Current issues of ACP Journal Club are published in Annals of Internal Medicine


Therapeutics

Abciximab and heparin given during coronary interventions reduced combined death, MI, and urgent revascularization

ACP J Club. 1999 Sept-Oct;131:40. doi:10.7326/ACPJC-1999-131-2-040


Source Citation

Lincoff AM, Tcheng JE, Califf RM, et al., for the EPILOG Investigators. Sustained suppression of ischemic complications of coronary intervention by platelet GP IIb/IIIa blockade with abciximab. One-year outcome in the EPILOG trial. Circulation. 1999 Apr 20;99:1951-8.


Abstract

Question

In patients who are having percutaneous coronary angioplasty (PTCA), will abciximab and adjusted heparin reduce ischemic morbidity and mortality at 1 year?

Design

Randomized (concealed), double-blind, placebo-controlled trial with 1-year follow-up.

Setting

69 centers in North America.

Patients

2792 patients scheduled for PTCA who did not have acute myocardial infarction (MI) or unstable angina in the previous 24 hours, planned stent implantation or rotational atherectomy, recent PTCA, or risk for excessive bleeding. Follow-up was 97%.

Intervention

All patients received aspirin. Patients were allocated to abciximab and low-dose heparin (n = 935), abciximab and standard-dose heparin (n = 918), or placebo and standard-dose heparin (n = 939). Abciximab was given as a 0.25-mg/kg of body weight bolus 10 to 60 minutes before PTCA, followed by a 0.125-µg/kg per minute infusion for 12 hours. Low-dose heparin was given as an initial bolus of 70 U/kg (maximum 7000 U) with additional boluses to maintain an activated clotting time of ≥ 200 seconds. Standard-dose heparin was given as an initial bolus of 100 U/kg (maximum 10 000 U) with additional boluses to maintain an activated clotting time of ≥ 300 seconds. Heparin use was discouraged after PTCA. Stents were used in 13% of patients.

Main outcome measure

The composite end point of death, MI, or need for urgent revascularization.

Main results

Both abciximab groups had a lower rate than placebo for the composite end point (P < 0.001 for both) (Table). At 1 year, both abciximab groups had lower rates of MI (5.1% for low-dose, 5.5% for standard-dose, and 10.4% for placebo, P < 0.001) and urgent revascularization (3.8% and 4.2% vs 7.2%, P ≤ 0.005) than the placebo group; the groups did not differ for all-cause mortality (1.7% and 1.8% vs 2.6%, P = 0.2). The benefits occurred in the first 30 days; the groups had similar incremental event rates thereafter.

Conclusions

Abciximab with low-dose or standard-dose adjusted heparin given during percutaneous coronary procedures reduced the composite end point of death, myocardial infarction, or urgent revascularization at 1 year. The treatment benefit was achieved early (at 30 d) and maintained throughout follow-up.

Sources of funding: Centocor, Inc., and Eli Lilly and Co.

For correspondence: Dr. A.M. Lincoff, Department of Cardiology, Desk F25, The Cleveland Clinic Foundation, Cleveland, OH 44195, USA. FAX 216-444-8050.


Table. Death, myocardial infarction, or urgent revascularization at 1 year for abciximab vs placebo during percutaneous coronary angioplasty*

Intervention group Abciximab Placebo RRR (95% CI) NNT (CI)
Abciximab and low-dose heparin 9.5% 16.1% 41% (24 to 54) 16 (11 to 29)
Abciximab and standard-dose heparin 9.5% 16.1% 41% (25 to 54) 16 (11 to 28)

*Abbreviations defined in Glossary; RRR, NNT, and CI calculated from data in article.


Commentary

The study by Lincoff and colleagues supports previous evidence from randomized trials (1, 2) showing that short-term platelet glycoprotein receptor IIb/IIIa blockade in patients who have PTCA reduced the rates of adverse cardiac events beyond the initial 30-day period. Trial data (3) in patients with elective or urgent PTCA shows that glycoprotein receptor blockade results in a highly clinically and statistically significant reduction in death and nonfatal MI at 48 to 96 hours and has sustained benefit at 6 months (2 to 3 events prevented/100 patients treated).

The investigators have previously shown that hemorrhagic complications can be minimized without loss of efficacy by using reduced doses of adjunctive heparin (4). The impressive benefit-to-risk ratio suggests that the key clinical question now is whether patients undergoing PTCA should receive a receptor blocker. The greatest absolute clinical and cost benefits would likely be realized in patients in the highest-risk subgroups (e.g., patients with unstable coronary syndromes requiring intervention) (2, 4, 5).

Do the results of the trial apply in the current era of higher rates of intracoronary stent use? Another trial (5) showed that glycoprotein receptor IIb/IIIa blockade substantially improved the 30-day outcome of elective procedures; in fact, PTCA with abciximab was safer than stenting without abciximab (5). Furthermore, 1-year mortality was lowest in the stent-plus-abciximab group, suggesting that this combination may offer the greatest benefit to patients who require PTCA (2).

Shaun Goodman, MSc, MD
St. Michael's HospitalToronto, Ontario, Canada


References

1. Topol EJ, Ferguson JJ, Weisman HF, et al. Long-term protection from myocardial ischemic events in a randomized trial of brief integrin beta3 blockade with percutaneous coronary intervention. EPIC Investigator Group. Evaluation of Platelet IIb/IIIa Inhibition for Prevention of Ischemic Complication. JAMA. 1997;278:479-84.

2. Topol EJ, Byzova TV, Plow EF. Platelet GPIIb-IIIa blockers. Lancet. 1999;353:227-31.

3. Kong DF, Califf RM, Miller DP, et al. Clinical outcomes of therapeutic agents that block the platelet glycoprotein IIb/IIIa integrin in ischemic heart disease. Circulation. 1998;98:2829-35.

4. The EPILOG Investigators. Platelet glycoprotein IIb/IIIa receptor blockade and low-dose heparin during percutaneous coronary revascularization. N Engl J Med. 1997;336:1689-96.

5. The EPISTENT Investigators. Randomised placebo-controlled and balloon-angioplasty-controlled trial to assess safety of coronary stenting with use of platelet glycoprotein-IIb/IIIa blockade. Evaluation of Platelet IIb/IIIa Inhibitor for Stenting. Lancet. 1998;352:87-92.