###CREDO 2002, Elective PCI ####Results 1. Clopidogrel pretreatment did not significantly reduce the combined risk of death, MI, or urgent target vessel revascularization at 28 days (P =.23) 2. Patients who received clopidogrel at least 6 hours before PCI had a 38.6% reduction in the risk events which was borderline statistically significant (p=0.051) ####Comments 1. Death 0 (Clopidogrel group) vs 4 (Placebo group) ###CURE 2001 Trial of Clopidogrel vs Aspirin in NSTEMI pts - Pretreatment ####Results In Rx group: 1. Less Cardiac death/Nonfatal myocardial infarction, or stroke in Rx group 2. More bleeding but not more life-threatening bleeding ####Comments 1. 12,000 pts enrolled 2. 2800 had PCI 3. 2000 had CABG, median 26 d after (12 - 70,5 d) In hospital CABG 12 d (8 - 19, 8 - 13) 4. No difference in mortality 5. Mechanism of stroke reduction? ###PCI-CURE Trial of Clopidogrel vs Aspirin in NSTEMI pts undergoing PCI ####Methods Pretreatment, median 6 d Primary Endpoint: Composite of cardiovascular death, myocardial infarction, or urgent target-vessel revascularisation within 30 days of PCI ####Results 4·5% patients in the clopidogrel group had the primary endpoint, compared with 6·4% in the placebo group (relative risk 0·70 [95% CI 0·50–0·97], p=0·03) ###CLARITY 2005, STEMI Clopidogrel vs placebo to pts with STEMI treated with fibrinolytics ###Results Treatment group had lower incidence of 1. Occluded infarct-related artery 2. Death 3. Recurrent myocardial infarction before angiography ####Comments 1. No difference in death 2. Cath was delayed for 48 h 3. Heparin dosing was carefully done 4. 6% CABG rate ###HORIZONS-AMI 2009, STEMI, Bivalirudin vs IV UFH + GP IIb/IIIa Clopidogrel 600 mg vs 300 mg, nonrandomized ####Results 1. 600-mg vs 300-mg clopidogrel loading dose group had lower 30-day mortality, reinfarction and stent thrombosis w/o more bleeding ####Comments 1. Non-randomized, observational. 2. Author himself says it needs to be confirmed by randomized trials 3. No placebo arm ###CURRENT-OASIS 7 2010, ACS Bivalirudin, 600 mg vs 300 mg Clopidogrel loading, Double dose vs regular dose Clopidogrel ####Results 1. 600 mg loading dose Clopidogrel preferable t0 300 mg **in PCI pts** 2. 150 mg Clopidogrel not better than 75 mg 2. 300 mg loading dose of ASA, after which 325 mg not superior to 75mg - 100 mg ####Comments 1. CABG 7.5% 2. Cath within ***72 h*** ###TRITON-TIMI 38 2007, ACS, Prasugrel **Coronary anatomy had to be known** before randomization ####Results 1. Composite endpoint lower in Rx group 2. No difference in death rate ####Comments Because coronary anatomy had to be known before randomization, CABG rate was the lowest of all trials - 4% ####Results Pretreatment with Ticagrelor reduced both CV complications AND death cf Clopidogrel ####Comments 1. Benefit attenuated in N. America (p = 0.045 vs < 0.001 for the overall trial) 2. Because Clopidogrel pretreatment was the "standard", this trial did not study no pretreatment 3. CABG rate 10.2%, of whom 2/3 underwent CABG within 7 d ###ACCOAST 2013, NSTEMI, Prasugrel ####Results Pretreatment with Prasugrel did not improve outcomes compared with giving the med in the cath lab. ####Comments More bleeding with pretreatment ###PLATO 2009, Ticagrelor, ACS (included STEMI pts) ###ATLANTIC 2014, STEMI, Ticagrelor in ambulance vs cath lab **Results** Prehospital administration of ticagrelor in patients with acute STEMI was safe but did not improve pre-PCI coronary reperfusion ###SUMMARY ####1. Clopidogrel pretreatment b/4 PCI is helpful ####2. Clopidogrel needs to be given >/ = 6 hours before cath/PCI ####3. Evidence of its pretreatment efficacy is therefore good for NSTEMI, but rather soft for STEMI ####4. No mortality benefit for Clopidogrel cf Ticagrelor ####5. Our patient population is likely closer to that of CURE population than to that of PLATO ####6. No standard on when should CABG be performed after ACS - but it does not have to be within a few days nor on the same admission ####Comments What do the guidelines say? ###2013 AHA/ACC STEMI guidelines ###Section on ###[Adjunctive antithrombotic Rx For Primary PCI](http://circ.ahajournals.org/content/127/4/529/T5.expansion.html)