The efficacy and safety of CYP2C19 genotype-guided antiplatelet therapy compared with conventional antiplatelet therapy in patients with acute coronary syndrome or undergoing percutaneous coronary intervention: A meta-analysis of randomized controlled trials

Abstract

Cytochrome P450 (CYP) 2C19 genotype is closely associated with the metabolism and efficacy of clopidogrel, thereby having an important impact on clinical outcomes of patients with acute coronary syndrome (ACS) or undergoing percutaneous coronary intervention (PCI). This study aimed to evaluate the efficacy and safety of CYP2C19 genotype-guided antiplatelet therapy in patients with ACS or undergoing PCI. PubMed, EMBASE, the Cochrane Library and clinicaltrials.gov were searched to identify randomized controlled trials (RCTs) comparing CYP2C19 genotype-guided antiplatelet therapy with conventional therapy in patients with ACS or undergoing PCI. Eight RCTs involving 6708 patients were included in this meta-analysis. CYP2C19 genotype-guided antiplatelet therapy was slightly superior to the conventional antiplatelet therapy in reducing the risk of MACE [RR(95%CI): 0.71(0.51–0.98), p = .04]. Meanwhile, the genotype-guided therapy group had significantly lower incidence of myocardial infarction [RR(95%CI): 0.56(0.40–0.78), p < .01], but similar risk of all-cause mortality, cardiovascular mortality, stent thrombosis, urgent revascularization and stroke compared to the conventional therapy group. Incidences of major/minor bleeding and major bleeding were comparable between the two groups. In patients with ACS or undergoing PCI, CYP2C19 genotype-guided antiplatelet therapy displayed benefit over conventional antiplatelet therapy in reducing the risk of MACE and myocardial infarction, without increasing bleeding risk. Further RCTs are needed to provide more evidences for CYP2C19 genotype-guided antiplatelet therapy.     

Valor pronóstico de las frecuencias cardiacas bajas en pacientes ingresados con infarto agudo de miocardio

Introduction and objectivesThe risk prediction scores adopted in acute coronary syndromes (ACS) use incremental models to estimate mortality for heart rate (HR) above 60 bpm. Nonetheless, previous studies reported a nonlinear relationship between HR and events, suggesting that low HR may have an unrecognized prognostic role. We aimed to assess the prognostic impact of low HR in ACS, defined as admission HR < 50 bpm.MethodsThis study analyzed data from the AMIS Plus registry, a cohort of hospitalized patients with ACS between 1999 and 2021. The primary endpoint was in-hospital all-cause mortality, while a composite of all-cause mortality, major cardiac/cerebrovascular events was set as the secondary endpoint. A multilevel statistical method was used to assess the prognostic role of low HR in ACS.ResultsThe study included 51 001 patients. Crude estimates showed a bimodal distribution of primary and secondary endpoints with peaks at low and high HR. A nonlinear relationship between HR and in-hospital mortality was observed on restricted cubic spline analysis. An HR of 50 to 75 bpm showed lower mortality than HR < 50 bpm (OR, 0.67; 95%CI, 0.47-0.99) only after primary multivariable analysis, which was not confirmed after multiple sensitivity analyses. After propensity score matching, progressive fading of the prognostic role of HR < 50 bpm was evident.ConclusionsLow admission HR in ACS is associated with a higher crude rate of adverse events. Nonetheless, after correction for baseline differences, the prognostic role of low HR was not confirmed. Therefore, low HR probably represents a marker of underlying morbidity. These results may be clinically relevant in improving the accuracy of risk scores in ACS.     

Transient vs In-Hospital Persistent Acute Kidney Injury in Patients With Acute Coronary Syndrome

BackgroundThe occurrence of acute kidney injury (AKI) among patients with acute coronary syndrome (ACS) undergoing invasive management is associated with worse outcomes. However, the prognostic implications of transient or in-hospital persistent AKI may differ.ObjectivesThe aim of this study was to evaluate the prognostic implications of transient or in-hospital persistent AKI in patients with ACS.MethodsIn the MATRIX (Minimizing Adverse Haemorrhagic Events by Transradial Access Site and Systemic Implementation of Angiox) trial, 203 subjects were excluded because of incomplete information or end-stage renal disease, with a study population of 8,201 patients. Transient and persistent AKI were defined as renal dysfunction no longer or still fulfilling the AKI criteria (>0.5 mg/dL or a relative >25% increase in creatinine) at discharge, respectively. Thirty-day coprimary outcomes were the out-of-hospital composite of death, myocardial infarction, or stroke (major adverse cardiovascular events [MACE]) and net adverse cardiovascular events (NACE), defined as the composite of MACE or Bleeding Academic Research Consortium type 3 or 5 bleeding.ResultsPersistent and transient AKI occurred in 750 (9.1%) and 587 (7.2%) subjects, respectively. After multivariable adjustment, compared with patients without AKI, the risk for 30-day coprimary outcomes was higher in patients with persistent AKI (MACE: adjusted HR: 2.32; 95% CI: 1.48-3.64; P < 0.001; NACE: adjusted HR: 2.29; 95% CI: 1.48-3.52; P < 0.001), driven mainly by all-cause mortality (adjusted HR: 3.43; 95% CI: 2.03-5.82; P < 0.001), whereas transient AKI was not associated with higher rates of MACE or NACE. Results remained consistent when implementing the KDIGO (Kidney Disease Improving Global Outcomes) criteria.ConclusionsAmong patients with ACS undergoing invasive management, in-hospital persistent but not transient AKI was associated with higher risk for 30-day MACE and NACE. (Minimizing Adverse Haemorrhagic Events by Transradial Access Site and Systemic Implementation of Angiox [MATRIX]; NCT01433627)     

Association of N-terminal pro-brain natriuretic peptide level with adverse outcomes in patients with acute myocardial infarction: A meta-analysis

BackgroundStudies evaluating the association of blood level of N-terminal pro-brain natriuretic peptide (NT-proBNP) with adverse prognosis have yielded conflicting results in patients with acute myocardial infarction (AMI). This meta-analysis sought to evaluate the prognostic value of blood level of NT-proBNP in patients with AMI.MethodsTwo authors independently searched articles in PubMed and Embase databases up to June 13, 2021. Studies evaluating the association of baseline NT-proBNP level with all-cause mortality or major adverse cardiovascular events (MACEs, including death, new or worsening heart failure, recurrent myocardial infarction, revascularization, stroke, etc.) among AMI patients were selected. Multivariable-adjusted risk ratio (RR) with 95% confidence interval (CI) was pooled by the highest vs. lowest category of NT-proBNP level.ResultsA total of 19 studies enrolling 12,158 AMI patients were identified. When compared highest with the lowest category of NT-proBNP level, the pooled RR was 5.28 (95% CI 2.87–9.73) for in-hospital/30-day death, 2.62 (95% CI 2.04–3.37) for follow-up all-cause mortality, and 2.50 (95% CI 1.91–3.28) for follow-up MACEs, respectively. Subgroup analysis further confirmed the value of NT-proBNP in predicting all-cause mortality and MACEs.ConclusionsElevated NT-proBNP level is independently associated with an increased risk of all-cause mortality and MACEs. Determination of blood NT-proBNP level can improve risk stratification of AMI patients.     

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.     

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.     

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.     

Growth differentiation factor-15 predicts major adverse cardiac events and all-cause mortality in patients with atrial fibrillation

Background: Growth-differentiation factor-15 (GDF-15) has recently been described as a potential biomarker for predicting risk of mortality and cardiovascular events in patients with atrial fibrillation (AF) but requires validation in clinical practice.Methods: The study population consisted of 362 patients (mean age: 71 years, 37% women) with non-valvular AF included in a prospective cohort study. Relationship of GDF-15 with all-cause mortality and major adverse cardiac events (MACE) was analyzed using Cox regression. Survival analysis stratified by GDF-15 was based on national death records, while MACE was recorded at personal follow-up. Further, we evaluated the recently developed GDF-15 based prognostic score towards prediction of all-cause mortality (ABC-death score).Results: Over a median observation period of 4.3 years, 81 (23.3%) patients died, and over a median personal follow-up of 316 days 47 MACE occurred. GDF-15 was independently associated with all-cause mortality (adjusted HR per double increase 2.33, 95%CI 1.74-3.13) and MACE (adjusted HR per double increase 2.33, 95%CI 1.60-3.39). GDF-15 levels, measured at follow-up, were similarly associated with mortality, and longitudinal measurements of GDF-15 did not significantly differ. Six-year survival probability of patients above vs. below the median GDF-15 level was 44% (95%CI 34-57) and 84% (95%CI 76-93), respectively. The ABC-death score revealed a C-statistic of 0.80.Conclusion: GDF-15 predicts risk of all-cause mortality and MACE in patients with non-valvular AF. Further, the ABC-death score showed good predictive accuracy in a “real-world” cohort. Therefore, introduction of GDF-15 into clinical practice would enhance risk prediction of morbidity and mortality in AF patients.     

Prevalence,determinants and prognostic value of high coronary artery calcium score in asymptomatic patients with diabetes: A systematic review and meta-analysis

BackgroundThe pharmacological management of diabetes is mostly based on its cardiovascular risk assessment. For this purpose, coronary artery calcium score (CACS) is proposed with a soft (class IIb) recommendation, as its prognostic implication requires further evidence in different subsets. Thus, we carried-out a systematic review and meta-analysis to address the prevalence of high CACS, its determinants and prognostic value in asymptomatic patients with diabetes, with a special focus on different sex and ethnic groups.MethodsWe carried out a systematic review of the published literature in several databases between 01/2000 and 01/2021. Original studies were included if they presented data on the prevalence, determinants and prognosis of high CACS in patients with diabetes without known cardiovascular disease. Using random effects models, we calculated pooled odds ratios (OR) for CACS determinants and Relative Risk (RR) for CACS prognostic value on all-cause mortality and/or fatal and non-fatal CV events in different categories.ResultsWe included 23 studies (n = 20,999 patients). Female sex and black ethnicity presented the lowest prevalence of CACS>0. Age, male sex, non-black ethnicity and diabetes duration were identified as risk factors for high CACS. Among the 10 studies (n = 110,396 person-years) with prognostic data, the pooled RR for the occurrence of all-cause death and/or cardiovascular events were 4.03 (95%CI: 3.04–5.34), 5.87 (95%CI: 4.32–7.99) and 9.04 (95%CI: 5.81–14.06) respectively for CACS>0 vs. CACS = 0, CACS≥100 vs. CACS<10 and CACS≥400 vs. CACS<10. For similar CACS, these RR were greater in women than in men.ConclusionOur meta-analysis demonstrates that the increase in CACS is strongly associated with an increased risk for all-cause mortality and/or fatal and non-fatal CV events in asymptomatic patients with diabetes.     

Impact of admission serum acid uric levels on in-hospital outcomes in patients with acute coronary syndrome

BackgroundTo assess the association between admission serum uric acid (SUA) levels and in-hospital outcomes in a real-world patients population with acute coronary syndrome (ACS) and to investigate the potential incremental prognostic value of SUA added to GRACE score (GRACE-SUA score).MethodsThe data of consecutive ACS patients admitted to Coronary Care Unit of San Paolo and Niguarda hospitals in Milan (Italy) were retrospectively analyzed.Results1088 patients (24% female) were enrolled. Mean age was 68 years (IQR 60–78). STEMI and NSTE-ACS patients were 504 (46%) and 584 (54%) respectively. SUA (OR 1.72 95%CI 1.33–2.22, p < 0.0001) and GRACE score (OR 1.04 95%CI 1.02–1.06, p < 0.0001) were significantly associated with an increased risk of in-hospital death at the multivariate analysis. Admission values of SUA were stratified in four quartiles. Rates of acute kidney injury, implantation of intra-aortic balloon pump and non-invasive ventilation use were significantly higher in the last quartile compared to Q1, Q2 and Q3 (p < 0.01). The areas under the ROC curve (AUC) for GRACE score and for SUA were 0.91 (95% CI 0.89–0.93, p < 0.0001) and 0.79 (95% CI 0.76–0.81, p < 0.0001) respectively. The AUC was larger for predicting in-hospital mortality with the GRACE-SUA score (0.94; 95% CI 0.93–0.95).ConclusionsHigh admission levels of SUA are independently associated with in-hospital adverse outcomes and mortality in a contemporary population of ACS patients. The inclusion of SUA to GRACE risk score seems to lead to a more accurate prediction of in-hospital mortality in this study population.     

Monocyte to high-density lipoprotein ratio predict long-term clinical outcomes in patients with coronary heart disease: A meta-analysis of 9 studies

Background:A novel inflammation-related biomarker, the monocyte to high-density lipoprotein cholesterol ratio (MHR), had a great relation to the development and prognosis of coronary atherosclerotic heart disease. Current study was to investigate whether the MHR was a potential tool in predicting the mortality and major adverse cardiac events (MACEs) in patients suffering coronary heart disease (CHD) by meta-analysis.Methods:The Cochrane Library, PubMed, MEDLINE, Scopus, EMBASE, and Web of science were searched for relevant cohort studies published prior to February 10, 2022. The association between MHR and mortality/MACEs was analyzed in patients with CHD. Hazard ratios (HR) with 95% confidence interval (CI) were calculated to estimate the strength of association.Results:In the meta-analysis, a total of 9 studies of 11,345 patients with CHD were included. Compared with the low level of MHR group, the high MHR value was associated with higher long-term MACEs (HR = 1.72 95% CI 1.36–2.18, P < .001), long-term mortality (HR = 1.71, 95% CI 1.10–2.66, P = .017), and in-hospital mortality/MACEs (HR = 2.82, 95% CI = 1.07–7.41, P = .036).Conclusions:This study suggested that increased MHR value might be associated with higher long-term mortality and long-term MACEs in CHD patients. MHR might serve as a potential prognostic indicator for risk stratification in patients with CHD.     

Association between monocyte count to high-density lipoprotein cholesterol ratio and mortality in patients undergoing peritoneal dialysis

Background and aimsPrevious studies had demonstrated that elevated monocyte count to high-density lipoprotein cholesterol ratio (MHR), a novel marker of inflammation, was associated with higher cardiovascular events and mortality in patients with pre-dialysis chronic kidney disease, diabetes, and coronary heart disease. However, the association between MHR and mortality in patients undergoing peritoneal dialysis (PD) has received little attention. The aim of this study was to investigate the association between MHR and all-cause and cardiovascular mortality in PD patients.Methods and resultsIn this single center retrospective cohort study, PD patients who had catheter insertion in our PD center from January 1, 2006 to December 31, 2016 were enrolled. All patients were divided into three groups according to the tertiles of baseline MHR levels and followed up until December 31, 2018. The associations of MHR levels with all-cause and cardiovascular mortality were assessed by using Cox proportional hazards models. Of 1584 patients, mean age was 46.02 ± 14.65 years, 60.1% were male, and 24.2% had diabetes. The mean MHR level was 0.39 ± 0.23. During a median follow up time of 45.6 (24.6–71.8) months, 349 patients died, and 181 deaths were caused by cardiovascular disease. After adjusting for confounders, the highest MHR tertile was significantly associated with all-cause and cardiovascular mortality with a hazard ratio of 1.43 (95%CI = 1.06–1.93, P = 0.019), 1.54 (95%CI = 1.01–2.35, P = 0.046), respectively.ConclusionHigher MHR level was an independent risk factor for all-cause and cardiovascular mortality in PD patients.     

Prognostic Value of Preprocedural LV Global Longitudinal Strain for Post-TAVR-Related Morbidity and Mortality: A Meta-Analysis

BackgroundLeft ventricular ejection fraction (LVEF) demonstrates limited prognostic value for post-transcatheter aortic valve replacement (TAVR) outcomes. Evidence regarding the potential role of left ventricular global longitudinal strain (LV-GLS) in this setting is inconsistent.ObjectivesThe aim of this systematic review and meta-analysis of aggregated data was to evaluate the prognostic value of preprocedural LV-GLS for post–TAVR-related morbidity and mortality.MethodsThe authors searched PubMed, Embase, and Web of Science for studies investigating the association between preprocedural 2-dimensional speckle-tracking–derived LV-GLS and post-TAVR clinical outcomes. An inversely weighted random effects meta-analysis was adopted to investigate the association between LV-GLS vs primary (ie, all-cause mortality) and secondary (ie, major cardiovascular events [MACE]) post-TAVR outcomes.ResultsOf the 1,130 identified records, 12 were eligible, all of which had a low-to-moderate risk of bias (Newcastle-Ottawa scale). On average, 2,049 patients demonstrated preserved LVEF (52.6% ± 1.7%), but impaired LV-GLS (−13.6% ± 0.6%). Patients with a lower LV-GLS had a higher all-cause mortality (pooled HR: 2.01; 95% CI: 1.59-2.55) and MACE (pooled odds ratio [OR]: 1.26; 95% CI: 1.08-1.47) risk compared with patients with higher LV-GLS. In addition, each percentage point decrease of LV-GLS (ie, toward 0%) was associated with an increased mortality (HR: 1.06; 95% CI: 1.04-1.08) and MACE risk (OR: 1.08; 95% CI: 1.01-1.15).ConclusionsPreprocedural LV-GLS was significantly associated with post-TAVR morbidity and mortality. This suggests a potential clinically important role of pre-TAVR evaluation of LV-GLS for risk stratification of patients with severe aortic stenosis. (Prognostic value of left ventricular global longitudinal strain in patients with aortic stenosis undergoing Transcatheter Aortic Valve Implantation: a meta-analysis; CRD42021289626)     

Impact of Acquired Thrombocytopenia on Cardiovascular Outcomes in Patients With Coronary Artery Disease Undergoing Percutaneous Coronary Intervention: A Systematic Review and Meta-Analysis

BackgroundAcquired thrombocytopenia (aTP) is associated with a high frequency of bleeding and ischemic complications in patients undergoing percutaneous coronary intervention (PCI). Herein, we report a meta-analysis evaluating the adverse effects of aTP on cardiovascular outcomes and mortality post-PCI.MethodsA literature search was performed using PubMed, Embase, Cochrane and, clinicaltrials.gov from the inception of these databases through October 2019. Patients were divided into two groups: 1) No Thrombocytopenia (nTP) and 2) Acquired Thrombocytopenia (aTP) after PCI. Primary endpoints were in-hospital, 30-day and all-cause mortality rates at the longest follow-up. The main summary estimate was random effects Risk ratio (RR) with 95% confidence intervals (CIs).ResultsSeven studies involving 57,247 participants were included. There was significantly increased in-hospital all-cause mortality (HR 10.73 [6.82–16.88]), MACE (HR 2.96 [2.24–3.94]), major bleeding (HR 4.78 [3.54–6.47]), and target vessel revascularization (TVR) (HR 7.53 [2.8–20.2]), in the aTP group compared to the nTP group. Similarly, aTP group had a statistically significant increased incidence of 30-day all-cause mortality (HR 6.08), MACE (HR 2.77), post-PCI MI (HR 1.98), TVR (HR 5.2), and major bleeding (HR 12.73). Outcomes at longest follow-up showed increased incidence of all-cause mortality (HR 3.98 [1.53–10.33]) and MACE (HR 1.24 [0.99–1.54]) in aTP group, while there was no significant difference for post-PCI MI (HR 0.94 [0.37–2.39]) and TVR (HR 0.96 [0.69–1.32]) between both groups.ConclusionsAcquired Thrombocytopenia after PCI is associated with increased morbidity, mortality, adverse bleeding events and the need for in-hospital and 30-day TVR.     

The association between triglyceride-glucose index and major adverse cardiovascular events in patients with acute coronary syndrome – dose–response meta-analysis

Background and aimsTriglyceride-Glucose (TyG) index is an accurate biomarker of insulin resistance, which is potentially associated with adverse cardiovascular events. We aimed to assess the dose–response relationship between Triglyceride-Glucose (TyG) Index and Major Adverse Cardiovascular Events (MACE) in patients with Acute Coronary Syndrome (ACS).Methods and resultsA systematic literature search was performed using PubMed, Scopus, and Embase for records published from the inception up until 7 February 2021. Studies that fulfilled all of these criteria were included: 1) prospective or retrospective observational studies reporting patients with ACS and 2) assessing the impact of TyG index on MACE with at least three quantitative classifications. The outcome of interest is MACE across the TyG index intervals. MACE was a composite of all-cause mortality, myocardial infarction, unstable angina pectoris, target vessel revascularization, cerebrovascular accidents, and heart failure. The effect estimates were reported as relative risks (RRs). There are 13,684 subjects from 4 studies included in this meta-analysis. This meta-analysis showed that the highest category of TyG index was associated with twofold MACE (RR 2.09 [1.59, 2.76], p < 0.001; I²: 68.4%, p = 0.02) compared to the lowest category in patients with ACS. Dose–response meta-analysis showed that the relationship between TyG index and MACE was non-linear (p < 0.001), with statistical significance reached around TyG index 8.9 and increased non-linearly. The dose–response curve became significantly steeper after TyG index of 9.1–9.2.ConclusionTyG index was associated with MACE in patients with ACS in a non-linear fashion.ProsperoCRD42021235765.     

Prognostic value of disability on mortality: 15-year follow-up of the Bambuí cohort study of aging

BackgroundDisability is a concern in the context of population ageing. The extent of an individual’s disability is a major determinant of whether or not they require long-term care or survival time. We investigated the effect of three disability domains as predictors of all-cause mortality over 15-year follow-up in a Brazilian socioeconomically disadvantaged and multiracial older adult population.MethodsWe estimated Cox proportional hazards models using data from 1333 community-dwelling individuals aged 60 and older from the Bambuí Cohort Study of Ageing. Disability was defined as a great difficulty or not being able to perform one and two or more activities in each domain: mobility, instrumental activities of daily living (IADL) and basic activities of daily living (BADL).ResultsThe overall mortality rate was 46.1 per 1000 person-years at risk (pyrs) and it was higher in men. Among men, the fully adjusted Hazard Ratios (HRs) were 1.92 (95%CI: 1.43-2.58), 2.07 (95%CI: 1.53-2.79) and 1.65 (95%CI: 1.11-2.45), and among women 1.75 (95%CI: 1.38-2.21), 1.43 (95%CI: 1.11-1.84) and 1.43 (95%CI: 1.05-1.95), for two or more disability in mobility tasks, IADLs and BADLs, respectively, compared to those with no difficulty or some difficulty to perform all the tasks.ConclusionA similar risk of death for mobility, IADL and BADL in both genders was found, suggesting that any of these domains can be used to identify risk of all-cause mortality among older adults. The number of activities with limitations in each domain was an important factor.     

Radial vs Femoral Access in ACS Patients Undergoing Complex PCI Is Associated With Consistent Bleeding Benefit and No Excess of Risks

BackgroundThe comparative effectiveness of transradial (TRA) compared with transfemoral (TFA) access in acute coronary syndrome (ACS) patients undergoing complex percutaneous coronary intervention (PCI) remains unclear.MethodsAmong 8404 ACS patients in the Minimising Adverse Haemorrhagic Events by Transradial Access Site and Systemic Implementation of AngioX (MATRIX)—Access trial, 5233 underwent noncomplex (TRA: n = 2590; TFA: n = 2643) and 1491 complex (TRA: n = 777; TFA: n = 714) PCI. Co-primary outcomes were major adverse cardiovascular events (MACE, the composite of all-cause mortality, myocardial infarction, or stroke) and the composite of MACE and Bleeding Academic Research Consortium (BARC) type 3 or 5 bleeding (net adverse cardiovascular events [NACE]) at 30 days.ResultsRates of 30-day MACE (HR 0.94, 95% CI 0.72-1.22) or NACE (HR 0.89, 95% CI 0.69-1.14) did not significantly differ between groups in the complex PCI group, whereas both primary end points were lower (HR 0.84, 95% CI 0.70-1.00; HR 0.83, 95% CI 0.70-0.98; respectively) with TRA among noncomplex PCI patients, with negative interaction testing (P_int = 0.473 and 0.666, respectively). Access-site BARC type 3 or 5 bleeding was lower with TRA, consistently among complex (HR 0.18, 95% CI 0.05-0.63) and noncomplex (HR 0.41, 95% CI 0.20-0.85) PCI patients, whereas the former group had a greater absolute risk reduction of 1.7% (number needed to treat: 59) owing to their higher absolute risk.ConclusionsAmong ACS patients, PCI complexity did not affect the comparative efficacy and safety of TRA vs TFA, whereas the absolute risk reduction of access-site major bleeding was greater with TRA compared with TFA in complex as opposed to noncomplex PCI.     

Comparison of glucagons like peptide-1 receptor agonists and dipeptidyl peptide-4 inhibitors regarding cardiovascular safety and mortality in type 2 diabetes mellitus: A network meta-analysis

AimThe effects of dipeptidyl peptide-4 inhibitors (DPP-4is) and sodium-glucose cotransporter-2 inhibitors (SGLT-2is) on type 2 diabetes mellitus (T2DM) on cardiovascular events and all-cause mortality were compared.MethodsThe literature on DPP-4is and SGLT-2is treatment of T2DM was searched through Pubmed, Embase, and the web of science databases with the search deadline May 15, 2020. Network meta-analysis (NMA) was used to compare the effects of two types of inhibitors on cardiovascular events (major adverse cardiovascular events (MACE), nonfatal myocardial infarction (MI), nonfatal stroke, and cardiovascular (CV) death) and all-cause mortality in T2DM patients.ResultsA total of 15 articles were screened, including 125,796 patients. Compared with DPP-4is, SGLT-2is can significantly reduce MACE [OR: 0.86 95% CI (0.78, 0.92)], CV death [OR: 0.85 95% CI (0.71, 1.01)], nonfatal MI [OR: 0.84 95%CI (0.74, 0.95)] and all-cause mortality [OR: 0.78 95% CI (0.69, 0.89)]. For nonfatal stroke, DPP-4is and SGLT-2is have no statistically significant difference [OR: 0.99 95% CI (0.91, 1.07)].ConclusionThese data indicate that SGLT-2is is more beneficial to MACE and all-cause mortality in T2DM patients than DPP-4is.     

Enxerto de Bypass de Artéria Coronária Guiado por Angiografia ou Fisiologia: Uma Metanálise

Background:While invasive coronary angiography is considered the gold standard for the diagnosis of coronary artery disease (CAD) involving the epicardial coronary vessels, coronary physiology-guided revascularization represents a contemporary gold-standard practice for the invasive management of patients with intermediate CAD. Nevertheless, the long-term results of assessing the severity of stenosis through physiology compared to the angiogram as the guide to bypass surgery – coronary artery bypass grafting (CABG) are still uncertain. This meta-analysis aims to assess the clinical outcomes of a physiology guided CABG compared to the angiography-guided CABG.Objectives:We sought to determine if outcomes differ between a physiology guided CABG compared to an angiography-guided CABG.Methods:We searched Medline, EMBASE, and the Cochrane Library. The last date for this search was June 2020, and all of the previous studies were included. We conducted a pooled risk-ratio meta-analysis for four main outcomes: all-cause death, myocardial infarction (MI), target vessel revascularization (TVR) and major adverse cardiovascular events (MACE). P-value <0.05 was considered as statistically significant. Heterogeneity was assessed with Cochran''s Q test and quantified by the I² index.Results:We identified five studies that included a total of 1,114 patients. A pooled meta-analysis showed no significant difference between a physiology guided strategy and an angiography-guided strategy in MI (risk ratio [RR] = 0.72; 95%CI, 0.39–1.33; I2 = 0%; p = 0.65), TVR (RR = 1.25; 95%CI = 0.73–2.13; I2 = 0%; p = 0.52), or MACE (RR = 0.81; 95%CI = 0.62–1.07; I2 = 0%; p = 1). The physiology guided strategy has 0.63 times the risk of all-cause death compared to the angiography-guided strategy (RR = 0.63; 95%CI = 0.42–0.96; I2 = 0%; p = 0.55).Conclusion:This meta-analysis demonstrated a reduction in all-cause death when a physiology guided CABG strategy was used. Nevertheless, the short follow-up period, small sample size of the included studies and the non-discrimination of the causes of death can largely justify these conclusions. Studies with an extended follow-up period of observation are required to draw more robust and definitive conclusions.