ADenosine Administration during and after Primary percutaneous coronary intervention in acute myocardial infarction Trial - ADAPT

Description:

Earlier small studies had demonstrated that intracoronary adenosine, due to its vasodilatory effect, is associated with improved myocardial perfusion in patients with ST-elevation myocardial infarction (STEMI). Accordingly, current American College of Cardiology/American Heart Association guidelines for primary percutaneous coronary intervention (PCI) in STEMI recommend using adenosine 30-60 µg for the treatment of microvascular dysfunction. ADAPT sought to study the effect of high-dose intracoronary adenosine in patients presenting with STEMI.

Hypothesis:

High-dose adenosine would be associated with improved myocardial perfusion and clinical outcomes in patients with STEMI, compared with placebo.

Study Design

Study Design:

Patients Screened: 507
Patients Enrolled: 448
Mean Follow Up: 30 days
Mean Patient Age: 62.5 years
Female: 25

Patient Populations:

  • Chest pain suggestive of ischemia for >30 minutes
  • Duration of symptoms <12 hours prior to admission
  • ECG showing ST elevations >0.1 mV in two or more leads

Exclusions:

  • Cardiogenic shock
  • Conditions associated with reduced life expectancy (<6 months)
  • On medications for chronic obstructive pulmonary disease

Primary Endpoints:

  • Incidence of residual ST-segment deviation <0.2 mV on 12-lead ECG, 30-60 minutes after PCI

Secondary Endpoints:

  • ST-segment elevation resolution
  • Myocardial blush grade
  • TIMI flow grade on angiogram after PCI
  • Enymatic infarct size (measured using CK-MB)
  • Clinical outcomes at 30 days

Drug/Procedures Used:

After initial angiography, patients were randomized to either two high-dose bolus injections of intracoronary adenosine (2 x 120 µg in 20 ml 0.9% NaCl) or placebo, after thrombus aspiration and after stenting.

Concomitant Medications:

Nitroglycerin 400 µg was given prior to each injection of adenosine. All patients received aspirin (500 mg), heparin (5000 IU), and clopidogrel (600 mg) as well. During PCI, all patients also received abciximab (0.25 mg/kg) unless contraindicated. All patients additionally received aspirin, clopidogrel (for ≥1 month), beta-blockers, lipid-lowering medications, and angiotensin-converting enzyme inhibitors/angiotensin-receptor blockers after PCI.

Principal Findings:

A total of 448 patients were enrolled; 226 received intracoronary adenosine, and 222 placebo. Baseline characteristics were fairly similar between the two groups. About 10% were diabetics, and 57% were smokers. The mean ischemic time was 165-180 minutes. Multivessel disease was noted in 57% of the patients. Thrombus was noted in the majority of the patients (82%), with TIMI 0/1 flow in about 60% of the patients. A thrombus aspiration device was utilized in about 96% of the patients. The majority of the patients (about 92.5%) received abciximab.

There was no difference in the incidence of residual ST-segment deviation <0.2 mV between the adenosine and placebo arms (46.2% vs. 52.2%, p > 0.05). Similarly, ST-segment resolution was similar between the two arms (68.3% vs. 66.3%, p > 0.05), as was myocardial blush grade 3 (28.6% vs. 35.3%, p > 0.05). TIMI 3 flow post-procedure was noted equally between the two arms (94.2% vs. 93.7%, p > 0.05). Similarly, the incidence of distal embolization was similar (12.1% vs. 8.6%). Creatine kinase-myocardial band (CK-MB) and CK rise were similar between the two arms. Clinical outcomes at 30 days, including mortality (1.3% vs. 0.9%) and reinfarction (1.3% vs. 0.5%), were similar between the two arms.

Side effects including bradycardia (20.2% vs. 3.1%), hypotension (14.3% vs. 1.3%), and second-degree atrioventricular (AV) block (18.5% vs. 1.3%) were more prevalent in the adenosine arm (p < 0.001).

Interpretation:

The results of this trial indicate that two injections of 120 µg of intracoronary adenosine after thrombus aspiration is not associated with improved myocardial perfusion or clinical outcomes in patients with STEMI. These results are intriguing, and are contrary to those noted from earlier smaller studies using intracoronary adenosine. Moreover, current primary PCI guidelines for STEMI also recommend a 30-60 µg dose of adenosine for the treatment of microvascular dysfunction.

One possible reason to explain the difference between the current and older studies is that with a high use of thrombus aspiration devices and contemporary pharmacoinvasive therapy such as glycoprotein IIb/IIIa inhibitors, there may be a limited additional role of adenosine in improving microcirculatory flow.

Other trials addressing this issue are needed, because if a lack of benefit with intracoronary adenosine is confirmed, unnecessary side effects such as hypotension, bradycardia, and AV blocks, albeit transient, can be avoided post-PCI.

References:

Fokkema ML, Vlaar PJ, Vogelzang M, et al. Effect of high-dose intracoronary adenosine administration during primary percutaneous coronary intervention in acute myocardial infarction: a randomized controlled trial. Circ Cardiovasc Intervent 2009;Jul 22:[Epub ahead of print].

Clinical Topics: Arrhythmias and Clinical EP, Invasive Cardiovascular Angiography and Intervention, Implantable Devices, EP Basic Science

Keywords: Myocardial Infarction, Creatine Kinase, MB Form, Hypotension, Coronary Disease, Immunoglobulin Fab Fragments, Vasodilator Agents, Percutaneous Coronary Intervention, Atrioventricular Block, Thrombosis, Chest Pain, Microcirculation, Bradycardia, Diabetes Mellitus, Platelet Glycoprotein GPIIb-IIIa Complex


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