Clinical Predictors of Major Atherothrombotic Events Following Elective PCI: A CREDO Substudy

Luis Gruberg, MD, FACC

Disclosures

December 30, 2003

Editorial Collaboration

Medscape &

Presenter: Steven Steinhubl, MD, University of North Carolina (Chapel Hill)

Patients who require percutaneous coronary intervention (PCI) for the treatment of progressive coronary artery disease are at risk for future atheroembolic events. Identifying patients at high risk for these events is crucial for prevention; these high-risk patients should be evaluated to determine whether they are candidates for more aggressive therapy.

Aim

Using data from the Clopidogrel for Reduction of Events During Observation (CREDO) trial,[1] the current study was undertaken to identify patient characteristics prior to elective PCI that significantly and independently influence the risk of death, myocardial infarction (MI), or stroke 1-year postintervention.[2]

Methods

The CREDO trial assessed the impact of clopidogrel loading dose and prolonged treatment with clopidogrel in patients who underwent PCI. A total of 2116 patients were randomized to either clopidogrel 300-mg loading dose followed by 1 year of clopidogrel 75 mg daily or standard therapy with only 1 month of clopidogrel 75 mg followed by placebo for 11 months. All patients received aspirin therapy. The primary 1-year efficacy endpoint was the composite incidence of death, MI, or stroke.

There was a significant reduction in the primary endpoint at 12-month follow-up in patients assigned to clopidogrel loading dose (11.5% vs 8.5%, P = .02). Using a Cox proportional hazards model, the authors identified baseline demographics and clinical, laboratory, or treatment variables that predicted the primary endpoint at 1-year follow-up. The relationship between continuous variables and outcome was evaluated using linear splines when appropriate. Bootstrapping techniques were employed to help validate the model.

Results

Approximately 50 candidate variables were evaluated, and 5 were found to be significant and independent predictors of the combined endpoint of death, MI, or stroke at 1 year. These variables included:

  • Clopidogrel vs placebo: OR = 0.73, P = .03

  • Age ≥ 70 years (10-year increment): OR = 2.4, P < .001

  • Age < 70 years (10-year increment): OR = 1.1, P = .43

  • Baseline calcium channel blocker: OR = 1.4, P = .02

  • Baseline creatinine: OR = 1.6, P = .04

  • Recent infarction (< 7 days): OR = 1.9, P < .001

When the same baseline characteristics were analyzed in order to develop a model predictive of those primary endpoints events occurring only between day 29 and 1 year, age > 70 years and randomization to clopidogrel remained significant and independent predictors of risk. In addition to age and use of clopidogrel, a history of diabetes, congestive heart failure, or bypass surgery were significant predictors of risk:

  • Clopidogrel vs placebo: OR = 0.63, P = .044

  • Age ≥ 70 years (linear spline): OR = 1.1, P < .001

  • History of diabetes: OR = 1.8, P = .01

  • History of congestive heart failure: OR = 2.5, P = .001

  • History of bypass surgery: OR = 2.0, P = .007

Conclusions
  • Patient characteristics available prior to PCI, such as older age, history of an MI within the preceding 7 days, and renal insufficiency, identified patients at higher risk for major atheroembolic events at 1-year follow-up

  • Older age (≥ 70 years) remains predictive of an increased risk for an atheroembolic event occurring between day 29 and 1 year, along with a history of diabetes, congestive heart failure, and prior bypass surgery

  • Randomization to 1 year of clopidogrel was the only baseline characteristic independently associated with significant protection from atheroembolic events at 1 year and between day 29 and 1 year

  • The increased risk associated with baseline calcium channel blocker use deserves further study

Editorial Commentary

The CREDO trial continues to provide important information regarding the prolonged use of dual antiplatelet therapy in patients who undergo PCI. This analysis identifies patients at higher risk for events (eg, older patients; those with diabetes, chronic renal insufficiency, or , congestive heart failure; and patients who have undergone bypass surgery) who would obtain maximum benefit from this treatment. Conversely, the original results from CREDO, Clopidogrel in Unstable Angina to prevent Recurrent ischemic Events (CURE),[3] and Percutaneous Coronary Intervention in the Clopidogrel in Unstable Angina to Prevent Recurrent Events (PCI-CURE)[4] leave little doubt that the majority of patients who undergo PCI will benefit from prolonged dual antiplatelet therapy.

References
  1. Steinhubl SR, Berger PB, Mann III JT, et al, for the CREDO Investigators. Early and sustained dual oral antiplatelet therapy following percutaneous coronary intervention: a randomized controlled trial. JAMA. 2002;288:2411-2420.

  2. Steinhubl S, Aronow H, Brennan DM, McErlean E, Topol EJ. Clinical predictors of major atherothrombotic events 1 year following elective PCI: insights from the CREDO trial. Circulation. 2003;108(Suppl IV):IV-457. Abstract 2099.

  3. Yusuf S, Zhao F, Mehta SR, Chrolavicius S, Tognoni G, Fox KK; The CURE Trial Investigators. Effects of clopidogrel in addition to aspirin in patients with acute coronary syndromes without ST-segment elevation. N Engl J Med. 2001;345:494-502.

  4. Mehta SR, Yusuf S, Peters RJ, et al. Effects of pretreatment with clopidogrel and aspirin followed by long-term therapy in patients undergoing percutaneous coronary intervention: the PCI-CURE study. Lancet. 2001;358:527-533.

Comments

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