EBQ:Major Cardiology Trials

Aspirin in MI

• VA Cooperative

• At 12w asa had 51% dec in death & MI. 1,266 men c USA 324mq ASA vs placebo.

Aspirin or Sulfinpyrazone

• ASA with 51 % decrease in death or MI
• ASA with 70% decrease in all cause mortality
• No benefit w sulfinpyrazone.

CURE: Clopidogrel in Unstable Angina to Prevent Recurrent Events

• 12,562 pt in Randomized Controlled Trial with Unstale Angina or NSTEMI
• Clopidogrel 300 mg loading dose followed by clopidogrel 75 mg daily for 3 to 12 months.
• All patients were administered aspirin 75 to 325 mg daily.
• Composite of CV mortality, non-fatal MI, or stroke with 9.3%(clopidogrel) vs 11.5(placebo)
• Also less inpatient ischemia & revascularization, less thrombolitic or GP IIb/IIIa administration
• Increased major and minor bleeding especially in CABG patients.

ESSENCE

• 3171 patients
• Compared enoxaparin (1mq/kg BID) to Unfractionated Heparin (5000 U bolus then ptt to PTT 55-56) 48h-8d
• 16.2% less death, MI, recurrent angina at 14 days and 19% less at 30 days
• Only trends in MI and death. Only 46% of UFH group reached target PTT by 12-24h.
• Major bleeding 6.5% (enoxaparin) vs 7.0% (UFH).

ESPIRIT

• Randomized controlled trial in which we assigned patients to aspirin (30—325 mg daily) with (n=1363) or without (n=1376) dipyridamole (200 mg twice daily) within 6 months of a transient ischaemic attack or minor stroke of presumed arterial origin
• Primary composite outcome of death from all vascular causes, stroke, myocardial infarction, or major bleeding complications of (13%) patients on aspirin and dipyridamole and in (16%) on aspirin alone

FRAXIS

• Prolonged nadroparin treatment was associated with an increase in major bleeding events and equal short term efficacy

ATACS<ref>Cohen M et al. Combination antithrombotic therapy in unstable rest angina and non-Q-wave infarction in nonprior aspirin users. Primary end points analysis from the ATACS trial. Antithrombotic Therapy in Acute Coronary Syndromes Research Group. Circulation. 1994 Jan;89(1):81-8 PDF

• Coumadin & ASA shows no long term benefit(e.q. ATACS)

OASIS pilot moderat dose dec by 58%.

OASIS-2: 3712 pts ASA plus moderate coumadin. CVD/MI/CVA p 5 months was 7.65% vs 8.4%.

CARS was discountinued early c NO benefit c either 1 or 3 mg plus 81mg ASA vs 160 ASA. Lancet 997; 350:389.

CHAMP: p MI no benefit c coumadin plus ASA 81 vs 162.

HTN

FRISC

Lancet 1996; 347:561

1,506 pt c USA or NQWMI c Dalteparin bid x 6d then QD x 35-45d. 63% reduction in death or MI in first 6d. Still seen at 40 days but excess events when dose decreased.

GUSTO IV- ACS

Lancet 2001;357:1915

->No benefit from abciximab in USA/NSTEMI s early invasive tx.

7800 pt c USA/NSTEMI & TnI or ST depression. ASA & UFH/LMWH c placebo, abciximab 24 h, or abciximab 48h. 30 d death or MI 8.O% vs 8.2 vs 9.1 (nonsignificant). 48h also s benefit.

LIFE

Lancet 3/02

4yr f/u

->Losartan showed reduction of CV M&M vs atenolol in pts c HTN and LVH. Most of benefit in stroke reduction. Also c 25% reduction in development of DM.

GPIIb/IIIa

PRISM

NEJM 1998;338:1498

->Benefit c tirofiban in USA/NQWMI especially c TnI.

3232 pts c USA/NQWMI comparing tirofiban c heparin: @48h 3.8% vs 5.6% for death/MI/refractory angina. @ 30d 15.9 vs 17.1% nonsignificant. @30d death or MI 5.8 vs 7.1% p=0.11. Subgroup analysis showed greater benefit c elevated TnI.

PRISM-PLUS

NEJM 1998;338:1488

-> Tirofiban and UFH combo is beneficial in USA/NQWMI c or s PCI.

1915 pts c USA/NQWMI tirofiban, UFH, or combination for 48-108h. Tirofiban alone arm was dropped 2� excess mortality. Combo reduced death/MI/refractory angina @ 7d from 17.9 to 12.9% p=0.004. @30 d reduced by 22%. Death or MI by 43% @7d, 30% @ 30d, 22% @ 6m.

--In pts not undergoing PCI, significant benefit was only seen in HIGH risk pts

PURSUIT

NEJM 1998; 339:436

->Eptifibatide beneficial in USA/NSTEMI c or s PCI.

10948 pts c USA/NSQWMI c Eptifibatide in addition to standard tx. @ 30d death/MI 14.2% vs 15.7%. @ 96h 7.6 vs 9.1%.

?EPIC (JACC 1997; 30:149-56) 321 pts

->Abciximab bolus + infusion vs abciximab bolus c placements infusion vs placebo in high risk patients undergroinq PCI . Abciximab bolus and infusion reduced rate of MI' death, revascularization by 35% at 30d, 23% at 6m, 13% at 3years. Most of affect from reduction of repeat CABG/PCI . Higher rate of bleedinq.

TIMI 11B

Circ 1999;100:1602.

Compared enoxaparin (30mg IV then SC) c UFH. Study included outpt portion. Death or MI were 5.7 vs 6.9% at 14d and 7.9vs 8.9 % at 43d. Minor bleeding 9.1 vs 2.5%. Major bleeding 1.5 vs 1.0%.