Chronic kidney disease is associated with increased platelet activation and poor response to antiplatelet therapy

Gremmel, Thomas; Müller, Markus; Steiner, Sabine; Seidinger, Daniela; Koppensteiner, Renate; Kopp, Christoph W.; Panzer, Simon

doi:10.1093/ndt/gft103

Cited by 112 publications

(109 citation statements)

References 36 publications

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“…20,21 Previous studies have shown that patients with CKD exhibited significantly higher platelet activation and on-treatment residual ADP-inducible platelet reactivity than patients without renal insufficiency. 20,[22][23][24] Moreover, a low response to clopidogrel might be an independent predictor of the poorer outcomes in these CKD patients. Nowadays, the use of higher than usual clopidogrel doses (600 mg as loading dose and 150 mg as maintenance dose), 25 longer therapy duration (beyond 12 months), 26 or alternative more potent thienopyridine agents such as prasugrel 27,28 or ticagrelor 29 have been proposed as ways to overcome the clopidogrel resistance in CKD.…”

Section: Discussionmentioning

confidence: 99%

Effect of Estimated Glomerular Filtration Rate Decline on the Efficacy and Safety of Clopidogrel With Aspirin in Minor Stroke or Transient Ischemic Attack

Zhou¹,

Pan²,

Wu³

et al. 2016

Stroke

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C hronic kidney disease (CKD) is associated with a high prevalence of stroke, 1,2 and reduced estimated glomerular filtration rate (eGFR) can be a strong predictor of higher recurrence, comorbidity, and mortality among patients with acute ischemic stroke. [3][4][5] As the backbone of P2Y12 inhibition, 6 clopidogrel is often recommended for preventing stroke, especially in patients with noncardioembolic ischemic stroke. 7 However, specific recommendations for antiplatelet therapy in patients with ischemicBackground and Purpose-Patients with chronic kidney disease (CKD) are at a particularly high risk for ischemic and bleeding events. Limited data exist as to the efficacy and safety of clopidogrel in stroke patients with renal dysfunction. Therefore, we sought to assess the impact of decreased kidney function on clinical outcomes for stroke patients on clopidogrel-aspirin treatment. Methods-Patients in the CHANCE trial (Clopidogrel in High-Risk Patients With Acute Nondisabling CerebrovascularEvents) were randomized to clopidogrel-aspirin or aspirin-alone treatment. The primary efficacy outcome was new stroke during 90 days, whereas bleeding was the safety outcome. Patients were stratified according to estimated glomerular filtration rate. Results-Dual clopidogrel-aspirin therapy was associated with a marked reduction in new strokes compared with the therapy of aspirin alone in patients with normal renal function (hazard ratio, 0.77; 95% confidence interval, 0. CKD is characterized as a state with a prothrombotic tendency where excessive platelet activation and dysfunction plays a pivotal role. On the contrary, the risk of all-cause major hemorrhage increased in a graded fashion across all stages of CKD. 8Bleeding complications may occur in patients even with a normal coagulation profile or elevated coagulation factors.2 Therefore, assessment of the efficacy and safety of dual antiplatelet therapy with clopidogrel and aspirin for treating and preventing cerebrovascular diseases in the setting of CKD is of great significance. 2,9The CHANCE trial (Clopidogrel in High-Risk Patients With Acute Nondisabling Cerebrovascular Events) was designed to determine the protection effect against stroke and bleeding risk of combination therapy of clopidogrel plus aspirin compared with aspirin alone among patients with minor stroke or transient ischemic attack (TIA).10,11 On the basis of the CHANCE trial, we aimed to investigate whether declined eGFR would be associated with altered efficacy and safety of dual antiplatelet therapy. Methods Study PopulationCHANCE was a randomized, double-blind, placebo-controlled clinical trial conducted at 114 clinical centers in China. Details about the CHANCE study design and results have been published elsewhere. [10][11][12] Within 24 hours after the onset of minor ischemic stroke or high-risk TIA, patients were randomly assigned to either clopidogrel plus aspirin (clopidogrel at an initial dose of 300 mg, followed by 75 mg per day for 90 days, plus aspirin at a dose of 75 mg per day for the fi...

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Section: Discussionmentioning

confidence: 99%

Effect of Estimated Glomerular Filtration Rate Decline on the Efficacy and Safety of Clopidogrel With Aspirin in Minor Stroke or Transient Ischemic Attack

Zhou¹,

Pan²,

Wu³

et al. 2016

Stroke

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“…Although several earlier reports have examined the association between renal impairment and platelet reactivity after PCI, results thus far have been inconsistent as previous studies were limited by modest sample sizes, inclusion of select cohorts, or lack of adequate multivariable adjustment. 14,16,17,24 In stable diabetic patients, for example, Angiolillo et al 24 previously demonstrated an independent association between CKD and HPR. Similarly, in a separate cohort involving 316 post-PCI patients with and without DM, Gremmel et al 16 also demonstrated a significant association between CKD and HPR using different assays.…”

Section: Discussionmentioning

confidence: 99%

“…14,16,17,24 In stable diabetic patients, for example, Angiolillo et al 24 previously demonstrated an independent association between CKD and HPR. Similarly, in a separate cohort involving 316 post-PCI patients with and without DM, Gremmel et al 16 also demonstrated a significant association between CKD and HPR using different assays. Our findings documenting a higher prevalence of HPR among those with versus without CKD, therefore, are largely confirmatory of these previous reports.…”

Section: Discussionmentioning

confidence: 99%

“…Indeed, ischemic event rates among patients with CKD and normal platelet reactivity were numerically higher than in those with HPR but preserved renal function. There are several possible explanations for the increased thrombotic risk of 16,24,27 also suggest a state of generalized platelet hyperactivity in the setting of CKD with or without concomitant diabetes mellitus. Second, increased levels of vascular smooth muscle cell tissue factor and serum fibrinogen in patients with CKD may lead to activation of the coagulation cascade, thereby increasing blood thrombogenicity.…”

Section: Discussionmentioning

confidence: 99%

“…10,11 Although CKD modulates platelet function, existing studies evaluating associations between CKD and HPR have been limited by modest sample sizes, lack of adequate multivariable adjustment, and limited follow-up. [12][13][14][15][16][17] Moreover, and perhaps more clinically relevant, whether HPR exerts a similar or differential impact on both ischemic and bleeding events among those with and without CKD after PCI is unknown. Accordingly, we sought to examine the cross-sectional and longitudinal associations among CKD, HPR, and clinical events in a contemporary cohort of patients undergoing PCI with DES.…”

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confidence: 99%

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Prevalence and Impact of High Platelet Reactivity in Chronic Kidney Disease

Baber

Mehran

Kirtane

et al. 2015

Circ: Cardiovascular Interventions

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A dverse cardiovascular events, including cardiac death and stent thrombosis, are markedly increased among those with versus without chronic kidney disease (CKD) after percutaneous coronary intervention (PCI).1-3 Residual atherothrombotic risk remains excessive among such patients even when treated with contemporary pharmacotherapy or novel stent platforms, including second-generation drug-eluting stents (DES). 4,5 Despite the strong epidemiological links between renal impairment and thrombotic risk, underlying causal and mechanistic insights have not been fully elucidated.High platelet reactivity (HPR) to adenosine diphosphate during clopidogrel therapy has also emerged as a strong and Background-Chronic kidney disease (CKD) is associated with increased rates of adverse events after percutaneous coronary intervention. We sought to determine the impact of CKD on platelet reactivity in clopidogrel-treated patients and whether high platelet reactivity (HPR) confers a similar or differential risk for adverse events among patients with CKD and non-CKD. Methods and Results-We performed a post hoc analysis of the Assessment of Dual Antiplatelet Therapy With DrugEluting Stents (ADAPT-DES) registry, which included 8582 patients undergoing percutaneous coronary intervention with drug-eluting stents and platelet function testing using the VerifyNow assay. We compared HPR and its impact on ischemic and bleeding events >2 years among patients with CKD and non-CKD. Patients with CKD (n=1367) were older, more often female, diabetic, and had lower ejection fraction compared with their non-CKD counterparts (n=7043). Although HPR prevalence increased with worsening renal function in unadjusted analyses, these associations were no longer present after adjustment. Major adverse cardiac event rates at 2 years among those without CKD or HPR, HPR alone, CKD alone, and both CKD and HPR were 9.0%, 11.2%, 13.3%, and 17.5%, respectively (P<0.001). Associations between HPR and adverse events were uniform across CKD strata without evidence of interaction. Conclusions-HPR is more common among those with versus without CKD, an association that is attributable to confounding risk factors that are more prevalent in CKD. The impact of HPR on ischemic and bleeding events is similar irrespective of CKD status. Clinical Trial Registration-URL: http://www.clinicaltrials.gov. Unique identifier: NCT00638794.(Circ Cardiovasc Interv. 2015;8:e001683.

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Impact of chronic kidney disease on 2‐year clinical outcomes in patients treated with 6‐month or 24‐month DAPT duration: An analysis from the PRODIGY trial

Gargiulo

Santucci

Piccolo

et al. 2017

Cathet Cardio Intervent

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Moderate-to-severe CKD did not modify the effect of a prolonged or shortened DAPT duration in largely unselected patients undergoing stent implantation. Our analysis suggests that CKD should not be a major driver in the decision-making on the duration of DAPT after stent implantation. This exploratory study is underpowered and should be considered hypothesis-generating only. © 2017 Wiley Periodicals, Inc.

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Chronic kidney disease is associated with increased platelet activation and poor response to antiplatelet therapy

Abstract: Patients with CKD exhibit increased platelet activation, and an attenuated response to dual antiplatelet therapy compared with patients without renal insufficiency.

Cited by 112 publications

References 36 publications

Effect of Estimated Glomerular Filtration Rate Decline on the Efficacy and Safety of Clopidogrel With Aspirin in Minor Stroke or Transient Ischemic Attack

Effect of Estimated Glomerular Filtration Rate Decline on the Efficacy and Safety of Clopidogrel With Aspirin in Minor Stroke or Transient Ischemic Attack

Prevalence and Impact of High Platelet Reactivity in Chronic Kidney Disease

Impact of chronic kidney disease on 2‐year clinical outcomes in patients treated with 6‐month or 24‐month DAPT duration: An analysis from the PRODIGY trial

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