Clinical Investigation
Acute Ischemic Heart Disease
Ethnic variation in adverse cardiovascular outcomes and bleeding complications in the Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilization, Management, and Avoidance (CHARISMA) study

https://doi.org/10.1016/j.ahj.2008.08.031Get rights and content

Background

Atherothrombosis is a common condition affecting individuals worldwide. Its impact on different ethnic groups receiving evidence-based therapy is unclear. We aimed to determine if ethnicity is an independent predictor for cardiovascular events and bleeding complications in a contemporary clinical trial on antiplatelet therapy.

Methods

This was a prospective observational study of 15,603 patients enrolled in the CHARISMA trial followed up every 6 months for a median of 28 months. The primary efficacy end point was the first occurrence of cardiovascular death, myocardial infarction, or stroke. The primary safety end point was bleeding.

Results

The cohort comprised 12,502 (80.1%) white, 486 (3.1%) black, 775 (5.0%) Asian, and 1,613 (10.3%) Hispanic patients. There was no difference in the occurrence of the primary composite end point among the 4 ethnic groups. Compared with Asians, cardiovascular and all-cause mortality occurred more frequently among black (adjusted hazard 2.19 and 2.04) and Hispanic (adjusted hazard, 1.83 and 1.69) patients. Although the occurrence of severe bleeding was similarly low among the 4 ethnic groups, Asian (adjusted hazard, 2.21) and black (adjusted hazard, 3.06) patients were more likely to have moderate bleeding complications than Hispanic patients.

Conclusion

In this trial of individuals at risk of vascular events, ethnicity was not a significant, independent predictor of the primary composite cardiovascular event. However, ethnicity was a significant, independent predictor of the secondary outcomes, cardiovascular and all-cause mortality (blacks and Hispanics), and moderate bleeding complications (blacks and Asians).

Section snippets

Methods

The study design8 and major findings6, 9 of the CHARISMA trial have been published previously. Briefly, patients with documented coronary artery disease, cerebrovascular disease, or peripheral arterial disease, or with multiple risk factors for atherothrombosis were enrolled and randomly assigned to clopidogrel plus aspirin or placebo plus aspirin in a double-blind fashion. Patients were excluded if they had indications or contraindications for open-label clopidogrel use or were at high risk of

Results

There were small but statistically significant differences in baseline characteristics among the 4 ethnic groups (Table I). White patients were older; more likely to have had hypercholesterolemia, previous MI, transient ischemic attacks, atrial fibrillation; and more likely to have undergone various revascularization procedures. Black patients had the highest BMI and proportion of female, were most likely to be smokers, and had hypertension, diabetes mellitus, and congestive heart failure

Discussion

The occurrence of the primary composite end point was similar among the 4 ethnic groups. However, there were important differences in the individual components of the composite end points. Compared with Asian patients, all-cause and cardiovascular mortality rates were substantially 2.56 and 1.90 times, respectively, higher for black patients, even after adjusting for differences in baseline characteristics. White patients were 1.64 times more likely than Hispanic patients to have MI. Although

Acknowledgements

The executive committee would like to acknowledge the efforts of Bernard Job, MD, and Christophe Gaudin, MD, from Sanofi-Aventis and Mel Blumenthal, MD, and Ravi Saini, MD, from Bristol-Myers Squibb on behalf of the CHARISMA trial.

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    • Antithrombotic Therapy After Acute Coronary Syndromes or Percutaneous Coronary Interventions in East Asian Populations

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      Accordingly, it has been an ongoing issue over the last decade as to whether differences in the clinical efficacy and safety of antithrombotic therapy after ACS or PCI exist between East Asian patients and other ethnic groups. Secondary analysis of the CHARISMA (Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilization, Management, and Avoidance) trial with patients receiving aspirin and clopidogrel in multiple geographic regions has revealed that Asian populations had the lowest incidence of cardiovascular mortality, but a higher rate of bleeding events compared with other ethnic cohorts.12 Another prior study of the National Cardiovascular Data Registry database in the United States comprising 423,965 cases has also shown that patients of Asian ethnicity had more favorable clinical outcomes following PCI, including a lower rate of death and myocardial infarction (MI), compared with black or Hispanic patients.13

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      Kang et al. conducted an individual patient-level meta-analysis of 16 518 patients (in 7 randomized clinical trials comparing DAPT duration) and demonstrated that major adverse cardiac events occurred more frequently in non-East Asian people (0.8% vs 1.8%, p < 0.001), whereas major bleeding occurred more frequently in East Asian people (0.6% vs 0.3%, p = 0.001) [21]. Furthermore, a subanalysis of the CHARISMA (Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilization, Management, and Avoidance) study showed that bleeding risk differed between ethnicities and that Black and Asian patients were at the highest risk of bleeding [22]. East Asian people were found to be more resistant to clopidogrel but to have fewer ischemic and more bleeding events, giving rise to the concept of the East Asian paradox, which suggests that patients from East Asia may have different appropriate therapeutic windows for platelet reactivity [23].

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    The CHARISMA trial is registered with ClinicalTrials.gov, NCT00050817.

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