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José R. González Juanatey
Servicio de Cardiología
Hospital Clínico Universitario
Santiago de Compostela. España
SERVICIO DE CARDIOLOGIA
HOSPITAL CLINICO DE SANTIAGO DE COMPOSTELA
XERENCIA DE XESTIÓN INTEGRADA DE SANTIAGO DE COMPOSTELA
DIABETES 2021.
VISIÓN DESDE LA CARDIOLOGÍA
Conflict of interest:
Research grants and honoraria from (research committees, clinical trials, personal,
Institutional)
Astra-Zeneca, Bayer, Boehringer Ingelheim, Lilly / Daiichi-Sankyo, Ferrer, MSD, Novartis,
Pfizer, Sanofi-Aventis, Servier, Amgen, Tecnofarma, Silanes, NovoNordisk
1. La Diabetes en los Procesos
Asistenciales en Cardiología
ADA, 2007
DM
100
126
140 200
Impaired
Glucose
tolerance
IFG +
IGT
Impaired
fasting
glycaemia
Normal
2h plasma glucose (mg/dl)
Fasting
plasma
glucose
(mg/dl)
Random plasma glucose
> 200 mg/dl + symptoms
DM
DM
2
3
1
4 HbA1c
> 6,5 %
x 2
x 2
x 1
x 2
ADA
T2DM and Pre-diabetes
T2D and CV Disease in Spain.
An Epidemiological Perspective
Diabetes + IHD 30-35% IHD PATIENTS WITH T2D 1
Diabetes + HF 27-47% HF PATIENTS WITH T2D 2
Diabetes + AF 24-34% AF PATIENTS WITH T2D 3
Redondo A et al. Rev Esp Cardiol 2015;68:777-84
Galvao C et al. Rev Esp Cardiol 2017; 70:425-32
Otero F et al. Rev Esp Cardiol 2010; 63:1371-6
Galve E et al. Rev Esp Cardiol 2016;69:931-8.
Varela A et al. Heart 2005; 91:489-94
Otero F et al. Rev Esp Cardiol 2007; 60:373-83
Agra R et al. Cardiol J 2017; epub ahead of print
Gómez-Otero et al. Rev Esp Cardiol 2017;70:338-46
Rodríguez-Mañero M et al. Rev Esp Cardiol. 2014;67:890–7
Carnero L et al. Rev Esp Cardiol. 2017;70:872–86
Rodríguez-Mañero M et al. Inter J Cardiol 2017; 243: 211–5
+ 20% DIAGNOSIS AT TIME OF ADMISSION
INSIGHTS SHARING – SANTIAGO DE
COMPOSTELA
ROADMAP FOR CARE ORGANIZATIONS - DIABETES
2. La Diabetes en la
Estratificación de Riesgo
Chronic/Acute Heart-Kidney Interactions
CHRONIC CARDIORENAL
SYNDROME
CHRONIC RENOCARDIAC
SYNDROME
Cardiovascular-Renal Spectrum of Diabetes
MACE, major adverse cardiovascular events (non-fatal stroke, non-fatal myocardial
infarction, and cardiovascular death).
Verma S et al. Lancet. 2019;393:3-5.
Heart
Failure
MACE
Renal
Disease
Diabetes affects the
FILTER
Diabetes affects the
PUMP
Diabetes affects the
PIPES
Diabetes and NSTEMI. Prognostic Implications
CardioCHUS-HUSJ Registry
MORTALIDAD CV MORTALIDAD TOTAL
GRACE>140 GRACE>140
Alvarez B, …, Gonzalez-Juanatey JR . Rev Esp Cardiol 2020 73: 35-42.
Incidence and
Predictors of Out-
of-Hospital Cardiac
Arrest Within 90
Days After
Myocardial
Infarction
Male Sex
Diabetes
eGFR < 30
Killip class > II
New-onset AF/Ft
LVEF 40-49%
LVEF 30-39%
LVEF < 30%
3. La Diabetes en la
Estrategia Terapéutica
New treatment paradigm in T2D
GlucoCentric Aproach
(CV) Events Reduction
Approach
Multifactorial Intervention
HbA1c as the central focus
Conventional glucose-lowering therapies have shown limited benefit in reducing CV risk2
HbA1c target individualised; generally ~7%
Lifestyle modification, then metformin/SGLT2i/GLP1a
Glucose
Lipid lowering
LDL < 55 / <70 or < 100 mg/dL (1.8 mmol/L); lifestyle, statin, ezetimibe, PCSK9i
Lipids
Target of <130/80 (140–130/90–80) mmHg
ACEi/ARB, BB
Blood pressure
Antiplatelet use
ASA (75–162 mg/day), DAPT
Antithrombotics
Lifestyle Changes
ARB, angiotensin receptor blocker; BB, beta blocker; CV, cardiovascular; DAPT, dual antiplatelet therapy;
GLP1a, glucagon-like peptide 1a; SGLT2i, sodium glucose transport protein 2 inhibitor.
Optimal CV risk reduction in Diabetic Patients is
achieved through targeting multiple risk factors
COMPLETE
REVASCULARIZATION
WITH MULTIVESSEL
PCI FOR
MYOCARDIAL
INFARCTION
(STEMI). T2D
Primary end-point
Co-Primary end-point
Metha S, et al NEJM 2019; DOI 10.1056.
ISCHEMIA Trial. Primary endpoint. Pre-specified Subgroups
DIABETES
Multivessel CAD and Diabetes PCI CABG
Favours CABG
Favours CABG
Favours CABG
REVASCULARIZATION
IN T2D
PATIENTES WITH
MULTIVESSEL
DISEASE
4. La Diabetes en la
Estrategia Terapéutica.
Selección Fármacos
1
1.5
IDENTIFY THE
RISK FACTOR
DIABETES AND CARDIOVASCULAR DISEASE PROTECTION
“CONTROL” THE
RISK FACTOR
REDUCE CV
EVENTS
AVOID SIDE
EFFECTS
THE “VIRTUOUS CHAIN” OF CARDIOVASCULAR PROTECTION IN DIABETES
DIABETES
DIAGNOSIS
REDUCE HB A1C
(“TREAT THE BLOOD TESTS”)
REDUCE CV RISK
(“TREAT THE PATIENT”)
AVOID
IATROGENY
(HYPOGLYCEMIA)
DIABETES
EHJ 2020
MACE: Cumulative incidence (adjusted)
GLP1 receptor agonists and the risk of CV events in diabetic patients
with an Acute Myocardial Infarction. SWEDEHEART.
3P-MACE
Trevisan M, et al. EHJ Cardiovasc Pharm 2021; 7: 337-104-111.
Superiority
MACE
Heart Failure Hospitalization
Mostly neutral except for albiglutdie
Proven Renal Benefit
Mostly albuminuria
SGLT2 inhibitors have been shown to reduce the risk of CV events,
including HHF and kidney outcomes
HR (95% CI)
3P-MACE
CV death
HHF
Kidney
outcomes
EMPA-REG OUTCOME1
(empagliflozin)
0.86 (0.74, 0.99)
p=0.04 superiority
0.62 (0.49, 0.77)
p<0.001†
0.65 (0.50, 0.85)
p=0.002†
CANVAS Program2
(canagliflozin)
0.86 (0.75, 0.97)
p=0.02 superiority*
0.87 (0.72, 1.06)‡
0.67 (0.52, 0.87)‡
CREDENCE5
(canagliflozin)
0.66 (0.53, 0.81)¶
ESKD (RRT or sustained eGFR
<15 ml/min/1.73 m2), doubling of serum
creatinine or kidney death; p<0.001
DECLARE-TIMI 583
(dapagliflozin)
0.93 (0.84, 1.03)
p=0.17
0.98 (0.82, 1.17)‡
0.73 (0.61, 0.88)‡
DECLARE-TIMI 583
(dapagliflozin)
0.53 (0.43, 0.66)‡
≥40% decrease in eGFR to
<60 ml/min/1.73 m2, new ESKD or
kidney death
EMPA-REG OUTCOME4
(empagliflozin)
0.54 (0.40, 0.75)§
Doubling of serum creatinine,
eGFR ≤45 ml/min/1.73 m2, RRT or
kidney death;
p<0.001
*Testing for superiority for 3P-MACE was part of the statistical analysis plan but was not part of the hierarchical testing strategy; †Nominal p-value; ‡Exploratory outcome, no p-value is reported
– only nominal effect estimate is given; §Exploratory outcome; ¶Prespecified outcome
1. Zinman B et al. N Engl J Med 2015;373:2117; 2. Neal B et al. N Engl J Med 2017;377:644; 3. Wiviott S et al. N Engl J Med 2019;380:347; 4. Wanner C et al. N Engl J Med 2016;375:323;
5. Perkovic V et al. N Engl J Med 2019;380:2295
Superiority
MACE
Heart Failure Hospitalization
Superiority
Proven Renal Benefit
Superiority
Eur Heart J, ehaa965, https://doi.org/10.1093/eurheartj/ehaa965
SGLT2 trials in heart failure – status and primary endpoints.
5. La Diabetes Principal
“Asignatura Pendiente”
de los Cardiólogos
Use of GLAs with demonstrated CV benefit
By therapeutic agent and class
Figure 2. ASCVD, atherosclerotic CVD; CV, cardiovascular; CVD, cardiovascular disease; GLA, glucose-lowering agent; GLP-1 RA, glucagon-like peptide-1
14
12
10
8
6
4
2
0
Empagliflozin Dapagliflozin Canagliflozin Liraglutide Dulaglutide Semaglutide
Overall
No CVD
Any CVD
ASCVD
SGLT2is GLP-1 RAs
GLAs with demonstrated CV benefit
receptor agonist; SGLT2i, sodium-glucose cotransporter-2 inhibitor
Vencio et al. P-945. Presented at the European Association for the Study of Diabetes (EASD) 56th Annual Meeting, 21–25 September 2020
Proportion
of
participants
(%)
IHD/HF/T2D Patient Pathway. The Challenge
HOSPITAL ADMISSION
HOSPITAL
DISCHARGE
EARLY
POST-
DISCHARGE
PHASE
LATE
POST-DISCHARGE
PHASE
Acute/Compensation GDMT Initiation GDMT Optimization
TRANSITION
TRANSITION TO ORAL THERAPIES
GLP1RA/SGLT2 I: “THE EARLIER THE BETTER”
Diabetes y
Cardiología;
o la Necesidad
de Abandonar
nuestra “Zona
de Confort”
Diabetes 2021. Cardiólogos y endocrinólogos: ¿matrimonio o divorcio?

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Diabetes 2021. Cardiólogos y endocrinólogos: ¿matrimonio o divorcio?

  • 1. José R. González Juanatey Servicio de Cardiología Hospital Clínico Universitario Santiago de Compostela. España SERVICIO DE CARDIOLOGIA HOSPITAL CLINICO DE SANTIAGO DE COMPOSTELA XERENCIA DE XESTIÓN INTEGRADA DE SANTIAGO DE COMPOSTELA DIABETES 2021. VISIÓN DESDE LA CARDIOLOGÍA Conflict of interest: Research grants and honoraria from (research committees, clinical trials, personal, Institutional) Astra-Zeneca, Bayer, Boehringer Ingelheim, Lilly / Daiichi-Sankyo, Ferrer, MSD, Novartis, Pfizer, Sanofi-Aventis, Servier, Amgen, Tecnofarma, Silanes, NovoNordisk
  • 2. 1. La Diabetes en los Procesos Asistenciales en Cardiología
  • 3. ADA, 2007 DM 100 126 140 200 Impaired Glucose tolerance IFG + IGT Impaired fasting glycaemia Normal 2h plasma glucose (mg/dl) Fasting plasma glucose (mg/dl) Random plasma glucose > 200 mg/dl + symptoms DM DM 2 3 1 4 HbA1c > 6,5 % x 2 x 2 x 1 x 2 ADA T2DM and Pre-diabetes
  • 4. T2D and CV Disease in Spain. An Epidemiological Perspective Diabetes + IHD 30-35% IHD PATIENTS WITH T2D 1 Diabetes + HF 27-47% HF PATIENTS WITH T2D 2 Diabetes + AF 24-34% AF PATIENTS WITH T2D 3 Redondo A et al. Rev Esp Cardiol 2015;68:777-84 Galvao C et al. Rev Esp Cardiol 2017; 70:425-32 Otero F et al. Rev Esp Cardiol 2010; 63:1371-6 Galve E et al. Rev Esp Cardiol 2016;69:931-8. Varela A et al. Heart 2005; 91:489-94 Otero F et al. Rev Esp Cardiol 2007; 60:373-83 Agra R et al. Cardiol J 2017; epub ahead of print Gómez-Otero et al. Rev Esp Cardiol 2017;70:338-46 Rodríguez-Mañero M et al. Rev Esp Cardiol. 2014;67:890–7 Carnero L et al. Rev Esp Cardiol. 2017;70:872–86 Rodríguez-Mañero M et al. Inter J Cardiol 2017; 243: 211–5 + 20% DIAGNOSIS AT TIME OF ADMISSION
  • 5. INSIGHTS SHARING – SANTIAGO DE COMPOSTELA ROADMAP FOR CARE ORGANIZATIONS - DIABETES
  • 6. 2. La Diabetes en la Estratificación de Riesgo
  • 7. Chronic/Acute Heart-Kidney Interactions CHRONIC CARDIORENAL SYNDROME CHRONIC RENOCARDIAC SYNDROME
  • 8. Cardiovascular-Renal Spectrum of Diabetes MACE, major adverse cardiovascular events (non-fatal stroke, non-fatal myocardial infarction, and cardiovascular death). Verma S et al. Lancet. 2019;393:3-5. Heart Failure MACE Renal Disease Diabetes affects the FILTER Diabetes affects the PUMP Diabetes affects the PIPES
  • 9. Diabetes and NSTEMI. Prognostic Implications CardioCHUS-HUSJ Registry MORTALIDAD CV MORTALIDAD TOTAL GRACE>140 GRACE>140 Alvarez B, …, Gonzalez-Juanatey JR . Rev Esp Cardiol 2020 73: 35-42.
  • 10. Incidence and Predictors of Out- of-Hospital Cardiac Arrest Within 90 Days After Myocardial Infarction Male Sex Diabetes eGFR < 30 Killip class > II New-onset AF/Ft LVEF 40-49% LVEF 30-39% LVEF < 30%
  • 11. 3. La Diabetes en la Estrategia Terapéutica
  • 12. New treatment paradigm in T2D GlucoCentric Aproach (CV) Events Reduction Approach Multifactorial Intervention HbA1c as the central focus
  • 13. Conventional glucose-lowering therapies have shown limited benefit in reducing CV risk2 HbA1c target individualised; generally ~7% Lifestyle modification, then metformin/SGLT2i/GLP1a Glucose Lipid lowering LDL < 55 / <70 or < 100 mg/dL (1.8 mmol/L); lifestyle, statin, ezetimibe, PCSK9i Lipids Target of <130/80 (140–130/90–80) mmHg ACEi/ARB, BB Blood pressure Antiplatelet use ASA (75–162 mg/day), DAPT Antithrombotics Lifestyle Changes ARB, angiotensin receptor blocker; BB, beta blocker; CV, cardiovascular; DAPT, dual antiplatelet therapy; GLP1a, glucagon-like peptide 1a; SGLT2i, sodium glucose transport protein 2 inhibitor. Optimal CV risk reduction in Diabetic Patients is achieved through targeting multiple risk factors
  • 14. COMPLETE REVASCULARIZATION WITH MULTIVESSEL PCI FOR MYOCARDIAL INFARCTION (STEMI). T2D Primary end-point Co-Primary end-point Metha S, et al NEJM 2019; DOI 10.1056.
  • 15. ISCHEMIA Trial. Primary endpoint. Pre-specified Subgroups DIABETES
  • 16. Multivessel CAD and Diabetes PCI CABG Favours CABG Favours CABG Favours CABG REVASCULARIZATION IN T2D PATIENTES WITH MULTIVESSEL DISEASE
  • 17. 4. La Diabetes en la Estrategia Terapéutica. Selección Fármacos
  • 18. 1 1.5 IDENTIFY THE RISK FACTOR DIABETES AND CARDIOVASCULAR DISEASE PROTECTION “CONTROL” THE RISK FACTOR REDUCE CV EVENTS AVOID SIDE EFFECTS THE “VIRTUOUS CHAIN” OF CARDIOVASCULAR PROTECTION IN DIABETES DIABETES DIAGNOSIS REDUCE HB A1C (“TREAT THE BLOOD TESTS”) REDUCE CV RISK (“TREAT THE PATIENT”) AVOID IATROGENY (HYPOGLYCEMIA)
  • 20. MACE: Cumulative incidence (adjusted) GLP1 receptor agonists and the risk of CV events in diabetic patients with an Acute Myocardial Infarction. SWEDEHEART. 3P-MACE Trevisan M, et al. EHJ Cardiovasc Pharm 2021; 7: 337-104-111.
  • 21. Superiority MACE Heart Failure Hospitalization Mostly neutral except for albiglutdie Proven Renal Benefit Mostly albuminuria
  • 22. SGLT2 inhibitors have been shown to reduce the risk of CV events, including HHF and kidney outcomes HR (95% CI) 3P-MACE CV death HHF Kidney outcomes EMPA-REG OUTCOME1 (empagliflozin) 0.86 (0.74, 0.99) p=0.04 superiority 0.62 (0.49, 0.77) p<0.001† 0.65 (0.50, 0.85) p=0.002† CANVAS Program2 (canagliflozin) 0.86 (0.75, 0.97) p=0.02 superiority* 0.87 (0.72, 1.06)‡ 0.67 (0.52, 0.87)‡ CREDENCE5 (canagliflozin) 0.66 (0.53, 0.81)¶ ESKD (RRT or sustained eGFR <15 ml/min/1.73 m2), doubling of serum creatinine or kidney death; p<0.001 DECLARE-TIMI 583 (dapagliflozin) 0.93 (0.84, 1.03) p=0.17 0.98 (0.82, 1.17)‡ 0.73 (0.61, 0.88)‡ DECLARE-TIMI 583 (dapagliflozin) 0.53 (0.43, 0.66)‡ ≥40% decrease in eGFR to <60 ml/min/1.73 m2, new ESKD or kidney death EMPA-REG OUTCOME4 (empagliflozin) 0.54 (0.40, 0.75)§ Doubling of serum creatinine, eGFR ≤45 ml/min/1.73 m2, RRT or kidney death; p<0.001 *Testing for superiority for 3P-MACE was part of the statistical analysis plan but was not part of the hierarchical testing strategy; †Nominal p-value; ‡Exploratory outcome, no p-value is reported – only nominal effect estimate is given; §Exploratory outcome; ¶Prespecified outcome 1. Zinman B et al. N Engl J Med 2015;373:2117; 2. Neal B et al. N Engl J Med 2017;377:644; 3. Wiviott S et al. N Engl J Med 2019;380:347; 4. Wanner C et al. N Engl J Med 2016;375:323; 5. Perkovic V et al. N Engl J Med 2019;380:2295
  • 24.
  • 25. Eur Heart J, ehaa965, https://doi.org/10.1093/eurheartj/ehaa965 SGLT2 trials in heart failure – status and primary endpoints.
  • 26. 5. La Diabetes Principal “Asignatura Pendiente” de los Cardiólogos
  • 27. Use of GLAs with demonstrated CV benefit By therapeutic agent and class Figure 2. ASCVD, atherosclerotic CVD; CV, cardiovascular; CVD, cardiovascular disease; GLA, glucose-lowering agent; GLP-1 RA, glucagon-like peptide-1 14 12 10 8 6 4 2 0 Empagliflozin Dapagliflozin Canagliflozin Liraglutide Dulaglutide Semaglutide Overall No CVD Any CVD ASCVD SGLT2is GLP-1 RAs GLAs with demonstrated CV benefit receptor agonist; SGLT2i, sodium-glucose cotransporter-2 inhibitor Vencio et al. P-945. Presented at the European Association for the Study of Diabetes (EASD) 56th Annual Meeting, 21–25 September 2020 Proportion of participants (%)
  • 28. IHD/HF/T2D Patient Pathway. The Challenge HOSPITAL ADMISSION HOSPITAL DISCHARGE EARLY POST- DISCHARGE PHASE LATE POST-DISCHARGE PHASE Acute/Compensation GDMT Initiation GDMT Optimization TRANSITION TRANSITION TO ORAL THERAPIES GLP1RA/SGLT2 I: “THE EARLIER THE BETTER”
  • 29. Diabetes y Cardiología; o la Necesidad de Abandonar nuestra “Zona de Confort”