Estudios Advance, Accord, - SENDIMAD€¦ · Estudios Advance, Accord, VADT, UKPDS, DCCT,...
Transcript of Estudios Advance, Accord, - SENDIMAD€¦ · Estudios Advance, Accord, VADT, UKPDS, DCCT,...
Estudios Advance, Accord,
VADT,
UKPDS, DCCT, Steno..…
¿Que nos enseñan? Alfonso L. Calle Pascual
Servicio de Endocrinología y Nutrición
HCSC, Madrid
Actualización en Endocrinología 2009
FJD 27 de Febrero de 2009
CONTEXTO 2000
Diabetes y riesgo microvascular
Diabetes y riesgo macrovascular
Aggregate clinical end points
conventional
0.5 1 2
0.88
0.90
0.94
0.84
1.11
0.75
0.029
0.34
0.44
0.052
0.52
0.0099
Any diabetes-related end point
Diabetes-related deaths
All-cause mortality
Myocardial infarction
Stroke
Microvascular
RR P
Favors Intensive
Relative Risk & 95% CI
UKPDS,Lancet 1998.
Glycemic threshold for
microvascular/cardiovascular risk
Relative
risk
3
2
1
Fasting Plasma glucose
(mmol/L) 4 5 6 7 8
Microvascular Cardiovascular
4 6 8 10 12 14 2-hour
- Glucose
- Blood pressure
- Lipids
- Antiplatelet agents
- COMBINED INTERVENTIONS
Multiple risk factors in T2DM
GAEDE P, et al. NEJM. 2003;348:383-393.
160 Danish type 2 diabetic patients with
persistent microalbuminuria
One example of a multifactorial strategy:
the STENO 2 study
Results of multifactorial intervention on primary end point (7.8
years’ follow-up)
Link between blood glucose and CV risk:
Association or causality?
Good diabetes control reduces CV risk in type
1 diabetes:
Convincing evidence in type 1 diabetes:
The DCCT/EDIC study
NEJM. 2005;353:2643.
Some comments on the DCCT/EDIC study:
– Good news for type 1 diabetic subjects!
– A major relative risk reduction: ~ 50%
– An illustration of the glucose memory effect
HbA1c during DCCT/EDIC:
- 1983: 9.1% // 9.1%
- 1993: 7.4% // 9.0%
- 2004: 8.0% // 7.9%
Glucose & CV events: meta-regression
RR RR
NB: 2 h G=140: RR=1.58 (1.19-2.10) Fasting G=110: RR=1.33 (1.06-1.67)
After removal of any DM: P=0.0006 for 2 h G
P=0.06 for FPG
Coutinho M, Gerstein HC, et al. Diabetes Care. 1999;22:233-240.
72 108 144 180 198 72 90 108 126 144 163
2 h glucose Fasting glucose
Glucose-lowering and CV risk - IGT Ambulatory IGT: STOP NIDDM analysis: Chiasson, et al. JAMA. 2003;290:486.
HR 0.51 (0.28-0.95) (ie, 32/686 vs 15/682 MI, angina, revasc, CV death, CHF, stroke, or PVD)
ESTRATEGIAS
FARMACOLOGICAS
• Farmacos que corrijan los defectos en la
acción y secreción de la insulina
• Seguros: HIPOGLUCEMIA
• Eficaces sobre el control glucémico
• Otros efectos sobre el control metabólico
What about intensified glucose control in
dysglycemia/type 2 diabetes?
• ADVANCE
• ACCORD
• VADT
• ORIGIN
• NAVIGATOR
.......
Trials ongoing:
Diseño Experimental
• Criterios inclusión: TTO dosis máximas
HO/insulina y HbA1c >7.5%. HbA1c
B>9%
• BMI <27 Kg.m-2: GlimeP+ Rosi Dosis
Max (1/2 Control)
• Antes de cualquier cambios en dosis oral se
suministra Insulina (HbA1c >6%)
Algunas características
Relevantes • Entre 2000-3 hasta 2008
• Edad >60 a Tev >11 años
– 72% HTA y 40% ECV;
– 52% insulina 42% HO dosis Max
• Exclusión:
– 34% HbA1c
– 16% no recibían Dosis Max HO/Insulina
• Seguimiento:
– Ganancia de peso >Intensivo (+4Kg)
– LDL < 80 mg/dl
Tamaño muestral
• Infraestima Tiempo
• Sobreestima riesgo
• Ocurrieron 499
eventos CV
• (264 vs 235 C vs Int)
• Podría esperarse una
reducción no
significativa
Muertes
Muertes (Inten vs Conv)
• CV: 40 vs 33
• Súbitas 11 vs 4; p=0.08
Efectos 2º (Inten vs Conv)
• Hipoglucemias severas:
24 % vs 18% p=0.05
• Disnea: Intensivo
p<0.006
• Neuropatia Autonómica
p=0.07
The Oxford Centre for Diabetes, Endocrinology and Metabolism
PRECAUCIONES • Aquellos que dicen que disminuir
la glucemia no es costo-eficaz
• Aquellos que dicen que el objetivo de 7.5% es “mas” adecuado, sin decir el motivo
• Aquellos que dicen que es suficiente bajar el colesterol y la TA
• Aquellos que quieren hacerse famosos diciendo cualquier cosa ruidosamente
STENO 2
HISTORIA: Reflexiones
• ACCORD: NO VALE TODO
• VADT: ESPERADO
• UKPDS (1998): microangiopatia (2008) macroangiopatia
• Steno 2003. Multifactorial; 2008 Macrovascular Objetivos óptimos. NUNCA ES TARDE
• ADVANCE Objetivos óptimos. Y ESTRATEGIAS
• No todos fármacos pueden ser idénticos (metformin vs SUs; TZDs pueden tener efectos adversos CV
• HIPOGLUCEMIAS ¿ARMAS?
___________________________
Krinsley. Crit Care Med 2008; 36:3008–3013
Retrospective review of 3252 medical surgical ICU patients excluding cardiac surgery. GV, assessed by SD of mean BG levels
Glycemic variability: A strong independent predictor of mortality in critically ill patients
Each of the increments of mean glucose level was subdivided into four quartiles of glycemic variability. Q1= lowest; Q4 =highest quartile
Hypoglycemia-associated Hospital
Mortality Relates to Comorbidities
Retrospective cohort of 31,970 patients admitted to the general wards
aimed to determine inhospital mortality (<70 mg/dL) -spontaneous and
drug-associated hypoglycemia.
RESULTS:
• A total of 10.5% of patients had ≥ episode of hypoglycemia. Patients
with hypoglycemia were older, had more comorbidities, and received
more antidiabetic agents.
• Hypoglycemia was associated with increased in-hospital mortality
(HR, 1.67; 95% CI, 1.33-2.09; P.001).
• Mortality risk was limited to patients with spontaneous hypoglycemia
(HR, 2.62; 95% CI, 1.97-3.47; P.001) and not to patients with drug-
associated hypoglycemia (HR, 1.06; 95% CI, 0.74-1.52; P.749).
• After adjustment for patient comorbidities, the association between
spontaneous hypoglycemia and mortality was eliminated (HR, 1.11;
95% CI, 0.76-1.64; P.582).
Boucai et al. Am J Med 124, 1028-1035, 2011
Number of Hypoglycemic Episodes and In-
Hospital Mortality
Boucai et al. Am J Med 124, 1028-1035, 2011
Mean Glucose & In-Hospital Mortality in 16,871 Patients with AMI
(Reference: Mean BG 100-110 mg/dl)
Kosiborod M et al. Circulation 2008:117:1018
BUENAS NOTICIAS
ORIGIN