TIA). The safety end point was defined as major bleeding events. We derived pooled risk ratios (RRs) with fixed-effect models. Six studies enrolling 6347 patients were included. Compared with conventional treatment, tailoring antiplatelet failed to reduce all-cause mortality (RR: 0.89, 95% confidence interval [CI]: 0.63–1.24, P = 0.48), MACE (RR: 1.02, 95% CI: 0.92–1.14, P = 0.69), MI (RR: 1.07, 95% CI: 0.95–1.21, P = 0.24), CV death (RR: 0.69, 95% CI: 0.40–1.19, P = 0.09), ST (RR: 0.83, 95% CI: 0.50–1.38, P = 0.23), stroke or TIA (RR: 1.08, 95% CI: 0.55–2.12, P = 0.83), revascularization (RR: 0.96, 95% CI: 0.69–1.33, P = 0.79), and major bleeding events (RR: 0.79, 95% CI: 0.53–1.17, P = 0.24).

Compared with traditional antiplatelet treatment, tailoring antiplatelet therapy according to platelet reactivity testing failed to reduce all-cause mortality, MACE, and major bleeding events in patients undergoing PCI.     

Effect of metformin on all-cause mortality and major adverse cardiovascular events: An updated meta-analysis of randomized controlled trials

AimsThe Italian Society of Diabetology and the Italian Association of Clinical Diabetologists are developing new guidelines for drug treatment of type 2 diabetes. The effects of anti-hyperglycaemic drugs on all-cause mortality and major adverse cardiovascular events (MACEs) were included among the critical clinical outcomes. We have therefore carried out an updated meta-analysis on the effects of metformin on these outcomes.Data synthesisA MEDLINE and EMBASE search was performed to identify all randomized controlled trials (RCTs) with duration ≥52 weeks (published up to August 2020), in which metformin was compared with either placebo/no therapy or active comparators. MACEs (restricted for RCT reporting MACEs within their study endpoints) and all-cause mortality (irrespective of the inclusion of MACEs among the pre-specified endpoints) were considered as the primary endpoints. Mantel-Haenszel odds ratio (MH–OR) with 95% confidence interval was calculated for all endpoints considered. Metformin was associated with a nonsignificant reduction of all-cause mortality (n = 13 RCTs; MH–OR 0.80 [95% CI 0.60, 1.07]). However, this association became statistically significant after excluding RCTs comparing metformin with sulfonylureas, SGLT-2 inhibitors or GLP-1 analogues (MH–OR 0.71 [0.51, 0.99]). Metformin was associated with a lower risk of MACEs compared with comparator treatments (n = 2 RCTs; MH–OR 0.52 [0.37, 0.73]), p < 0.001. Similar results were obtained in a post-hoc analysis including all RCTs fulfilling criteria for inclusion in the analysis (MH–OR: 0.57 [0.42, 0.76]).ConclusionsThis updated meta-analysis suggests that metfomin is significantly associated with lower risk of MACEs and tendentially lower all-cause mortality compared to placebo or other anti-hyperglycaemic drugs.     

Surgical Aortic Valve Replacement Versus Conservative Treatment in Asymptomatic Severe Aortic Stenosis: An Updated Systematic Review and Meta-Analysis

BackgroundWhile aortic valve replacement (AVR) is indicated for symptomatic severe aortic stenosis (AS), the appropriate management of asymptomatic severe AS remains unclear. We conducted an updated meta-analysis to compare the outcomes of surgical AVR (SAVR) versus conservative treatment in patients with asymptomatic severe AS.MethodsWe searched PubMed, EMBASE, Cochrane, clinicaltrials.gov, and Google Scholar for studies comparing outcomes of SAVR versus conservative treatment in asymptomatic severe AS. Risk ratios (RRs) and 95% confidence intervals (CIs) were calculated for each individual study. Outcomes included all-cause mortality, cardiovascular and non-cardiovascular mortality, 30-day operative mortality, sudden cardiac death (SCD), heart failure hospitalization (HFH), myocardial infarction (MI), and stroke.ResultsA total of 8 studies with 2685 patients were included. The mean age was above 60 years, and the median follow-up duration was 4 years. Compared to conservative treatment, SAVR was associated with significantly lower all-cause mortality (RR 0.39; 95% CI 0.23–0.64) and HFH rates (RR 0.18; 95% CI 0.05–0.71). There were no significant differences in cardiovascular mortality (RR 0.24; 95% CI 0.03–1.67), non-cardiovascular mortality (RR 0.49; 95% CI 0.23–1.03), 30-day operative mortality (RR 0.48; 95% CI 0.10–2.32), SCD (RR 0.37; 95% CI 0.05–2.89), MI (RR 0.48; 95% CI 0.04–5.52), and stroke rates (RR 1.20; 95% CI 0.35–4.11) between the two strategies.ConclusionsIn patients with asymptomatic severe AS, SAVR is associated with significantly lower all-cause mortality and HFH compared to conservative treatment. While SAVR is a promising option for asymptomatic severe AS, most studies were observational and nonrandomized; randomized trials are needed to establish a clear benefit.     

Increased serum interleukin-6 level as a predictive biomarker for atrial fibrillation: A systematic review and meta-analysis

BackgroundAtrial fibrillation (AF) is related to a higher risk of thromboembolic events and mortality. Some studies have demonstrated that the inflammatory biomarker interleukin-6 (IL-6) is associated with a higher risk of higher thrombosis in AF patients, but the real effect of IL-6 remains a controversy.MethodsWe conducted a systematic review and meta-analysis to investigate the association between IL-6 and thromboembolic events, as well as bleeding events, acute coronary syndrome (ACS) events and all-cause mortality in AF.ResultsA total of five studies involving 22 928 patients met our inclusion criteria for the systematic review. The higher level of IL-6 in AF patients is related to long-term thromboembolic events including stroke (RR 1.44, CI 95% 1.09-1.90, p=0.01). IL-6 meant a higher risk of long-term bleeding risk (RR 1.36, CI 95% 1.06-1.74, p=0.02), ACS risk (RR 1.81, CI 95% 1.43-2.30, p<0.001) and all-cause mortality (RR 2.35, CI 95% 2.09-2.65, p<0.001).ConclusionA higher level of IL-6 may predict a greater number of long-term thromboembolic events and bleeding events, ACS events and mortality in AF patients. Further studies such as the cut-off point of IL-6 need to be conducted in the future.     

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.     

Homocysteine level and risk of different stroke types: A meta-analysis of prospective observational studies

Background and aimsInconsistent findings have been reported regarding the association between elevated plasma homocysteine (Hcy) levels and the risk of different types of strokes. We conducted this meta-analysis to identify the association between homocysteine (Hcy) levels and different kinds of strokes or recurrences of strokes.Methods and resultsPubMed and Embase databases were searched for relevant studies published prior to April 2013. Only prospective studies that compared elevated Hcy levels with the risk of different types of strokes were selected. Results were presented as the relative risk (RR) and the corresponding 95% confidence intervals (CI) comparing the highest Hcy category group with the lowest Hcy category group. Nine studies composed of 13,284 participants were included. The pooled RR of ischemic strokes when comparing the highest Hcy category group with the lowest Hcy category group was 1.69 (95% CI: 1.29–2.20) in a fixed-effect model. The pooled RR of hemorrhagic strokes and recurrent strokes when comparing the highest Hcy category group with the lowest Hcy category group in a fixed-effect model was 1.65 (95% CI: 0.61–4.45) and 1.76 (95% CI: 1.37–2.24), respectively.ConclusionsThis meta-analysis indicated that elevated Hcy levels are associated with an increased risk for ischemic strokes and recurrent strokes but had no distinct association with hemorrhagic strokes.