Clopidogrel for Saphenous Vein Graft PCI

Abstract & Commentary

By Michael H. Crawford, MD, Editor

Source: Sachdeva A, et al. Discontinuation of long-term clopidogrel therapy is associated with death and myocardial infarction after saphenous vein graft percutaneous coronary intervention. J Am Coll Cardiol 2012;60:2357-2363.

Saphenous vein graft patency after coronary artery bypass grafting failure rates are as high as 40% at 18 months. How many of these failures are due to the discontinuation of clopidogrel is the subject of this observational study done at a regional heart center in the Southern California Kaiser system that includes detailed pharmacy records. The primary endpoint was all-cause mortality or myocardial infarction (MI). During the 9-year study period, 603 patients had saphenous vein percutaneous coronary interventions (PCI). Almost all patients got one or more stents, with half receiving bare metal and half drug eluting. The median follow-up period was 3.4 years and at the point of clopidogrel cessation, 411 patients were event free. The incidence rate of death or MI after stopping clopidogrel decreased with increasing duration of therapy: 1.26 per 1000 patient days at < 90 days, 0.41 between 90 and 365 days, and 0.41 between 1 to 2 years. In a multivariate analysis, the incidence rate ratio comparing < 90 days to 90-365 days was 2.58. Regardless of the duration of therapy, about half of the events in the year after stopping clopidogrel occur in the first 90 days. These results were consistent across subgroups by sex, stent type, and diabetes status. The 5-year cumulative event rate was lowest in patients treated for > 2 years with a risk ratio of 0.48 for > 2 years of therapy vs < 6 months of therapy. The authors conclude that death and MI cluster in the first 90 days after clopidogrel therapy cessation regardless of the length of treatment. Also, event rates were lower with longer duration of therapy.

Commentary

This is the first study of clopidogrel use in patients with saphenous vein grafts. It demonstrates two points: First, death and MI are less common the longer the duration of therapy and second, adverse events mainly occur in the first 90 days after clopidogrel cessation regardless of the duration of therapy. The most obvious reason for these observations is that clopidogrel is a highly effective therapy and as soon as it is stopped, most adverse events occur within 90 days. The investigators also studied whether this early clustering was due to non-compliance during therapy or cessation for bleeding events, which may be related to comorbidities associated with a hypercoagulable state, but neither seemed to be the explanation.

This study is not ideal because clopidogrel use was not randomized, nor stratified in time prospectively, but there was a high overall incidence of events over the course of the study (30%), which strengthens the validity of the observations made. Also, the Kaiser system involves more health-motivated individuals and controls all aspects of the patient’s care, including prescriptions. Given that there are no other data on this topic, I believe the authors are correct in stating that the study provides new insight into the use of clopidogrel after saphenous vein PCI. The main take-home message is that after saphenous vein PCI, clopidogrel therapy should be continued, along with aspirin, for at least 2 years, possibly indefinitely.