Comparison of Platelet Reactivity and Periprocedural Outcomes in Patients With Versus Without Diabetes Mellitus and Treated With Clopidogrel and Percutaneous Coronary Intervention

doi:10.1016/j.amjcard.2010.04.015

The American Journal of Cardiology

Volume 106, Issue 5, 1 September 2010, Pages 619-623

https://doi.org/10.1016/j.amjcard.2010.04.015 Get rights and content

The effect of periprocedural platelet reactivity and clinical outcomes in diabetic patients taking clopidogrel and undergoing percutaneous coronary intervention (PCI) is unclear. The aim of the present study was to prospectively evaluate the influence of diabetes mellitus (DM) on platelet reactivity measured by the VerifyNow P2Y12 assay and on periprocedural outcomes in patients receiving clopidogrel and undergoing PCI. A total of 285 consecutive clopidogrel-treated patients undergoing elective PCI were included. Platelet function analysis was performed using the VerifyNow P2Y12 assay. High platelet reactivity (HPR) after clopidogrel was defined as a platelet reaction unit value ≥240. Cardiac biomarkers were measured before and 8 and 24 hours after intervention. Patients with DM had significantly higher platelet reactivity before PCI compared to nondiabetics (214 ± 83 vs 193 ± 68 platelet reaction units, p = 0.02). HPR was more frequently observed in diabetics (36% vs 22%, p = 0.01) before PCI. Patients with DM had an increased incidence of periprocedural myocardial infarction (MI; 11% vs 4%, p = 0.04). When the entire population was divided by the presence or absence of DM and HPR, patients with DM and HPR presented the highest incidence of periprocedural MI (p for trend = 0.0008). HPR was an independent predictor of periprocedural MI (odds ratio 8.34, 95% confidence interval 2.60 to 26.76, p = 0.0003). In conclusion, patients with DM undergoing PCI have higher platelet reactivity at the time of PCI despite adequate clopidogrel pretreatment and subsequently worse periprocedural outcomes. Point-of-care platelet function testing may help to identify patients at higher risk of periprocedural MI.

Section snippets

Methods

A total of 285 consecutive clopidogrel-treated patients undergoing elective PCI for stable angina or non–ST-elevation acute coronary syndromes were recruited. All patients received a 600-mg clopidogrel loading dose ≥6 hours before intervention or were pretreated with clopidogrel 75 mg/day for ≥5 days. Exclusion criteria were ST-elevation myocardial infarction (MI), upstream use of glycoprotein IIb/IIIa inhibitors, platelet count <70 × 10⁹/L, high bleeding risk, coronary artery bypass surgery in

Results

One hundred four diabetic (36%) and 181 nondiabetic patients were enrolled. The main clinical and procedural features are presented in Table 1, Table 2.

Patients with DM had significantly higher platelet reactivity before PCI compared to nondiabetics (214 ± 83 vs 193 ± 68 PRU, p = 0.02). HPR was more frequently observed in diabetics versus nondiabetics (36% vs 22%, p = 0.01; Figure 1) before PCI. This association remained significant after adjustment for factors potentially related to HPR (i.e.,

Discussion

In the present study, we evaluated platelet function using the VerifyNow P2Y12 assay and found that diabetic patients have higher platelet reactivity before PCI despite adequate clopidogrel pretreatment compared to nondiabetics, in agreement with previous work. However, these data show for the first time that diabetic patients taking clopidogrel and aspirin have significantly higher rates of periprocedural MI compared to nondiabetics. Furthermore, the combination of DM and HPR despite

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Cited by (71)

Association Between Platelet Reactivity and Long-Term Bleeding Complications After Percutaneous Coronary Intervention According to Diabetes Status
2022, American Journal of Cardiology
The relation between diabetes mellitus (DM) and bleeding complications after percutaneous coronary intervention (PCI) is controversial. This study investigates the role of low platelet reactivity (LPR) in the bleeding risk stratification of patients who underwent PCI according to DM status. A total of 472 patients who underwent PCI on aspirin and clopidogrel were included retrospectively. Platelet reactivity was assessed using the VerifyNow P2Y(12) assay. LPR was defined as platelet reactivity unit ≤178. The primary end point was the occurrence of any bleeding at 5 years stratified by DM status and LPR. DM was present in 30.5% of patients. LPR was less frequent in patients with DM (p = 0.077). Overall, 11.9% of patients experienced a bleeding complication at 5 years. The incidence of bleeding did not differ in subjects with and without DM (p = 0.24). LPR had a similar value for stratifying the increased bleeding risk in patients with and without DM (interaction p between DM and LPR 0.69). A stepwise increase in the crude rates of bleeding complications was observed across patients with and without LPR and DM (log-rank p = 0.004), with those affected by both conditions having the highest crude incidence rate. In conclusion, on top of aspirin, approximately 1/3 of patients who underwent PCI on clopidogrel have LPR. Assessment of LPR provides a significant incremental value for predicting bleeding irrespective of DM status. Although the presence of DM per se does not increase the incidence of hemorrhagic complications, the coexistence of DM and LPR identifies the subgroup with the highest bleeding risk.
Effect of renal insufficiency and diabetes mellitus on in-hospital mortality after acute coronary syndromes treated with primary PCI. Results from the ALKK PCI Registry
2019, International Journal of Cardiology
It is known that patients with acute coronary syndromes (ACS) and diabetes mellitus (DM) are at higher risk for in-hospital adverse events. However, we hypothesized that the higher event rate is due to the patients' subgroup with renal failure (RF), a common sequel of DM.
We used data of the prospective ALKK-PCI registry including all consecutive percutaneous coronary interventions (PCI) for ACS of 48 hospitals between 2008 and 2013. We divided 69,651 patients in four groups according to their history of DM and RF (GFR < 60 ml/min). All-cause, in-hospital mortality of the following four groups: noDM/noRF, DM/noRF, DM/RF, RF/noDM, was: 3.5%, 6.6%, 21.9%, and 14.1% for STEMI and 1.5%, 2.1%, 7.2%, and 5.4% for NSTE-ACS. In a multivariate analysis we looked for independent mortality-predictors. Odds ratios with confidence intervals for the following variables: DM without RF, DM with RF, RF without DM were: 1.62 (1.37–1.90), 3.02 (2.43–3.76), and 2.13 (1.80–2.52) for STEMI and 1.20 (0.99–1.45), 2.72 (2.18–3.88), and 2.08 (1.69–2.56) for NSTE-ACS. We also calculated mortality in four groups (60–90, 45–60, 45–30, <30 ml/min) according to the estimated glomerular filtration rate (eGFR). Mortality rates were: 5.0%, 12.8%, 17.7%, and 31.5% for STEMI and 2.1%, 3.8%, 7.1%, and 12.0% for NSTE-ACS (p for trend <0.0001 for both).
In-hospital death after PCI in patients with ACS and DM is mainly observed in the subgroup with co-existing RF. In a multivariate analysis, DM without RF was a significant mortality-predictor in STEMI, but not in NSTE-ACS. RF, irrespective of co-existent DM, was a stronger predictor than DM alone for both ACS-types (OR > 3) and mortality increased with decreasing eGFR.
Meta-Regression to Identify Patients Deriving the Greatest Benefit from Dual Antiplatelet Therapy after Stroke or Transient Ischemic Attack Without Thrombolytic or Thrombectomy Treatment
2019, American Journal of Cardiology
Citation Excerpt :
We observed that the higher was the prevalence of diabetes in the studies, the lower was the efficacy of DAPT. A higher baseline platelet reactivity and an impaired response to clopidogrel in patients with diabetes compared to those without may explain our findings.25,26 However, the presence of confounders in the present analysis resulting in an apparent association at the trial level between diabetes and DAPT efficacy cannot be excluded.
The patient's profile drawing the greatest benefit from dual antiplatelet therapy (DAPT) after a noncardioembolic, ischemic cerebrovascular event is not well characterized. Aim of this metaregression analysis was to compare DAPT versus single antiplatelet therapy (SAPT) in patients with stroke or transient ischemic attack (TIA). We searched randomized trials evaluating clinical outcome with aspirin plus a P₂Y₁₂ inhibitor versus SAPT in patients with noncardioembolic stroke or TIA. Primary end point was the incidence of recurrent stroke; safety outcome measure was major bleeding. Eleven trials were included in the analysis, enrolling 24,175 patients treated with DAPT (aspirin plus clopidogrel, n = 12,074) or SAPT (n = 12,101) after a stroke or TIA event. In the DAPT group the rates of recurrent stroke were lower (7.1% vs 8.8% with SAPT; odds ratios [OR] 0.74, 95% confidence interval 0.62 to 0.88; p = 0.0007) and the incidence of major bleeding was twofold higher (OR 2.01, 1.35 to 3.01; p = 0.0006). Metaregression indicated a positive correlation between prevention of recurrent stroke by DAPT and baseline stroke severity (p = 0.019), baseline risk profile (p = 0.0001), or prevalence of carotid atherosclerosis (p = 0.040). DAPT was more effective when initiated ≤7 days (OR 0.67, 0.58 to 0.77; p < 0.00001) and used for ≤3 months (OR 0.66, 0.58 to 0.76; p < 0.00001) after the event. In conclusion, in patients with stroke or TIA, the highest benefit of DAPT was observed in patients with higher baseline risk profile, greater stroke severity, or concomitant carotid disease, and when DAPT was initiated early and given for ≤3 months.
Platelet reactivity and coronary microvascular impairment after percutaneous revascularization in stable patients receiving clopidogrel or prasugrel
2018, Atherosclerosis
Increased platelet reactivity (PR) associated with variable degree of coronary microvascular impairment has been reported in patients on clopidogrel after elective percutaneous coronary intervention (PCI). Prasugrel provides more potent platelet inhibition than clopidogrel, though it is unknown whether it might also prevent PCI-related platelet activation. In stable patients undergoing elective PCI, we compared: (1) the effects of prasugrel vs. clopidogrel on peri-procedural variations of PR and (2) the correlation of platelet inhibition potency with PCI-induced coronary microvascular impairment.
Forty thienopyridine-naive patients were randomly assigned to a loading dose of either prasugrel 60 mg (n = 20) or clopidogrel 600 mg (n = 20) at least 12 h before PCI. At the time of PCI, we assessed adenosine diphosphate (ADP)-induced PR with the Multiplate Analyzer, and the pressure-derived index of microvascular resistance (IMR) in the treated coronary, both at baseline and post-procedure.
ADP-induced PR was significantly lower in the prasugrel compared with clopidogrel group both at baseline (16.0 ± 8.7 vs. 33.9 ± 18.0 aggregation units [AU], p < 0.001) and post-procedure (16.2 ± 9.0 vs. 39.0 ± 18.6 AU, p < 0.001). A significant peri-procedural increase in PR was observed in the clopidogrel group (p = 0.008), but not in the prasugrel group (p = 0.822). A significant correlation was found between IMR and PR both at baseline (r = 0.458, p = 0.003) and post-PCI (r = 0.487, p = 0.001).
A loading dose of prasugrel compared with clopidogrel is able to attenuate PCI-related increase in PR in patients with stable CAD undergoing PCI, which might contribute to the beneficial effect of this drug on peri-procedural coronary microvascular function.
Association Between Ischemic and Bleeding Risk Scores and the Use of New P2Y<inf>12</inf> Inhibitors in Patients With Acute Coronary Syndrome
2018, Revista Espanola de Cardiologia
Las guías sobre síndrome coronario agudo (SCA) recomiendan el uso de los nuevos inhibidores del P2Y12 (prasugrel y ticagrelor) antes que el clopidogrel para los pacientes con riesgo isquémico moderado-alto, siempre que no tengan un riesgo hemorrágico elevado. El objetivo de nuestro estudio es evaluar la escala de riesgo isquémico GRACE y la de riesgo hemorrágico CRUSADE en relación con la prescripción de los nuevos inhibidores del P2Y12 al alta en pacientes con SCA.
Análisis retrospectivo de un registro multicéntrico de SCA. Se incluyó a 3.515 pacientes consecutivos. La asociación entre las escalas de riesgo y la prescripción de los nuevos inhibidores del P2Y12 se evaluó mediante análisis de regresión logística binaria.
Se trató con prasugrel o ticagrelor a 1.021 pacientes (29%). En el análisis multivariable, tanto la escala GRACE (cada 10 puntos, OR = 0,89; IC95%, 0,86-0,92; p < 0,001) como la escala CRUSADE (cada 10 puntos, OR = 0,96; IC95%, 0,94-0,98; p < 0,001) se asociaron inversamente con el uso de los nuevos inhibidores del P2Y12. Además, otros factores no incluidos en estas escalas (tipo de revascularización, trombosis del stent hospitalaria, hemorragia mayor e indicación concomitante de terapia anticoagulante) también fueron predictores del uso de los nuevos inhibidores del P2Y12.
Los nuevos inhibidores del P2Y12 se prescribieron con mayor frecuencia a los pacientes con SCA con menor riesgo hemorrágico CRUSADE. Sin embargo, se encontró una paradoja en cuanto al riesgo isquémico, con mayor uso de estos agentes para pacientes con menor riesgo estimado con la escala GRACE. Estos resultados subrayan la importancia de la estratificación de riesgos para prescribir con seguridad las terapias óptimas.
Acute coronary syndrome (ACS) guidelines recommend the use of newer P2Y12 inhibitors (prasugrel and ticagrelor) over clopidogrel in patients with moderate-to-high ischemic risk, unless they have an increased bleeding risk. The aim of our study was to assess the GRACE risk score and the CRUSADE bleeding risk score relative to prescription of newer P2Y12 inhibitors at discharge in ACS patients.
Retrospective analysis of a multicenter ACS registry; 3515 consecutive patients were included. The association between risk scores and prescription of newer P2Y12 inhibitors was assessed by binary logistic regression analysis.
A total of 1021 patients (29%) were treated with prasugrel or ticagrelor. On multivariate analyses, both GRACE (OR per 10 points, 0.89; 95%CI, 0.86-0.92; P < .001) and CRUSADE (OR per 10 points, 0.96; 95%CI, 0.94-0.98; P < .001) risk scores were inversely associated with the use of newer P2Y12 inhibitors. Moreover, other factors not included in these scores (revascularization approach, in-hospital stent thrombosis, major bleeding, and concomitant indication for anticoagulation therapy) also predicted the use of newer P2Y12 inhibitors.
New P2Y12 inhibitors were more frequently prescribed among ACS patients with lower CRUSADE bleeding risk. However, an ischemic risk paradox was found, with higher use of these agents in patients with lower ischemic risk based on GRACE risk score estimates. These results underscore the importance of risk stratification to safely deliver optimal therapies.
Full English text available from: www.revespcardiol.org/en
Impact of glycemic variability on the occurrence of periprocedural myocardial infarction and major adverse cardiovascular events (MACE) after coronary intervention in patients with stable angina pectoris at 6 months follow-up
2017, Clinica Chimica Acta
We explored the impact of glycemic variability on the occurrence of periprocedural myocardial infarction and major adverse cardiovascular events (MACE) after coronary intervention in patients with stable angina pectoris (SAP) at 6 months follow-up.
From May 2015 to April 2016, a total of 746 patients with SAP were divided to high glycemic variability group (H group) (n = 261) and low glycemic variability group (L group) (n = 485). The primary end point was incidence of periprocedural myocardial infarction and MACE at 6 months follow-up.
The occurrence of periprocedural myocardial infarction occurred in 18.8% of patients in H group and in 12.4% in L group (P = 0.03). The incidence of MACE at 6 months follow-up was 9.6% in H group and 4.5% in L group (P = 0.01). Multivariable analysis suggested that high glycemic variability conferred a 53% risk increment of 6 months follow-up MACE (odds ratio 2.13, 95% confidence interval 1.85–5.38; P = 0.01).
The trial shows that higher blood glucose variability was correlated with higher incidence of periprocedural myocardial infarction and MACE at 6 months follow-up.

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Coronary artery diseaseComparison of Platelet Reactivity and Periprocedural Outcomes in Patients With Versus Without Diabetes Mellitus and Treated With Clopidogrel and Percutaneous Coronary Intervention

Section snippets

Methods

Results

Discussion

Thromb Res

J Am Coll Cardiol

J Am Coll Cardiol

J Am Coll Cardiol

Am Heart J

J Am Coll Cardiol

J Am Coll Cardiol

J Am Coll Cardiol

J Am Coll Cardiol

J Am Coll Cardiol

JACC Cardiovasc Interv

Validation of a VerifyNow-P2Y12 cartridge for monitoring platelet inhibition with clopidogrel

Methods Find Exp Clin Pharmacol

Definition, diagnosis and classification of diabetes mellitus and its complicationsPart 1: diagnosis and classification of diabetes mellitus provisional report of a WHO consultation

Diabet Med

Universal definition of myocardial infarction

Circulation

Coronary artery disease
Comparison of Platelet Reactivity and Periprocedural Outcomes in Patients With Versus Without Diabetes Mellitus and Treated With Clopidogrel and Percutaneous Coronary Intervention