Pretreatment With Intracoronary Adenosine - Pretreatment With Intracoronary Adenosine

Description:

The goal of the trial was to evaluate the effect of pretreatment with intracoronary adenosine compared with no treatment on post-procedural myonecrosis among patients undergoing nonurgent percutaneous coronary intervention (PCI).

Study Design

Study Design:

Patients Enrolled: 62
Mean Follow Up: 30 days
Mean Patient Age: Mean age 59 years
Female: 23

Patient Populations:

Patients ages 21 to 75 years undergoing nonurgent PCI of de novo lesions for treatment of stable or unstable angina, and baseline CK and CK-MB within normal limits

Exclusions:

Presence of lesions with TIMI grade 0 flow, thrombus-laden lesions, significant left main disease, left ventricular ejection fraction <30%, inability to give informed consent, allergy to adenosine, bradycardia with heart rate <50 bpm, and myocardial infarction within 1 week

Primary Endpoints:

Incidence of myonecrosis, defined as any elevation of CK-MB >6 mg/L

Secondary Endpoints:

Median peak CK-MB level and occurrence of post-procedural myocardial infarction

Drug/Procedures Used:

Patients were randomized in an open-labeled manner to adenosine pretreatment (dose 50 µg in 5 ml saline; n = 31) or no pretreatment (n = 31). Drug was administered into the target coronary artery prior to guidewire advancement.

Concomitant Medications:

Clopidogrel loading dose of 300 mg pre-PCI if given >6 hours prior to procedure or 600 mg if given <6 hours prior to PCI procedure. Post-procedure, aspirin 100 mg/day indefinitely and clopidogrel 75 mg/day for ≥1 month.

Principal Findings:

Treatment arms were similar in patient clinical characteristics and PCI indications, as well as dose of clopidogrel pretreatment. No study patient received glycoprotein IIb/IIIa inhibitors and all received a statin. There was no statistically significant difference in lesion and procedural characteristics between treatment arms, although there was a trend towards increased use of post-stenting balloon dilatation in the adenosine arm (35% vs. 16%) and shorter median stent length in the adenosine arm (23 mm vs. 33 mm). Drug-eluting stents were implanted in 12 (39%) and 15 (48%) patients, and multivessel stenting was performed in nine (29%) and 10 (32%) patients in the adenosine and control arm, respectively.

No patient developed significant bradycardia or heart block following adenosine administration, and there was no difference in procedure time between arms. The primary endpoint of post-PCI myonecrosis occurred less frequently in the adenosine group (13%, n = 4) than in the control group (39%, n = 12; odds ratio [OR] 0.23; 95% confidence interval [CI] 0.05-0.95; p = 0.02). The median peak values of creatine kinase-myocardial band (CK-MB) in the adenosine and standard groups were 2 and 4 mg/L, respectively (p = 0.033). The incidences of myocardial infarction were 6% (n = 2) and 16% (n = 5) in the adenosine and standard groups, respectively (OR 0.36; 95% CI 0.03-2.46; p = 0.229).

Interpretation:

Among patients with stable or unstable angina undergoing nonurgent PCI, pretreatment with intracoronary adenosine bolus was associated with a reduction in the incidence of post-procedural myonecrosis.

Despite standard use of antiplatelet agents and statins, myocardial damage following PCI with stenting complicates upwards of 30% of cases. The rationale for adenosine pretreatment is that the adenosine-induced coronary dilatation and hyperemia could improve venous clearance of microemboli, which are believed to contribute to myonecrosis through microvasculature occlusion.

A smaller (n = 32) study by Desmet et al. (Heart, 2002) demonstrated that in a nonurgent PCI population, intracoronary infusion of adenosine at 1-2 mg/min x 10 minutes resulted in a statistically smaller increase in post-procedural CK-MB. This study by Lee et al. is larger than Desmet et al. (n = 62) and used bolus administered of adenosine. Their results support previous data and additionally demonstrate a trend towards fewer post-procedural myocardial infarction following adenosine pretreatment. Study limitations include its small size and nonblinded design. The multivariate analysis is limited by sample size, and the contribution of lesion differences to outcome differences is hard to assess. Additionally, all patients were Asian in ethnicity, which could limit generalizability.

References:

Lee CH, Low A, Tai BC, et al. Pretreatment with intracoronary adenosine reduces the incidence of myonecrosis after non-urgent percutaneous coronary intervention: a prospective randomized study. Eur Heart J 2007;28:19-25.

Clinical Topics: Arrhythmias and Clinical EP, Invasive Cardiovascular Angiography and Intervention, Vascular Medicine, Implantable Devices, Interventions and Vascular Medicine

Keywords: Odds Ratio, Myocardial Infarction, Multivariate Analysis, Platelet Aggregation Inhibitors, Drug-Eluting Stents, Creatine Kinase, MB Form, Dilatation, Ticlopidine, Angioplasty, Balloon, Coronary, Hyperemia, Purinergic P2Y Receptor Antagonists, Heart Block, Bradycardia, Confidence Intervals


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