EBQ:Major Cardiology Trials

ASA in USA

VA Cooperative

NEJM 1983;309: 396-403

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

Cairns JA: asa or sulfinpyrazone. ASA c 51 % dec in death or MI and 70% dec in all cause mortality. No benefit c sulf.

CURE: Clopidogrel in USA to prevent Recurrent ischemic Events.

12,562 pt in RCT c USA or NSTEMI -> clopidogrel c/in 24 h (300 then 75) in addition to ASA. 9.3 vs 11.5 % CV death , MI, or stroke. Also less inpt ischemia & revascularization, less thrombolitic or GP IIb/IIIa. But excess major bleeding and minor especially in CABG. *Enoxaparin shows modest benefit with inc in minor bleeding not major in USA. Other LMWH dont.

ESSENCE

NEJM 1997;337:447

3171 patients

Compared enoxaparin (1mq/kg BID) to UFH (5000 U bolus then ptt to 55-56) 48h-8d. 16.2% less death, MI, recurrent angina at 14days and 19% less at 30d. Only trends in MI and death. Only 46% of UFH group reached target PTT by 12-24h. Minor bleeding: 11.9 vs 7.2% in UFH. Major bleeding 6.5 vs 7.0%.

EPILOG

1328 pts

->Follow up to EPIC: addition of low-

dose heparin to abciximab brought bleeding risk same as placebo c 64% reduction of death, MI, and revascularization.

ESPIRIT

Lancet 2000; 356:2037-44

->Primary endpoint of death, MI, revascularization, or bailout GP was reduced from 10.5 to 6.6%. More bleeding but no diff in transfusion.

FRAXIS

EurHJ 1999;20:1553

Nardoparin pts had more events than UFH.

Coumadin & ASA.

• Several earlier small trials showed benefit to long term coumadin c ASA. (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%.