August 30, 2011
View Full PaperPlatelet Reactivity and Cardiovascular Outcomes After Percutaneous Coronary Intervention
Key Result
Achieving on-treatment platelet reactivity <208 PRU after PCI was associated with a lower risk of cardiovascular death, MI, or stent thrombosis at 6 months (HR 0.43; 95% CI 0.23-0.82; P=0.01).
Study Design
Type
Cohort (n=2,800)
Structured PICO
Does achieving on-treatment platelet reactivity <208 PRU reduce the risk of cardiovascular events in patients after percutaneous coronary intervention?
P
Population
2,800 patients evaluated for on-treatment platelet reactivity after percutaneous coronary intervention, followed for 6 months.
E
Exposure
Achievement of on-clopidogrel platelet reactivity <208 P2Y12 reaction units (PRU) at 12 to 24 hours post-PCI or during follow-up
C
Comparator
On-treatment platelet reactivity ≥208 P2Y12 reaction units (PRU)
O
Outcome
Composite of cardiovascular death, myocardial infarction, and stent thrombosiscomposite
Achieving on-clopidogrel platelet reactivity <208 PRU after PCI is associated with a lower risk of cardiovascular events, suggesting a potential therapeutic target for individualized antiplatelet therapy.
Main Result
Hazard Ratio: 0.43 (95% CI 0.23–0.82)
p-value: p=0.01
Abstract
BACKGROUND: In the Gauging Responsiveness With A VerifyNow P2Y12 Assay: Impact on Thrombosis and Safety (GRAVITAS) trial, 6 months of high-dose clopidogrel did not reduce cardiovascular events compared with standard-dose clopidogrel in patients with high on-treatment platelet reactivity (OTR) after percutaneous coronary intervention, defined as OTR ≥230 P2Y12 reaction units according to the VerifyNow P2Y12 platelet function test. The aim of this analysis was to examine the relationship between outcomes and OTR over the course of the trial. METHODS AND RESULTS: OTR was measured at 12 to 24 hours and 30±7 days after percutaneous coronary intervention. Cox proportional hazards models with OTR as a time-varying covariate were used to determine the association between OTR and the primary end point of cardiovascular death, myocardial infarction, and stent thrombosis. Of the 2800 enrolled patients, 2796 (99.98%) had evaluable platelet function data. OTR <208 P2Y12 reaction units was significantly associated with a lower risk of the primary end point at 60 days (hazard ratio, 0.18; 95% confidence interval, 0.04 to 0.79; P=0.02) and at 6 months (hazard ratio, 0.43; 95% confidence interval, 0.23 to 0.82; P=0.01). After adjustment for other significant predictors of outcome, OTR <208 P2Y12 reaction units remained independently associated with the primary end point at 60 days (hazard ratio, 0.23; 95% confidence interval, 0.05 to 0.98; P=0.047) and tended to be associated at 6 months (adjusted hazard ratio, 0.54; 95% confidence interval, 0.28 to 1.04; P=0.065). CONCLUSIONS: In the GRAVITAS trial, achievement of on-clopidogrel reactivity <208 P2Y12 reaction units at 12 to 24 hours after percutaneous coronary intervention or during follow-up was associated with a lower risk for cardiovascular events. The efficacy of an individualized strategy to target a level of OTR below this threshold merits investigation. Clinical Trial Registration- http://www.clinicaltrials.gov. Unique identifier: NCT00645918.