Prasugrel Maintenance Dose Research Articles

Periprocedural antiplatelet medication assessed by VerifyNow for neuroendovascular treatment: Comparison of prasugrel with clopidogrel

Objective The maintenance dose of prasugrel (PRAS) for neuroendovascular treatment requires much research. We report the antiplatelet effect of PRAS measured by VerifyNow P2Y12 reaction units (PRUs) in patients during the perioperative period of neuroendovascular treatment. Methods Between January 2017 and January 2023, 230 patients who underwent endovascular treatment for unruptured intracranial aneurysms or carotid artery stenosis at our institution were retrospectively identified. Patients received dual antiplatelet therapy with 100 mg aspirin (ASA) and 75 mg clopidogrel (CLP)/day (CLP group, n = 186) or 100 mg ASA and 3.75 mg PRAS/day (PRAS group, n = 44) 2 weeks before the procedures. The PRU value was compared between the CLP and PRAS groups. In the study, we defined 95≦PRU < 208 as the optimal range. Perioperative complications within seven days of surgery were also analyzed. Results The mean value of PRU was significantly low in the PRAS group (179.13 ± 66.03 in CLP vs. 154.75 ± 54.01 in PRAS, p = 0.024). The proportion of the patients who exhibited 95≦PRU < 208 was significantly higher in the PRAS group (55.4% vs. 72.7%, p = 0.036). Ischemic and hemorrhagic complication rates were not significantly different between the CLP and PRAS groups (7.6% vs. 0%, p = 0.076; 4.7% vs. 0%, p = 0.361). The ischemic complication rate was higher in patients with a PRU > 208 than in those with PRU < 208 (12.5% vs. 3.8%, p = 0.044). The hemorrhagic complication rate was not significantly different between the PRU < 95 and 95≦PRU groups (8.4% vs. 3.2%, p = 0.224). Conclusions Maintenance dose PRAS further decreased the PRU value and reached the optimal range in more cases than CLP during the perioperative period of neuroendovascular treatment. Ischemic complications significantly increased in the 208 < PRU group.

Reduced-dose prasugrel monotherapy without aspirin after PCI with the SYNERGY stent in East Asian patients presenting with chronic coronary syndromes or non-ST-elevation acute coronary syndromes: rationale and design of the ASET Japan pilot study

The Acetyl Salicylic Elimination Trial (ASET) Japan pilot study is a multicentre, single-arm, open-label, proof-of-concept study with a stopping rule based on the occurrence of definite stent thrombosis. This study aims to demonstrate the feasibility and safety of low-dose prasugrel monotherapy following percutaneous coronary intervention (PCI) in Japanese patients presenting with chronic coronary syndromes (CCS) or non-ST-elevation acute coronary syndromes (NSTE-ACS). Four hundred patients with a SYNTAX score <23 requiring PCI due to CCS or NSTE-ACS will be screened and considered eligible for the study. The enrolment is planned in two phases: 1) 200 patients presenting with CCS, followed by 2) 200 patients presenting with NSTE-ACS. After optimal PCI with implantation of a SYNERGY (Boston Scientific) stent, patients will be enrolled and loaded with prasugrel 20 mg, followed by a maintenance dose of prasugrel 3.75 mg once daily without aspirin continued for 3 months in Phase 1 (CCS patients), and for 12 months in Phase 2 (NSTE-ACS patients). After these follow-up periods, prasugrel will be replaced by standard antiplatelet therapy according to local practice. The primary endpoint is a composite of cardiac death, target vessel myocardial infarction, or definite stent thrombosis after the index procedure. The primary bleeding endpoint is any Bleeding Academic Research Consortium type 3 or 5 bleeding occurring within 3 months of the index PCI for CCS patients, or 12 months for NSTE-ACS patients. The ASET Japan study is designed to demonstrate the feasibility and safety of reduced-dose prasugrel monotherapy after PCI in East Asian patients with acute and chronic coronary syndromes.

Prasugrel switching from clopidogrel after percutaneous coronary intervention for acute coronary syndrome in Taiwanese patients: an analysis of safety and efficacy

The recommended maintenance dose of prasugrel for East Asian populations (i.e., Japanese and Taiwanese) is 3.75 mg as part of dual antiplatelet therapy (DAPT) for the prevention of recurrent ischemia and stent thrombosis in acute coronary syndrome (ACS). This modified dosage regimen has been established in studies conducted in Japan; however, the efficacy and safety of switching from clopidogrel to prasugrel DAPT among Taiwanese patients remain to be explored. In this phase IV, multicenter, single-arm, open-label study, we evaluated the 4-week pharmacodynamic response, and the 48-week safety outcomes of prasugrel 3.75 mg after a switch from clopidogrel in Taiwanese ACS patients. A total of 203 prasugrel-naïve ACS patients (over 90% male) who had received post-PCI clopidogrel DAPT for at least 2 weeks were enrolled from ten medical centers in Taiwan and subsequently switched to prasugrel 3.75 mg DAPT. Four weeks after the switch, P2Y12 reaction unit (PRU) values were significantly decreased in the total cohort (mean − 18.2 ± 48.1; 95% confidence interval − 24.9 to − 11.5, p < 0.001), and there was an overall consistent antiplatelet response in the treated subjects. The proportion of patients with high on-treatment platelet reactivity (HPR; PRU > 208) dropped from 23.5 to 10% (p < 0.001). Female sex was associated with a greater PRU reduction with prasugrel, whereas HPR at baseline, age ≥ 65 years, and body mass index ≥ 25 best predicted HPR at Week 4. Throughout the 48-week treatment with prasugrel, the incidences of MACE (1.0%) and TIMI major bleeding (2.0%) were rather low, accompanying an acceptable safety profile of TIMI minor (6.4%) and non-major, non-minor clinically relevant bleeding (3.0%). Overall, switching to the maintenance dose of prasugrel (3.75 mg) was observed to be effective and well tolerated among post-PCI ACS patients in Taiwan. Clinical Trial Registration Number: NCT03672097.

Efficacy of 2.5-mg Prasugrel in Elderly or Low-Body-Weight Patients.

Due to concern about bleeding complications, a maintenance dose of prasugrel 2.5 mg may be used in elderly or low-body-weight patients in Japan. There is little information, however, on the efficacy and safety of a 2.5-mg maintenance dose of prasugrel. Methods and Results: In this single-center, prospective, open-label, cross-over study, a total of 44 elderly (≥75 years old) or low body-weight (<50 kg) Japanese patients >1 month after percutaneous coronary intervention who were treated with aspirin 81-100 mg and clopidogrel 75 mg were randomized to either prasugrel 2.5 mg or 3.75 mg instead of clopidogrel for 14 days, with a cross-over directly to the alternate treatment for another 14 days. Platelet inhibition was assessed with the VerifyNow assay (Accumetrics, San Diego, CA, USA) at 3 time points: baseline; day 14; and day 28. P2Y12 reaction units (PRU) ≤95 was defined as low on-treatment platelet reactivity (LPR), and PRU ≥262 as high on-treatment platelet reactivity (HPR). The prevalence of LPR was 2.2% in patients treated with clopidogrel, 2.2% in those with prasugrel 2.5 mg, and 22.7% in those with prasugrel 3.75 mg (P<0.001). Clopidogrel resulted in the higher prevalence of HPR compared with 2.5-mg and 3.75-mg prasugrel (40.9% vs. 18.2% vs. 6.8%, P<0.001). Prasugrel 2.5 mg may be more appropriate in elderly or lower-body-weight Japanese patients.

P3673In-hospital bleeding and utility of a maintenance dose of prasugrel 2.5 mg in high bleeding risk patients with acute coronary syndrome

P3673In-hospital bleeding and utility of a maintenance dose of prasugrel 2.5 mg in high bleeding risk patients with acute coronary syndrome

In-Hospital Bleeding and Utility of a Maintenance Dose of Prasugrel 2.5 mg in High Bleeding Risk Patients With Acute Coronary Syndrome.

Data on bleeding events in Japanese patients with acute coronary syndrome (ACS) are insufficient. In addition, the efficacy and safety of a maintenance dose of prasugrel 2.5 mg/day in high bleeding risk patients are unknown.Methods and Results:We prospectively enrolled 1,167 consecutive patients with suspected ACS and undergoing percutaneous coronary intervention. The maintenance dose of prasugrel 2.5 mg/day was prescribed for patients with a low body weight (≤50 kg), elderly (≥75 years), or renal insufficiency (eGFR ≤30 mL/min/1.73 m2). In-hospital events were assessed in 992 ACS patients treated with drug-eluting stents. Excluding 29 in-hospital deaths, out-of-hospital events were assessed in 963 ACS patients. The primary safety outcome measure was major bleeding (Bleeding Academic Research Consortium types 3 and 5). The incidence of in-hospital major bleeding was 3.4%. Multivariate analysis showed that being elderly, low body weight, renal insufficiency, stroke history, femoral approach, and mechanical support usage were independent predictors of in-hospital major bleeding. The cumulative 1-year incidence of out-of-hospital major bleeding was not significantly different between the prasugrel 2.5 mg/day (n=284) and 3.75 mg/day (n=487) groups (1.6% vs. 0.7%, log-rank P=0.24). That of out-of-hospital definite or probable stent thrombosis was 0% in both groups. The maintenance dose of adjusted prasugrel 2.5 mg/day seems to be one option in ACS patients at high bleeding risk.

WHAT ARE THE OPPORTUNITIES OF PRASUGREL IN THE TREATMENT OF PATIENTS WITH ACUTE CORONARY SYNDROME

The aim of the review is presenting the possibilities and perspectives of the third generation of thienopyridine P2Y12 receptor inhibitor prasugrel in the treatment of patients with acute coronary syndrome (ACS). The main pathogenetic stage of ACS is intracoronary thrombosis, which develops on the surface of a damaged atherosclerotic plaque. The use of acetylsalicylic acid with addition of the second antiplatelet agent, so-called dual antiplatelet therapy, is a standard component in the treatment of any type of ACS, regardless of reperfusion and the selected treatment strategy. Due to some limitations in the use of clopidogrel as the second component of dual antiplatelet therapy, the possibility of prasugrel or ticagrelor usage should be considered in patients with ACS with percutaneous coronary intervention (PCI). Prasugrel therapy is associated with better clinical outcomes as compared with clopidogrel therapy in moderate or high-risk patients who undergo PCI. Because of higher bleeding risk and the lack of clinical benefits in special subgroups of patients, prasugrel must not be used in patients with a stroke or transient ischemic attack in the past. If, after a thorough individual benefit-risk assessment a decision is in favor of prescribing prasugrel to the patient older than 75 years or with a small body weight the maintenance dose of prasugrel is to be reduced by half. Real clinical practice data has shown that with following these recommendations prasugrel demonstrates optimal efficacy, safety, and even more significant impact on the prognosis than this in clinical trials. Prasugrel is able to reduce significantly the incidence of cardiovascular events such as cardiovascular death, myocardial infarction and stroke in patients with ACS who undergo PCI.

Absence of differential effect of ticagrelor versus prasugrel maintenance dose on endothelial function in patients with stable coronary artery disease

BackgroundEndothelial function may be improved by ticagrelor through adenosine-mediated mechanisms. We aimed to assess the effect of ticagrelor versus prasugrel on endothelial function in patients with stable coronary artery disease (CAD). MethodsIn a prospective, randomized, crossover study, 22 stable CAD patients under prasugrel 10 mg once daily maintenance dose (MD) for at least 3 months were randomized to either ticagrelor 90 mg twice daily or prasugrel 10 mg once daily for 15 days with a direct treatment-crossover for another 15 days. Endothelial function was assessed by peripheral arterial tonometry (EndoPAT 2000 system, Itamar Medical, Caesarea, Israel) at Day 0 (randomization), Day 15, and Day 30. Reactive Hyperemia Index (RHI) was calculated by using an automated software, and endothelial dysfunction (ED) was defined as RHI <1.67. RHI at the end of the two treatment periods did not differ between ticagrelor and prasugrel MD treatments. Least squares estimates (95% confidence interval) were 1.78 (1.58-1.99) versus 1.88 (1.67-2.08), with a fixed estimate of −0.099 (95% CI: −0.45 to 0.25) for the difference between them (p = 0.5). ED rate did not differ significantly between ticagrelor and prasugrel (45.5% vs 45.5%, p = 0.6). ConclusionsIn CAD patients, we have failed to find evidence of alteration of endothelial function following ticagrelor compared to prasugrel MD treatment, as assessed by peripheral arterial tonometry. Clinicaltrials.gov unique identifierNCT01957540.

Evaluation of the Pharmacokinetics and Pharmacodynamics of Prasugrel in Japanese Elderly Subjects.

Background and ObjectiveAn increased incidence in bleeding events has been reported in Western elderly patients receiving prasugrel. Therefore, doses in Japanese elderly subjects need to be carefully determined. We assessed the pharmacokinetic and pharmacodynamic effects of prasugrel at the clinical dose used in Japan in healthy Japanese elderly subjects compared with non-elderly subjects.MethodsIn an open-label parallel-group study conducted in Japan, two groups (elderly, aged >75 years; non-elderly, aged 45–65 years) received a 20-mg loading dose and a 3.75-mg maintenance dose of prasugrel for 7 days. Plasma concentration of its active metabolite, R-138727, and pharmacokinetic parameters were determined on days 1 and 7 after dosing. Pharmacodynamic response to 20 µM of adenosine diphosphate-induced platelet aggregation was measured by light transmission aggregometry.ResultsA total of 47 subjects were enrolled (23 elderly, 24 non-elderly). There was no statistically significant difference in pharmacokinetic parameters between groups: area under the plasma concentration–time curve up to the last quantifiable time and maximum plasma concentration were about 174–175 ng·h/mL and 134–153 ng/mL, respectively, after the loading dose; and about 25–26 ng·h/mL and 25 ng/mL, respectively, after the maintenance dose. Inhibition of platelet aggregation was higher in the elderly subjects than in the non-elderly subjects, with a statistically significant difference from 24 h after the loading dose. No serious adverse events (bleeding or non-bleeding) occurred.ConclusionsPrasugrel (20-mg loading dose; 3.75-mg maintenance dose) produced a slight increase in antiplatelet efficacy in elderly compared with non-elderly subjects, despite no statistically significant difference in the pharmacokinetics.Electronic supplementary materialThe online version of this article (doi:10.1007/s40261-017-0525-0) contains supplementary material, which is available to authorized users.

Platelet Aggregation Inhibitory Effects and Pharmacokinetics of Prasugrel Used in Combination With Aspirin in Healthy Japanese Subjects.

We evaluated the pharmacokinetics and pharmacodynamics of prasugrel used in combination with aspirin in healthy Japanese subjects. All subjects received aspirin 100 mg/day. Subsequently, in the single‐administration study, 23 subjects also received prasugrel 20 or 30 mg, and in the multiple‐administration study, 20 subjects received a loading dose of prasugrel 20 or 30 mg on day 1, followed by a maintenance dose of prasugrel 5 or 7.5 mg/day, respectively, on days 2–5. In both studies, the plasma concentration of the active metabolite of prasugrel, R‐138727, reached a maximum 0.5 hours after administration and rapidly decreased within 4 hours. In the single‐administration study, the inhibitory effect on adenosine diphosphate–induced platelet aggregation was significantly higher in the prasugrel 20‐ and 30‐mg groups than in the placebo group at all times (1–144 hours) after administration. In the multiple‐administration study, a similar antiplatelet effect was found after both the loading dose and the maintenance dose and was maintained for 3–6 days after the last administration. There were study drug‐related adverse events; however, all were mild, and none was clinically significant.

GW27-e0576 Relevance of the CYP2C19 Polymorphism for Loading and Maintenance dose of Prasugrel and Clopidogrel Treatment Effect in Coronary Artery Disease Patients Undergoing Percutaneous Coronary Intervention: The PRAISE-GENE Study

GW27-e0576 Relevance of the CYP2C19 Polymorphism for Loading and Maintenance dose of Prasugrel and Clopidogrel Treatment Effect in Coronary Artery Disease Patients Undergoing Percutaneous Coronary Intervention: The PRAISE-GENE Study

Bleeding events and maintenance dose of prasugrel: BLESS pilot study

ObjectiveTo evaluate changes in residual platelet reactivity (RPR) over time, and bleeding and ischaemic events rate using 5 vs 10 mg maintenance dose (MD) regimens of prasugrel 1 month after...

Platelet effect of prasugrel and ticagrelor in patients with ST-segment elevation myocardial infarction

Recent studies have suggested that ticagrelor 90mg twice daily provides stronger platelet inhibition than prasugrel 10mg once daily in acute coronary syndrome patients undergoing percutaneous coronary intervention. To compare the effects of ticagrelor 90 mg twice daily and prasugrel 10mg once daily on platelet reactivity in patients with ST-segment elevation myocardial infarction (STEMI), using: the VerifyNow(®) P2Y12 (VN-P2Y12) assay, expressed in P2Y12 reaction units (PRU); measurement of the vasodilator-stimulated phosphoprotein platelet reactivity index (VASP-PRI; %); and light transmission aggregometry (LTA), expressed as residual platelet aggregation (RPA; %). Platelet reactivity was evaluated prospectively using the three assays 30 days after primary PCI in 118 patients with STEMI on a maintenance dose of prasugrel 10mg once daily (n=60) or ticagrelor 90mg twice daily (n=58). On-treatment platelet reactivity, assessed by the VN-P2Y12 assay, was lower for ticagrelor compared with prasugrel (20.91 ± 4.59 PRU vs. 43.50±6.98 PRU; P=0.008) but was not significantly different when using the more specific VASP-PRI assay (13.05 ± 1.61% vs. 17.44 ± 1.97%; P=0.09) or RPA assessed by LTA (10.49 ± 1.44% vs. 7.20 ± 1.27%; P=0.09). The difference in platelet reactivity between ticagrelor and prasugrel varies according to the platelet function test in patients with STEMI. The differences observed may be related more to the tests than to the drugs used.

Residual platelet reactivity and outcomes with 5 mg prasugrel therapy in elderly patients undergoing percutaneous coronary intervention

BackgroundIn acute coronary syndrome (ACS) patients older than 75years old, prasugrel 10mg maintenance therapy has shown less clinical efficacy and higher risk of bleeding. In patients older than 75years, a prasugrel dose of 5mg should be used if treatment is deemed necessary. ObjectiveThe aim of this study was to compare platelet reactivity and outcomes in elderly patients receiving prasugrel 5mg therapy with non-elderly patients receiving prasugrel 10mg therapy. Methods and resultsConsecutive ACS patients undergoing percutaneous coronary intervention (PCI) treated with prasugrel were included. Of 718 patients, 228 (32%) had ≥75years and received prasugrel 5mg/day. Residual platelet reactivity (RPR) was 47±18% and 36±16% in the elderly and non-elderly group, respectively (p=0.001). High RPR (≥70%) was found in 9% and 2% (p=0.0001) in elderly and non-elderly patients, respectively. In the 6-month follow-up, there was no difference in mortality, stent thrombosis, and reinfarction rates between the 2 groups but a higher rate of TIMI minor bleeding (7.9% vs 2.4%; p=0.001) in elderly as compared with younger patients. Age≥75years was independently associated with bleeding events (HR 2.162 [1.105–4.229]; p=0.024). ConclusionsElderly patients receiving prasugrel 5mg are more likely to experience high RPR than younger patients treated by prasugrel 10mg. Despite the use of a reduced prasugrel maintenance dose and a higher level of RPR, elderly patients show increased risk of bleeding during prasugrel therapy as compared to younger patients.

Predictors of antiplatelet response to prasugrel during maintenance treatment

Insufficient P2Y12 receptor inhibition is associated with a higher risk of thrombotic events after percutaneous coronary intervention (PCI). The third generation thienopyridine prasugrel achieves stronger platelet inhibition as compared to its predecessor clopidogrel. Little is known about predictors of prasugrel drug responsiveness. The aim of this study was to explore predictors of prasugrel responsiveness in patients with a recent PCI on prasugrel maintenance dose (MD) treatment. In a registry of PCI-treated patients (n = 163, recruited between August 2009 and March 2012) on prasugrel MD treatment, the ADP-induced platelet aggregation (PA) was assessed on a Multiplate analyzer. The mean (interquartile range (IQR)) ADP-induced PA on prasugrel MD treatment was 206 (138–331) AU × min. Obese (defined by a body mass index (BMI) ≥ 30) patients (n = 42) (303 [192–467] vs. 187 [117–305] AU × min, p = 0.0001), patients (n = 70) with a history of clopidogrel low responsiveness (278 [161–409] vs. 192 [126–282] AU × min, p = 0.002) and patients (n = 18) on a low (5 mg) prasugrel MD (483 [252–798] vs. 198 [133–313] AU × min; p = 0.0001) showed higher PA values on prasugrel MD as compared to the remaining patients. In a multivariable linear regression model, the latter three variables were independently associated with higher PA values on prasugrel MD treatment. In summary response variability is observed in patients on prasugrel MD treatment. Obesity, a history of clopidogrel low responsiveness and a reduced prasugrel MD of 5 mg are independent predictors of an attenuated response to prasugrel treatment. Further studies are needed to explore clinical implications of this observation.

Pharmacodynamic effects of standard dose prasugrel versus high dose clopidogrel in non-diabetic obese patients with coronary artery disease

Increased body weight is independently associated with impaired clopidogrel pharmacodynamic (PD) response. Prasugrel has more potent PD effects compared with clopidogrel, although its PD effects in obese patients are unknown. The aim of this prospective, randomised, study was to compare the PD effects of standard-dose prasugrel [60 mg loading dose (LD)/10 mg daily maintenance dose (MD)] with high-dose clopidogrel (900 mg LD/150 mg daily MD) in non-diabetic obese [body mass index (BMI) ≥30 kg/m²] patients, with coronary artery disease (CAD) on aspirin therapy. PD assessments (baseline, 2 hours post-LD and 6 ± 2 days after MD) were conducted using four platelet function assays, and the platelet reactivity index (PRI) assessed by VASP was used for sample size estimation. A total of 42 patients with a BMI of 36.42 ± 5.6 kg/m² completed the study. There were no differences in baseline PD measures between groups. At 2 hours post-LD, prasugrel was associated with lower PRI compared with clopidogrel (24.3 ± 5.5 vs 58.7 ± 5.7, p≤0.001), with consistent findings for all assays. At one-week, PRI values on prasugrel MD were lower than clopidogrel MD without reaching statistical significance (34.7 ± 5.8 vs 42.9 ± 5.8, p=0.32), with consistent findings for all assays. Accordingly, rates of high on-treatment platelet reactivity were markedly reduced after prasugrel LD, but not after MD. In conclusion, in non-diabetic obese patients with CAD, standard prasugrel dosing achieved more potent PD effects than high-dose clopidogrel in the acute phase of treatment, but this was not sustained during maintenance phase treatment. Whether an intensified prasugrel regimen is required in obese patients warrants investigation.

TCT-165 Ticagrelor vs Prasugrel maintenance dose in patients with acute coronary syndrome: a pharmacodynamic comparison

TCT-165 Ticagrelor vs Prasugrel maintenance dose in patients with acute coronary syndrome: a pharmacodynamic comparison

Obesity and a history of low response to clopidogrel treatment are predictors for a reduced antiplatelet action of prasugrel treatment

Background: Insufficient P2Y12 receptor inhibition is associated with a higher risk for thrombotic events after PCI. The 3rd generation thienopyridine prasugrel achieves stronger platelet inhibition as compared to its predecessor clopidogrel. Little is known about predictors of prasugrel drug responsiveness. The aim of this study was to explore predictors of prasugrel responsiveness in PCI treated patients on prasugrel maintenance dose (MD) treatment. Methods: In a registry of PCI-treated patients (n=165, recruited between August 2009 and March 2012) on prasugrel MD treatment, the ADP-induced platelet aggregation (PA, in AU x min) was assessed on a Multiplate analyzer. Results: Seventy one (43%) from the 165 patients in this registry received prasugrel treatment following a switch over from clopidogrel treatment due to measured clopidogrel low responsiveness and 94 (57%) patients were on prasugrel MD treatment due to a prior PCI in the setting of an ACS. The ADP-induced platelet aggregation (median [IQR]) on prasugrel MD treatment was 206 [140-328] AU x min. Obese (defined by a body mass index (BMI) ≥ 30) patients (n=42) (303 [192-467] vs. 187 [120-303] AU x min, p<0.001), patients (n=71) with a history of clopidogrel low responsiveness (272 [162-409] vs. 193 [128-280] AU x min; p=0.002) and patients (n=18) on a low (5 mg) prasugrel MD (483 [252-798] vs. 198 [134-313] AU x min; p<0.001) showed higher PA values on prasugrel MD as compared to the remaining patients. In a multivariable linear regression model (including age, smoking, gender, BMI, diabetes, history of clopidogrel low responsiveness and a low (5 mg) prasugrel MD as independent variables), BMI (p=0.02), low response to clopidogrel (p=0.04) and a low prasugrel MD (p<0.001) were independently associated with higher PA values on prasugrel MD treatment, whereas the remaining variables were not (p≥0.20). Conclusion: Response variability is observed on prasugrel MD treatment. Obesity and a history of clopidogrel low responsiveness are independent predictors of an attenuated response to prasugrel treatment. Further studies are needed to explore clinical implications of this observation.

GW24-e2375 Onset of antiplatelet effect of prasugrel and ticagrelor is delayed in patients with acute coronary syndromes

ObjectivesA more rapid onset of antiplatelet effect following loading with prasugrel and ticagrelor compared to clopidogrel was demonstrated for healthy subjects and patients with stable coronary artery disease. These results...

Factors Affecting Residual Platelet Aggregation in Prasugrel Treated Patients

Identification of factors affecting platelet reactivity (PR) and high PR (HPR) or high platelet inhibition (HPI) rates while on prasugrel maintenance dose (MD) might be helpful in avoiding ischemic or bleeding complications. We retrospectively analyzed all patients (n=233) treated in our institution between April 2010 and November 2012 who had platelet function assessment pre-prasugrel and following prasugrel 10 mg MD for at least 5 days, using the Verify Now P2Y12 platelet function assay. Multiple linear regression and logistic regression models were applied to identify independent factors affecting post-prasugrel PR level, HPR and HPI status. The amount of variance in PR under prasugrel MD that could be explained by the model was 25.9% (adjusted R²), p<0.001. Pre-prasugrel treatment PR, acute coronary syndrome (ACS), prasugrel loading and smoking uniquely accounted for 10.8%, 1.3%, 3.5% and 1.2% of the observed variance, respectively. HPR and HPI were observed in 7.7% and 13.7% of the cases, respectively. On multivariate analysis, pre-prasugrel PR in the upper quartile (>313 PRU) was the only independent factor associated with HPR under prasugrel MD. In contrast, pre-prasugrel PR in the lower quartile (<242 PRU) and prasugrel loading emerged as the only independent predictors of HPI. In patients under different clinical settings receiving prasugrel 10 mg MD a significant amount of the PR variability in response to prasugrel may be explained by pre- treatment PR level, ACS, prasugrel loading and smoking status. A high pre- treatment PR is associated with HPR, while a low pre-treatment PR and prasugrel loading predict HPI.