Impact of Chronic Kidney Disease on Platelet Reactivity and Outcomes of Patients Receiving Clopidogrel and Undergoing Percutaneous Coronary Intervention

doi:10.1016/j.amjcard.2013.12.018

The American Journal of Cardiology

Volume 113, Issue 7, 1 April 2014, Pages 1124-1129

https://doi.org/10.1016/j.amjcard.2013.12.018 Get rights and content

The impact of chronic kidney disease (CKD) on residual platelet reactivity (PR) in patients undergoing percutaneous coronary intervention (PCI) is still debatable. We sought to investigate the interaction between PR and renal function and the related clinical outcomes in patients with coronary artery disease treated with PCI. Immediately before PCI, we measured PR (as P2Y12 reaction units [PRUs]) in 800 patients on clopidogrel with the VerifyNow P2Y12 assay. High PR was defined as a PRU value of ≥240 and low PR as a PRU value of ≤178. Based on a glomerular filtration rate of < or ≥60 ml/min/1.73 m², patients were respectively grouped into those with or without moderate-to-severe CKD. Primary end point was the incidence of 30-day net adverse clinical events (NACEs). Patients with moderate-to-severe CKD (n = 173, 21.6%) and those without showed similar PRU values (208 ± 67 vs 207 ± 75, p = 0.819). Yet, NACEs were significantly higher in patients with moderate-to-severe CKD (19.7% vs 9.1%, p <0.001), in terms of both ischemic (12.1% vs 7.2%, p = 0.036) and bleeding events (8.7% vs 2.1%, p <0.001). NACEs were significantly higher when moderate-to-severe CKD was associated with either high PR or low PR (25.4%, p for trend <0.001); this association was the strongest predictor of NACE at multivariate analysis (odds ratio 3.4, 95% confidence interval 2.0 to 5.6, p <0.001). In conclusion, we did not find an association between moderate-to-severe CKD and residual PR on clopidogrel. However, the association of moderate-to-severe CKD with either high or low PR was a strong determinant of adverse events after PCI.

Section snippets

Methods

This prospective observational study enrolled consecutive patients undergoing PCI for stable CAD or non–ST elevation acute coronary syndrome at the Department of Cardiovascular Sciences, Campus Bio-Medico University, Rome, Italy, and at Cardiovascular Center Aalst, Aalst, Belgium. Exclusion criteria were ST elevation myocardial infarction (MI), radial approach, upstream use of glycoprotein IIb/IIIa inhibitors, platelet count <70 × 10⁹/L, active bleeding or bleeding diathesis, dialysis, and any

Results

A total of 800 patients were included in the study. Baseline clinical characteristics, laboratory data, and angiographic features are described in Table 1. Procedural success was achieved in all patients. A total of 173 patients (22%) had moderate-to-severe CKD. Patients with moderate-to-severe CKD were more likely to be older than those without (68 ± 10 vs 66 ± 10, p = 0.008), although the 2 groups did not differ in terms of cardiovascular risk factors and clinical presentation (Table 1). A

Discussion

The main finding of the present study is that the association of moderate-to-severe CKD with either high or low PR is a strong determinant of adverse events after PCI. However, we did not find any association between decreased renal function and platelet response to clopidogrel.

Patients with CKD are at increased risk of adverse cardiovascular events.17, 18 The responsible factors for this detrimental effect of CKD are not clearly understood but may include the greater frequency of risk factors

Disclosures

The authors have no conflicts of interest to disclose.

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Cited by (33)

Atrial fibrillation in chronic kidney disease
2016, European Journal of Internal Medicine
Citation Excerpt :
A significant trend toward a higher prevalence clopidogrel resistance was reported for eGFR < 60 ml/min/1.73 m2 [114]; although renal function was not found to influence residual platelet reactivity on clopidogrel in another study [115]. Although clopidogrel reduced cardiovascular events in the general population in the CURE and CREDO trials [116,117], a reanalysis of these studies in patients with CKD (eGFR < 60 ml/min) showed a abridged or no benefit from clopidogrel treatment and an amplified risk of bleeding [118]. The role of antiplatelet therapy in stroke prevention in hemodialysis patients with AF is unclear.
Atrial fibrillation (AF), one of the most common dysrhythmia in clinical practice, remains frequently in people with chronic kidney disease (CKD). AF is associated with a fivefold risk of stroke, a threefold incidence of heart failure, and an increased risk of death. Co-existence of AF and CKD raises substantially morbidity and mortality. Moreover, the optimal treatment approach (rate versus rhythm control) remains debated due to lack of hard evidence. Oral anticoagulation is challenging, since these patients have both a prothrombotic state and an increased risk of stroke and an inherent platelet and vascular dysfunction and an amplified rate of bleeding. Although promising, the newer anticoagulation agents were not tested in severe CKD. Furthermore, fatal bleeding has been reported.
Platelet reactivity in patients with impaired renal function receiving dual antiplatelet therapy with clopidogrel or ticagrelor
2016, Vascular Pharmacology
Citation Excerpt :
Therefore, they concluded that a higher rate of co-morbidities in patients with CKD could be the major cause for the apparent impact on HRPR, rather than CKD itself. A lack of association between moderate to severe CKD and residual platelet reactivity on clopidogrel was showed by Mangiacapra et al. [37] in another recent study. In addition, few studies assessed the possible role of renal failure on HRPR in patients with new ADP antagonists, like ticagrelor.
Suboptimal platelet inhibition still represents an important challenge, especially for patients undergoing percutaneous coronary interventions (PCI). Chronic kidney disease (CKD) is a common comorbidity of patients with coronary artery disease, and may potentially influence platelet reactivity. So far only few studies have assessed the role of CKD on response to dual antiplatelet therapy (DAPT) with conflicting results. Therefore, the aim of our study was to evaluate the impact of CKD on platelet function in patients treated with DAPT after a recent acute coronary syndrome (ACS) or PCI.
Patients treated with DAPT, acetylsalicylic acid (ASA) + adenosine diphosphate antagonist (ADP-antagonist) such as clopidogrel or ticagrelor, for ACS or elective patients undergoing PCI were scheduled for platelet function assessment at 30–90 days post-discharge. Platelet function was assessed by whole blood impedance aggregometry (Multiplate®- Roche Diagnostics AG), high residual platelet reactivity (HRPR) was considered for ASPI test > 862 AU*min (for ASA) and ADP test values ≥ 417 AU*min (for ADP-antagonists). Chronic renal failure was defined as an estimated glomerular filtration rate of 60 mol/min/1.73m² or less, calculated by applying MDRD (Modification of Diet in renal Disease) formula.
Our population included a total of 537 patients of which 308 (57.3%) received ASA and clopidogrel and 229 (42.6%) received ASA and ticagrelor. Patients with renal failure at baseline (101 out of 537, 18.8%) were older, with higher prevalence of hypertension, previous myocardial infarction and coronary artery bypass graft surgery. Moreover, they had a lower ejection fraction at baseline and were more often in therapy with diuretics, but less often with statins at admission. They had lower haemoglobin and higher glycated haemoglobin. HRPR was observed in 1.5% of patients treated with ASA with no difference according to renal function (p = 0.18). HRPR for ADP-antagonists was observed in 23.7% of patients, with no difference according to renal function (p = 0.50). This result was confirmed either with clopidogrel (31.9% versus 38%, p = 0.41) and ticagrelor (13.1% versus 10.8%, p = 0.99), also after correction for all baseline confounders (clopidogrel: adjusted OR[95%CI] = 1.26 [0.60–2.63], p = 0.54) (ticagrelor: adjusted OR[95%CI] = 0.95 [0.54–1.65], p = 0.84). The absence of association between renal function and platelet reactivity was confirmed at linear regression analysis both with clopidogrel (r = − 0.04, p = 0.52) and ticagrelor (r = 0.006, p = 0.92).
In patients receiving DAPT, chronic renal failure did not influence ADP-mediated platelet reactivity, with both ticagrelor or clopidogrel. No influence of chronic renal failure was found on the effectiveness of ASA.
A pharmacodynamic comparison of a personalized strategy for anti-platelet therapy versus ticagrelor in achieving a therapeutic window
2015, International Journal of Cardiology
Citation Excerpt :
In particular, we performed a search for measures of HPR and LPR as defined using the Verify-Now P2Y12 assay. A comprehensive summary of all studies with demonstrated associations to ischemic (Table 4) and bleeding (Table 5) clinical endpoints are included [3–6,22-32]. Of note, our therapeutic window mirrors closely data derived from the Platelet reactivity and clinical outcomes after coronary artery implantation of drug-eluting stents (ADAPT-DES) registry, which is the largest study and comprised of over 8000 patients [5,22].
A therapeutic window in antiplatelet treatment has been associated with concurrent lowering of bleeding and ischemic risks. Prasugrel and ticagrelor provide potent platelet inhibition, but may increase bleeding. No study has evaluated a personalized therapy with selective use of novel P2Y12 inhibitory agents compared to empiric ticagrelor use. The objective of this study was to compare a personalized anti-platelet therapy strategy to empiric ticagrelor in achieving a therapeutic window.
Using the CAPITAL registry, we performed a retrospective analysis to evaluate a personalized anti-platelet therapy (PAT) strategy, using a pharmacogenetic approach, and compared it to empiric ticagrelor. In the PAT group, carriers of CYP2C19*2 received prasugrel and non-carriers received clopidogrel. The primary outcome was the proportion of patients within a validated therapeutic window, after a steady state treatment (≥ 48 h) of antiplatelet therapy, as measured by a P2Y12 reaction unit (PRU) > 85 and < 208.
Of 199 patients with platelet function measurements, 150 received PAT, while 49 received ticagrelor. Significantly more patients on PAT achieved the primary outcome (50.0% vs. 4.1%, p < 0.0001). This was predominantly driven by an increase in low on-treatment reactivity with ticagrelor (95.9% vs. 37.3%, p < 0.0001). Multivariable analysis demonstrated PAT to be the strongest predictor of achieving PRU values within the therapeutic window (odds ratio 20.27; 95% CI: 4.33–94.82, p = 0.0001).
Patients treated with PAT were more likely to achieve a therapeutic window compared to a strategy of ticagrelor. Future prospective evaluation of novel PAT strategies will be required to prove clinical utility.
Antiplatelet Therapy in End-stage Renal Disease Patients on Maintenance Dialysis: a State-of-the-art Review
2023, Cardiovascular Drugs and Therapy
Effects of ticagrelor and prasugrel on coronary microcirculation in elective percutaneous coronary intervention
2023, Heart
P2y<inf>12</inf> inhibitor monotherapy after 1–3 months dual antiplatelet therapy in patients with coronary artery disease and chronic kidney disease undergoing percutaneous coronary intervention: a meta-analysis of randomized controlled trials
2023, Frontiers in Cardiovascular Medicine

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Coronary Artery DiseaseImpact of Chronic Kidney Disease on Platelet Reactivity and Outcomes of Patients Receiving Clopidogrel and Undergoing Percutaneous Coronary Intervention

Section snippets

Methods

Results

Discussion

Disclosures

Am J Cardiol

Am J Cardiol

J Am Coll Cardiol

J Am Coll Cardiol

J Am Coll Cardiol

JACC Cardiovasc Interv

JACC Cardiovasc Interv

JACC Cardiovasc Interv

J Am Coll Cardiol

Am J Cardiol

J Am Coll Cardiol

J Am Coll Cardiol

Am J Cardiol

Kidney Int

JACC Cardiovasc Interv

Coronary Artery Disease
Impact of Chronic Kidney Disease on Platelet Reactivity and Outcomes of Patients Receiving Clopidogrel and Undergoing Percutaneous Coronary Intervention