Tailored Clopidogrel Loading Dose According to Platelet Reactivity Monitoring to Prevent Stent Thrombosis - VASP

Nov 10, 2008
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Date Presented:
01/01/2008
Date Published:
01/01/2009
Date Updated:
11/10/2008
Original Posted Date:
11/10/2008
References

Description:

Several studies have demonstrated that there is a large variation in patient response to clopidogrel. A low response rate has been linked with an increased risk of adverse outcomes, including major adverse cardiac events (MACE) and stent thrombosis. This study sought to assess the utility of a vasodilator-associated stimulated phosphoprotein (VASP) index to guide management in patients undergoing percutaneous coronary intervention (PCI) for nonemergent causes.

Hypothesis:

VASP-guided therapy would be safe and efficacious in patients receiving clopidogrel prior to nonemergent PCI.

Study Design

Patients Screened: 1,122
Patients Enrolled: 429
Mean Follow Up: 30 days
Mean Patient Age: 66.5 years
Female: 20

Patient Populations:

  • Nonemergent PCI
  • VASP index ≥50%

Exclusions:

  • ST-elevation MI

Primary Endpoints:

  • Stent thrombosis

Secondary Endpoints:

  • MACE (cardiovascular death, MI and urgent target vessel revascularization)
  • TIMI major and minor bleeding

Drug/Procedures Used:

All patients received aspirin 250 mg and clopidogrel 600 mg prior to the procedure. Patients with VASP index of ≥50% were then randomized to routine management, or VASP-guided further loading doses until VASP index <50% before PCI. Up to 3 additional doses of 600 mg of clopidogrel every 24 hours could be used.

Concomitant Medications:

Aspirin 160 mg daily, clopidogrel 75 mg daily

Principal Findings:

A total of 429 patients were randomized, 214 to VASP-guided therapy, and 215 as controls. Baseline characteristics were fairly similar between the two arms. About 36% of the patients had diabetes, 62% had hypertension, and 51% presented with acute coronary syndromes. The number of treated vessels was about 1.6, with a mean number of 1.9 stents per patient. Glycoprotein IIb/IIIa inhibitors were used in about 24% of the patients.

The baseline VASP index after the first loading dose was 67 in both arms. Following additional loading doses of clopidogrel 600 mg, the mean VASP in the treatment arm was 37. Despite 4 loading doses, 8% of the patients still had a VASP index ≥50% at the time of PCI.

At the end of 1 month, stent thrombosis was noted more frequently in the control group, compared with the VASP-guided group (4.7% vs. 0.47%, p = 0.03). MACE was also significantly reduced in the VASP-guided group compared with the control group (0.5% vs. 8.9%, p < 0.001, driven by a significant reduction in the incidence of MI in the VASP-guided group (0.5% vs. 4.8%, p = 0.01). The rates of cardiovascular death (0% vs. 1.8%, p = 0.06) and urgent revascularization (0% vs. 2.3%, p = 0.06) tended to be lower in the VASP-guided group as well.

The rates of all bleeding were similar between the VASP-guided and control arms (3.7% vs. 2.8%, p = 0.8), including TIMI major (0.9% vs. 0.9%, p = 1.0), and TIMI minor (2.8% vs. 1.9%, p = 0.8) bleeding.

Interpretation:

The results of this trial indicate that adjusting the loading dose of clopidogrel based on platelet reactivity is associated with a significant reduction in stent thrombosis, MACE, and MI, without an increase in the risk of bleeding, compared with routine management, in patients with a hypo- or non-responsiveness to clopidogrel, as assessed by the VASP index. The VASP index measures the efficacy of blockade of the P2Y12 receptors, which are the main targets for clopidogrel.

These results are intriguing, and provide further evidence toward the need to assess platelet response in patients receiving clopidogrel. Although the VASP index was tested here, it is not a bedside test, and requires a sophisticated laboratory to run the assay, thereby limiting its utility in routine practice, at least for now. Other bedside platelet reactivity assays are currently under investigation as well, and may play a role in routine management of patients being loaded with clopidogrel in the future.

References:

Bonello L, Camoin-Jau L, Armero S, et al. Tailored clopidogrel loading dose according to platelet reactivity monitoring to prevent acute and subacute stent thrombosis. Am J Cardiol. 2009 Jan 1;103(1):5-10.

Presented by Dr. Frank Paganelli at the American Heart Association Annual Scientific Sessions, New Orleans, November 2008.


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