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===ASA in USA===
===Aspirin in MI<ref>Lewis HD et al. Protective effects of aspirin against acute myocardial infarction and death in men with unstable angina. Results of a Veterans Administration Cooperative Study. N Engl J Med. 1983 Aug 18;309(7):396-403</ref>===


*VA Cooperative


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


NEJM 1983;309: 396-403
===Aspirin or Sulfinpyrazone<ref>Cairns J et al. Aspirin, Sulfinpyrazone, or Both in Unstable Angina — Results of a Canadian Multicenter Trial. N Engl J Med. 1985 Nov 28;313(22):1369-75</ref>===
*ASA with 51 % decrease in death or MI
*ASA with 70% decrease in all cause mortality
*No benefit w sulfinpyrazone.


At 12w asa had 51% dec in death & MI. 1,266 men c USA 324mq ASA vs placebo.
===CURE: Clopidogrel in Unstable Angina to Prevent Recurrent Events<ref>Yusuf S, et al. "Effects of Clopidogrel in Addition to Aspirin in Patients with Acute Coronary Syndromes without ST-Segment Elevation". The New England Journal of Medicine. 2001. 345(7):494-502[http://www.nejm.org/doi/pdf/10.1056/NEJMoa010746 PDF]</ref>===
*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.  


Cairns JA: asa or sulfinpyrazone. ASA c 51 % dec in death or MI and 70% dec in all cause mortality. No benefit c sulf.
===ESSENCE<ref>Cohen M, et al. "A Comparison of Low-Molecular-Weight Heparin with Unfractionated Heparin for Unstable Coronary Artery Disease". The New England Journal of Medicine. 1997. 337(7):447-452 [http://www.nejm.org/doi/pdf/10.1056/NEJM199708143370702 PDF]</ref>===
 
*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
===CURE: Clopidogrel in USA to prevent Recurrent ischemic Events.===
*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).
 
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===
===EPILOG===
 
*1328 pts
 
*Follow up to EPIC: addition of low-
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.
dose heparin to abciximab brought bleeding risk same as placebo c 64% reduction of death, MI, and revascularization.

Revisión del 03:02 30 mar 2014

Aspirin in MI[1]

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

Aspirin or Sulfinpyrazone[2]

  • 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[3]

  • 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[4]

  • 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).

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%.

  1. ↑ Lewis HD et al. Protective effects of aspirin against acute myocardial infarction and death in men with unstable angina. Results of a Veterans Administration Cooperative Study. N Engl J Med. 1983 Aug 18;309(7):396-403
  2. ↑ Cairns J et al. Aspirin, Sulfinpyrazone, or Both in Unstable Angina — Results of a Canadian Multicenter Trial. N Engl J Med. 1985 Nov 28;313(22):1369-75
  3. ↑ Yusuf S, et al. "Effects of Clopidogrel in Addition to Aspirin in Patients with Acute Coronary Syndromes without ST-Segment Elevation". The New England Journal of Medicine. 2001. 345(7):494-502PDF
  4. ↑ Cohen M, et al. "A Comparison of Low-Molecular-Weight Heparin with Unfractionated Heparin for Unstable Coronary Artery Disease". The New England Journal of Medicine. 1997. 337(7):447-452 PDF
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