Antiplatelet therapy reduced cardiac and noncardiac events after placement of coronary artery stents
ACP J Club. 1996 Sept-Oct;125:31. doi:10.7326/ACPJC-1996-125-2-031
Schömig A, Neumann FJ, Kastrati A, et al. A randomized comparison of antiplatelet and anticoagulant therapy after the placement of coronary-artery stents. N Engl J Med. 1996 Apr 25;334:1084-9. [PubMed ID: 8598866]
To compare the effectiveness of 2 different antithrombotic regimens in patients in whom intracoronary stents were successfully placed after percutaneous transluminal coronary angioplasty (PTCA).
Randomized controlled trial with 30-day follow-up.
University medical center in Germany.
517 patients (mean age 62 y, 76% men) who had had coronary artery stents successfully placed after PTCA and had no contraindications to the study drugs and no indication for anticoagulant therapy. Patients were excluded if stenting was done primarily as a bridge to aortocoronary bypass grafting or if the patient had cardiogenic shock or needed mechanical ventilation before having PTCA.
After successful placement of stents, 257 patients were allocated to antiplatelet therapy with ticlopidine, 250 mg twice a day started immediately after the procedure and continued for 4 weeks, and 260 were allocated to anticoagulant therapy with phenprocoumon for 4 weeks with a target international normalized ratio (INR) of 3.5 to 4.5. All patients received 100 mg of aspirin twice daily. A heparin infusion (titrated to a partial thromboplastin time of 80 to 100 sec) was started in all patients just before PTCA and was discontinued 12 hours after stent placement for patients allocated to ticlopidine and was maintained until the target INR was reached for patients receiving phenprocoumon.
Main outcome measures
The primary cardiac outcome was a composite measure of death from cardiac causes or the occurrence of a myocardial infarction (MI), aortocoronary bypass surgery, or repeated PTCA. The primary noncardiac outcome was death from noncardiac causes or the occurrence of cerebrovascular accident, or severe peripheral vascular or hemorrhagic events requiring surgery or blood transfusions.
A primary cardiac end point was reached by 4 patients (2%) receiving antiplatelet therapy compared with 16 patients (6%) receiving anticoagulant therapy (P = 0.01) (Table). This difference resulted from an 82% reduction in the incidence of MI and a 78% lower rate of reintervention among patients assigned to antiplatelet therapy. A primary noncardiac end point was reached by 3 patients (1%) receiving antiplatelet therapy compared with 32 patients (12%) receiving anticoagulant therapy (P < 0.001) (Table).
Compared with anticoagulant therapy, antiplatelet therapy after successful placement of coronary artery stents reduced the incidence of both cardiac events and hemorrhagic and vascular complications.
Sources of funding: In part, Siemens Medical Systems; Scimed-Boston Scientific; Johnson and Johnson Interventional Systems.
For article reprint: Dr. A. Schömig, 1. Medizinische Klinik der Technischen Universität München, Klinikum rechts der Isar, Ismaninger Strasse 22, 81675 Munich, Germany. FAX 49-89-4140-4900.
Table. Antiplatelet vs anticoagulant therapy after placement of coronary artery stents*
|Outcomes at 4 wk||Antiplatelet therapy||Anticoaguant therapy||RRR (95% CI)||NNT (CI)|
|Primary cardiac end point†||2%||6%||75% (29 to 91)||22 (12 to 71)|
|Primary noncardiac endpoint†||1%||12%||91% (71 to 97)||9 (6 to 14)|
†Death from cardiac causes or the orrurence of a MI, aortocoronary bypass surgery,
or repeated PTCA
†Death from noncardiac causes or the occurrence of cerebrovascular accident, or severe peripheral vascular or hemorrhagic events requiring surgery or blood transfusions
*Abbreviations defined in Glossary. RRR, NNT, and CI calculated from data in article.
The study by Schömig and colleagues provides support for the abandonment of intensive and prolonged anticoagulant therapy after stenting. Many catheterization laboratories have already adopted this practice, at least for some patients. The stenting procedure used in this study combines high-pressure balloon inflation with early sheath removal, which are recent improvements in technique that may have contributed to the low complication rates that were seen.
The study results are applicable to everyday practice because most of the patients who were potentially eligible for the study at the single center where the study was done were actually recruited into the study. The study-mandated hospital stay of 10 days after the procedure, however, is impractical outside of the study setting. This requirement in the study probably did not influence the results substantially, but it did allow for reliable and detailed data collection for study purposes; therefore, it does not imply that prolonged inpatient observation is required in everyday practice. On the basis of lower rates of vessel occlusion and complications in the antiplatelet arm compared with the oral anticoagulation arm, the investigators concluded that prolonged heparin or oral anticoagulation therapy may, in fact, be prothrombotic for patients with stents. This hypothesis does have some mechanistic support but is not proven by this study.
Because the study had an open design, bias may have contributed to the findings. This is the best data to date, however, that shows that antiplatelet therapy with ticlopidine and aspirin is a safe and effective alternative to prolonged heparin and oral anticoagulation after satisfactory stent deployment.
Steven Borzak, MD
Henry Ford HospitalDetroit, Michigan, USA
Our study provides the rationale for replacing anticoagulation with combined antiplatelet therapy, ticlopidine plus aspirin, after coronary stenting. The findings promoted the adoption of the antiplatelet regimen in the catheterization laboratories. They also showed the key role of platelets in the development of stent thrombosis. The group of patients with anticoagulation therapy had a high rate of complications despite the use of high-pressure balloon inflation. The inability of high-pressure inflation to reduce the incidence of thrombotic complications was confirmed in a subsequent randomized study (1).
The findings were confirmed in other studies (2) and served as the basis for the ubiquitous use of thienopyridines as an adjunct therapy after coronary stenting. Currently, ticlopidine is gradually being replaced with another thienopyridine derivative, clopidogrel, with a better safety profile and equivalent efficacy (3).
Albert Schömig, MD
Deutsches HerzzentrumMunich, Germany
1. Dirschinger J, Kastrati A, Neumann FJ, et al. Influence of balloon pressure during stent placement in native coronary arteries on early and late angiographic and clinical outcome: A randomized evaluation of high-pressure inflation. Circulation 1999;31:918-23.
3. Bertrand ME, Rupprecht HJ, Urban P, Gershlick AH. Double-blind study of the safety of clopidogrel with and without a loading dose in combination with aspirin compared with ticlopidine in combination with aspirin after coronary stenting: the Clopidogrel Aspirin Stent International Cooperative Study (CLASSICS). Circulation. 2000;102:624-9.