Prof. Jindřich Špinar, MD Head of the Internal Cardiology dpt., University Hospital Brno Focuses on clinical cardiology, acute and chronic heart failure, ischemic heart gisease, hypertension Vice head of the Czech acreditation committee cardiology Head of the Czech grant commitee of ministry of health
THE ROLE OF ANTIPLATELET DRUGS IN CVS RISK PREVENTION Jindřich Špinar
PTCA IKK FNB PTCA = 1 500/year PPTCA = 450/year
Direktní PCI in Czech republic
PTCA 60/1 000 000 = 1992 624/1 000 000 = 1998 1 220/1 000 000 = 2006 20x
PTCA 60/1 000 000 = 1992 624/1 000 000 = 1998 1 220/1 000 000 = 2006 2 250/1 000 000 = 2009 37x
STENT 5/1 000 000 = 1992 449/1 000 000 = 1998 1 082/1 000 000 = 2007 200x
STENT 5/1 000 000 = 1992 449/1 000 000 = 1998 1 082/1 000 000 = 2007 2 850/1 000 000 = 2009 570x
REPERFUSION REMODELATION ETROMBOSIS 4R RESTENOSIS
RAAS blocade Beta blocade Statins Antiagregation
The effect of ASA Inhibition of cyklooxygenase and tromboxanem A 2 induced agregation of platelets
ANTIPLATELET TRIALISTS COLLABORATION CV death, MI, stroke Studies Endpoint Popultion 3 Primary 1176 27210 20 Stroke 1916 9530 11 Post MI 2270 15529 11 AMI 2783 18126 12 AP 398 3450 20 CABG/PTCA 245 3057 28 PAD 444 3864 51 Trombosis 67 4771 30 Other 283 3948 189 All 9789 90297 ASA vs control RRR ± SD 12 ± 6 % 24 ± 5 % 24 ± 4 % 26 ± 4 % 39 ± 9 % 33 ± 13 % 25 ± 10 % 42 ± 19 % 44 ± 10 % 25 ± 2 % Br Med J 1994 0.0 0.5 1.0 1.5 2.0 2p < 0.00001
Antiagregation therapy = dual antiagregtion
Herbert. Exp Opin Invest Drugs 1994;3:449-455. CLOPIDOGREL platelet ADP Gp IIb/IIIa Fibrinogen Fibrinogen binding reduced Selective inhibition of ADP receptors and lowers the activity Gp IIb/IIIa.
CLOPIDOGREL EBM DATA
CLOPIDOGREL EBM DATA CAPRIE study Patients with anamnesis of symptomatic atherosclerotic disease (cerebral or cardiac infarction or peripheral arterial disease) medication: clopidogrel 75 mg/day versus ASA 325 mg/day CAPRIE Steering Committee. Lancet 1996; 348: 1329 39.
Cumulative number of incidents (%) CLOPIDOGREL EBM DATA 16 CAPRIE ASA 8.7% 12 clopidogrel 8 4 0 8,7% reduction of relative risk (ITT) in primary endpoint (IM, ischemic stroke or vascular death) p = 0,043; n = 19185 0 6 12 18 24 30 36 months CAPRIE Steering Committee. Lancet 1996; 348: 1329 39.
Patients CAPRIE : Bleeding 300 250 200 150 100 50 0 104 71 (0.74%) (1.08%) Hospitalization for GI bleeding 1 191 255 GI bleeding (p<0.002) 2 Clopidogrel Aspirin 1 Bogousslavsky. Cerebrovasc Dis 1998;8(suppl 4):43. Abstract CLI 76. 2 CAPRIE Steering Committee. Lancet 1996;348:1329-1339.
CURE Day 0 Patients with ACS AKS (unstable AP or non-q IM without ST elevations) R Clopidogrel 300 mg Loading dose Placebo úvodní dávka Den 1 Den 1 12 month 12 mnoth Clopidogrel 75 mg 1x d. + standard therapy (n=6259) Placebo 1 tbl 1x denně + standard therapy (n=6303) R=randomization, 24 hours of symptoms CURE Study Investigators. Eur Heart J 2000; 21:2033 2041 The CURE Investigators. N Eng J Med August 2001
Kumulativní riziko 0,14 0,12 0,10 0,08 0,06 0,04 0,02 0,00 5.4% 4.3% 30 d 21% Primary endpoint MI/Stroke/CV death ASA* Clopidogrel + ASA* 11.4% 9.3% 11.7% 9.5% 0 3 6 9 12 Měsíce sledování 19% Relative Risk Reduction The CURE Trial Investigators. N Engl J Med. 2001;345:494-502. P = 0.00009 N = 12,562 LD Clopidogrel (300mg) / 75 mg/d + ASA (75-325 mg) vs ASA
CURE - Primary endpoint Clopidogrel + Standard terapie RR standard therapy only (n=6259) (n=6303) (%) (%) CI Primary endpoint 9.3 11.4 0.80 0.72 0.90* CV death 5.1 5.5 MI 5.2 6.7 Stoke 1.2 1.4 *p=0.00009 The CURE Investigators. N Eng J Med August 2001
COMMIT/CCS-2 (ClOpidogrel & Metoprolol in Myocardial Infarction Trial) 45 852 patients in 1250 centres
Design STEMI 24 hours n=~46,000 R Clopidogrel 75 mg QD* Double blind 4 weeks (n ~ 23,000) Placebo* (n ~ 23,000) (2 2 Factorial with metoprolol) * All ASA 162mg/day 1. Chen ZM et al. ACC 2005.
Mortality (%) 9 8 7 6 5 4 3 2 1 Mortality - 7% Placebo (8.1%) Clopidogrel (7.5%) RRR=7% p=0.03 0 0 7 14 21 28 Dayes 1. Chen ZM et al. ACC 2005.
Death, MI, stroke 9% Placebo + ASA: 2311 (10.1%) Clopidogrel + ASA: 2125 (9.3%) Příhody (%) (2P=0.002) Dayes
STROKE epidemiology mortality burden
STROKE VORLDWIDE STROKE WORLDWIDE Annually 15 Mil. people suffer from stroke. Od these 5 Mil. die another 5 Mil. are left permanently disabled. Major risk factors for stoke are similar to CHD High BP and smoking (modifiable) HF, MI and atrial fibrilation WHO stroke
IS ADMINISTRATION OF CLOPIDOGREL IN SECONDARY PREVENTION OF ISCHEMIC STROKE EVIDENCE BASED?
CLOPIDOGREL EBM DATA CARESS study Patients with recent symptomatic carotic stenosis 50% Medication: clopidogrel (first 2 days: 300 mg/day; 3rd to 7th day 75 mg/day) + ASA 75 mg/day versus ASA 75 mg/day Markus H, et al. Circulation 2005; 111: 2233 40.
CLOPIDOGREL EBM DATA CARESS RRR = 39,8% p = 0,005 Markus H, et al. Circulation 2005; 111: 2233 40.
CLOPIDOGREL EBM DATA Patients undergoing carotic stenting medication: ASA + clopidogrel versus ASA + heparin (24 hours) McKevitt FM, et al. Eur J Vasc Endovasc Surg 2005; 29: 522-7.
CLOPIDOGREL EBM DATA Study terminated prematurely due to hemorrhagic complication in the group ASA + heparin McKevitt FM, et al. Eur J Vasc Endovasc Surg 2005; 29: 522-7.
CLOPIDOGREL EBM DATA p > 0,05 McKevitt FM, et al. Eur J Vasc Endovasc Surg 2005; 29: 522-7.
CLOPIDOGREL EBM DATA p = 0,02 McKevitt FM, et al. Eur J Vasc Endovasc Surg 2005; 29: 522-7.
CLOPIDOGREL EBM DATA p > 0,05 McKevitt FM, et al. Eur J Vasc Endovasc Surg 2005; 29: 522-7.
2008
PRoFESS Totally 20332 patients were observed for the period of average 2.5 years Sacco RL, et al., for the PRoFESS Study Group. N Engl J Med 2008; 359: 1238-51.
PRoFESS Sacco RL, et al., for the PRoFESS Study Group. N Engl J Med 2008; 359: 1238-51.
PRoFESS Sacco RL, et al., for the PRoFESS Study Group. N Engl J Med 2008; 359: 1238-51.
PRoFESS Sacco RL, et al., for the PRoFESS Study Group. N Engl J Med 2008; 359: 1238-51.
PRoFESS Sacco RL, et al., for the PRoFESS Study Group. N Engl J Med 2008; 359: 1238-51.
PRoFESS Stroke recurrence risk in patients with noncardio-embologenic stroke, treated with ASA + ERDP vs. CLOP is similar as the risk of stroke (IM) death for vascular reason Clear benefit of patient s risk of recurrence of the stroke or development of important hemorrhagic incident is similar in both groups, regardless higher hemorrhagic stroke risk in ASA + ERDP group There was no significant difference in the risk of fatal or invalidating stroke between both groups Sacco RL, et al., for the PRoFESS Study Group. N Engl J Med 2008; 359: 1238-51
AND WHAT IS THE FUTURE?
August 30, 2009 at 08.00 CET
PLATO All patients* Ticagrelor (n=9,333) Clopidogrel (n=9,291) HR for (95% CI) p value Primary objective, n (%) CV death + MI + stroke 864 (9.8) 1,014 (11.7) 0.84 (0.77 0.92) <0.001 Secondary objectives, n (%) Total death + MI + stroke 901 (10.2) 1,065 (12.3) 0.84 (0.77 0.92) <0.001 CV death + MI + stroke + ischaemia + TIA + arterial thrombotic events Myocardial infarction CV death Stroke 1,290 (14.6) 1,456 (16.7) 0.88 (0.81 0.95) <0.001 504 (5.8) 353 (4.0) 593 (6.9) 442 (5.1) 0.84 (0.75 0.95) 0.79 (0.69 0.91) 0.005 0.001 125 (1.5) 106 (1.3) 1.17 (0.91 1.52) The percentages are K-M estimates of the rate of the endpoint at 12 months. 0.22 Total death 399 (4.5) 506 (5.9) 0.78 (0.69 0.89) <0.001