Introduction: In the setting of a suspected acute coronary syndrome (ACS), aspirin (ASA) is the primary treatment used for platelet inhibition. However, recent studies have demonstrated that up to 20% of patients do not respond to ASA therapy. The ARTIST trial tested whether treatment of ASA resistance with either higher doses of ASA or additional antiplatelet agents would improve responsiveness to platelet inhibition. Methods: Patients presenting to the emergency department (ED) with a chief complaint of chest pain who were either on outpatient aspirin therapy or who received aspirin in the ED were eligible. A total of 772 patients were enrolled at 5 centers. ASA resistance was tested using the VerifyNow® (Accumetrics) device. Patients who exhibited ASA resistance, defined as aspirin resistance units (ARU) ≥550, were randomized to receive one of four therapies: additional ASA 325 mg, clopidogrel 300 mg or 600 mg, or standard therapy (no additional ASA or clopidogrel). ARU were measured at baseline, 2 hours, and 6-8 hours post-treatment, and the changes in ARU values for each treatment arm were calculated.

Results: Changes in ARU values differed significantly between the four treatment arms (p<0.007), with the greatest reduction in ARU seen in patients who received additional ASA. The mean ARU values in the ASA treatment arm were 631 at baseline, 440 at 2 hours, and 450 at 6-8 hours. There was no significant difference among the four arms with respect to amount of aspirin taken before treatment, the duration of outpatient ASA therapy or baseline ARU. The mean clopidogrel resistance units (PRU) in the group given 300 mg of clopidogrel were 194 at 2 hours and 195 at 6-8 hours. PRU values for the group given 600 mg of clopidogrel 238 at 2 hours and 194 at 6 hours. PRU values for the two groups receiving different doses of clopidogrel were not significantly different.Conclusions: In aspirin resistant patients presenting to the ED with a suspected acute coronary syndrome, additional aspirin appears to be an effective treatment for ASA resistance.

Title: Effects of Various Treatments on Aspirin Resistance in Patients Presenting to the Emergency Department with Chest Pain: Preliminary Results of the Aspirin Resistance Testing and Initial Strategy

for Treatment (ARTIST) Multicenter TrialJennifer Beede, Susan R Isakson, Lori B Daniels, William F. Penny, W. Frank Peacock, Donald Moffa Jr., Richard Nowak, Michele Moyer, Alan Wu, Alex Harrison, Karen Herbst, J. Douglas Kirk, Deborah Diercks, Alan S Maisel

 Aspirin Responder

(n=674)Aspirin Resistant

(n=89) p-value

Age (years) 58.2 ± 14.0 58.5 ± 13.9 .845

Sex Male 400 (87.1%) 59 (12.9%) .308

Female 275 (89.6%) 32 (10.4%)

Race Caucasian 238 (91.9%) 21 (8.1%) .032

African American 327 (86.7%) 50 (13.3%)  

Hispanic 72 (80.9%) 17 (19.1%)  

Asian 22 (95.7%) 1 (4.3%)  

History of CAD no 390 (88.4%) 51 (11.6%) .810

yes 253 (87.8 %) 35 (12.2 %)

History of CHF no 518 (89.2%) 63 (10.8%) .062

yes 146 (83.9%) 28 (16.1%)

History of Hypertension no 161 (87.0%) 24 (13.0%) .630

yes 508 (88.3%) 67 (11.7%)

History of CRI no 603 (89.1%) 74 (10.9%) .012

yes 61 (79.2%) 16 (20.8%)

Table 1. Patient Characteristics

Figure 1. Mean ARU values in the four treatment groups at baseline, 2 hours and 6-8 hours.

Figure 2. Mean PRU values at 2 hour and 6-8 hours in the groups receiving 300 mg or 600 mg of clopidogrel.

Time (hrs)

2 3 4 5 6

Pla

vix

Res

ista

nce

Uni

ts

140

160

180

200

220

240

260

280

Clopidogrel 300Clopidogrel 600

Time (hrs)

0 1 2 3 4 5 6

Asp

irin

Res

ista

nce

Uni

ts

420

440

460

480

500

520

540

560

580

600

620

640

StandardASAClopidogrel 300Clopidogrel 600