Haemodialysis impairs clopidogrel but not aspirin responsiveness in patients with end-stage renal disease

Htun, Patrik; Kan, Tatiana; Mueller, Eda; Pohle, Cosima; Schindler, Ralf; Geisler, Tobias; Gawaz, Meinrad; Bocksch, Wolfgang; Fateh-Moghadam, Suzanne

doi:10.1160/th13-04-0289

Cited by 12 publications

(9 citation statements)

References 43 publications

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“…It is unknown if HD impairs or improves aspirin resistance or responsiveness. Only one study addressed this issue . In this pilot study, 31 patients were evaluated for aspirin and clopidogrel responsiveness before and immediately after HD.…”

Section: Discussionmentioning

confidence: 99%

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Low‐dose aspirin for prevention of cardiovascular disease in patients on hemodialysis: A 5‐y prospective cohort study

Pan

Chen

et al. 2016

Hemodialysis International

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Introduction Aspirin is an effective antiplatelet drug for preventing cardiovascular events in high-risk subjects. However, for patients with chronic kidney disease and undergoing hemodialysis (HD), its preventive efficacy remains controversial. The present study aimed to determine whether aspirin therapy reduces the risk of cardiovascular disease (CVD) and all-cause mortality in patients on HD. Methods We conducted a 5-y prospective cohort study involving patients on HD. Major exposure variables included prescription of aspirin (100 mg/d) and no aspirin (nonaspirin). The primary outcomes included all-cause death, cardiovascular events, hemorrhage, and ischemic stroke. The secondary outcome included bleeding events defined by the requirement of hospitalization. Findings In this study, 406 patients on regular HD were involved during a 5-y follow-up. Among these, 152 and 254 propensity-matched patients were enrolled in the aspirin and nonaspirin cohort, respectively. The cumulative survival rate was not significantly higher in the aspirin than in the nonaspirin users (log rank χ = 1.080, P = 0.299). Aspirin use was not significantly associated with reduced all-cause mortality, fatal and nonfatal congestive heart failure, as well as acute myocardial infarction and ischemic stroke. The risk of fatal cerebral hemorrhage was not significantly increased in the aspirin users (HR = 1.795, 95% CI 0.666-4.841, P = 0.174). After adjustment for other confounders, aspirin use was also not associated with decreased risk of all-cause mortality and CVD. Discussion The present prospective cohort study suggests that low-dose aspirin use is not associated with a significant decrease in the risks of all-cause mortality, CVD, and stroke in population undergoing HD (ClinicalTrials.gov number, NCT02261025).

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Section: Discussionmentioning

confidence: 99%

“…Only one study addressed this issue. 19 In this pilot study, 31 patients were evaluated for aspirin and clopidogrel responsiveness before and Cox models were adjusted for age, sex, hemoglobin, albumin, duration of T2DM, cancer, and ultrafiltration. All statistical tests were two sided, and P < 0.05 indicated statistical significance.…”

Section: Discussionmentioning

confidence: 99%

Low‐dose aspirin for prevention of cardiovascular disease in patients on hemodialysis: A 5‐y prospective cohort study

Pan

Chen

et al. 2016

Hemodialysis International

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“…We have seen examples where drugs such as statins, shown to be effective in the predialysis CKD population, are of no benefit when used in HD patients (37,38). Let us next examine data that exists for P2Y 12 receptor inhibitor use in HD patients (39)(40)(41)(42)(43)(44)(45)(46)(47) ( Table 3).…”

Section: Oral P2y 12 Inhibitors In Hd Patientsmentioning

confidence: 99%

“…The VerifyNow assay can be done at the point of care, is simple to perform, but there is some controversy as to what the best cutoff value for the test is and the optimal timing of the assay. Studies on whether to perform platelet aggregation testing before or after HD with the VerifyNow assay are conflicting with one study showing no effect (39), another indicating a slight decrease in clopidogrel responsiveness postHD (46), and a third showing slightly increased responsiveness postHD (47).…”

Section: P2y 12 Inhibitors In Hd Patientsmentioning

confidence: 99%

Oral P2Y₁₂ Receptor Inhibitors in Hemodialysis Patients Undergoing Percutaneous Coronary Interventions: Current Knowledge and Future Directions

Jain

Reilly

2016

Seminars in Dialysis

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Oral P2Y12 receptor inhibitors are commonly used drugs in patients on hemodialysis (HD) to treat acute coronary syndrome with or without percutaneous coronary intervention (PCI), and patients with stable coronary artery disease after PCI. Clopidogrel is the most commonly prescribed P2Y12 receptor inhibitor because it is effective in the general population and is not as costly as newer FDA-approved agents (prasugrel, ticagrelor). However, increasing evidence is accumulating that clopidogrel may not be as effective in reducing mortality and preventing future ischemic events in patients with kidney disease. In this review, we will explore some of the studies that form the basis for this statement and discuss potential pharmacokinetic and pharmacodynamic reasons why clopidogrel might be less effective in HD patients, as well as explore potential risks and benefits of alternatives to clopidogrel therapy.

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“…The results were unchanged pre/post‐HD. Contrary to these results, hemodialysis was found in one study to decrease platelet reactivity and in another study to increase platelet reactivity by the VerifyNow assay . The increase in platelet reactivity appeared to be membrane dependent .…”

Section: Pharmacology Of Clopidogrel In the General Population And Eskdmentioning

confidence: 99%

Clopidogrel Use in End‐Stage Kidney Disease

Tanios

Itani

Zimmerman

2014

Seminars in Dialysis

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Clopidogrel irreversibly binds to the P2Y12 platelet receptor and acts as a potent inhibitor of platelet activation and aggregation. It is currently recommended for the prevention of cardiovascular events in patients with acute coronary syndromes, recent ischemic stroke, and peripheral arterial disease. Clopidogrel is a prodrug requiring hepatic conversion into its active metabolite. In the general population, genetic polymorphisms in the CYP2C19 gene interfering with hepatic conversion and the ABCB1 gene interfering with gut absorption of clopidogrel, account for the large interindividual response to clopidogrel and clopidogrel resistance. Chronic kidney disease (CKD) and ESKD are independent risk factors for clopidogrel resistance; 50-80% of patients with ESKD have high on-treatment residual platelet reactivity when treated with clopidogrel. This may partially explain the abysmal outcomes for patients with kidney disease post coronary intervention. Several assays are used to determine residual on-treatment platelet reactivity; however, their use in tailoring the suitability of clopidogrel treatment in patients with ESKD is unclear. Although clopidogrel decreased cardiovascular events in the general population after acute coronary syndromes and percutaneous intervention in the CURE and CREDO trials, a reanalysis of these studies in patients with CKD (eGFR <60 ml/minute) showed either a reduced or no benefit from clopidogrel treatment. ESKD patients were not represented in these two large trials; this is true for most of the trials that established clopidogrel as an integral part of the therapeutic armamentarium for cardiovascular disease. Furthermore, clopidogrel has been associated with an increased risk of death, death from bleeding, and hospitalization for bleeding in patients with ESKD. In conclusion, current evidence suggests that ESKD patients may not derive the same benefits from clopidogrel therapy as the general population and this therapy may be associated with harm. Properly designed observational studies and randomized controlled trials are needed to establish the role of clopidogrel in patients with ESKD, the use of platelet assays to tailor therapy, and the role of other antiplatelet agents such as prasugrel or ticagrelor in patients who exhibit high on-treatment residual platelet reactivity.

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Haemodialysis impairs clopidogrel but not aspirin responsiveness in patients with end-stage renal disease

Cited by 12 publications

References 43 publications

Low‐dose aspirin for prevention of cardiovascular disease in patients on hemodialysis: A 5‐y prospective cohort study

Low‐dose aspirin for prevention of cardiovascular disease in patients on hemodialysis: A 5‐y prospective cohort study

Oral P2Y₁₂ Receptor Inhibitors in Hemodialysis Patients Undergoing Percutaneous Coronary Interventions: Current Knowledge and Future Directions

Clopidogrel Use in End‐Stage Kidney Disease

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Haemodialysis impairs clopidogrel but not aspirin responsiveness in patients with end-stage renal disease

Cited by 12 publications

References 43 publications

Low‐dose aspirin for prevention of cardiovascular disease in patients on hemodialysis: A 5‐y prospective cohort study

Low‐dose aspirin for prevention of cardiovascular disease in patients on hemodialysis: A 5‐y prospective cohort study

Oral P2Y12 Receptor Inhibitors in Hemodialysis Patients Undergoing Percutaneous Coronary Interventions: Current Knowledge and Future Directions

Clopidogrel Use in End‐Stage Kidney Disease

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Oral P2Y₁₂ Receptor Inhibitors in Hemodialysis Patients Undergoing Percutaneous Coronary Interventions: Current Knowledge and Future Directions