Long Term Adherence to Clopidogrel and Late Adverse Cardiac Events after Off-Label Use of Sirolimus-Eluting Stents: Results of the MATRIX Registry

March 31, 2008 By Lauren Ciaglo [mailto: lciaglo@perfuse.org]

SCAI-ACCi2 08-Chicago, IL: Results from the MATRIX Registry, a large community-based registry consisting of patients who were treated with drug-eluting stents (DES), were presented today at the SCAI-i2 summit Annual Scientific Sessions in Chicago by Dr. George Dangas of Columbia University Medical Center.

The registry analyzed data from 1,510 patients. The mean age of patients was 64.8±11 years and 74.6% were male. The population for this study varied from previous studies in that 33.3% of patients had a previous myocardial infarction (MI), 44.4% had a prior percutaneous coronary intervention (PCI), 21% had former cardiac bypass grafting surgery (CABG), 33.7% had diabetes, and 27.7% had unstable angina (UA).

Outcomes were evaluated at 2 years following off-label use of sirolimus-eluting stenting (SES) and all patients were to receive aspirin (325 mg daily for 1 month followed by 81 mg indefinitely) along with clopidogrel (75 mg daily for 1 year followed by physician discretion).

At 6 month follow-up, 90% of patients were taking clopidogrel, at one year this number decreased to 82.4%, and at the two year follow-up it had dropped to 65.5%. Of the 10% that discontinued their clopidogrel use at 6 months, approximately half of them had restarted the medication at either the one or two year follow-up.

At one year, in 9.9% of patients, clopidogrel discontinuation was due to doctor’s advise, 5.2% was due to bleeding, 2.1% was due to surgery, 1.7% due to rash/allergy, and 0.4% due to cost. Moreover, 39.5% of patients discontinued the medication for an unknown reason and 41.2% discontinued it because the one year dosing period had ended.

The investigators divided patients into two groups to further evaluate clinical outcomes:
 * Those who continued taking clopidogrel and
 * Those who ceased taking clopidogrel.

They found that the composite endpoint was significantly higher among patients who were non-adherent to clopidogrel at one year (4.8% vs. 1.4%, respectively, p=0.005). There were trends toward differences in the rate of cardiac death (1.1% vs. 0.2%, p=0.054), non cardiac death (2.7% vs. 1.0%, p=0.08), and unknown death (1.0% vs. 0.3%, p=0.16) between the two groups. Target lesion revascularization as well as target vessel revascularization (TVR) was significantly lower in the non-adherent group compared with the adherent group (0% vs. 5.5%, p=0.001 and 0.5% vs. 6.1%, p=0.002, respectively).

At two year follow-up, death/myocardial infarction was significantly higher among those who discontinued clopidogrel vs. those who were on clopidogrel [HR 2.19, 95% CI (1.14-4.20), p=0.0182].

The researchers found that there were various reasons for clopidogrel non-adherence at one year and this study reiterates the importance of continued adherence to dual antiplatelet therapy following DES implantation. The investigators demonstrated that patients off-clopidogrel at 12 months had higher mortality and fewer repeat coronary procedures at follow-up. In addition based on the reasons for clopidogrel discontinuation, patients who stopped clopidogrel for acute events or side-effects appeared to have a trend towards higher mortality at follow-up. A significant proportion of patients who discontinued clopidogrel were able to be treated again with this agent at a later time point

Source

 * 1) Late Breaking Clinical Trials Session: SCAI Annual Scientific Sessions in partnership with ACC i2 summit, March 31, 2008 Chicago