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| 2017 ESC experts understand diabetes and cardiovascular disease |
The conference was co-chaired by Professor Stefano Del Prato, an endocrinology and metabolism expert at the University of Pisa, Italy, and Professor Darren K. McGuire, a medical specialist at the University of Texas Southwestern Medical Center. He also invited Professor David Cherney, a nephrologist at the University of Toronto, Canada, and endocrine in the University of Toronto, Canada. Professor Lamrence Leiter, a metabolic expert, and four experts have conducted in-depth interpretation and discussion on the treatment of type 2 diabetes and cardiovascular disease.
Professor Lawrence Leiter pointed out that diabetes can cause a variety of microvascular and macrovascular diseases such as diabetic retinopathy, diabetic nephropathy, diabetic neuropathy, and cardiovascular disease and stroke. Over the past 20 years, with the improvement of diabetes care, diabetes-related cardiovascular complications have shown a downward trend, but end-stage renal disease (ESRD) has not changed much.
What is the impact of intensive glycemic control on the risk of complications? Studies have shown that as blood glucose levels rise, the relative risk of diabetic complications increases, and can lowering blood sugar reduce these risks? The large epidemiological study DCCT/EDIC in patients with type 1 diabetes confirmed that glycemic control is associated with a reduced risk of cardiovascular complications. Controlling blood glucose can significantly reduce the risk of diabetic complications, especially microvascular complications. However, there were different outcomes in patients with type 2 diabetes, and the UKPDS initial results, ACCORD study, ADVANCE study, and VADT study did not confirm benefit. The long-term follow-up of the UKPDS and VADT studies and meta-analysis of some studies confirmed the cardiovascular benefit of glycemic control, with a median follow-up of 8.5 years in the UKPDS extended study and a median follow-up of 9.8 years in the VADT study. Professor Lawrence Leiter pointed out that this suggests that compared with measures such as antihypertensive and lipid-lowering, the cardiovascular benefit of hypoglycemic may take about 10 years of long-term follow-up to appear, and early glycemic control has a long-term complication. effect.
Analysis of randomized clinical trials comparing intensive and routine treatment in patients with type 2 diabetes showed that the difference in cumulative glucose exposure (%HbA1c×year) between the trial groups was strongly associated with a decreased risk ratio for major adverse cardiovascular events (MACE) or surrogate endpoint events. Similar results were obtained for studies comparing hypoglycemic agents with placebo. The results suggest that the time to strengthen glycemic control and the degree of HbA1c reduction are important factors in clinical decision-making. The recently published EMPA-REG study, LEADER study, and SUSTAIN 6 study have reduced the risk of more MACE than previously, which may be partially related to hypoglycemic effects. However, glycosylated hemoglobin (HbA1c) levels are still high in most treatment groups. In the EUROASPIRE IV study, only 53% of people with diabetes control HbA1c to <7%. Even in the EMPA-REG study with good results, the mean HbA1c level at most of the follow-up points was still higher than 7.5%. Therefore, we still need to strengthen blood sugar control, and good glycemic control is one of the important components of the comprehensive risk reduction strategy for diabetes.
The role of different DPP-4 inhibitors in type 2 diabetes patients at risk of heart failure
Based on the SAVOR TIMI 53 study, the EXAMINE study, and the TECOS study, the three completed DPP-4 inhibitor cardiovascular endpoint studies were generally safe for DPP-4 inhibitors. Professor Darren K. McGuire explored the differences in the results of the three completed research centers. In the SAVOR TIMI 53 study of saxagliptin, the risk of hospitalization for heart failure was significantly higher in the saxagliptin group than in the placebo group (3.5% vs 2.8%, HR: 1.27, P=0.007); alogliptin The overall risk of heart failure in the treatment group studied by EXAMINE was not significantly different from that in the placebo group (HR: 1.19, 95% CI: 0.90 to 1.58, P = 0.22), but there was a significant difference between the two groups in patients with no previous heart failure ( HR: 1.76, 95% CI: 1.07 to 2.90, P = 0.026). Therefore, on April 5, 2016, the US Food and Drug Administration (FDA) increased the drug safety warning label, stating that pharmaceutical preparations containing saxagliptin and alogliptin may increase the risk of heart failure, especially In patients with heart disease or kidney disease.
However, in the TECOS study of sitagliptin, there was no significant difference in the risk of heart failure hospitalization between the sitagliptin group and the first trial (HR: 1.00, 95% CI: 0.84 to 1.20, P = 0.95). There were no significant differences in multivariate corrections and adjusted baseline heart failure, and there were no significant differences in heart failure-related outcomes such as hospitalization for heart failure or cardiovascular death, hospitalization for heart failure, or all-cause death.
Professor Darren K. McGuire pointed out that there are some wrong information in the existing scientific literature. For example, the 2016 ESC guidelines for acute and chronic heart failure indicate that DPP-4 inhibitors do not reduce and may increase the risk of cardiovascular events and aggravate heart failure, and have not cited any cardiovascular endpoint trials published for at least 1 year (CVOT) The American Heart Association (AHA) scientific statement that may trigger or aggravate heart failure drugs indicates that sitagliptin has a higher risk of heart failure and aggravate myocardial dysfunction (level B evidence), based on an observation Sex studies did not mention the heart failure results of the TECOS study published more than a year ago.
Relatively speaking, the European Medicines Agency (EMA) product manual is more up to date. Among them, saxagliptin reported data on the increased risk of aging in the SAVOR study center and cautioned that it should be used in patients with heart failure or risk factors for heart failure; the alogliptin and linagliptin instructions did not mention the heart Decay; Vigretaxin specification indicates that it has no effect on ejection fraction and is not recommended for patients with grade 4 heart failure (no data); the sitagliptin specification indicates that it is neutral for heart failure.
Professor Darren K. McGuire concluded that there are still many questions about heart failure: Is this a single drug or a class effect? Is there patient specificity? What is the mechanism of action? These questions are waiting for future answers.
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