CARDIOACTUALIDAD: LO MÁS RELEVANTEDE LA CARDIOLOGÍA EUROPEA Y MUNDIAL

EN EL ÚLTIMO AÑO

CARDIOPATÍA ISQUEMICA

Dra. Magda HerasICT, Hospital Clínic, Barcelona

Congreso Nacional Enfermedades CVBarcelona, Octubre 2009

Conflictos de interés:

• GSK (beca no condicionada)• Menarini (Consultoría)• AstraZeneca (Coordinación estudio)

• SÍNDROME CORONARIO AGUDO

• PREVENCIÓN SECUNDARIA

PLATO Study Design

Primary endpoint: • CV death + MI + Stroke Key secondary: • CV death + MI + Stroke in patients intended for invasive management • Total mortality + MI + Stroke • CV death + MI + Stroke + recurrent ischaemia + TIA + arterial thrombotic events • MI alone / CV death alone / Stroke alone / Total mortalityPrimary safety: • Total major bleeding

6–12 month exposure

ClopidogrelIf pre-treated, no additional loading dose;if naive, standard 300 mg loading dose,

then 75 mg qd maintenance;(additional 300 mg allowed pre PCI)

Ticagrelor180 mg loading dose, then

90 mg bid maintenance;(additional 90 mg pre-PCI)

UA/NSTEMI (moderate-to-high risk) STEMI (if primary PCI)All receiving ASA; clopidogrel-treated or naive;

randomised within 24 hours of index event (N=18,624)

James S, et al. Am Heart J. 2009;157:599-605. 4

TICAGRELOR IN ACS. THE PLATO STUDY

All Patients*All Patients*Ticagrelor Ticagrelor (n=9,333)(n=9,333)

Clopidogrel Clopidogrel (n=9,291)(n=9,291)

HR for ticagrelor HR for ticagrelor (95% CI)(95% CI) PP value value✝✝

Primary Objective, n (%/yr)

CV death + MI + stroke 864 (9.8) 1,014 (11.7) 0.84 (0.77-0.92) 0.0003Secondary Objectives, n Secondary Objectives, n (%/yr)(%/yr)

Total death + MI + stroke 901 (10.2) 1,065 (12.3) 0.84 (0.77-0.92) 0.0001

CV death + MI + stroke + severe + recurrent ischemia

+ TIA + arterial thrombus1,290 (14.6) 1,456 (16.7) 0.88 (0.81-0.95) 0.0006

MI 504 (5.8) 593 (6.9) 0.84 (0.75-0.95) 0.0045CV death 353 (4.0) 442 (5.1) 0.79 (0.69-0.91) 0.0013

Stroke 125 (1.5) 106 (1.3) 1.17 (0.91-1.52) 0.2249

Total Death 399 (4.5) 506 (5.9) 0.78 (0.69-0.89) 0.0003

Hierarchical Testing of Major Efficacy EndpointsHierarchical Testing of Major Efficacy Endpoints

Wallentin L, et al. New Engl J Med. 2009;361.

No. at risk

ClopidogrelTicagrelor

9,2919,333

8,5218,628

8,3628,460

8,124

Days after randomisation

6,7436,743

5,0965,161

4,0474,147

0 60 120 180 240 300 360

121110

9876543210

13

Cum

ulat

ive

inci

denc

e (%

)9.8

11.7

8,219

Clopidogrel

Ticagrelor

K-M = Kaplan-Meier; HR = hazard ratio; CI = confidence interval

Wallentin L, et al. New Engl J Med. 2009;361.6

TICAGRELOR IN ACS. THE PLATO STUDY

Death, MI or Stroke

p=0.0003HR 0.84 (95% CI 0.77–0.92)

RRR = 16%, ARR = 1.87%, NNT = 54

Mehta S, et al ESC 2009, Hot Line

CLOPIDOGREL IN ACS. THE CURRENT STUDY

Mehta S, et al ESC 2009, Hot Line

PRASUGREL IN STEMI. THE TRITON – TIMI 38 STUDY

Montalescot G et al. Lancet 2009; 373: 723–31

PRASUGREL IN STEMI. THE TRITON – TIMI 38 STUDY

Montalescot G et al. Lancet 2009; 373: 723–31

Death, MI, stroke Death, MI, urgent TVR

Stent thrombosis TIMI major bleeding, non-CABG related

0

2

4

6

8

10

12

14

Death,MI,RIUR,BO Death, MI Major bleeding

Early eptifibatide Early placebo

% p

ts

96 h 30 d 120 h

P=0.02

P=0.08

GP IIb/IIIa antagonists in NSTEMIThe EARLY-ACS study

Giugliano et al. NEJM 2009; 360: 2176-90Giugliano et al. NEJM 2009; 360: 2176-90

• Routine early eptifibatide vs provisional use after angiography (decision by MD)• High risk: troponins, ST changes, >60 y. Randomization < 24h. Angio 8-12h• UFH 35%, LMWH 53%, both 7%, other 6%. Clopidogrel before angio 75%• 59% PCI, 13% CABG, 28% medical therapy. 37% provisional arm eptifibatide

OTAMIXABAN IN NSTEMI. THE SEPIA-ACS 1 STUDY

Sabatine M. ESC 2009 [ figura REC 2009;62:1149-60]

GP IIb/IIIa antagonists in STEMI . The BRAVE-3 study

800 pts with AMI ≤ 24hASA, heparin, 600 mg clopidogrel. Abciximab vs placebo before pPCI1º end-point: Infarct size (SPECT) 2º: Death+AMI+TVR+stroke 30 d.

02468

1012141618

Infarct size 30 ddeath,MI,Rev,stroke

Abciximab Placebo

% p

ts No differences in major bleeding

Mehilli J, et al. Circulation 2009;119: 1933-40

ROUTINE PCI AFTER FIBRINOLYSIS IN STEMI The TRANSFER study

1059 pts with high risk AMI ≤ 12h, in non-PCI centresASA, TNK, heparin, clopidogrel (recom). Randomized early routine PCI ≤ 6h (99%) vs standard treatment (1/3 required urgent PCI)1º end-point: Death+AMI+ Rec isch+ CHF, shock 30 d.

Cantor WJ, et al. NEJM 2009;360: 2705-18

02468

1012141618

Prim end-point Rec isch CHF

Standard Tt Early PCI

P=0.004

P=0.003P=0.04

RR 0.64 0.09 0.54

% p

ts

PRIMARY PCI VS FIBRINOLYSIS IN STEMI IN THE ELDERLY. The TRIANA study

266 pts with AMI > 75 yrs, admitted to active pPCI (23 centres) Randomized to pPCI vs TNK ASA, heparin, clopidogrel (recom). 1º end-point: Death+AMI+ stroke 30 d.

Bueno H, et al ESC 2009, Hot Line

0

5

10

15

20

25

30

Death,AMI,CVA Death AMI CVA

pPCI Fibrinolysis

OR 1.31 (0.67-2.56) P = 0.43

OR 1.60 (0.60-4.25) P = 0.35

OR 4.03 (0.44-36.5)P = 0.18

OR 1.46 (0.81-2.61) P = 0.21

• SÍNDROME CORONARIO AGUDO

• PREVENCIÓN SECUNDARIA

N= 3.491

N= 2.730N= 761

Mega JL, et al. Lancet 2009; 374: 29-38

RIVAROXABAN IN SECONDARY PREVENTION. THE ATLAS STUDY

RIVAROXABAN IN SECONDARY PREVENTION. THE ATLAS STUDY

Mega JL, et al. Lancet 2009; 374: 29-38

BLEEDING

2 EFFICACY

5,5

3,9

1 EFFICACY

5,6

7,0

Apixaban 2,5 HR 1,78, NSApixaban 10 HR 2,45, p=0,005

BLEEDINGISTH MAJOR, CR NON-MAJOR

Apixaban 2,5 HR 0,73, NSApixaban 10 HR 0,61, p=0,07

EFFICACYDEATH, MI, REC ISCH, STROKE

APIXABAN IN SECONDARY PREVENTION. THE APPRAISE STUDY

Appraise Investigators. Circulation 2009; 119: 2877- 85

CR: Clinically relevant

THROMBIN RECEPTOR ANTAGONIST SCH 530348THE TRA-PCI STUDY

Becker RC, et al Lancet 2009; 373: 919-28

CONCLUSIONES

SCA• Nuevos fármacos antiagregantes, prasugrel y ticagrelor • El traslado para ICP tras fibrinolíticos reduce los eventos• Estudio TRIANA: la ICPp es > fibrinolisis en pacientes >75 a;

no provoca exceso de hemorragias

PREVENCIÓN SECUNDARIA• Nuevos tratamientos antiplaquetarios (inhibidor receptor trombina) y anticoagulantes orales (inhibidores FXa)