The efficacy and safety of short- and long-term dual antiplatelet therapy in patients with mild or moderate chronic kidney disease: Results from the Clopidogrel for the Reduction of Events During Observation (CREDO) Trial

Patricia Best, Steven R. Steinhubl, Peter B. Berger, Arijit Dasgupta, Danielle M. Brennan, Lynda A. Szczech, Robert M. Califf, Eric J. Topol

Research output: Contribution to journalArticle

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Abstract

Background: Mild and moderate chronic kidney disease (CKD) is associated with decreased survival and increased adverse events after a percutaneous coronary intervention (PCI). Therapy with clopidogrel decreases adverse events in large patient populations. Therefore, we sought to determine the efficacy and safety of long-term clopidogrel therapy in patients with CKD. Methods: Two thousand two patients from the CREDO trial in whom an elective PCI of a single or multiple vessels was planned were analyzed. Patients were randomly assigned to a 300-mg loading dose of clopidogrel before PCI followed by clopidogrel 75 mg/d for a year versus a placebo loading dose at the time of the PCI procedure and clopidogrel 75 mg/d for 28 days and placebo for the remainder of a year. Patients were categorized by their estimated creatinine clearance (>90 [normal, n = 999], 60-89 [mild CKD, n = 672], <60 mL/min [moderate CKD, n = 331]). Results: Diminished renal function was associated with worse outcomes. Patients with normal renal function who received 1 year of clopidogrel had a marked reduction in death, myocardial infarction, or stroke compared with those who received placebo (10.4% vs 4.4%, P < .001), whereas patients with mild and moderate CKD did not have a significant difference in outcomes with clopidogrel therapy versus placebo (mild: 12.8% vs 10.3%, P = .30; moderate: 13.1% vs 17.8%, P = .24). Clopidogrel use was associated with an increased relative risk of major or minor bleeding, but this increased risk was not different based on renal function (relative risk 1.2, 1.3, 1.1). Conclusions: Clopidogrel in mild or moderate CKD patients may not have the same beneficial effect as it does in patients with normal renal function, but was not associated with a greater relative risk of bleeding based on renal function. Further studies are needed to define the role of clopidogrel therapy in patients with CKD.

Original languageEnglish (US)
Pages (from-to)687-693
Number of pages7
JournalAmerican Heart Journal
Volume155
Issue number4
DOIs
StatePublished - Apr 1 2008

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clopidogrel
Chronic Renal Insufficiency
Observation
Safety
Percutaneous Coronary Intervention
Kidney
Placebos
Therapeutics
Hemorrhage

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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The efficacy and safety of short- and long-term dual antiplatelet therapy in patients with mild or moderate chronic kidney disease : Results from the Clopidogrel for the Reduction of Events During Observation (CREDO) Trial. / Best, Patricia; Steinhubl, Steven R.; Berger, Peter B.; Dasgupta, Arijit; Brennan, Danielle M.; Szczech, Lynda A.; Califf, Robert M.; Topol, Eric J.

In: American Heart Journal, Vol. 155, No. 4, 01.04.2008, p. 687-693.

Research output: Contribution to journalArticle

Best, Patricia ; Steinhubl, Steven R. ; Berger, Peter B. ; Dasgupta, Arijit ; Brennan, Danielle M. ; Szczech, Lynda A. ; Califf, Robert M. ; Topol, Eric J. / The efficacy and safety of short- and long-term dual antiplatelet therapy in patients with mild or moderate chronic kidney disease : Results from the Clopidogrel for the Reduction of Events During Observation (CREDO) Trial. In: American Heart Journal. 2008 ; Vol. 155, No. 4. pp. 687-693.
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abstract = "Background: Mild and moderate chronic kidney disease (CKD) is associated with decreased survival and increased adverse events after a percutaneous coronary intervention (PCI). Therapy with clopidogrel decreases adverse events in large patient populations. Therefore, we sought to determine the efficacy and safety of long-term clopidogrel therapy in patients with CKD. Methods: Two thousand two patients from the CREDO trial in whom an elective PCI of a single or multiple vessels was planned were analyzed. Patients were randomly assigned to a 300-mg loading dose of clopidogrel before PCI followed by clopidogrel 75 mg/d for a year versus a placebo loading dose at the time of the PCI procedure and clopidogrel 75 mg/d for 28 days and placebo for the remainder of a year. Patients were categorized by their estimated creatinine clearance (>90 [normal, n = 999], 60-89 [mild CKD, n = 672], <60 mL/min [moderate CKD, n = 331]). Results: Diminished renal function was associated with worse outcomes. Patients with normal renal function who received 1 year of clopidogrel had a marked reduction in death, myocardial infarction, or stroke compared with those who received placebo (10.4{\%} vs 4.4{\%}, P < .001), whereas patients with mild and moderate CKD did not have a significant difference in outcomes with clopidogrel therapy versus placebo (mild: 12.8{\%} vs 10.3{\%}, P = .30; moderate: 13.1{\%} vs 17.8{\%}, P = .24). Clopidogrel use was associated with an increased relative risk of major or minor bleeding, but this increased risk was not different based on renal function (relative risk 1.2, 1.3, 1.1). Conclusions: Clopidogrel in mild or moderate CKD patients may not have the same beneficial effect as it does in patients with normal renal function, but was not associated with a greater relative risk of bleeding based on renal function. Further studies are needed to define the role of clopidogrel therapy in patients with CKD.",
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T1 - The efficacy and safety of short- and long-term dual antiplatelet therapy in patients with mild or moderate chronic kidney disease

T2 - Results from the Clopidogrel for the Reduction of Events During Observation (CREDO) Trial

AU - Best, Patricia

AU - Steinhubl, Steven R.

AU - Berger, Peter B.

AU - Dasgupta, Arijit

AU - Brennan, Danielle M.

AU - Szczech, Lynda A.

AU - Califf, Robert M.

AU - Topol, Eric J.

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N2 - Background: Mild and moderate chronic kidney disease (CKD) is associated with decreased survival and increased adverse events after a percutaneous coronary intervention (PCI). Therapy with clopidogrel decreases adverse events in large patient populations. Therefore, we sought to determine the efficacy and safety of long-term clopidogrel therapy in patients with CKD. Methods: Two thousand two patients from the CREDO trial in whom an elective PCI of a single or multiple vessels was planned were analyzed. Patients were randomly assigned to a 300-mg loading dose of clopidogrel before PCI followed by clopidogrel 75 mg/d for a year versus a placebo loading dose at the time of the PCI procedure and clopidogrel 75 mg/d for 28 days and placebo for the remainder of a year. Patients were categorized by their estimated creatinine clearance (>90 [normal, n = 999], 60-89 [mild CKD, n = 672], <60 mL/min [moderate CKD, n = 331]). Results: Diminished renal function was associated with worse outcomes. Patients with normal renal function who received 1 year of clopidogrel had a marked reduction in death, myocardial infarction, or stroke compared with those who received placebo (10.4% vs 4.4%, P < .001), whereas patients with mild and moderate CKD did not have a significant difference in outcomes with clopidogrel therapy versus placebo (mild: 12.8% vs 10.3%, P = .30; moderate: 13.1% vs 17.8%, P = .24). Clopidogrel use was associated with an increased relative risk of major or minor bleeding, but this increased risk was not different based on renal function (relative risk 1.2, 1.3, 1.1). Conclusions: Clopidogrel in mild or moderate CKD patients may not have the same beneficial effect as it does in patients with normal renal function, but was not associated with a greater relative risk of bleeding based on renal function. Further studies are needed to define the role of clopidogrel therapy in patients with CKD.

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