ACS Trials

Question 1

PLATO

Answer 1

Ticagrelor (Brilenta, 180 + 90 BID) vs clopidogrel (300 + 75)
Non-thienopyridine P2Y12 ADP receptor antagonist
18,624 patients, all ACS
Death, MI, stroke at 1 year 9.8% v 11.7%
Statistically significant reduced death, CV death, and recurrent MI
Same overall bleeding risk. Higher fatal intracranial, lower fatal non-intracranial. BBW - only use ASA 81mg.
Stop 5 days prior to surgery
NEJM 2009

Question 2

TRITON TIMI 38

Answer 2

Prasugrel vs clopidogrel
Effient, 60mg+10mg. Plavix 300mg + 75mg
13,608 patients, ACS with planned PCI (after dx LHC)
29% reduction in CV death/MI/CVA (9.9% vs 12.1%)
Primarily reduction in nonfatal MI
Higher life-threatening (1.4% vs 0.9%) and fatal (0.4% vs 0.1%) bleeding
BBW - Hx CVA/TIA, age>75, Wt<60kg, high bleeding risk
Stop 7 days prior to surgery
NEJM 2007

Question 3

TIMACS

Answer 3

Timing of angiography in NSTE-ACS, 36h
3031 patients, UA or NSTEMI (2/3: age>60, +trop, EKG changes)
No diff in death/MI/CVA at 6mo (9.5% vs 12.9%, p=0.15)
20.5% crossover to early angiography
In high risk (GRACE>140) 13.9% vs 21% in favor of early
NEJM 2009

Question 4

ICTUS

Answer 4

Early invasive vs conservative in NSTEMI
1200 patients, routine angio <48h vs selective (instability, refractory angina, +stress)
No diff in death/MI/hosp, or mortality
ASA+Plavix+Lipitor+Lovenox x48h
Higher recurrent (peri-procedural) MI
NEJM 2005

Question 5

TIMI-IIIb
VANQWISH
FRISC II
TACTICS-TIMI 18
RITA 3

Answer 5

Early/routine vs conservative/selective for NSTEMI/UA
TIMI-IIIb 1995 - no diff
VANQWISH 1998 - high mortality early
FRISC II 1999 - lower death/MI, better meds
TACTICS-TIMI 2001 - lower death/MI/hosp
RITA 3 2002 - lower death/MI/refractory angina in low to moderate risk

Question 6

ESSENCE

Answer 6

Lovenox vs Heparin in UA/NSTEMI
3,171 patients, 1mg/kg q12h vs 5000 units + gtt
20% reduction in death/MI/recurrent angina at 14 days (16.6% vs 19.8%)
Increase in minor bleeding (SC site bruising), no diff in major bleeding
Excluded in CrCl<30
NEJM 1997

Question 7

FREEDOM

Answer 7

CABG vs PCI in diabetics with multivessel disease
1900 patients
Composite death/MI/CVA, 18.7% vs 26.6%
Reduced all-cause mortality (p=0.049) and MI (P<0.001)
Increased rate of stroke in CABG group
NEJM 2012

Question 8

SOAP II

Answer 8

Dopamine vs norepinephrine
1679 patients in shock
No difference in death (52.5% vs 48.5%)
More arrhythmia in dopamine (24.1% vs 12.4%)
Dopamine increased death in cardiogenic shock subgroup
NEJM 2010

Question 9

IABP-SHOCK 2

Answer 9

IABP vs standard therapy
600 patients with ACS c/b cardiogenic shock
No benefit in mortality at 30 days (39.7% vs 41.3%)
No increased harm (bleeding, stroke, AKI, or limb ischemia)
Significant crossover (10% of standard group)
May still benefit high risk patients, those that develop mechanical complications (excluded from this trial)
Class I indication –> IIa
NEJM 2012

Question 10

PROVE IT-TIMI 22

Answer 10

Atorvastatin (80mg) vs pravastatin (40mg)
4162 patients with ACS
16% reduction in death/MI/hosp/revasc/CVA (22.4% vs 26.3%)
Discontinuation about 22% at 1 year, 33% at 2 years
ALT >3x ULN in 3.3% vs 1.1%
No rhabdo
NEJM 2004

Question 11

MIRACL

Answer 11

Atorvastatin vs placebo
3086 patients with UA/NSTEMI, starting within 24-96h
16% reduction in death/MI/cardiac arrest/recurrent symptomatic ischemia requiring hospitalization
JAMA 2001

Question 12

COURAGE

Answer 12

PCI vs optimal medical therapy in stable CAD
35,539 patients with stable angina (70% lesion with resting ST dep/TWI or positive stress test, or 80% lesion with classic angina)
On ASA or Plavix, metop succinate or Imdur or Norvasc, lisinopril or losartan, simvastatin
No diff in Death/MI (19% vs 18.5%)
Reduced revascularization, symptoms.

Question 13

FAME 2

Answer 13

FFR in PCI vs OMT for stable CAD
1220 patients, FFR <0.81
Stopped early
Reduction in death/MI/repeat revascularization 4.3% vs 12.7%
Death 0.2% vs 0.75 (p=0.31)
Urgent revascularization (1.6% vs 11.1%)
Non-urgent revascularization (1.6% vs 8.6%)
NEJM 2012

Question 14

PROSPECT

Answer 14

Natural history of CAD
697 patients with ACS followed
At 3.4 years, 20.4% reached endpoint (cardiac death, cardiac arrest, MI, or rehospitalization for UA)
Of the untreated lesions that caused coronary events, only a small minority (<5%) were angiographically severe at index PCI
NEJM 2011

Question 15

PRAMI

Answer 15

Non-Culprit Lesions in STEMI
465 patients with multivessel disease, randomized to immediate PCI for all lesions >50% or only for objective e/o ischemia.
Stopped early.
Reduced death/MI/refractory angina with objective e/o ischemia (9% vs 23%)
Primarily reduction in reinfarction and recurrent ischemia
No increased complications
NEJM 2013

Question 16

RIFLE

Answer 16

Radial vs femoral
1001 patients, STEMI
Decreased cardiac death/MI/CVA/target lesion revascularization/bleeding not related to CABG (13.6% vs 21%)
Decreased bleeding (7.8% vs 12.2%) and cardiac death (5.2% vs 9.2%)
30 radial to femoral crossover vs 5
No change in door to balloon time
JACC 2012

Question 17

ISAR REACT 2

Answer 17

Abciximab vs placebo
2022 patients, high risk NSTE-ACS s/p clopidogrel 600mg and ASA 500mg requiring PCI
Reduced death/MI/target revascularization at 30 days (8.9% vs 11.9%), but not individual components
Increased thrombocytopenia but not bleeding
Takehome: abciximab should be used in STEMI and high risk NSTE-ACS only at time of PCI (GUSTO IV showed poss harm if no PCI)
JAMA 2006

Question 18

CURE

Answer 18

Clopidogrel vs placebo + ASA
12,562 patients, NSTE-ACS
Load with 300mg then 75mg daily x 9 months
20% reduction in CV death/MI/CVA (9.3% vs 11.4%)
14% reduction in CV death/MI/CVA/refractory ischemia (16.5% vs 18.8%)
Increase in major bleeding (3.7% vs 2.7%) but not life threatening bleeding (2.2% vs 1.8%, p=0.13)
Class I for UA/NSTEMI, 1 month to 1 year
NEJM 2001

Question 19

CURRENT-OASIS

Answer 19

2x2 clopidogrel and aspirin dosing
25,086 patients undergoing PCI
Clopidogrel 600mg x1, 150mg days 2-7, then 75mg, vs 300mg x1 then 75mg
Aspirin 300-325mg vs 75-100mg
Reduced CV death/MI/CVA and stent thrombosis in higher dose clopidogrel
No difference in high vs low dose ASA
Lancet 2010

Question 20

COMMIT-CCS2

Answer 20

Early IV metoprolol vs placebo
45,852 patients in China with ACS (STEMI or new LBBB in 93%, ST depressions in 7%, with symptoms), not in cardiogenic shock (Killip Class IV)
MTP 5mg IV q3min x3 doses, then 50mg PO q6h x 4 doses, then XL 200mg daily
No difference in all-cause mortality
Less reinfarction, VT/VF, but increased cardiogenic shock
Lancet 2005

Question 21

COMMIT-CCS2, part 2

Answer 21

Clopidogrel vs placebo in tPA
45,852 patients in China with ACS (STEMI or new LBBB in 93%, ST depressions in 7%, with symptoms), not in cardiogenic shock (Killip Class IV), and NOT undergoing PCI
9% reduction in mortality/reinfarction/CVA
7% reduction in mortality
Lancet 2005

Question 22

WOEST

Answer 22

Triple therapy vs double therapy after PCI
573 patients undergoing PCI
Warfarin+clopidogrel+aspirin vs no aspirin
Reduction of any bleeding episode at 1 year (19.4% vs 44.4%) in double therapy
Reduction of death/MI/CVA/revasc/stent thrombosis (11.1% vs 17.6%)
Reduction in all-cause mortality (2.5% vs 6.3%)
Lancet 2013

Question 23

HOPE

Answer 23

Ramipril vs placebo in normal EF but high CV risk (vascular disease or DM plus another risk factor)
9297 patents, high CV risk, age>55
22% relative risk reduction in composite MI, CVA, CV death
Reduction in all individual endpoints
NEJM 2000

Question 24

DAPT

Answer 24

30 month dual anti platelet therapy