High Platelet Reactivity Rates Research Articles

Pharmacodynamic effect of prasugrel 5 mg vs clopidogrel 150 mg in elderly patients with high on-clopidogrel platelet reactivity

Elderly patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI) frequently exhibit high platelet reactivity (HPR) while on clopidogrel. In the elderly cohort, either prasugrel is not recommended or, if used, halving of the dose has been suggested. We aimed to test the hypothesis that in elderly patients exhibiting HPR after standard treatment with clopidogrel, prasugrel-reduced dose (5 mg) could be more effective than high-dose (150 mg) clopidogrel. Consecutive elderly (≥75 years old) patients with ACS undergoing PCI and loaded with clopidogrel were considered for platelet reactivity (PR) assessment at 24 hours after PCI with the VerifyNow assay (Accumetrics Inc, San Diego, CA), measured in P2Y12 reaction units (PRU). Of 63 screened patients, 30 (47.6%) were found with HPR (defined as PRU ≥230) and 27 of them participated in a prospective, randomized, single-center, single-blind, investigator-initiated, crossover study of platelet inhibition by prasugrel 5 mg/d vs clopidogrel 150 mg/d, with a 15-day treatment period. The primary end point of PR at the end of the 2 study periods was lower in patients receiving low-dose prasugrel than those receiving high-dose clopidogrel (least squares estimates 190.8 [95% CI 161.5-220.1] and 240.8 [95% CI 211.0-270.6], respectively; P = .008). The secondary end point of HPR rate at the end of treatment periods was lower for prasugrel (8/24; 33.3%) compared with clopidogrel (16/24; 66.7%), P = .02. In elderly patients with ACS undergoing PCI and exhibiting HPR after standard clopidogrel treatment, prasugrel 5 mg/d is significantly more efficacious than clopidogrel 150 mg/d in reducing PR and HPR rate.

High on-thienopyridine platelet reactivity in elderly coronary patients: the SENIOR-PLATELET study

The aim of this study was to compare on-thienopyridine platelet reactivity of elderly patients (≥75 years) vs. younger patients (<75 years). Elderly patients represent a growing and challenging segment of the coronary population for whom the effect of dual antiplatelet therapy on platelet inhibition has not been specifically addressed. The SENIOR-PLATELET study included 1331 coronary patients chronically (>14 days) treated with aspirin and a thienopyridine (clopidogrel 75 mg, n= 1027; clopidogrel 150 mg, n= 139; or prasugrel 10 mg, n= 165). Platelet response to clopidogrel and prasugrel was assessed by the VerifyNow assay and light transmission aggregrometry (LTA). Response to treatment, rate of high platelet reactivity (HPR), and inhibition (HPI) were compared in the two age categories. On-treatment platelet reactivity with clopidogrel 75 mg, 150 mg or prasugrel 10 mg was higher in elderly patients (n= 205) than in younger patients (n= 1126) whichever the test used. The difference in P2Y(12) reaction units (PRU) between the two populations was +45 in patients treated with clopidogrel 75 mg (P< 0.0001), +30 in patients treated with clopidogrel 150 mg (P= 0.17), and +20 with prasugrel 10 mg (P= 0.10). Differences in residual platelet aggregation were consistent when measured by LTA. Elderly patients treated with clopidogrel 75 mg were more likely to have HPR than younger patients (38.2 vs. 18.2%, OR: 2.58, 95% CI: 1.76-3.79; P< 0.0001) even after adjustment for potential confounders (adj OR: 1.83, 95% CI: 1.16-2.87; P= 0.009). Elderly patients present an impaired response to clopidogrel with a high rate of HPR. Clopidogrel 150 mg or prasugrel 10 mg blunt, but do not eliminate the difference in response observed between old and young patients.

Platelet function profiles in the elderly: Results of a pharmacodynamic study in patients on clopidogrel therapy and effects of switching to prasugrel 5 mg in patients with high platelet reactivity

Studies specifically designed to assess clopidogrel response in the elderly as well as treatment alternatives to improve platelet inhibition in this high-risk population are lacking. This study aimed to define pharmacodynamic (PD) profiles, including high platelet reactivity (HPR) rates, among elderly patients on maintenance clopidogrel therapy and to assess the PD effects of prasugrel 5 mg/day in elderly with HPR. This was a prospective observational PD study enrolling consecutive ≥ 75-year-old patients on maintenance clopidogrel therapy (75 mg/day) who were tested for clopidogrel response by the VerifyNow P2Y12 assay and light transmittance aggregometry (LTA). HPR rates were estimated using multiple definitions. HPR patients identified by the VerifyNow P2Y12 assay [P2Y12 reaction unit (PRU) ≥ 230] were switched to prasugrel 5 mg/day, and platelet function testing was performed after 15 days of treatment. PD testing was completed in 100 patients. The HPR prevalence varied between 25% and 32%, depending on the definition used. A PRU ≥ 230 was observed in 25 patients; of these, 20 switched to prasugrel 5 mg/day. This resulted in significant reduction in PRU mean values (279.8 ± 45.1 vs. 171.7 ± 65.2, p=0.0002) with an absolute between-treatment difference of 108.1 (95% confidence intervals 75.2-140.9). Accordingly, switching to prasugrel 5 mg/day overcame HPR in most (80%) patients. Consistently, all LTA measures were significantly lower after prasugrel compared with clopidogrel. In conclusion, a considerable proportion of elderly patients exhibit HPR while on standard clopidogrel therapy. Switching to 5 mg/day prasugrel in elderly patients with HPR is associated with enhanced platelet inhibition and overcomes HPR in the majority of these patients.

High Residual Platelet Reactivity After Clopidogrel: Extent of Coronary Atherosclerosis and Periprocedural Myocardial Infarction in Patients With Stable Angina Undergoing Percutaneous Coronary Intervention

We tested the hypothesis that residual platelet reactivity after clopidogrel correlates with the extent and severity of coronary atherosclerosis in patients undergoing elective percutaneous coronary intervention (PCI). Platelets are actively involved in vascular atherosclerosis. We prospectively enrolled 338 patients undergoing PCI for stable angina, loaded with 600-mg clopidogrel. Platelet reactivity was assessed 12 h later by measuring P2Y12 reactivity unit (PRU) with VerifyNow P2Y12 assay (Accumetrics, San Diego, California). High platelet reactivity (HPR) was defined as PRU value >or=240. Presence of multivessel disease (MVD) and total stent length (TSL) were used as surrogate markers of atherosclerosis severity and extension. Patients with MVD showed higher PRU compared with single-vessel disease (SVD) patients (222 +/- 85 vs. 191 +/- 73; p < 0.001). The PRU increased with the number of stenotic coronaries (1-vessel disease: 191 +/- 73; 2-vessel disease: 220 +/- 88; 3-vessel disease: 226 +/- 80; p = 0.002). The PRU was higher in the third TSL tertile compared with first tertile (217 +/- 83 vs. 191 +/- 73; p = 0.048). The HPR was most frequently observed among MVD patients (40.5% vs. 21.6% in patients with SVD, respectively; p < 0.001) and those in the third TSL tertile (35.8% vs. 22.2% first tertile; p = 0.028). Higher incidence of periprocedural myocardial infarction was observed in patients with HPR (41.2% vs. 26.7% in patients without HPR; p = 0.008) and in those in the third tertile TSL (37.7% vs. 23.1% first tertile; p = 0.020). By multivariate analysis, HPR was the only independent predictor of periprocedural myocardial infarction (p = 0.034). Patients with more extensive coronary atherosclerosis have a higher rate of HPR, which might partly account for higher risk of periprocedural MI.