American Heart Association Meeting
It is a huge international heart conference, the largest in this topic, with 16000 delegates from all the World, 800 sessions, 5000 presentations, 4000 abstracts and 26 program communities. Everything is presented with high technology.
AHA and Diabetes 2019
At the American Heart Meeting AHA in Chicago during Nov 9-12 this year there is especially much focus on diabetes and cardiovascular disease (CVD), especially heart failure.
There are many oral lectures and posters highlighting on eary diagnosis, active prevention and optmized treatment of CVD in diabetes.
”Know diabetes by heart”
This is an awakeness compaign from the organisation with aims to raise awareness on the link connection especially type 2 diabetes and cardiovascular disease, but also focus on type 1 diabetes.
Declare trial
Today in the afternoon the long awaited T2DM trial with dapagliflozin (DAPA), SGLT2i and CVD outcome study was presented, DECLARE
Patients with T2DM are at high risk for development, and, complication from atherosclerotic CVD events and heart failure.
Prior CV outcomes with sglt2i have shown reduction in CV and renal events, predominantly in secondary prevention patients with known atherosclerotic CVD (ACVD).
17160 T2DM patients with established CV disease (6974) or multiple risk fastors (10186) were randomized 1:1 to DAPA or placebo. After 5.2 years the trial should evaluate primary endpoints and dual efficacy CVD/HHF (Hospitalized because of heart failure), MACE (major adverse CV events; CV death, nonfatal AMI, nonfatal stroke).
453 patients from Sweden was in the trial, as well as Europe, US, South America, Asia, 33 countries. 
Mean age 64 years, BMI 32, duration of T2DM 11 years, HbA1c 65 mmol per mol, established CV 41 per cent and history of HF 10 per cent
HbA1c difference 4.2 mmol per mol lower in DAPA versus placebo, weight 1,8 kg lower, syst blood pressure 2.7 mm Hg lower and diastolic pressure 1,7 mm Hg lower. All after 48 months
CV outcome
Primary endpoints
CVD/HHF 4.9 per cent versus 5.8. Hazard ratio HR 0,83 (0,73-0.95), p superior 0.005. It means significantly 17 per cent less relative risk
8,8 vs 9,4 per cent, HR 0,93 with 0,84-1.03, p non inferiority less than 0.001, p superiority 0,17
Secondary endpoints
Renal composite endpoints (EP), that is 40 per cent better eGFR, ESRD, renal or CV death) 4.3 versus 5.6 per cent, HR 0,76 (0,67–0,87), p less than 0.001
All cause mortality
6,2 vs 6.6 per cent, HR 0,93 (0,82-1.04) p is 0.20. Not sign
Rate per 1000 patient years
DAPA 6,2 Placebo 8,5
HR 0,73 (0,61-0,88)
Rate per 1000 patient years
40 per cent reduction in eGFR, ESRD or renal death
DAPA 3.7. Placebo 7,0 HR 0,53
At the meeting there was a meta-analysis of CV outcome trials of SGLT2i, empa, canvas, declare and MACE by presence of atherosclerotic.
CVD with HR in summary 0,85 (0,80-0,93)
Declare was the largest SGLT2i trial, which included a broad representation of primary and secondary prevention patients
1. DAPA reduced significantly CVD/HHF
2. Neither increased or decreased MACE
3. Reduction in CVD/HHF was consistent regardless of baseline ASCVD or HF
4. DAPA was safe and well tolerated, no difference in amputation, stroke or fractures, less hypoglycemia than the Placebo Group, and simular small increased in genital infections as in other SGLT2i trials, also as known before a very small increase in diab ketoacidosis
Discussion from the trial
SGLT2i drugs have robust effects on reducing the risk of heart failure and renal outcomes, which do not appear dependent on baseline atherosclerotic risk, prior HF or renal function.
Additional info Publication
Google the two titles down to read the full article free as pdf from now on
Dapagliflozin and cardiovascular outcomes in type 2 diabetes N Engl J Med
SGLT2 inhibition for primary and secondary prevention of cardiovascular and renal outcomes in type 2 diabetes: a systematic review and meta-analysis of cardiovascular outcome trials The Lancet
Discussant Javed Butler, prof of medicine, univ of Mississippi USA was invited to review the declare trial
1. Well conducted trial
2. Highest proportion of patients with risk factors but without ASCVD
3. Confirm and replicate data from other SGLT2i trials
Safety, HbA1c, blood pressure, weight
1. All cv complications are important
2. Macrovascular complications does not include heart failure
3. Risk factors are important.
From the NDR study from August 16 2018 N Engl J Med with 5 risk factors in T2DM (HbA1c, smoking, LDL, blood pressure and albuminerna).
If all are controlled normal and less risk for acute myocardial infarction than control population without diabetes, HR 0,84 (0,75-0,93) and nearly normal for stroke 0,95 (0,84-1.07).
BUT the risk for heart failure with all 5 risk factors controlled were still 45 per cent higher, -1,45 (1,34-1,57), p less than 0.001.
Treatment of T2DM
1. Primary and secondary cohort for one disease may or may not apply to a different disease
2. For patients similar to those studied in the SGLT2i trials - these drugs should be used for heart failure irrespective of their effect on MACE outcome
3. For patients not studied adequately for exemple T2DM with no risk factors or with manifest HF further data are needed.
What’s Now?
1. HbA1c
2. Cv risk factors
1. HbA1c
2. Cv risk factors
3. Reduce CV mortality
4. Reduce MACE
2018 onwards
1. HbA1c
2. Cv risk factors
3. Reduce CV mortality
4. Reduce MACE
5. Reduce HF risk
6. Reduce chronic kidney disease
Nyhetsinfo (sa)
www red DiabetologNytt
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