Recent Cardiovascular Outcome Trials Research Articles

Prediction of cardiovascular risk in patients type 2 diabetes using the SCORE2-Diabetes risk score

Abstract Background/Introduction The SCORE2-Diabetes risk score was developed to predict the risk of cardiovascular events (CV-death, non-fatal MI and non-fatal stroke) in patients with T2DM without known cardiovascular disease. Current ESC guidelines recommend the use of this risk score to tailor treatment strategies in this population. Purpose We sought to determine whether the SCORE2-Diabetes risk score was able to appropriately stratify an international cohort of patients from recent cardiovascular clinical outcomes trials. Furthermore, we sought to determine the accuracy and precision of the model including in patients with and without known cardiovascular disease. Methods Patients from 4 randomized cardiovascular outcome trials (DEVOTE, LEADER, PIONEER-6, SUSTAIN-6) were included (n=23,464). Mean follow-up was 2.6 years and outcomes were adjudicated. The SCORE2-Diabetes risk score was calculated using the uncalibrated version which does not account for risk-region. Patients were stratified into low (<5%), moderate (5-<10%), high (10-<20%), and very high risk (≥20%) groups. The SCORE2-Diabetes risk predication model was designed to predict 10-year risk; however, given the mean follow-up from the cohort, outcomes were reported at 36 months. The Brier score, which evaluates estimated risk, and c-index, which evaluates the ability to discriminate between participants, were used to evaluate the precision of the risk score. We further compared the risk score with an estimated risk of MACE calculated using a cause specific Cox model that accounts for competing risk. Results Most patients in the cohort did not have prior myocardial infarction or stroke (57.4%, n=13,467). The SCORE2-Diabetes risk score was able to stratify patients into low, moderate, high, and very high risk cohorts (Figure 1). Observed cardiovascular events at 36 months were higher than the SCORE2-Diabetes risk score predicted (Table 1). The risk score, when included in a regression model, independently predicted cardiovascular death, myocardial infarction, or stroke (HRadj 1.03, p<0.001) and non-cardiovascular death (HRadj 1.05, p<0.001). Including the score in models with only age and sex improved the discrimination and performance of the model. The c-index for the risk score in the overall cohort was 0.62 and was 0.66 in the cohort without known cardiovascular disease. When using the Brier score to evaluate the utility of the model, the Brier score of the SCORE2-D model was 0.08 which is no different than a null model which assumes a baseline risk of 10% in all patients. Conclusion In a cohort of patients that was older, more geographically diverse, and at higher risk of cardiovascular events, the SCORE2-D risk score appropriately stratified patients into categories of risk. However, the overall risk prediction underestimated the risk of cardiovascular events and the discrimination of the risk score was modest.Figure:CV events over timeTable:CV events by risk group

Brief report: U.S. trends in use of colchicine by cardiologists and other specialties, 2018 to 2024

Colchicine has emerged as an effective agent for reducing ASCVD based on recent large cardiovascular outcome trials and exerts its benefit through targeting inflammation. In light of the robust body of data and FDA approval of low-dose colchicine for ASCVD prevention, this paper aimed to use the National Prescription Audie to quantify the volume and trends of colchicine prescriptions dispensed rough U.S. retail pharmacies between March 2018 and February 2024. Despite a 6% increase in total monthly prescriptions since 2020, driven primarily by cardiologists, this specialty still represents only 2.8-4% of the national monthly totals with small absolute numbers (i.e. estimated ∼4000 incremental prescriptions/month since 2020), suggesting limited cardiologist adoption of colchicine for ASCVD prevention despite favorable clinical trial data.

Effect of GLP-1 Receptor Agonists on Renal Functions and Diabetic Nephropathy in Type 2 Diabetes Mellitus (T2DM) Patients: A Systematic Review and Meta-Analysis.

Diabetes mellitus (DM) causes multiple kidney problems ultimately leading to renal failure, with a marked rise in the number of patients worldwide requiring renal replacement therapy (RRT). Diabetic kidney disease (DKD) remains a leading cause of morbidity and death despite advancements in treatment; however, recent cardiovascular outcome trials have highlighted the potential benefits of glucagon-like peptide-1 (GLP-1) receptor agonists and sodium-glucose cotransporter 2 (SGLT2) inhibitors in managing chronic kidney disease (CKD) and cardiovascular risks in type 2 diabetes (T2DM) patients, leading to recommendations for their use following metformin in clinical guidelines. The meta-analysis was run on RevMan 5.4 (The Cochrane Collaboration, 2020). Risk of bias was done using the Cochrane Risk of Bias (RoB) 2 tool for the quality assessment of studies. Eleven studies were selected for this systematic review, all of which provided sufficient data for the outcomes. The effect size calculated for urinary albumin excretion rate (UAER) was calculated to be d = -0.48, CI = 95% (-1.72, 0.75) and for estimated glomerular filtration rate (eGFR) %and eGFR mL/min, it was found to be d = -0.71, CI = 95% (-2.00, 0.58) and d = -0.71, CI = 95% (-2.00, 0.58), respectively. Overall, this meta-analysis supports the use of GLP-1 receptor agonists as an effective therapeutic option to protect renal function in T2DM patients, particularly those at high risk of or with existing DKD.

A Review of the Novel Antidiabetic Medications: Efficacy, Safety and Innovation

Introduction: Type 2 diabetes is a chronic health condition affecting hundreds of millions of people. Type 2 diabetes has traditionally been combated with a combination of lifestyle modification, insulin therapy and pharmacological agents, including sulfonylureas, biguanides, thiazolidinediones and alpha-glucosidase inhibitors. Type 2 diabetes is associated with an increased risk of cardiovascular disease and the development of diabetic kidney disease. Although sulfonylureas are low-cost drugs and widely prescribed, they have been shown in recent cardiovascular outcome trials to present a high risk of hypoglycemia, which in turn increases the risk of negative cardiovascular outcomes. Metformin, a biguanide that is the most commonly-prescribed antidiabetic agent worldwide, is contraindicated in patients with risk factors for lactic acidosis, including heart failure and chronic kidney disease. Objectives: The last decade has seen significant advances in the development of novel antidiabetic agents shown to possess both reno- and cardioprotective qualities. This article aims to review the available literature and recent studies demonstrating the efficacy and safety of these agents individually, as well as exploring areas of future development in the field. Methods: The reporting of this review is based on the 2020 PRISMA statement. A literature search for all papers related to antidiabetic medication was conducted using reliable sources such PubMed and Google Scholar Databases, including a recent meta-analysis of renal and cardiovascular outcome trials. Conclusion: A critical analysis of clinical trials on type 2 diabetes and the two most severe comorbidities in cardiovascular and chronic kidney diseases may help cardiologists, urologists and diabetes specialists to adapt their therapeutic approaches to individual patients. Data related to antidiabetic effects of agents of natural origin accompanied by their Cardioprotective and renoprotective capacity testify benefits of these compounds as novel therapeutic agents.

Rationale for different formulations of omega-3 fatty acids leading to differences in residual cardiovascular risk reduction

Rationale for different formulations of omega-3 fatty acids leading to differences in residual cardiovascular risk reduction

Optimal Management of Glucose in Patients with Diabetes and Heart Failure

Type 2 diabetes confers a two-fold excess risk of heart failure. Established risk factors for developing heart failure in people with type 2 diabetes include old age, obesity, poor glycemic control, impaired kidney function and pre-existing coronary heart disease. Prognosis of people with comorbid type 2 diabetes and heart failure is poor with up to one quarter of them dying at 1 year and half not surviving at 5 years. Glucose-lowering drugs have divergent effects on the progression of heart failure. Thiazolidinediones and dipeptidyl-peptidase 4 inhibitors may induce or worsen symptoms of heart failure, although these risks do not appear to extend to other incretin-based therapy, namely glucagon-like peptide-1 receptor agonists, whereas metformin has been shown to improve prognosis in people with comorbid type 2 diabetes and heart failure in observational studies. Recent cardiovascular outcome trials provided robust evidence for sodium-glucose co-transporter-2 (SGLT-2) inhibitors in preventing death and/or hospitalization for heart failure. Current guideline recommends initiation of SGLT-2 inhibitors in people with type 2 diabetes and heart failure, independent of the need of additional glucose lowering. However, consideration must be given to risks of hypoglycemia, dehydration and euglycemic ketoacidosis upon initiation of SGLT-2 inhibitors, as the majority of people in the treatment group are old, have kidney dysfunction, on diuretics, or have long diabetes duration with high likelihood of insulin deficiency. Type 2 diabetes confers a two-fold excess risk of heart failure. Established risk factors for developing heart failure in people with type 2 diabetes include old age, obesity, poor glycemic control, impaired kidney function and pre-existing coronary heart disease. Prognosis of people with comorbid type 2 diabetes and heart failure is poor with up to one quarter of them dying at 1 year and half not surviving at 5 years. Glucose-lowering drugs have divergent effects on the progression of heart failure. Thiazolidinediones and dipeptidyl-peptidase 4 inhibitors may induce or worsen symptoms of heart failure, although these risks do not appear to extend to other incretin-based therapy, namely glucagon-like peptide-1 receptor agonists, whereas metformin has been shown to improve prognosis in people with comorbid type 2 diabetes and heart failure in observational studies. Recent cardiovascular outcome trials provided robust evidence for sodium-glucose co-transporter-2 (SGLT-2) inhibitors in preventing death and/or hospitalization for heart failure. Current guideline recommends initiation of SGLT-2 inhibitors in people with type 2 diabetes and heart failure, independent of the need of additional glucose lowering. However, consideration must be given to risks of hypoglycemia, dehydration and euglycemic ketoacidosis upon initiation of SGLT-2 inhibitors, as the majority of people in the treatment group are old, have kidney dysfunction, on diuretics, or have long diabetes duration with high likelihood of insulin deficiency.

Interpreting Absolute and Relative Risk Reduction in the Context of Recent Cardiovascular Outcome Trials in Patients with Type 2 Diabetes.

The cardiovascular benefits of sodium-glucose cotransporter-2 inhibitors (SGLT2i) and glucagon-like peptide 1 receptor agonists (GLP-1 RA) have increased the focus of type 2 diabetes mellitus (T2DM) care on comprehensive cardiovascular risk reduction. Herein, we review the results of the cardiovascular outcomes trials of SGLT2i and GLP-1 RA, discuss the concepts of relative vs. absolute risk reduction in the context of these trials, and highlight the importance of individualized risk assessment when applying trial results to clinical practice. To enable personalized treatment approaches, multiple clinical risk scores have been developed to assess risk of atherosclerotic cardiovascular disease (ASCVD) outcomes and hospitalization for heart failure (HHF) in patients with T2DM. In addition, circulating biomarkers of myocardial injury (cardiac troponin) and hemodynamic stress (natriuretic peptides) have been shown to further refine risk prediction of these clinically important cardiovascular complications. When making decisions about whether to initiate SGLT2i and GLP-1 RA, clinicians should consider the anticipated relative and absolute treatment benefits from these antihyperglycemic therapies. Clinicians can use available clinical and biomarker-based risk tools when counseling patients about their individual cardiovascular risk profiles and when estimating absolute treatment benefits from SGLT2i and GLP-1 RA.

Asymptomatic Diabetic Cardiomyopathy: an Underrecognized Entity in Type 2 Diabetes.

Type 2 diabetes (T2D) is associated with an increased risk of heart failure (HF), with diabetic cardiomyopathy (DbCM) referring to abnormal heart structure in the absence of other driving cardiac factors such as hypertension, coronary artery disease (CAD), and valvular heart disease. Stage B DbCM is commonly asymptomatic and represents a form of stage B HF; DbCM thus represents a transitional phenotype prior to onset of symptomatic HF. The pathogenesis of DbCM is not fully elucidated but involves hyperglycemia, insulin resistance, increased free fatty acids (FFA), lipotoxicity, oxidative stress, advanced glycation end product (AGE) formation, activation of the renin-angiotensin-aldosterone system (RAAS) with an increase in angiotensin II, and dyshomeostasis of calcium, which all contribute to left ventricular hypertrophy (LVH) and cardiac systolic and diastolic dysfunction. Although DbCM is an established pathogenic process, it is underrecognized clinically due to its commonly asymptomatic nature. Raising awareness to identify high-risk individuals with stage B HF due to DbCM, who may subsequently progress to overt HF (stage C/D HF), as well as identifying new pharmacological agents and approaches to prevent functional decline, may help reduce this global health problem. The aim of this review is to focus on stage B DbCM; provide data on diagnostic approaches, current therapies, and potential therapies under investigation; and highlight the need to raise awareness and interdisciplinary dialogue among clinicians and researchers. There are no currently approved therapeutic strategies to treat or prevent progression of stage B DbCM, but multiple attempts are being made to target different pathogenic mechanisms involved in the development of DbCM. Recent cardiovascular (CV) outcome trials (CVOTs) have identified newer therapeutic agents with CV benefit, such as sodium-glucose cotransporter-2 (SGLT-2) inhibitors that reduce hospitalization for HF and glucagon-like peptide-1 (GLP-1) receptor agonists that reduce major adverse CV events (MACE), though without consistent effect on HF outcomes. Recent clinical practice guidelines recommend screening patients at high risk for HF. Further definition and interdisciplinary discussion of high-yield populations to screen, appropriate subsequent evaluation and intervention are needed to advance this area. DbCM is a complex entity that results from multiple pathogenic mechanisms triggered by impairment of glucose and lipid metabolism over many years. DbCM is commonly asymptomatic and represents a form of stage B HF. It is an underrecognized process that may progress to functional decline and overt HF. Although newer medications approved for the treatment of T2D may play an important role in reducing the risk of HF complications, less focus has been placed on earlier recognition and treatment of DbCM while asymptomatic. Additional efforts should be made to further study and target this stage in order to decrease the overall burden of HF.

Is There a Diabetes-Kidney-Heart Continuum? Perspectives From the Results of the Cardiovascular and Renal Outcome Clinical Trials With SGLT2 Inhibitors.

Heart failure is associated with a substantial risk of mortality and morbidity. Findings from recent cardiovascular outcome trials have shown promise for sodium-glucose cotransporter-2 (SGLT2) inhibitors in preventing heart failure in patients with type 2 diabetes mellitus (T2DM). Notably, the benefits of SGLT2 inhibitors were consistent despite the presence of risk factors like atherosclerosis. Increasing evidence suggests that SGLT2 inhibitors may confer their cardioprotective effects through multiple mechanisms, ranging from improving cardiac and vascular performance to metabolism. The reduction of heart failure risk by SGLT2 inhibitors may also be attributed to the preservation of renal function. Indeed, renal insufficiency is a frequent comorbidity of patients with heart failure and T2DM; hence, the natriuretic and kidney protective effects offered by SGLT2 inhibitors may contribute to limiting adverse cardiac outcomes. In this article, we discuss the latest findings from the cardiovascular and renal outcome trials, paying special attention to the interlink between heart and kidney function, and how effective treatment of heart failure—irrespective of T2DM diagnosis—may require agents that offer both cardiac and renal protection.

What Is the Mechanism Driving the Reduction of Cardiovascular Events from Glucagon-like Peptide-1 Receptor Agonists?-A Mini Review.

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are considered the standard of care for type 2 diabetes in many countries worldwide. These molecules have profound anti-hyperglycaemic actions with a favourable safety profile. They are now being considered for their robust cardiovascular (CV) protective qualities in diabetic patients. Most recent CV outcome trials have reported that GLP-1 RAs reduce major adverse cardiovascular events (MACE). Furthermore, the GLP-1 RAs seem to target the atherosclerotic CV disease processes preferentially. GLP-1 RAs also improve a wide range of routinely measured surrogate markers associated with CV risk. However, mediation analysis suggests these modest improvements may contribute indirectly to the overall anti-atherogenic profile of the molecules but fall short in accounting for the significant reduction in MACE. This review explores the body of literature to understand the possible mechanisms that contribute to the CV protective profile of GLP-1 RAs.

Glucagon-Like Peptide-1 Receptor Agonists-Use in Clinical Practice.

In the past 2decades, eight glucagon-like peptide-1 receptor agonists (GLP-1RAs) have been approved for the management of type 2 diabetes, each with its peculiar molecular structure, pharmacokinetics, and metabolic effects. Along with their marked glucose-lowering actions, which occur both at fasting and in the postprandial phase without an increased risk of hypoglycemia, GLP-1RAs have provided marked reductions in body weight and ancillary improvements in blood pressure and lipid profile. Recent cardiovascular outcome trials have established the benefits of GLP-1RAs on major cardiovascular events and all-cause mortality, independent of glucose control, with minor effects on preventing hospitalization for heart failure. Novel evidence is also emerging on the protection of GLP-1RAs against diabetic kidney disease, mainly preventing the onset of macroalbuminuria. Several mechanisms have been proposed to explain the cardiorenal protective properties of GLP-1RAs, which may be direct or mediated by additional hemodynamic and anti-inflammatory/antioxidant effects. With their favorable cardiometabolic properties and safety profile, GLP-1RAs may offer an ideal pharmacological option for the management of diabetic kidney disease. In this review, we discuss pharmacokinetic properties, glucometabolic effects, and cardioprotective actions of GLP-1RAs, highlighting the available evidence for a kidney protective role and the proposed mechanisms.

How to Assess Diabetic Kidney Disease Progression? From Albuminuria to GFR.

Diabetic kidney disease (DKD) is one of the most relevant complications of type 2 diabetes and dramatically increases the cardiovascular risk in these patients. Currently, DKD is severely infra-diagnosed, or its diagnosis is usually made at advanced stages of the disease. During the last decade, new drugs have demonstrated a beneficial effect in terms of cardiovascular and renal protection in type 2 diabetes, supporting the crucial role of an early DKD diagnosis to permit the use of new available therapeutic strategies. Moreover, cardiovascular and renal outcome trials, developed to study these new drugs, are based on diverse cardiovascular and renal simple and composite endpoints, which makes difficult their interpretation and the comparison between them. In this article, DKD diagnosis is reviewed, focusing on albuminuria and the recommendations for glomerular filtration rate measurement. Furthermore, cardiovascular and renal endpoints used in classical and recent cardiovascular outcome trials are assessed in a pragmatic way.

Population diversity of cardiovascular outcome trials and real-world patients with diabetes in a Chinese tertiary hospital.

Background:Recent cardiovascular outcome trials (CVOTs) changed the therapeutic strategy of guidelines for type 2 diabetes. We compared the characteristics of patients from real-world hospital settings with those of participants in recent pragmatic randomized trials.Methods:This electronic medical record (EMR)-based retrospective observational study investigated the data of patients with diabetes from inpatient and outpatient settings in West China Hospital of Sichuan University from January 1, 2011, to June 30, 2019. We identified patients meeting the inclusion criteria of a pragmatic randomized trial (EMPA-REG OUTCOME) based on EMRs and compared their baseline characteristics with those of the trial participants. The cutoff for the clinical significance of each characteristic was set as its minimal clinically important difference based on expert consultation.Results:We included 48,257 inpatients and 36,857 outpatients with diabetes and found that 8389 (17.4%) inpatients and 2646 (7.2%) outpatients met the inclusion criteria for the EMPA-REG OUTCOME trial. Compared with the trial population, the real-world inpatients meeting the eligibility criteria of the EMPA-REG OUTCOME had similar age, blood pressure, and lipid profiles but comprised of fewer males, metformin users, anti-hypertensive drug users, and aspirin users, and had a lower body mass index. The group of outpatients meeting the eligibility criteria had fewer males, similar age, fewer metformin users, fewer insulin users, fewer anti-hypertensive drug users, and fewer aspirin users compared with the trial population.Conclusions:The trial population in EMPA-REG OUTCOME represents only a small portion of patients with diabetes from the inpatient and outpatient departments of a Chinese tertiary medical center. Evidence localization in different clinical settings and validation are essential to enabling extrapolation of the results from CVOTs in patients with diabetes to Chinese clinical practice.

Cardiovascular Outcome Trials with Glucose-Lowering Drugs.

This review summarizes recent cardiovascular outcome trials (CVOTs) with glucose-lowering drugs. The majority of recent CVOTs with glucose-lowering drugs have tested dipeptidyl peptidase-4 inhibitors (DPP4-i), glucagon-like peptide-1 receptors agonists (GLP1-RA), and sodium-glucose cotransporter 2 inhibitors (SGLT2i), but studies have also been performed with other agents including thiazolidinediones and insulin. All CVOTs with DPP4-I, GLP1-RA, and SGLT2-i have demonstrated the cardiovascular (CV) safety of these agents compared to usual care. However, certain GLP1-RAs (liraglutide, subcutaneous semaglutide, albiglutide, dulaglutide) and SGLT2-i (empagliflozin, canagliflozin) have demonstrated a CV benefit, showing significant reductions in composite cardiovascular outcomes. Furthermore, all SGLT2-i also significantly decreased the risk for hospitalization for heart failure. Results from these studies have altered clinical guidelines worldwide and have resulted in new indications for some glucose-lowering drugs. In patients with T2D and high risk for CVD, GLP-1RA or SGLT2-i with proven cardiovascular benefit are recommended, irrespective of glycemic control.

Diabetes and Stroke

Stroke is one of the major complications of diabetes and increases morbidity and mortality. Hyperglycemia confers increased risk of stroke occurrence. Furthermore, cardiometabolic risk factors such as hypertension and dyslipidemia frequently coexist in patients with diabetes and increase the risk of stroke. Some recent cardiovascular outcome trials of newer anti-diabetic medications have shown beneficial effects on cardiovascular complications. Prevention and improving outcomes of stroke in patients with diabetes requires proper management of hyperglycemia and additional risk factors. This review is an evidence-based approach to the epidemiology, glycemic control, effects of anti-diabetic medications on stoke, and risk factor management for prevention and improving outcomes of stroke for patients with diabetes. Keywords: Diabetes mellitus; Glycemic control; Risk factors; Stroke

Triglyceride lowering by omega-3 fatty acids: a mechanism mediated by N-acyl taurines.

Interest in omega-3 fatty acids (colloquially known as fish oils) to lower residual cardiovascular risk in statin-treated patients has increased markedly in the wake of recent cardiovascular outcome trials. The triglyceride-lowering effects of omega-3 fatty acids are generally thought to occur by reduced hepatic VLDL production. In this issue of the JCI, Grevengoed et al. used mouse models and human plasma samples to reveal an additional mechanism whereby these polyunsaturated fatty acids can lower plasma triglycerides. Their findings indicate that omega-3 fatty acid-derived N-acyl taurines (NATs) greatly accumulate in bile and also in plasma following omega-3 supplementation. The authors further show that one of these NATs (C22:6 NAT) inhibited intestinal triglyceride hydrolysis and lipid absorption, which resulted in lower plasma triglycerides and protection against hepatic triacylglycerol accumulation in mice fed a high-fat diet. The findings open a potential avenue for triglyceride lowering by omega-3 fatty acids conjugated to taurine.

Preventing Diabetes and Atherosclerosis in the Cardiometabolic Syndrome.

Cardiometabolic syndrome is characterized by abdominal adiposity, insulin resistance, hypertension, and dyslipidemia. There is a growing burden of cardiometabolic disease in many parts of the world. This review highlights the critical preventive and therapeutic measures that need to be implemented to reduce the impact of cardiometabolic syndrome on cardiovascular health. Recent cardiovascular outcome trials demonstrated that newer glucose-lowering medications reduce cardiovascular and renal events in patients with type 2 diabetes mellitus (T2DM). These medications should be considered in patients with T2DM and atherosclerotic cardiovascular disease (ASCVD). These novel drugs may also play a role in primary prevention of cardiovascular disease (CVD) and renal disease in high-risk patients without T2DM. To manage dyslipidemia associated with cardiometabolic syndrome, in addition to lifestyle interventions and statin therapy, ezetimibe, and proprotein convertase subtilisin/Kexin type 9 (PCSK9), inhibitors can be used to reduce the risk of major adverse cardiovascular outcomes (MACE) especially in patients with T2DM and coronary artery disease (CAD). The residual risk of MACE in such a high-risk population can be further mitigated by treatment with an omega-3 fatty acid such as icosapent ethyl. Lifestyle modifications and the use of proven pharmacological therapies are essential for the prevention and progression of diabetes and ASCVD in those with the cardiometabolic syndrome.

Macrovascular Risk Equations Based on the CANVAS Program.

Widely used risk equations for cardiovascular outcomes for individuals with type 2 diabetes mellitus (T2DM) have been incapable of predicting cardioprotective effects observed in recent cardiovascular outcomes trials (CVOTs) involving individuals with T2DM at high risk for or with established cardiovascular disease (CVD). We developed cardiovascular and mortality risk equations using patient-level data from the CANVAS (CANagliflozin cardioVascular Assessment Study) Program to address this shortcoming. Data from 10,142 patients with T2DM at high risk for or with established CVD, randomized to canagliflozin + standard of care (SoC) or SoC alone and followed for a mean duration of 3.6 years in the CANVAS Program were used to derive parametric risk equations for myocardial infarction (MI), stroke, hospitalization for heart failure (HHF), and death. Accumulated knowledge from the widely used UKPDS-OM2 (United Kingdom Prospective Diabetes Study Outcomes Model 2) was leveraged, and any departures in parameterization were limited to those necessary to provide adequate goodness of fit. Candidate explanatory covariates were selected using only the placebo arm to minimize confounding effects. Internal validation was performed separately by study treatment arm. UKPDS-OM2 predicted CANVAS Program outcomes poorly. Recalibrating UKPDS-OM2 intercepts improved calibration in some cases. Refitting the coefficients but otherwise preserving the UKPDS-OM2 structure improved the fit substantially, which was sufficient for stroke and death. For MI, reselecting UKPDS-OM2 covariates and functional form proved sufficient. For HHF, selection from a broad set of candidate covariates and inclusion of a canagliflozin indicator was required. These risk equations address some of the limitations of widely used risk equations, such as the UKPDS-OM2, for modeling cardioprotective treatments for individuals with T2DM and high cardiovascular risk, including derivation from overly healthy patients treated with agents that lack cardioprotection and have been described as reflecting a different therapeutic era. Future work is needed to examine external validity.

Pharmacological management of South Asians with type 2 diabetes: Consensus recommendations from the South Asian Health Foundation.

South Asians constitute approximately 1.6 billion people from the Indian subcontinent, comprising Afghanistan, Bangladesh, Bhutan, India, Maldives, Nepal, Pakistan and Sri Lanka; and make up the largest diaspora globally. Compared to the White European population, this group is at a higher risk of developing type 2 diabetes along with cardiovascular, renal and eye complications. Over the recent years, a number of new therapies for type 2 diabetes have become available for which cardiovascular outcome trials (CVOTs) have been published. The recent ADA/EASD consensus guidelines on diabetes, pre-diabetes and cardiovascular diseases' offer a transitional shift in type 2 diabetes management. The new consensus recommendations are based on recent CVOTs, many of which had a representation of South Asian cohorts. In light of this new evidence, there is urgent need for an integrated, evidence-based, cost-effective and individualised approach specific for South Asians. This review takes into consideration the evidence from these CVOTs and provides best practice recommendations for optimal management of South Asian people with type 2 diabetes, alongside the previously published consensus report from South Asian Health Foundation in 2014 [1].

Clinical Translation of Cardiovascular Outcome Trials in Type 2 Diabetes: Is There More or Is There Less Than Meets the Eye?

Randomized controlled trials (RCTs) have become the gold standard of clinical evidence and the staple of guided clinical practice. RCTs are based on a complex set of principles and procedures heavily strung by statistical analysis, primarily designed to answer a specific question in a clinical experiment. Readers of clinical trials need to apply critical appraisal skills before blindly accepting the results and conclusions of trials, lest they misinterpret and misapply the findings. We introduce the fundamentals of an RCT and discuss the relationship between relative risk (RR) and absolute risk (AR) in terms of the different information each conveys. The top results of some recent cardiovascular outcome trials using sodium–glucose cotransporter 2 inhibitors and glucagon-like peptide 1 receptor agonists in patients with type 2 diabetes are used to exemplify the merit of assessing both RR and AR changes for a balanced translation of findings into shrewd clinical judgment. We also suggest practical points to assist with a clinically useful interpretation of both within-trial and across-trial reports. Finally, we mention an alternative approach, namely, the restricted mean survival time, to obtaining unbiased estimates of the mean time of missed events in the treatment versus placebo arm for the duration of the trial.