Tratamiento prolongado antiagregante en subgrupos de pacientes. José F. Díaz, MD, FESC Complejo Hospitalario de Huelva

Transcripción

1 Tratamiento prolongado antiagregante en subgrupos de pacientes José F. Díaz, MD, FESC Complejo Hospitalario de Huelva

2 Endpoint (%) Primary Endpoint CV Death,MI,Stroke CV Death / MI / Stroke Clopidogrel Prasugrel HR 0.81 ( ) P= TIMI Major NonCABG Bleeds Wiviot SD, Braunwald E, McCabe CH et al NEJM 2007 Days Prasugrel Clopidogrel HR 1.32 ( ) P=0.03

3 Endpoint (%) Diabetic Subgroup N= CV Death / MI / Stroke Clopidogrel Prasugrel HR 0.70 P<0.001 NNT = TIMI Major NonCABG Bleeds Days Clopidogrel 2.6 Prasugrel 2.5 Wiviot SD, Circulation 2008

4 Endpoint (%) STEMI Cohort N: CV Death / MI / Stroke Clopidogrel Prasugrel TIMI Major NonCABG Bleeds Montalescot et al. Lancet 2009; 373: Days Prasugrel Clopidogrel

5 TRITON TIMI 38 Net clinical benefit: Bleeding risk subgroups Prior stroke/tia Yes No Pint = Risk (%) Age 75 <75 Pint = Weight <60 kg 60 kg Pint = OVERALL Prasugrel better Wiviot SD, Braunwald E, McCabe CH et al NEJM 2007 HR Clopidogrel better

6 Cumulative Incidence (%) PLATO Study N: Days after randomization Wallentin L et al. N Engl J Med 2009;361:

7 James SK et al. BMJ 2011; 342:d3527 Mortality reduction in Invasive and non-invasive treatment strategies

8 Ticagrelor y función renal Variable primaria compuesta MuerteCV, IM, Ictus Variable de Seguridad James S. Circulation 2010;122:

9 Población con Ictus/TIA previo Variable primaria compuesta MuerteCV, IM, Ictus Mortalidad Total HR: 0.87 (95% CI = ) HR: 0.62 (95% CI = ) P int = 0.84 P int = 0.19 HR: 0.84 (95% CI = ) HR: 0.81 (95% CI = ) HR: 0.99 (95% CI = ) ---- Clopidogrel Ticagrelor HR: 1.04 (95% CI = ) P int = 0.77 Sangrados Mayores James SK, et al. Circulation. 2012;125:

10 PLATO CABG Mortalidad según días previos de interrupción de tratamiento Variable Principal Muerte CV/IM/Ictus HR: 0.84 (95% CI = ), p=0.29 Sangrados Held C, et al. J Am Coll Cardiol 2011;57:

11 Subgrupo de Diabéticos (n=4662) Variable primaria según presencia de DM Sangrado según presencia de DM James S. Eur Heart J 2010;31:

12 STEMI-PCI

13 Montalescot et al. Lancet 2009; 373: TRITON STEMI-PCI

14 K-M Estimated Rate (% Per Year) PLATO STEMI: All Cause Mortality 7 6 Clopidogrel Ticagrelor No. at risk Ticagrelor Clopidogrel HR 0.82 (95% CI = ), p = Months 4,201 4,005 3,962 3,876 3,150 2,413 1,993 4,229 4,029 3,989 3,912 3,195 2,471 1,980 CI=Confidence Interval; HR=Hazard Ratio; K-M=Kaplan-Meier; PLATO=PLATelet Inhibitiion and Patient Outcomes; STEMI=ST-Elevation Myocardial Infarction Steg PG, et al. Circulation 2010;122:

15 TRITON-TIMI 38: Mortality in STEMI All Cause Death (%) Hazard Ratio, 0.76 (95% CI, ) p = Days from Randomization Clopidogrel 4.3% Prasugrel 3.3% Number at Risk: Prasugrel Clopidogrel Data on File, Daiichi Sankyo, Inc. and Eli Lilly and Company CI=Confidence Interval; STEMI=ST-Elevation Myocardial Infarction; TRITON-TIMI=TRial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet InhibitioN with Prasugrel Thromobolysis In Myocardial Infarction

16 Tratamiento en subgrupos

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18 PCI CURE

19 Definite/Probable ST Any Stent (N=12.844) Wiviot SD, Braunwald E, McCabe CH et al NEJM 2007

20 Definite/Probable ST Any Stent (N=12.844) Antman EM. NYHA 2007

21 Definite Stent Thrombosis

22 K-M estimated rate (% per year) Wallentin L et al. N Engl J Med 2009;361: Safety of Long Term DAPT % at the 1st month Ticagrelor Clopidogrel No. at risk Ticagrelor 9,235 Clopidogrel 9, ,246 7,305 Days from first IP dose 6,826 6,930 HR 1.04 (95% CI ), p= ,545 6,670 5,129 5,209 3,783 3,841 3,433 3,479

23 Timing of Benefit Landmark Analysis Wiviot SD, Braunwald E, McCabe CH et al NEJM 2007

24 Antman EM. NYHA 2007; Timing of Benefit (Landmark Analysis 30 days) NNT=70 NNT=227

25 Cumulative incidence (%) Wallentin L et al. N Engl J Med 2009;361: Cumulative incidence (%) Primary efficacy endpoint over time (composite of CV death, MI or stroke) Clopidogrel Ticagrelor Clopidogrel 5.28 Ticagrelor HR 0.88 (95% CI ), p= HR 0.80 (95% CI ), p< No. at risk Days after randomisation Days after randomisation * Ticagrelor 9,333 8,942 8,827 8,763 8,673 8,543 8,397 7,028 6,480 4,822 Clopidogrel 9,291 8,875 8,763 8,688 8,688 8,437 8,286 6,945 6,379 4,751 *Excludes patients with any primary event during the first 30 days

26 Primary efficacy endpoint and TIMI Major Bleeding Through 30 months (Overall Population)

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29 PEGASUS TIMI 54 Pacientes con IM en los 1-3 años y con al menos un factor de riesgo aterotrombótico (n=21,000) Ticagrelor 60 mg BID mg ASA Ticagrelor 90 mg BID mg ASA Placebo mg ASA Mínimo de 12 meses de seguimiento Objetivo de Eficacia primaria: Muerte CV, IM o Ictus Objetivo Primario de Seguridad: Sangrado mayor TIMI

30 CONCLUSIONES Los nuevos antiagregantes nos dan la opción de adaptar el tipo de tratamiento al tipo de paciente A diferencia de clopidogrel, ambos, aunque sobre todo ticagrelor, mantienen e incluso incrementan la eficacia en el seguimiento. La seguridad no parece verse comprometida

31 La importancia del tratamiento a medida

32 HUELVA