Anti DM drug and HF .pptx
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Impact of Newer Glucose-Lowering Agents in CVD & HF , and Novel Therapeutic Strategies Han Naung Tun MBBS, MD, FACTM, FACC, FESC UVM Medical Centre Larner College of Medicine , University of Vermont ,VT , USA
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Anti DM drug and HF .pptx
- 1. Impact of Newer Glucose-Lowering Agents in CVD & HF , and Novel Therapeutic Strategies Han Naung Tun MBBS, MD, FACTM, FACC, FESC UVM Medical Centre Larner College of Medicine , University of Vermont ,VT , USA @HanCardiomd Outline of HF Treatment In Diabetes:
- 2. Conflict of interest Nothing to declare
- 3. DM is a major risk factor for both HF and CAD Tun HN (2018) J Cardiovasc Med Cardiol 5(4): 081-084
- 4. Current antihyperglycemic therapies and potential therapeutic targets that could modulate DM associated HF Helena. C.Kenny , Cir Research, 2019
- 5. Managing Type 2 DM Eur Heart Journal 2018, 34(39)
- 6. Increased risk of stroke , CHD , CHF and Mortality in patients with CKD and > 2 SH events Yu et al. Neurology , 2014 Atsushi Goto et al.2015 BMJ
- 10. First generation of CV outcome trials for SGLT2i
- 11. Jing Cui, et al. Front CV Med , 2021
- 12. Second generation of CKD focused trials for SGLT2i
- 13. Second generation of HF focused trials for SGLT2i
- 15. Key CV outcomes trial for GLP-1R agonists
- 17. Adapted Bhatt DL et al. Cell Metabolism , 2019
- 18. Adapted from Ferro et al , Cardio Clinic , 2021
- 24. Take Home Message • SGLT2i and GLP1 agonists should be included in the treatment of patients with T2DM and underlying comorbidities such as CV pathology and CV risk • SGLT2i are used in the Rx of T2DM with HF either with HFrEF or HFpEF , and SGLT2i is the treatment of choice in HF regardless of DM status • GLP1 agonists are indicated in the primary and secondary prevention of CV incident in pts with DM, and early treatment initiation should be imperative • Embrace the evidence and switch from traditional diabetes medications to newer therapies with proven CV benefit
Editor's Notes
- Outline of HF Treatment
- Patients with diabetes have >2× the risk for developing heart failure (HF; HFrEF and HFpEF). Cardiovascular outcomes, hospitalization, and prognosis are worse for patients with diabetes mellitus relative to those without. Of course, DM can contribute to the development of CAD and HF via systemic, myocardial, and cellular mechanisms.
- DM is a multi-organ disease state characterized by hyperglycemia and dyslipidemia. Current commonly used therapies may achieve normoglycemia, but they have variable effects on heart failure risk and outcomes. In facts , alternative targets, that could be amenable to pharmacological treatment and that may increase the risk of heart failure in diabetes mellitus .
- When we manage DM , we are goanna focus not just on the glycemic control, but of course , we also focus on to reduce CV risk and comorbidities since the increased incidence of HF in diabetic patients persists even after adjusting for other risk factors such as age, hypertension, hypercholesterolemia, and coronary artery disease.
- Many landmarks clinical trials have addressed the relationship between tight glycemic control and cardiovascular end points. The ADVANCE trial showed that intensive glucose control, which lowered HbA1c to 6.5% in type 2 diabetics, showed no evidence of a reduction in macrovascular events with no increase in mortality. I n contrast, the ACCORD trial (Action to Control Cardiovascular Risk in Diabetes), which targeted HbA1c to 6% in the intensive therapy group, had an increased mortality of 22% suggesting a potentially unexpected increased risk of intensive glucose lowering in high-risk patients with T2DM.
- These available evidence suggests that DPP-4 inhibitors have a weak CV protective effect. SAVOR-TIMI-53 Trial reported a significant increase in hospitalization for HF in patients on saxagliptin vs placebo EXAMINE and TECOS trials do not reveal increased HF risk . Experimental studies in humans and animals show improvements in cardiac function when GLP-1 was activated by DPP4 inhibitor However, in clinical application, it should be selected according to the actual situation. In patients with T2DM with advanced CVD or HF associated with renal function deterioration, DPP-4 inhibitors appear to be safe to use from a cardiological point of view.
- In EMPA -REG OUTCOME, patients with type 2 diabetes at high risk for cardiovascular events who received empagliflozin, as compared with placebo, had a lower rate of the primary composite cardiovascular outcome and of death from any cause when the study drug was added to standard care.
- SGLT2 improves CV risk factors (weight reduction, reduction in SBP and improved lipid profile) EMPA-REG OUTCOME trial reported a reduction in CV mortality and hospitalization from HF using empagliflozin CANVAS trial reported similar results for canagliflozin43 Major international guidelines all highly recommend the use (or combined use) of SGLT2 inhibitors in patients with T2DM with comorbid CVDs (or high risk of CVDs) and/or CKD. SGLT2 inhibitors exhibited superiority; thus, we cardiologist approves that SGLT2 inhibitors should be used in great property, at least in T2DM patients with high CV risk.
- First generation of CV outcome trials for SGLT2i Since 2015, all 4 SGLT2i have been evaluated in the context of double-blinded, placebo-controlled clinical trials: canagliflozin, dapagliflozin, empagliflozin, and ertugliflozin. The first generation of SGLT2i trials were traditional CVOTs designed to show the CV safety of these medications; there- fore, they compared SGLT2i with placebo
- The therapeutic focus of T2DM has also changed, from an exclusive focus on glucose-lowering parameters, to comprehensive management, and then to the current therapeutic focus on cardiac benefits and renal outcomes
- Second generation of CKD focused SGLT2i . These observations called for dedicated and structured trials among patients with CKD, which led to the second generation of SGLT2i trials, in which the traditional MACE primary outcome was substituted with a primary MARCE outcome
- Second generation of HF focused trials for SGLT2i . Therefore, it was assumed that the benefit of SGLT2i was mainly in the prevention of new-onset HF and associated hospitalizations as we see. There are the trials among patients with HF, which led to the second generation of SGLT2i trials, in which the traditional MACE primary outcome was substituted with a primary outcome of CV mortality or HHF
- Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) is viewed as the primary DPP-4 substrate capable of modulating CV function. Most trials revealed a modest improvement in ejection fraction in HF patients Trial of GLP-1 agonist in advanced HF revealed a trend toward increased hospitalization in diabetes mellitus subgroup34 The study found that use of GLP-1 RAs was associated with significant reductions in CV and all-cause mortality, and of course, suggesting that GLP-1 RAs should be used as a first-line treatment in patients with T2DM at higher CV risk or as a first-line treatment in patients with metformin resistance
- The study found that use of GLP-1 RAs was associated with significant reductions in CV and all-cause mortality, and of course, suggesting that GLP-1 RAs should be used as a first-line treatment in patients with T2DM at higher CV risk or as a first-line treatment in patients with metformin resistance . As we all agree, GLP-1 RA have been reliably associated with a significant reduction in MACE . there are the total of 7 CVOTs have been conducted for GLP-1 RA.
- So, again , we have enough evidence with SGLT2 inhibition in HF with or without DM ,these all major trials show benefits of SGLT2i in Hf with or without DM .
- Once again , this is the Story of SGLT2 inhibitors in heart failure. The perception of SGLT2 inhibitors from being primarily glucose-lowering agents to what may now be considered chiefly a cardiorenal protective class of therapies.
- This is the Timeline of landmark events in noninsulin diabetes drug development showing 12 years of CVOTs unequivocally showed the CV safety of these agents and led to the identification of 2 drug classes with broad cardiometabolic benefits .
- The 2019 ESC guidelines feature compelling evidence from important CVOTs highlighting the role of newer anti-diabetic medications in reducing CVD events in patients with DM.
- Both American and European guidelines recommend the use of SGLT-2 inhibitor and GLP1-RAs for CVD prevention in DM patients at high or very high risk. While the trials data looks favorable, new information and increased costs for the newer drugs may impact decision making in routine clinical practice. You know, The burden of diabetes continues to increase in the US and worldwide, and the resulting adverse health and economic implications warrant improved cost-effective management strategies for DM and the resulting CVD complications
- This is 4 pillars , multifactorial approach to reduction in risk of DM complications for the management of Diabetes . Since DM is a biggest enemy of CV and renal , we have to consider for choosing agents with both CV and Kidney benefits
- There is an immediate need for clinicians to embrace the evidence and switch from traditional diabetes medications to newer therapies with proven CV benefit. Physician education and increasing awareness of these persuasive clinical trial results will increase their comfort level in making this transition. Cost considerations, however, remain to be addressed. Physician education and increasing awareness of these persuasive clinical trial results will increase their comfort level in making this transition. Cost considerations, however, remain to be addressed.