Cardiovascular events and all-cause mortality in patients with type 2 diabetes treated with dipeptidyl peptidase-4 inhibitors: An extensive meta-analysis of randomized controlled trials

AimsMeta-analyses of randomized trials on Dipeptidyl Peptidase-4 inhibitors (DPP4i) reported discordant results on major cardiovascular events (MACE), mortality, and heart failure. Aim of this meta-analysis of randomized trials is the assessment of the cardiovascular safety of DPP4i.Data synthesisA Medline, Embase, Cochrane database search for sitagliptin, vildagliptin, omarigliptin, saxagliptin, alogliptin, trelagliptin, anagliptin, linagliptin, gemigliptin, evogliptin, and teneligliptin was performed up to up January 1st, 2020. All trials with a duration ≥24 weeks and comparing the effects of DPP4i with placebo or active drugs were collected. Mantel–Haenszel odds ratio (MH-OR) with 95% Confidence Interval (95% CI) was calculated for all outcomes defined above. A total of 182 eligible trials were identified. DPP-4i were not associated with an increased risk of MACE (MH-OR 0.99 [0.93, 1.04]), all-cause mortality (MH-OR 0.99 [0.93, 1.06]), and heart failure (MH-OR 1.05 [0.96, 1.15]) with no significant differences across individual molecules, except for saxagliptin, which was associated with an increased risk of heart failure.ConclusionsAs a class, DPP4i are not associated with any increase or reduction of MACE, all-cause mortality, and heart failure. Saxagliptin seems to be associated with an increased risk of hospitalization for heart failure.     

Dipeptidyl peptidase-4 inhibitors and heart failure: A meta-analysis of randomized clinical trials

Background & aimsRecently, the SAVOR TIMI-53 (Saxagliptin Assessment of Vascular Outcomes Recorded in patients with diabetes mellitus – Thrombolysis in Myocardial Infarction-53) reported a significant increase in the risk of hospitalizations for heart failure in patients treated with saxagliptin in comparison with placebo. Aim of the present meta-analysis is the systematic collection and synthesis of information on treatment-emergent cases of acute heart failure described in randomized clinical trials with DPP4.Methods & resultsData sources: An extensive Medline, Embase, and Cochrane Database search for “vildagliptin”, “sitagliptin”, “saxagliptin”, “alogliptin”, “linagliptin”, and “dutogliptin” was performed, collecting all randomized clinical trials on humans up to October 1st, 2013. Studies were included if they satisfied the following criteria: i) randomized trials, ii) duration ≥24 weeks; iii) on type 2 diabetes; iv) comparison of DPP4i with placebo or active drugs. The principal outcome was the effect of DPP4i on the incidence of acute heart failure. A total of 84 eligible trials was identified. The overall risk of acute heart failure was higher in patients treated with DPP4i in comparison with those treated with placebo/active comparators (MH–OR: 1.19[1.03; 1.37]; p = 0.015). When trials with non-cardiovascular outcomes were analysed separately no signal of risk was detectable.ConclusionAvailable data from RCTs suggest that DPP4i could be associated with an increased risk of heart failure, without any clear evidence of differences among drugs of the class. Although it is plausible that the risk is greater in some sub-populations of patients, current evidence is not yet sufficient to identify susceptible patients.     

Major cardiovascular events,heart failure,and atrial fibrillation in patients treated with glucagon-like peptide-1 receptor agonists: An updated meta-analysis of randomized controlled trials

Background and aimsGlucagon-like Peptide 1 Receptor Agonists (GLP1-RA) has been associated with a reduction of major cardiovascular events (MACE) and mortality on the basis of the results of cardiovascular outcome trials (CVOT). Several meta-analyses on this issue have been recently published; however, they were all restricted to CVOT, with the exclusion of all studies designed for other endpoints; moreover, other cardiovascular endpoints, such as atrial fibrillation and heart failure have not been fully explored.Methods and resultsA Medline search for GLP-1 receptor agonists (exenatide, liraglutide, lixisenatide, albiglutide, dulaglutide, or semaglutide) was performed, collecting all randomized clinical trials with a duration ≥52 weeks, enrolling patients with type 2 diabetes, and comparing a GLP-1 receptor agonist with placebo or any other non-GLP-1 receptor agonist drug. We included 43 trials, enrolling 63,134 patients. A significant reduction of MACE (MH-OR 0.87 [0.83, 0.92]), all-cause mortality (MH-OR 0.89 [0.83, 0.96]), and a nonstatistical trend toward reduction of heart failure (MH-OR 0.93 [0.85, 1.01]) was observed – GLP1-RA did not increase the risk of atrial fibrillation (MH-OR 0.94 [0.84, 1.04]).ConclusionThe present meta-analysis confirms the favorable effects of glucagon-like peptide-1 receptor agonists on major cardiovascular events, cardiovascular and all-cause mortality, stroke, and possibly myocardial infarction. Conversely, the effects on heart failure remain uncertain. Available data on atrial fibrillation seems to exclude any major safety issues in this respect.Registration number (PROSPERO)CRD42018115577.     

Development and Internal Validation of a Risk Prediction Model for Acute Cardiovascular Morbidity in Preeclampsia

BackgroundWomen with preeclampsia are at increased short-term risk of adverse cardiovascular outcomes during pregnancy and the early postpartum period. We aimed to develop and internally validate a risk assessment tool to predict acute cardiovascular morbidity in preeclampsia.MethodsThe study was conducted at an academic obstetrics hospital. Participants with preeclampsia at delivery from 2007 to 2017 were included. A model to predict acute cardiovascular morbidity at delivery and within 6 weeks after delivery was developed and evaluated. The primary composite outcome included pulmonary edema/acute heart failure, myocardial infarction, aneurysm, cardiac arrest/ventricular fibrillation, heart failure/arrest during surgery or procedure, cerebrovascular disorders, cardiogenic shock, conversion of cardiac rhythm, and difficult-to-control severe hypertension. We assessed model discrimination and calibration. We used bootstrapping for internal validation.ResultsA total of 4171 participants with preeclampsia were included. The final model comprised 8 variables. Predictors positively associated with acute cardiovascular morbidity (presented as odds ratio with 95% confidence interval) were: gestational age at delivery (20-36 weeks: 5.36 [3.67-7.82]; 37-38 weeks: 1.75 [1.16-2.64]), maternal age (≥ 40 years: 1.65 [1.00-2.72]; 35-39 years: 1.49 [1.07-2.09]), and previous caesarean delivery (1.47 [1.01-2.13]). The model had an area under the receiver operating characteristic curve of 0.72 (95% CI 0.69-0.74). Moreover, it was adequately calibrated and performed well on internal validation.ConclusionsThis risk prediction tool identified women with preeclampsia at highest risk of acute cardiovascular morbidity. If externally validated, this tool may facilitate early interventions aimed at preventing adverse cardiovascular outcomes in pregnancy and postpartum.     

Prognostic Value of Quantitative Metrics From Positron Emission Tomography in Ischemic Heart Failure

ObjectivesThe aim of this study was to investigate the prognostic and clinical value of quantitative positron emission tomographic (PET) metrics in patients with ischemic heart failure.BackgroundAlthough myocardial flow reserve (MFR) is a strong predictor of cardiac risk in patients without heart failure, it is unknown whether quantitative PET metrics improve risk stratification in patients with ischemic heart failure.MethodsThe study included 254 patients referred for stress and rest myocardial perfusion imaging and viability testing using PET. Major adverse cardiac event(s) (MACE) consisted of death, resuscitated sudden cardiac death, heart transplantation, acute coronary syndrome, hospitalization for heart failure, and late revascularization.ResultsMACE occurred in 170 patients (67%) during a median follow-up of 3.3 years. In a multivariate Cox proportional hazards model including multiple quantitative PET metrics, only MFR predicted MACE significantly (p = 0.013). Beyond age, symptom severity, diabetes mellitus, previous myocardial infarction or revascularization, 3-vessel disease, renal insufficiency, ejection fraction, as well as presence and burden of ischemia, scar, and hibernating myocardium, MFR was strongly associated with MACE (adjusted hazard ratio per increase in MFR by 1: 0.63; 95% confidence interval: 0.45 to 0.91). Incorporation of MFR into a risk assessment model incrementally improved the prediction of MACE (likelihood ratio chi-square test [16] = 48.61 vs. chi-square test [15] = 39.20; p = 0.002).ConclusionsIn this retrospective analysis of a single-center cohort, quantitative PET metrics of myocardial blood flow all improved risk stratification in patients with ischemic heart failure. However, in a hypothesis-generating analysis, MFR appears modestly superior to the other metrics as a prognostic index.     

Disparities in health care are driven by where minority patients seek care: examination of the hospital quality alliance measures

BACKGROUND: Racial/ethnic disparities in health care are well documented, but less is known about whether disparities occur within or between hospitals for specific inpatient processes of care. We assessed racial/ethnic disparities using the Hospital Quality Alliance Inpatient Quality of Care Indicators. METHODS: We performed an observational study using patient-level data for acute myocardial infarction (5 care measures), congestive heart failure (2 measures), community-acquired pneumonia (2 measures), and patient counseling (4 measures). Data were obtained from 123 hospitals reporting to the University HealthSystem Consortium from the third quarter of 2002 to the first quarter of 2005. A total of 320,970 patients 18 years or older were eligible for at least 1 of the 13 measures. RESULTS: There were consistent unadjusted differences between minority and nonminority patients in the quality of care across 8 of 13 quality measures (from 4.63 and 4.55 percentage points for angiotensin-converting enzyme inhibitors for acute myocardial infarction and congestive heart failure [P<.01] to 14.58 percentage points for smoking cessation counseling for pneumonia [P=.02]). Disparities were most pronounced for counseling measures. In multivariate models adjusted for individual patient characteristics and hospital effect, the magnitude of the disparities decreased substantially, yet remained significant for 3 of the 4 counseling measures; acute myocardial infarction (unadjusted, 9.00 [P<.001]; adjusted, 3.82 [P<.01]), congestive heart failure (unadjusted, 8.45 [P=.02]; adjusted, 3.54 [P=.02]), and community-acquired pneumonia (unadjusted, 14.58 [P=.02]; adjusted, 4.96 [P=.01]). CONCLUSIONS: Disparities in clinical process of care measures are largely the result of differences in where minority and nonminority patients seek care. However, disparities in services requiring counseling exist within hospitals after controlling for site of care. Policies to reduce disparities should consider the underlying reasons for the disparities.     

An assessment of adverse effects of vildagliptin versus comparators on the liver,the pancreas,the immune system,the skin and in patients with impaired renal function from a large pooled database of Phase II and III clinical trials

Aim: To assess the safety of vildagliptin versus all comparators (ACs) with regard to organs, systems or tissues of particular interest in type 2 diabetes (T2DM) and areas of potential concern with dipeptidyl peptidase‐IV (DPP‐4) inhibitors. Methods: Data were pooled from 38 studies where vildagliptin was given for ≥12 to > 104 weeks in patients with T2DM. Absolute and exposure‐adjusted incidence rates and Peto odds ratios (ORs) versus ACs with corresponding 95% confidence intervals (CI) were calculated. Results: There were > 7000 subject‐years of exposure (SYE) to vildagliptin 50 mg bid and > 6500 SYE to ACs. For mild hepatic enzyme elevations with and without elevated bilirubin levels, the ORs for vildagliptin 50 mg bid were 1.24 (95% CI: [0.80, 1.93]) and 1.19 (95% CI: [0.29, 4.90]), respectively. The exposure‐adjusted incidences of markedly elevated hepatic enzymes and for enzyme elevations with bilirubin ≥ 2× ULN with vildagliptin 50 mg bid were ≤ those in the ACs group. For hepatic and pancreatitis‐related AEs, the ORs for vildagliptin 50 mg bid were 0.87 (95% CI: [0.64, 1.19]) and 0.70 (95% CI: [0.26, 1.88]), respectively, and for any AE in the infections and infestations SOC, this was 1.04 (95% CI: [0.96, 1.13]). The incidences of skin‐related AEs were low and the risk with vildagliptin 50 mg bid was not significantly different from ACs [(OR = 1.10 (95% CI: [0.80, 1.51])]. Conclusions: The present meta‐analyses indicate that vildagliptin was not associated with increased risk of hepatic events or hepatic enzyme elevations indicative of drug‐induced liver injury, pancreatitis, infections or skin‐related toxicity.     

Treatment of patients with myocardial infarction who present with a paced rhythm

BACKGROUND: A paced rhythm can mask the electrocardiographic features of an acute myocardial infarction, complicating timely recognition and treatment. OBJECTIVE: To evaluate characteristics, treatment, and outcomes among patients presenting with paced rhythms during myocardial infarction. DESIGN: Retrospective cohort study. SETTING: U.S. acute care hospitals. PATIENTS: 102 249 Medicare beneficiaries at least 65 years of age who were treated for acute myocardial infarction between 1994 and 1996. MEASUREMENTS: Provision of three treatments for acute myocardial infarction (emergent reperfusion, aspirin, and beta-blockers), death at 30 days, and long-term follow-up. RESULTS: 1954 patients (1.9%) presented with paced rhythms during myocardial infarction. These patients were older; were predominantly male; and had higher rates of congestive heart failure, diabetes, and previous infarction. They were significantly less likely to receive emergent reperfusion (relative risk [RR], 0.27 [95% CI, 0.22 to 0.33]), aspirin (RR at admission, 0.91 [CI, 0.88 to 0.94]; RR at discharge, 0.87 [CI, 0.83 to 0.92]), and beta-blockers at admission (RR, 0.89 [CI, 0.82 to 0.96]). In addition, there was a trend toward decreased use of beta-blockers at discharge (RR, 0.91 [CI, 0.76 to 1.06]). Crude mortality rates were higher among patients with paced rhythms than among those without at 30 days (25.8% vs. 21.3%; P = 0.001) and at 1 year (47.1% vs. 36.1%; P = 0.001). Among patients with paced rhythms, risk for death at 30 days decreased after adjustment for illness severity and decreased use of therapy (RR, 1.03 [CI, 0.93 to 1.14]). Patients with paced rhythms remained at additional risk for long-term mortality (hazard ratio, 1.12 [CI, 1.06 to 1.18]). CONCLUSIONS: Patients with paced rhythms were less likely than those without to receive treatment for acute myocardial infarction and had poorer short- and long-term outcomes. However, this mortality risk diminished after adjustment for treatment. This suggests that improved recognition and treatment of myocardial infarction may improve outcomes, particularly in the short term.     

Prognostic value of copeptin in patients with acute myocardial infarction treated with percutaneous coronary intervention: a prospective cohort study

BackgroundIschemic myocardial injury leads to neurohormonal system activation and increased release of copeptin. Although diagnostic value of copeptin has been widely described, data on its prognostic performance in patients with myocardial infarction is inconclusive. The aim of this study was to asses if elevated copeptin concentration provides prognostic information for long-term adverse cardiac events in a cohort of first acute myocardial infarction patients treated with percutaneous coronary intervention.MethodsCopeptin concentration was assessed in a cohort of 100 consecutive patients (39% women; mean age 63±7 years) presenting with first acute myocardial infarction and subjected to percutaneous coronary intervention. Samples were collected at the time of admission and on the 4^th/5^th day of hospitalisation. All patients were followed-up prospectively for 12 months for the occurrence of major adverse cardiovascular events defined as reinfarction, unscheduled coronary revascularisation and all-cause death.ResultsElevated copeptin concentration on the 4^th/5^th day of hospitalisation was identified as a predictor of major adverse cardiovascular events (P=0.0445). The increase between copeptin level on admission and on day 4^th/5^th was associated with the requirement for unscheduled coronary revascularisation in receiver operating characteristics (ROC) analysis (AUC =0.639; 95% CI: 0.504–0.773; P=0.0430). In a multivariate analysis, copeptin concentration on the 4^th/5^th day of hospitalisation and left ventricular ejection fraction assessed by transthoracic echocardiography, were the only predictors for major adverse cardiac events during follow-up (P=0.024 and P=0.001, respectively).ConclusionsCopeptin seems to be a prognostic marker in patients with first myocardial infarction treated with percutaneous coronary intervention.     

Maternal Education Before Childbirth and Cardiovascular Diseases in Offspring During Early Adulthood: A Danish Population-Based Cohort Study

BackgroundCardiovascular disease (CVD) is increasing in youths, but there is limited knowledge about the etiology of early-onset CVD. We aimed to examine the association between maternal education before childbirth and CVD risk in offspring during early adulthood (20 to 40 years of age).MethodsThis population-based cohort study included 112,3600 subjects born in Denmark during 1977 to 1996.ResultsCompared with offspring born to mothers with high education, offspring born to mothers with low or medium education had 27% (hazard ratio, 1.27; 95% confidence interval, 1.23-1.30) or 12% (1.12; 1.09-1.15) increased overall risk of early-onset CVD, respectively. Increased risks were observed for most type-specific CVDs: in particular, for myocardial infarction (low [2.03; 1.55-2.65] or medium education [1.52; 1.16-1.99]), heart failure (low [1.59; 1.24-2.03] or medium education [1.51; 1.19-1.92]), and ischemic stroke (low [1.50; 1.28-1.76] or medium education [1.29; 1.10-1.51]). We observed high incidences of CVD in offspring of mothers with comorbid CVD (low [1.67; 1.51-1.86] or medium education [1.46; 1.29-1.64]), compared with those of mothers with high education and no history of CVD.ConclusionsLow maternal education before childbirth, especially with maternal comorbid CVD, is significantly associated with increased risk of overall CVD and most type-specific CVDs in offspring in early adulthood. The influence of maternal education on future offspring CVD should be taken into consideration in the assessment of CVD risks from early decades of life.     

Effect of Alirocumab on Incidence of Atrial Fibrillation After Acute Coronary Syndromes: Insights from the ODYSSEY OUTCOMES Trial

BackgroundUsing data from the ODYSSEY OUTCOMES trial (NCT01663402), we sought to identify factors associated with the development of incident atrial fibrillation in patients with recent acute coronary syndrome without prior atrial fibrillation and to determine whether alirocumab treatment influenced risk of incident atrial fibrillation.MethodsODYSSEY OUTCOMES compared alirocumab treatment with placebo in 18,924 patients with recent acute coronary syndrome and dyslipidemia despite high-intensity or maximum-tolerated statin therapy. The primary outcome of major adverse cardiovascular events (MACE) comprised death from coronary heart disease, non-fatal myocardial infarction, fatal or non-fatal ischemic stroke, or unstable angina requiring hospitalization. Patients were classified as having previous atrial fibrillation (present prior to or at randomization) or no previous atrial fibrillation. A multivariable model was used to determine factors associated with incident atrial fibrillation.ResultsAmong 18,262 participants without prior atrial fibrillation at baseline, 499 (2.7%) had incident atrial fibrillation during follow-up. Older age, history of heart failure or myocardial infarction, and higher body mass index were significantly associated with incident atrial fibrillation. Treatment with alirocumab or placebo did not influence the cumulative incidence of atrial fibrillation (hazard ratio 0.91; 95% confidence interval, 0.77-1.09). Patients with vs without a history of atrial fibrillation had a higher incidence of MACE (8.8 vs 3.7 events per 100 patient-years), without significant interaction between atrial fibrillation and randomized treatment on risk of MACE (P_interaction = .78).ConclusionsWhile alirocumab did not modify risk of incident atrial fibrillation after acute coronary syndrome, it did reduce the risk of MACE, regardless of prior atrial fibrillation history. History of atrial fibrillation is an independent predictor of recurrent cardiovascular events after acute coronary syndrome.     

Continuous glucose profiles with vildagliptin versus sitagliptin in add-on to metformin: Results from the randomized Optima study

AimTo compare continuous glucose monitoring (CGM) profiles on vildagliptin versus sitagliptin in addition to metformin, in patients with inadequately controlled type 2 diabetes mellitus (HbA_1c 6.5–8.0%).MethodsA multicenter, prospective, randomised, open-label study with blinded endpoint analysis. CGM data acquired over three days – firstly on metformin alone and then 8 weeks after the addition of either vildagliptin (n = 14) or sitagliptin (n = 16) –were blinded and analyzed centrally.ResultsIn comparable populations with a mean baseline HbA_1c of 7.1%, 24-hour glucose variability – measured by mean amplitude of glucose excursions and standard deviation of mean glucose concentration – showed similar improvement on both drugs versus metformin alone. In contrast, a series of predefined parameters reflecting daily glycaemic control – mean 24-hour blood glucose concentration, and the times spent in the optimal glycaemic range (70–140 mg/dL) and above the hyperglycaemic thresholds of 140 and 180 mg/dL together with the corresponding AUC values – were significantly improved from baseline only in the vildagliptin arm. In addition, overall hyperglycaemia (AUC[24 h] >100 mg/dL) significantly dropped from baseline on vildagliptin [–37%] but not on sitagliptin [–9%], while postprandial hyperglycaemia (AUC[0–4 h] × 3) was significantly reduced on both, and basal hyperglycaemia (overall – postprandial hyperglycaemia was reduced only on vildagliptin [–41%; P = 0.04]).ConclusionsThe addition of a DPP-4 inhibitor significantly reduced glycaemic variability with no difference between the two drugs. However, vildagliptin induced better circadian glycaemic control than sitagliptin with a significant decrease on overall hyperglycemia, mainly driven by reduction on basal hyperglycaemia.     

Cardiovascular safety of vildagliptin in patients with type 2 diabetes: A European multi‐database,non‐interventional post‐authorization safety study

The aim of this non‐interventional, multi‐database, analytical cohort study was to assess the cardiovascular (CV) safety of vildagliptin vs other non‐insulin antidiabetic drugs (NIADs) using real‐world data from 5 European electronic healthcare databases. Patients with type 2 diabetes aged ≥18 years on NIAD treatment were enrolled. Adjusted incidence rate ratios (IRRs) and 95% confidence intervals (CIs) for the outcomes of interest (myocardial infarction [MI], acute coronary syndrome [ACS], stroke, congestive heart failure [CHF], individually and as a composite) were estimated using negative binomial regression. Approximately 2.8% of the enrolled patients (n = 738 054) used vildagliptin at any time during the study, with an average follow‐up time of 1.4 years, resulting in a cumulative current vildagliptin exposure of 28 330 person‐years. The adjusted IRRs (vildagliptin [±other NIADs] vs other NIADs) were in the range of 0.61 to 0.97 (MI), 0.55 to 1.60 (ACS), 0.02 to 0.77 (stroke), 0.49 to 1.03 (CHF), and 0.22 to 1.02 (composite CV outcomes). The IRRs and their 95% CIs were close to 1, demonstrating no increased risk of adverse CV events, including the risk of CHF, with vildagliptin vs other NIADs in real‐world conditions.     

Cardiovascular effectiveness of glucagon-like peptide 1 receptor agonists versus dipeptidyl peptidase-4 inhibitors in type 2 diabetes: A meta-analysis based on propensity score-matched studies

Glucagon-like peptide 1 receptor agonists (GLP-1RA) and dipeptidyl peptidase-4 inhibitors (DPP-4i) are two novel classes of hypoglycemic agents. The relative cardiovascular effectiveness between these two drug classes in patients with type 2 diabetes (T2D) is unestablished due to the absence of large cardiovascular outcome trials directly comparing DPP-4i with GLP-1RA. We aimed to incorporate large propensity score-matched cohort studies to conduct a meta-analysis, to determine the relative effectiveness of GLP-1RA versus DPP-4i on cardiovascular endpoints in T2D patients. Compared to DPP-4i, GLP-1RA was associated with the significantly lower risks of major adverse cardiovascular events [MACE] (HR 0.76, 95% CI 0.63?0.92), cardiovascular mortality (HR 0.59, 95% CI 0.37?0.95), myocardial infarction (HR 0.89, 95% CI 0.80?0.98), stroke (HR 0.86, 95% CI 0.76?0.96), and all-cause mortality (HR 0.63, 95% CI 0.42?0.96) in T2D patients; whereas these two drug classes had the similar risk of hospitalization for heart failure [HHF] (HR 0.95, 95% CI 0.77–1.16). Meta-regression analyses showed that six factors (i.e., mean age, female proportion, cardiovascular disease proportion, heart failure proportion, and the proportions of receiving metformin and insulin at baseline) did not significantly affect the effects of GLP-1RA on MACE and HHF (P ≥ 0.076). This meta-analysis provides the direct evidence regarding the relative cardiovascular effectiveness of GLP-1RA versus DPP-4i from real-world studies, and its findings suggest that among T2D patients GLP-1RA should be considered in preference to DPP-4i as for preventing atherosclerotic cardiovascular events and death in clinical practice.     

Hemoglobin,Frailty, and Long-term Cardiovascular Events in Community-Dwelling Older Men Aged ≥ 70 Years

BackgroundAnemia is associated with increased risk of all-cause mortality in older populations. However, the relationship between hemoglobin and major adverse cardiovascular events (MACE), and whether this is modulated by frailty, is unclear.MethodsCHAMP (Concord Health and Ageing in Men Project) is a prospective study of community-dwelling men aged ≥ 70 years. The relationship between hemoglobin and 7-year MACE was analysed by means of Cox regression. The Youden index was used to determine the optimal hemoglobin cutoff point in predicting MACE. Frailty was assessed with the use of the Fried criteria.ResultsThe cohort comprised 1604 men (mean ± SD age 76.9 ± 5.5 years). Decreasing hemoglobin was associated with increased comorbidity, frailty, and MACE (P < 0.001), with 140 g/L the optimal cutoff point for predicting MACE. Hemoglobin, age, and frailty independently predicted MACE (all P < 0.001). Each 10 g/L decrement in hemoglobin level was associated with increased risk of MACE (hazard ratio [HR] 1.13, 95% confidence interval [CI] 1.06-1.20; P < 0.001), all-cause mortality (HR 1.20, 95% CI 1.12-1.29; P < 0.001), cardiovascular mortality (HR 1.07, 95% CI 1.01-1.14; P = 0.025), myocardial infarction (HR 1.17, 95% CI 1.09-1.25; P < 0.001), and heart failure (HR 1.17, 95% CI 1.09-1.25; P < 0.001). When stratified into hemoglobin quintiles, men in the lowest 2 quintiles (Hb 133-140 g/L and < 132g/L, respectively) were at increased risk of MACE, cardiovascular mortality, myocardial infarction, and heart failure (all P < 0.05). This relationship for MACE was independent from frailty status, with the test for interaction between frailty and hemoglobin not reaching significance (P = 0.24).ConclusionsLow hemoglobin was associated with increased MACE in community-dwelling older men independently from frailty. A hemoglobin cutoff point of 140 g/L, a level that is above contemporary definitions of anemia, predicted long-term MACE.     

Dipeptidyl peptidase-4 as a new target of action for type 2 diabetes mellitus: a systematic review

Type 2 diabetes mellitus is a metabolic disease leading to microvascular and macrovascular complications including coronary artery disease and stroke. Management of diabetes has been challenging, particularly in the presence of the enormous prevalence of obesity. In recent years, various inhibitors of the enzyme dipeptidyl peptidase (DPP)-4 have been developed to treat diabetes. The enzyme DPP-4 cleaves incretins, which, among other functions, stimulate insulin and suppresses glucagon. Inhibition of this enzyme results in an increase in the half-life and the sustained physiologic action of incretins, leading to an improvement in hyperglycemia. One such agent, namely sitagliptin (MK-04,310), has been introduced into the United States market, and another agent, vildagliptin (LAF237), is being used in Europe and elsewhere. This article is intended to evaluate the effectiveness of DPP-4 inhibitors as a therapeutic modality for managing type 2 diabetes. The authors conducted a literature search of various databases to identify the clinical trials involving the DPP inhibitors and concluded that the DPP-4 inhibitors, for example, sitagliptin and vildagliptin, are efficacious for managing diabetes as monotherapy or combination therapy.     

Discrepancy between stress electrocardiographic changes and nuclear myocardial perfusion defects in the prognostic assessment of patients with chest pain

ObjectivesThe aim of the present study was to determine the long-term prognostic value provided by the exercise electrocardiographic (ECG) response to nuclear myocardial perfusion imaging (MPI) in the evaluation of patients with chest pain, focusing on patients with a discrepancy between the two tests.MethodsA total of 1460 consecutive patients (777 female; 62.6±11.4 years) undergoing exercise myocardial single-photon emission computed tomography (SPECT) were included. The endpoint was the occurrence of acute coronary syndrome, heart failure or cardiac death during follow-up.ResultsIschemic ECG changes were observed during stress testing in 271 patients (18.5%) and 362 patients (24.7%) had positive (abnormal) exercise MPI results. There was a discrepancy between ECG and SPECT findings in 471 patients (32.2%). During the follow-up period (14.0-39.6 months), 224 patients (15.3%) presented cardiac events. The hazard ratios (HR) of ECG and MPI results to predict events were 1.506 (95% CI: 1.113-2.039) and 10.481 (95% CI: 7.799-14.080), respectively. In patients with negative MPI, the ECG response did not predict events (HR 1.214 [95% CI: 0.646-2.282]), the same as in patients with positive MPI (HR 1.203 [95% CI: 0.848-1.705]). Only in hypertensive patients with positive SPECT did the ECG show significant prognostic value (HR 1.937 [95% CI: 1.030-3.642]). In multivariate analysis, positive MPI proved an independent long-term prognostic factor (HR 10.536 [95% CI: 7.759-14.308]), but not ECG (HR 1.356 [95% CI: 0.994-1.850]).ConclusionMPI results (normal vs. abnormal) had strong predictive value and discrepant ECG results had no significant additive prognostic value.     

Clinical Outcomes with β-Blockers for Myocardial Infarction: A Meta-analysis of Randomized Trials

BackgroundDebate exists about the efficacy of β-blockers in myocardial infarction and their required duration of usage in contemporary practice.MethodsWe conducted a MEDLINE/EMBASE/CENTRAL search for randomized trials evaluating β-blockers in myocardial infarction enrolling at least 100 patients. The primary outcome was all-cause mortality. Analysis was performed stratifying trials into reperfusion-era (> 50% undergoing reperfusion or receiving aspirin/statin) or pre-reperfusion-era trials.ResultsSixty trials with 102,003 patients satisfied the inclusion criteria. In the acute myocardial infarction trials, a significant interaction (P_interaction = .02) was noted such that β-blockers reduced mortality in the pre-reperfusion (incident rate ratio [IRR] 0.86; 95% confidence interval [CI], 0.79-0.94) but not in the reperfusion era (IRR 0.98; 95% CI, 0.92-1.05). In the pre-reperfusion era, β-blockers reduced cardiovascular mortality (IRR 0.87; 95% CI, 0.78-0.98), myocardial infarction (IRR 0.78; 95% CI, 0.62-0.97), and angina (IRR 0.88; 95% CI, 0.82-0.95), with no difference for other outcomes. In the reperfusion era, β-blockers reduced myocardial infarction (IRR 0.72; 95% CI, 0.62-0.83) (number needed to treat to benefit [NNTB] = 209) and angina (IRR 0.80; 95% CI, 0.65-0.98) (NNTB = 26) at the expense of increase in heart failure (IRR 1.10; 95% CI, 1.05-1.16) (number needed to treat to harm [NNTH] = 79), cardiogenic shock (IRR 1.29; 95% CI, 1.18-1.41) (NNTH = 90), and drug discontinuation (IRR 1.64; 95% CI, 1.55-1.73), with no benefit for other outcomes. Benefits for recurrent myocardial infarction and angina in the reperfusion era appeared to be short term (30 days).ConclusionsIn contemporary practice of treatment of myocardial infarction, β-blockers have no mortality benefit but reduce recurrent myocardial infarction and angina (short-term) at the expense of increase in heart failure, cardiogenic shock, and drug discontinuation. The guideline authors should reconsider the strength of recommendations for β-blockers post myocardial infarction.