PARIS, France—In patients who are not given or do not respond to clopidogrel before elective percutaneous coronary intervention (PCI), intracoronary infusion with adenosine may be an effective alternative for reducing myonecrosis and even cardiovascular events, according to results presented May 27 at EuroPCR 2010.

Gennaro Sardella, MD, of “Sapienza” University of Rome (Rome, Italy), explained that pretreatment with clopidogrel significantly reduces MI in elective PCI patients, but in actual practice many patients arrive at the cath lab without appropriate pre-medication.

For the RACE (Randomized comparison of Adenosine intracoronary infusion and Clopidogrel pretreatment on myonecrosis occurrence in Elective PCI) trial, Dr. Sardella and colleagues randomized 160 elective PCI patients to 50 µg intracoronary adenosine infusion prior to wire placement (for multivessel stenting, an additional 50 µg for each vessel) or clopidogrel (300 mg > 6 hours before procedure or 600 mg < 6 hours before procedure).

Baseline characteristics were well matched between the adenosine (n = 80) and clopidogrel (n = 80) groups, although there was a trend for more hypertension in the adenosine group (86.2% vs. 75.0%; P = 0.071). The 2 groups were also well matched in terms of medical therapy with aspirin, statins, nitrates, and several other agents.

The primary endpoint of myonecrosis (CK-MB levels > 3x ULN) reached statistical significance at 12 hours and showed a strong trend in favor of the adenosine group at 24 hours (table 1).

Table 1. Primary Endpoint (CK-MB > 3x ULN)

Treatment with adenosine was a strong predictor for decreased myonecrosis at both 12 hours (OR 0.19; 95% CI 0.3-0.62; P = 0.011) and 24 hours (OR 0.10; 95% CI 0.018-0.31; P = 0.0001). There was no difference between the adenosine and clopidogrel groups in patients with troponin T levels 3x ULN at 6, 12, and 24 hours.

Difference in CV Events

Interestingly, at 30 days there was a trend for decreased MACCE (cardiac death, MI, and stroke) in the adenosine group (0 vs. 3.75%; P = 0.082). This difference became statistically significant at 6 months (0 vs. 7.5%; P = 0.012), with 1 cardiac death, 2 MIs, and 3 strokes in the clopidogrel group. In addition, multivariable analysis found that treatment with adenosine was associated with a reduced likelihood of MACCE (OR 0.216; 95% CI 0.009-0.352; P = 0.006).

Dr. Sardella readily acknowledged the small size of the study and the fact that it was an open-label trial not powered to analyze clinical endpoints.

Still, “in this study, 50 µg of intracoronary adenosine infusion decreased the incidence of myonecrosis after non-urgent PCI compared with clopidogrel loading dose pretreatment and seems to reduce MACCE at long-term follow-up,” Dr. Sardella concluded. “In the real-world, the adherence to clopidogrel pretreatment is very low. The use of adenosine in elective PCI could be a useful alternative in the setting of no-pretreatment or no-responder patients to reduce the incidence of periprocedural myonecrosis.”

Session co-chair Laura Mauri, MD, MSc, of Brigham and Women’s Hospital (Boston, MA), commented to Dr. Sardella that “the question really is, should we improve the pretreatment strategy of loading with clopidogrel [or move toward] giving a dose of adenosine in the cath lab?”

Dr. Sardella noted that clopidogrel pretreatment is a guideline-approved strategy. “But we’ve found a good response to adenosine treatment during the procedure, even though it’s not in the guidelines,” he said.

Disclosures:

• Drs. Sardella and Mauri report no relevant conflicts of interest.

Related Story:

• No Advantage for Adjunctive Adenosine in Primary PCI