Article

Incidence of Death and Acute Myocardial Infarction Associated With Stopping Clopidogrel After Acute Coronary Syndrome

Denver VA Medical Center, Denver, Colorado 80220, USA.
JAMA The Journal of the American Medical Association (Impact Factor: 35.29). 03/2008; 299(5):532-9. DOI: 10.1001/jama.299.5.532
Source: PubMed

ABSTRACT

It is unknown whether patients are at increased short-term risk for adverse events following clopidogrel cessation.
To assess the rates of adverse events after stopping treatment with clopidogrel in a national sample of patients with acute coronary syndrome (ACS).
Retrospective cohort study of 3137 patients with ACS discharged from 127 Veterans Affairs hospitals between October 1, 2003, and March 31, 2005, with posthospital treatment with clopidogrel.
Rate of all-cause mortality or acute myocardial infarction (AMI) after stopping treatment with clopidogrel.
Mean (SD) follow-up after stopping treatment with clopidogrel was 196 (152) days for medically treated patients with ACS without stents (n = 1568) and 203 (148) days for patients with ACS treated with percutaneous coronary intervention (PCI) (n = 1569). Among medically treated patients, mean (SD) duration of clopidogrel treatment was 278 [corrected] (169) [corrected] days and death or AMI occurred in 17.1% (n = 268) of patients, with 60.8% (n = 163) of events occurring during 0 to 90 days, 21.3% (n = 57) during 91 to 180 days, and 9.7% (n = 26) during 181 to 270 days after stopping treatment with clopidogrel. In multivariable analysis including adjustment for duration of clopidogrel treatment, the first 90-day interval after stopping treatment with clopidogrel was associated with a significantly higher risk of adverse events (incidence rate ratio [IRR], 1.98; 95% confidence interval [CI], 1.46-2.69 vs the interval of 91-180 days). Similarly, among PCI-treated patients with ACS, mean (SD) duration of clopidogrel treatment was 302 [corrected] (151) [corrected] days and death or AMI occurred in 7.9% (n = 124) of patients, with 58.9% (n = 73) of events occurring during 0 to 90 days, 23.4% (n = 29) during 91 to 180 days, and 6.5% (n = 8) during 181 to 270 days after stopping clopidogrel treatment. In multivariable analysis including adjustment for duration of clopidogrel treatment, the first 90-day interval after stopping clopidogrel treatment was associated with a significantly higher risk of adverse events (IRR, 1.82; 95% CI, 1.17-2.83).
We observed a clustering of adverse events in the initial 90 days after stopping clopidogrel among both medically treated and PCI-treated patients with ACS, supporting the possibility of a clopidogrel rebound effect. Additional studies are needed to confirm the clustering of events after stopping clopidogrel, including associations with cardiovascular mortality and reasons for stopping clopidogrel, as well as to determine the mechanism of this phenomenon, and to identify strategies to reduce early events after clopidogrel cessation.

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Available from: Robert Jesse, Aug 05, 2014
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    • "Using a retrospective cohort study design, data for this study were collected as part of the Department of Veterans Affairs (VA) Veterans Health Administration Cardiac Care Follow-up Clinical Study, which has been described in detail elsewhere [29,30]. Briefly, the records of all patients with ACS, as defined by acute myocardial infarction (AMI) and a random sample of all patients with unstable angina (UA), discharged from a VA hospital were abstracted as part of a national VA cardiac care initiative. "
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    ABSTRACT: Background Chronic kidney disease (CKD) is associated with worse outcomes among patients with acute coronary syndrome (ACS). Less is known about the impact of CKD on longitudinal outcomes among clopidogrel treated patients following ACS. Methods Using a retrospective cohort design, we identified patients hospitalized with ACS between 10/1/2005 and 1/10/10 at Department of Veterans Affairs (VA) facilities and who were discharged on clopidogrel. Using outpatient serum creatinine values, estimated glomerular filtration rate [eGFR (1.73 ml/min/m2)] was calculated using the CKD-EPI equation. The association between eGFR and mortality, hospitalization for acute myocardial infarction (AMI), and major bleeding were examined using Cox proportional hazards models. Results Among 7413 patients hospitalized with ACS and discharged taking clopidogrel, 34.5% had eGFR 30–60 and 11.6% had eGFR < 30. During 1-year follow-up after hospital discharge, 10% of the cohort died, 18% were hospitalized for AMI, and 4% had a major bleeding event. Compared to those with eGFR > =60, individuals with eGFR 30–60 (HR 1.45; 95% CI: 1.18-1.76) and < 30 (HR 2.48; 95% CI: 1.97-3.13) had a significantly higher risk of death. A progressive increased risk of AMI hospitalization was associated with declining eGFR: HR 1.20; 95% CI: 1.04-1.37 for eGFR 30–60 and HR 1.47; 95% CI: 1.22-1.78 for eGFR < 30. eGFR < 30 was independently associated with over a 2-fold increased risk in major bleeding (HR 2.09; 95% CI: 1.40-3.12) compared with eGFR > = 60. Conclusion Lower levels of kidney function were associated with higher rates of death, AMI hospitalization, and major bleeding among patients taking clopidogrel after hospitalization for ACS.
    Full-text · Article · May 2013 · BMC Nephrology
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    • "From a cardiac perspective, discontinuation of clopidogrel is associated with an increased incidence of myocardial infarction or mortality in patients treated either medically or with coronary stenting for acute coronary syndrome. In both groups over half the events occurred within 90 days of stopping clopidogrel therapy [19]. "
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    ABSTRACT: Background An increasing number of elderly patients are managed with long-term antiplatelet therapy. Such patients often present with hip fracture requiring surgical intervention and may be at increased risk of perioperative bleeding and complications. The aim of this study was to ascertain whether it is necessary to stop clopidogrel preoperatively to avoid postoperative complications following hip hemiarthroplasty surgery in patients with intracapsular hip fracture. Materials and methods A retrospective review of 102 patients with intracapsular hip fracture with either perioperative clopidogrel therapy [clopidogrel group (CG)] or no previous clopidogrel exposure [no clopidogrel group (NCG)] who underwent hip hemiarthroplasty surgery was undertaken. Statistical comparison on pre- and postoperative haemoglobin, American Society of Anesthesiologists (ASA) grade, comorbidities, operative time, transfusion requirements, hospital length of stay (LOS), wound infection, haematoma and reoperation rate between the two groups was undertaken. Regression analysis was undertaken to ascertain the risk ratios (RR) of complications and transfusion associated with clopidogrel. Results There was no difference with respect to ASA grade, comorbidities (except cardiac comorbidities), pre- and postoperative haemoglobin levels, operation time, age or gender between the two groups. Four and two patients, respectively, required transfusion postoperatively in the CG and NCG (p = 0.37). There was no difference with respect to LOS, wound infection, haematoma or reoperation rate between the two groups postoperatively. The covariate-adjusted RR for complications and transfusion while being on clopidogrel were 0.43 [95 % confidence interval (CI) 0.07–2.60] and 3.96 (95 % CI 0.40–39.68), respectively. Conclusion Continuing clopidogrel therapy throughout the perioperative period in patients with intracapsular hip fracture is not associated with an increased risk of complications following hip hemiarthroplasty surgery.
    Full-text · Article · Apr 2013 · Journal of Orthopaedics and Traumatology
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    • "Early observational studies have suggested that extended use of clopidogrel in patients with a DES may be associated with reduced risk of death and myocardial infarction (MI) [7]. Additional studies have observed a clustering of adverse events in the initial 90 days after discontinuation of clopidogrel; this suggested the possibility of a clopidogrel rebound effect [16]. Based on those results, and also taking into account results from the Clopidogrel versus Aspirin in Patients at Risk of Ischemic Events (CAPRIE) study, some experts have advocated indefinite clopidogrel therapy [17]. "
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    ABSTRACT: Background Dual antiplatelet therapy with aspirin and thienopyridine is required after placement of coronary drug-eluting stents (DES) to prevent thrombotic complications. Current clinical guidelines recommend at least 6 to 12 months of treatment after a DES implantation, but it may be beneficial to apply dual antiplatelet therapy for a longer duration. Methods/design The optimal dual antiplatelet therapy (OPTIDUAL) study aims to compare the benefits and risks of dual antiplatelet therapy applied for either 12 or 48 months. We will examine the occurrence of major adverse cardiovascular and cerebrovascular events (MACCE) in patients undergoing percutaneous coronary intervention with DES for the treatment of coronary lesions. The OPTIDUAL study is an open-label multicenter, randomized, national trial that will include 1,966 patients treated with DES. All patients will be treated with dual antiplatelet therapy for 12 months (+/− 3). Then, patients with no MACCE or major bleeding will be randomized to receive either 36 additional months of clopidogrel plus aspirin or aspirin only. The primary end-point is the combination of death from all causes, myocardial infarction, stroke and major bleeding. The secondary end points include the individual components of the primary end-point, stent thrombosis, repeat revascularization of the treated vessel and minor bleeding. Discussion This randomized trial is designed to assess the benefits and safety of 12 versus 48 months of dual antiplatelet therapy in patients that receive a DES. We aim to determine whether substantial prolongation of clopidogrel (a thienopyridine) after DES implantation offers an advantage over its discontinuation. Trial registration ClinicalTrials.gov Identifier: NCT00822536
    Full-text · Article · Feb 2013 · Trials
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