Clinical InvestigationAcute Ischemic Heart DiseaseBleeding, mortality, and antiplatelet therapy: Results from the Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilization, Management, and Avoidance (CHARISMA) trial
Section snippets
Methods
Details of the CHARISMA trial have been previously described.17 Briefly, CHARISMA was a prospective, multicenter, double-blind, randomized, placebo-controlled trial comparing clopidogrel 75 mg/d versus placebo long term in patients 45 years or older who had either documented atherosclerotic vascular disease or were at high-risk of having vascular disease based on a combination of risk factors. All patients also received aspirin (75-162 mg/d). Patients were excluded if they were believed to be
Results
Among the 15,603 patients enrolled, 487 (3.1%) had a moderate or severe bleeding episode. The median time from enrollment to the moderate or severe bleeding episode was 362 days (mean 397 ± 266 days). Table I shows the baseline characteristics of patients who did or did not have a moderate or severe bleeding episode. Compared with those who did not, patients who bled were older and more likely to have a history of hypertension, heart failure, stroke, or atrial fibrillation.
The unadjusted
Discussion
The 2 most important findings of this study are, first, that bleeding in the outpatient setting is associated with an increased risk of all-cause mortality, cardiovascular mortality, and cancer mortality. This increased risk remains significant after adjustment for demographic characteristics, clinical risk factors, medication use, and severities present with both moderate and severe bleeding. The second major finding is that when the relationship between bleeding and mortality are analyzed in
Disclosures
Dr Jeffrey Berger has received research support and honoraria for advisory board participation from Astra Zeneca (modest).
Dr Bhatt has received research grants (to the institution) from Astra Zeneca, Bristol-Myers Squibb, Eisai, Sanofi-Aventis, and The Medicines Company.
Dr Steg reports receiving a research grant (to the institution) from Sanofi-Aventis and having received honoraria for speaking or consulting from Astellas, AstraZeneca, Bayer, Boehringer-Ingelheim, Bristol-Myers Squibb, Endotis,
Acknowledgements
Dr Jeffrey Berger was partially funded by an American Heart Association Fellow to Faculty Award (0775074N). The authors are solely responsible for the design and conduct of this study, all study analyses, and the drafting and editing of the paper and its final contents.
References (30)
- et al.
Low-dose aspirin in patients with stable cardiovascular disease: a meta-analysis
Am J Med
(2008) Ischaemia versus bleeding: the art of clinical decision-making
Lancet
(2009)- et al.
Impact of bleeding severity on clinical outcomes among patients with acute coronary syndromes
Am J Cardiol
(2005) - et al.
The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies
Lancet
(2007) Bleeding and thrombosis in the myeloproliferative disorders
Blood
(1984)Hematologic abnormalities in patients with nonhematologic malignancies
Hematol Oncol Clin North Am
(1987)- et al.
Soluble HLA class I, HLA class II, and Fas ligand in blood components: a possible key to explain the immunomodulatory effects of allogeneic blood transfusions
Blood
(1999) - et al.
Deleterious clinical effects of transfusion-associated immunomodulation: fact or fiction?
Blood
(2001) - et al.
Predicting endometrial cancer among older women who present with abnormal vaginal bleeding
Gynecol Oncol
(1995) Collaborative meta-analysis of randomised trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high risk patients
BMJ
(2002)
Clinical aspects of platelet inhibitors and thrombus formation
Circ Res
Aspirin in the primary and secondary prevention of vascular disease: collaborative meta-analysis of individual participant data from randomised trials
Lancet
Intensifying platelet inhibition—navigating between Scylla and Charybdis
N Engl J Med
Prognostic modeling of individual patient risk and mortality impact of ischemic and hemorrhagic complications: assessment from the Acute Catheterization and Urgent Intervention Triage Strategy trial
Circulation
Therapeutic goals for effective platelet inhibition: a consensus document
Rev Cardiovasc Med
Cited by (0)
- k
On behalf of the CHARISMA investigators.