CHICAGO – Clopidogrel use after endovascular lower-extremity revascularization was significantly associated with 1-year freedom from amputation and survival, but only 38% of the Medicare population was on the drug post intervention in a large retrospective analysis.
Patients with the most severe peripheral vascular disease, ulceration, or gangrene benefited the most from post revascularization clopidogrel (Plavix), but were the least likely to be using the drug, Dr. Mark L. Janzen said at the annual meeting of the Midwestern Vascular Surgical Society.
Patrice Wendling/Frontline Medical News
Dr. Mark L. Janzen
The analysis involved 14,353 patients, 65 years and older, who underwent lower-extremity revascularization in 2007 and 2008 and were identified from the Medicare Provider Analysis and Review files using ICD-9 codes. Of these, 5,697 had claudication (50%), 1,467 rest pain (10%), and 7,189 ulceration or gangrene (50%).
Overall amputation rates for patients started on clopidogrel right after the procedure were significantly lower than for nonusers at 30 days (10.34% vs. 14.1%), 90 days (14.1% vs. 18.7%), and 1 year (19.7% vs. 24.1%; all P values less than .0001), said Dr. Janzen of the University of Missouri Hospitals and Clinics, Columbia.
Among patients with ulceration or gangrene, limb loss was 21.2% and 26.6% with and without clopidogrel at 30 days, 28.5% and 34.8% at 90 days (P less than .0001), and 38.2% and 43.5% at 1 year.
Only 35.7% of patients with ulceration or gangrene were on post-procedure clopidogrel, compared with 37.4% with rest pain and 40.4% with claudication, according to National Drug Code Directory and Medicare Part D files. Combination therapy with aspirin and clopidogrel or other antiplatelet therapies was not evaluated.
Interestingly, clopidogrel did not significantly affect amputation rates in patients with claudication or rest pain, Dr. Janzen said.
Multivariate logistic regression analyses adjusted for patient demographics, comorbidities, and disease severity, confirmed that clopidogrel nonusers were more likely than users to undergo amputation at 30 days (odds ratio, 1.28), 90 days (OR, 1.29), and 1 year (OR, 1.16).
In the ulceration/gangrene subgroup, failure to use clopidogrel increased the odds of amputation (OR, 1.2) "to levels approaching renal failure (OR, 1.24) and diabetes (OR, 1.6), two known risk factors for below-the-knee amputation," he observed.
Cox regression analyses revealed a 20% higher hazard of death at 1 year among all patients for nonusers than for clopidogrel users (hazard ratio 1.2; P less than .0001).
During a discussion of the study, Dr. Sean Patrick Lyden of the Cleveland Clinic, questioned the impact of end-stage renal disease (ESRD) on the results, remarking that ESRD is probably the strongest predictor of limb loss in patients with ulceration or gangrene and that clopidogrel is typically not given to ESRD patients because the pharmacodynamics are unknown.
Dr. Janzen said it was a valid point, but that the study did not look specifically at ESRD.
This line of questioning was picked up by another attendee, who asked whether amputation rates were calculated for patients with ESRD and diabetes. Although the analysis did not look at outcomes for this lethal combination of comorbidities, Dr. Janzen said a prior study reported a 5-year amputation rate of about 27% in patients with peripheral vascular disease and diabetes (Diabetes Care 2003;26:491-4).
Dr. Iraklis Pipinos, professor of surgery at the University of Nebraska Medical Center in Omaha, commented that "This is a fantastic study and a tremendously important question."
He went on to ask whether the patients with ulceration or gangrene underwent additional lower extremity revascularization procedures, observing that the 1-year amputation rates were quite high in this subgroup.
Dr. Janzen said the study was not designed to determine rates of procedure repetition, although it was noted that overall clopidogrel users were less likely to convert to open bypass early in their post-procedure course.
Finally, the audience asked about the optimal duration of post-procedure clopidogrel, with one attendee observing that it’s not unusual for patients to discontinue clopidogrel 6 weeks after an endovascular revascularization procedure. Dr. Janzen said new cardiology trends recommend that patients with both bare metal and drug-eluting stents remain on clopidogrel for a full year after stent placement and that the optimal duration for patients undergoing endovascular lower limb revascularization is unknown and hopefully will be answered in properly powered randomized trials.
Dr. Janzen and his coauthors reported having no financial disclosures.