Mesa 3: Efectos cardiovasculares de fármacos antidiabéticos / Table 3: Cardiovascular effects of anti-diabetic drugs

Los eventos cardiovasculares representan la mayor complicación de la diabetes. La evidencia sugiere que la metformina mejora los resultados cardiovasculares en pacientes con diabetes, especialmente en el United Kingdom Prospective Diabetes Study (UKPDS) y otros estudios posteriores, por distintos mecanismos. Hay pocos estudios de seguridad cardiovascular para sulfonilureas aunque no tendrían un perfil seguro a este nivel. La gliclazida parece ser la de mejor performance de las drogas de este grupo. Algo similar ocurre con las meglitinidas, para las cuales los datos indican que no aumentarían el riesgo pero tampoco mejorarían la incidencia de eventos cardiovasculares. Las tiazolidinedionas son las drogas más cuestionadas, aunque los estudios y metaanálisis son contradictorios no habría dudas que aumentan el riesgo de insuficiencia cardíaca. Los inhibidores de la DPPIV mostraron resultados neutros a excepción de saxagliptina que aumentaría el riesgo de internación por insuficiencia cardíaca. Existen datos convincentes que los inhibidores de los receptores SGLT-2 a nivel renal y los análogos del GLP-1 intestinal tienen efectos positivos a nivel cardiovascular, con algunas diferencias entre los integrantes de esta familia. En cuanto a las insulinas, los estudios sugieren que tanto los análogos lentos como rápidos tendrían un mejor perfil cardiovascular, ligado principalmente a la menor incidencia de hipoglucemias severas, que insulina NPH y regular respectivamente.

Cardiovascular events represent the greatest complication of diabetes. Evidence suggests that metformin improves CV outcomes in patients with diabetes, especially in the United Kingdom Prospective Diabetes Study (UKPDS) and other subsequent studies, by different mechanisms. There are few cardiovascular safety studies for sulfonylureas although they would not have a safe profile at this level. Gliclazide appears to be the best performing drug in this group. Something similar occurs with meglitinides for which the data indicates that they would not increase the risk but neither would they improve the incidence of cardiovascular events. Thiazolidinediones are the most questioned drugs, although the studies and meta-analyzes are contradictory, there would be no doubt that they increase the risk of heart failure. DPPIV inhibitors showed neutral results except for saxagliptin, which would increase the risk of hospitalization for heart failure. There is convincing data that SGLT-2 receptor inhibitors at the renal level and intestinal GLP-1 analogues have positive effects at the cardiovascular level with some differences between the members of these families. Regarding insulins, studies suggest that both slow and fast analogues would have a better cardiovascular profile, mainly linked to the lower incidence of severe hypoglycemia, than NPH and regular insulin, respectively

Clinical Profile and Major Adverse Cardiovascular Outcomes in Patients who Underwent Coronary Revascularization for Left Main Coronary Artery Disease and Left Main Equivalent Coronary Artery Disease in a Tertiary Hospital

@#BACKGROUND: Percutaneous coronary intervention (PCI) for left main (LMCA) coronary artery disease (CAD) was found to be non-inferior and had similar major adverse cardiovascular events (MACE) to coronary artery bypass grafting (CABG). In the local setting, the clinical profile and MACE of patients who underwent either revascularization are, however, unknown. OBJECTIVES: To determine the clinical profile and in-hospital MACE of patients who underwent revascularization (PCI or CABG) for LMCA and left main equivalent CAD. METHODS: This is a prospective descriptive study. Clinical profile and in-hospital, 30-days and 90-days post revascularization MACE were determined. RESULTS: Thirty-seven (37) adults were included. Most were males, diabetics, dyslipidemics, smokers, with previous cardiovascular events and premature CAD. Hypertension was significantly prevalent in the CABG group (PCI=62.50% vs CABG=90.48%, p=0.04). Patients who underwent CABG mostly presented with stable angina (p=0.0453). The majority of the PCI (68.75%) was done as an emergent/urgent procedure, with clear indications for PCI (i.e. STEMI). In-hospital all-cause mortality was significantly higher in the PCI group (PCI=50% vs CABG=0%, p<<0.05). CONCLUSION: Patients with LMCA and left main equivalent CAD were mostly males and had traditional CAD risk factors. In-hospital mortality was significantly higher among the PCI group; however, those who underwent PCI were unstable and unlikely to be good surgical candidates for CABG.

Cardiovascular Outcome Trials of Sodium Glucose Cotransporter 2 Inhibitor and Its Possible Cardioprotective Mechanism

Patients with type 2 diabetes (T2D) have a significantly higher risk of developing cardiovascular diseases such as myocardial infarction, heart failure, and stroke. Current anti-diabetic drugs are highly effective for managing hyperglycemia. However, most T2D patients are still at high risk for cardiovascular disease. Over the past decade, many studies have assessed the efficacy of anti-diabetic drugs in regards to cardiovascular disease outcomes in T2D patients. However, despite the effective glycemic control of these drugs, they failed to show significant benefits that impact the morbidity and mortality of cardiovascular disease (CVD). In recent years, anti-diabetic drugs, developed with other mechanisms, have shown significant results for improving the risk of CVD. In addition, sodium glucose cotransporter 2 inhibitors have shown promising results that impact CVD outcomes in several trials. This article will review the cardiovascular outcomes and possible cardioprotective mechanisms of sodium glucose cotransporter 2 inhibitors.

Cardiovascular Outcome Trials of Incretin Therapy (Dipeptidyl Peptidase-4 Inhibitors/Glucagon-Like Peptide-1 Receptor Agonist)

In 2008, the United States Food and Drug Administration issued guidance which mandated long-term cardiovascular outcome trials (CVOTs) to assess the safety of new antidiabetic drugs for type 2 diabetes. Since 2008, three CVOTs that have studied dipeptidyl peptidase-4 (DPP-4) inhibitors and four CVOTs of a glucagon-like peptide-1 (GLP-1) receptor agonist (GLP-1RA) have been reported. Each of the completed CVOTs showed the noninferiority of respective drugs to placebo for primary CV composite endpoint. Among them, liraglutide and semaglutide showed a reduction of major adverse cardiovascular events. However, the mechanisms for the observed cardiovascular differences between DPP-4 inhibitors and GLP-1RA, and across individual GLP-1RA are not clearly understood. Therefore, this review will summarize the CVOTs of the DPP-4 inhibitors and GLP-1RA, interpretation of cardioprotective results of incretin-based therapy and the possible mechanism of action.

Sustained uremic toxin control improves renal and cardiovascular outcomes in patients with advanced renal dysfunction: post-hoc analysis of the Kremezin Study against renal disease progression in Korea

BACKGROUND: We investigated the long-term effect of AST-120, which has been proposed as a therapeutic option against renal disease progression, in patients with advanced chronic kidney disease (CKD). METHODS: We performed post-hoc analysis with a per-protocol group of the K-STAR study (Kremezin study against renal disease progression in Korea) that randomized participants into an AST-120 and a control arm. Patients in the AST-120 arm were given 6 g of AST-120 in three divided doses, and those in both arms received standard conventional treatment. RESULTS: The two arms did not differ significantly in the occurrence of composite primary outcomes (log-rank P = 0.41). For AST-120 patients with higher compliance, there were fewer composite primary outcomes: intermediate tertile hazard ratio (HR) 0.62, 95% confidence interval (CI) 0.38 to 1.01, P = 0.05; highest tertile HR 0.436, 95% CI 0.25 to 0.76, P = 0.003. The estimated glomerular filtration rate level was more stable in the AST-120 arm, especially in diabetic patients. At one year, the AST-120-induced decrease in the serum indoxyl sulfate concentration inversely correlated with the occurrence of composite primary outcomes: second tertile HR 1.59, 95% CI 0.82 to 3.07, P = 0.17; third tertile HR 2.11, 95% CI 1.07 to 4.17, P = 0.031. Furthermore, AST-120 showed a protective effect against the major cardiovascular adverse events (HR 0.51, 95% CI 0.26 to 0.99, P = 0.046). CONCLUSION: Long-term use of AST-120 has potential for renal protection, especially in diabetic patients, as well as cardiovascular benefits. Reduction of the serum indoxyl sulfate level may be used to identify patients who would benefit from AST-120 administration.

What the results of Acarbose Cardiovascular Evaluation(ACE) Study will be? / 中华内分泌代谢杂志

The prevalence of prediabetes is increasing rapidly in China, and with higher prevalence in coronary heart disease and hypertension patients. Diabetes can be controlled and prevented, previous studies have confirmed that lifestyle interventions and drug interventions can delay the progression of prediabetes to diabetes, and acarbose can be used for the primary prevention of cardiovascular events in impaired glucose tolerance(IGT) and diabetic patients, but benefits of drug intervention for secondary prevention of cardiovascular disease in IGT population are uncertain. The Acarbose Cardiovascular Evaluation(ACE) Study is a multicentre, randomized, placebo-controlled, double-blind study, with the aim of assessing the use of acarbose to reduce the risk of cardiovascular events and the onset of diabetes in IGT patients with cardiovascular disease in China , the results will be very meaningful and valuable for the prevention and treatment of diabetes. We will predict the results of ACE Study based on previous evidences.

Effect of Dipeptidyl Peptidase-4 Inhibitor on All-Cause Mortality and Coronary Revascularization in Diabetic Patients

BACKGROUND: Anti-atherosclerotic effect of dipeptidyl peptidase-4 (DPP-4) inhibitors has been suggested from previous studies, and yet, its association with cardiovascular outcome has not been demonstrated. We aimed to evaluate the effect of DPP-4 inhibitors in reducing mortality and coronary revascularization, in association with baseline coronary computed tomography (CT). METHODS: The current study was performed as a multi-center, retrospective observational cohort study. All subjects with diabetes mellitus who had diagnostic CT during 2007-2011 were included, and 1866 DPP-4 inhibitor users and 5179 non-users were compared for outcome. The primary outcome was all-cause mortality and secondary outcome included any coronary revascularization therapy after 90 days of CT in addition to all-cause mortality. RESULTS: DPP-4 inhibitors users had significantly less adverse events [0.8% vs. 4.4% in users vs. non-users, adjusted hazard ratios (HR) 0.220, 95% confidence interval (CI) 0.102-0.474, p = 0.0001 for primary outcome, 4.1% vs. 7.6% in users vs. non-users, HR 0.517, 95% CI 0.363-0.735, p = 0.0002 for secondary outcome, adjusted variables were age, sex, presence of hypertension, high sensitivity C-reactive protein, glycated hemoglobin, statin use, coronary artery calcium score and degree of stenosis]. Interestingly, DPP-4 inhibitor seemed to be beneficial only in subjects without significant stenosis (adjusted HR 0.148, p = 0.0013 and adjusted HR 0.525, p = 0.0081 for primary and secondary outcome). CONCLUSION: DPP-4 inhibitor is associated with reduced all-cause mortality and coronary revascularization in diabetic patients. Such beneficial effect was significant only in those without significant coronary stenosis, which implies that DPP-4 inhibitor may have beneficial effect in earlier stage of atherosclerosis.