Efficacy and Safety of Adjusted-Dose Prasugrel Compared With Clopidogrel in Japanese Patients With Acute Coronary Syndrome

Saïto, Shigeru; Isshiki, Takaaki; Kimura, Takeshi; Ogawa, Hisao; Yokoi, Hiroyoshi; Nanto, Shinsuke; Takayama, Morimasa; Kitagawa, Kazuo; Nishikawa, Masakatsu; Miyazaki, Shunichi; Nakamura, Masato

doi:10.1253/circj.cj-13-1482

Cited by 283 publications

(283 citation statements)

References 11 publications

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“…49 The incidence of TIMI major, minor, or clinically relevant bleeding was 9.6% in both groups. 49 The results of PRASFIT-ELECTIVE study 50 were presented in 2013, but have not been peer-reviewed or published.…”

Section: Consensus Statementsmentioning

confidence: 86%

“…A comparison of outcomes in all Asian (n = 1,106) versus non-Asian (n = 17,515) patients has been reported in abstract form, and found no significant differences between the two groups in the primary composite outcome (cardiovascular death, MI, and stroke), major bleeding, or net clinical benefit. 48 The relative efficacy and safety of the newer P2Y 12 inhibitors compared with clopidogrel has been specifically examined in East Asian patients in only three modestly sized trials, one of which (the PRASFIT-ACS study 49 ) has been published in a peer-reviewed journal. The results of two other trials cannot be considered to provide the same level of evidence.…”

Section: P2y 12 Inhibitors In East Asian Patientsmentioning

confidence: 99%

“…In the phase III, double-blind, randomized PRASFIT-ACS trial, 49 the clinical efficacy and safety of low-dose prasugrel (20 mg loading and 3.75 mg daily maintenance) was compared with clopidogrel (300 mg loading and 75 mg daily maintenance) in 1,363 Japanese patients with ACS who were undergoing PCI. The incidence of the primary composite end point (cardio vascular death, nonfatal MI, and ischaemic stroke) was numerically lower with prasugrel than with clopidogrel, but this difference was not significant (9.4% vs 11.8%; HR 0.77, 95% CI 0.56-1.07, P = 0.12).…”

Section: P2y 12 Inhibitors In East Asian Patientsmentioning

confidence: 99%

“…The incidence of the primary composite end point (cardio vascular death, nonfatal MI, and ischaemic stroke) was numerically lower with prasugrel than with clopidogrel, but this difference was not significant (9.4% vs 11.8%; HR 0.77, 95% CI 0.56-1.07, P = 0.12). 49 TIMI major bleeding not …”

Section: P2y 12 Inhibitors In East Asian Patientsmentioning

confidence: 99%

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World Heart Federation expert consensus statement on antiplatelet therapy in East Asian patients with ACS or undergoing PCI

et al. 2014

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| Guideline recommendations on the use of dual antiplatelet therapy (DAPT) in patients with acute coronary syndromes and in those undergoing percutaneous coronary intervention (PCI) have been formulated by both the ACC/AHA and the ESC. These recommendations are based primarily on large, phase III, randomized, controlled trials of the P2Y 12 inhibitors clopidogrel, prasugrel, and ticagrelor. However, few East Asian patients have been included in the trials to assess the use of these agents, particularly the newer agents prasugrel and ticagrelor. Additionally, an increasing body of data suggests that East Asian patients have differing risk profiles for both thrombophilia and bleeding compared with white patients, and that a different 'therapeutic window' of on-treatment platelet reactivity might be appropriate in East Asian patients. Furthermore, a phenomenon referred to as the 'East Asian paradox' has been described, in which East Asian patients have a similar or even a lower rate of ischaemic events after PCI compared with white patients, despite a higher level of platelet reactivity during DAPT. Recognizing these concerns, the World Heart Federation has undertaken this evidence-based review and produced this expert consensus statement to determine the antiplatelet treatment strategies that are most appropriate for East Asian patients.

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Section: Consensus Statementsmentioning

confidence: 86%

Section: P2y 12 Inhibitors In East Asian Patientsmentioning

confidence: 99%

Section: P2y 12 Inhibitors In East Asian Patientsmentioning

confidence: 99%

Section: P2y 12 Inhibitors In East Asian Patientsmentioning

confidence: 99%

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World Heart Federation expert consensus statement on antiplatelet therapy in East Asian patients with ACS or undergoing PCI

et al. 2014

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“…Prasugrel and clopidogrel are thienopyridine derivatives with adenosine diphosphate (ADP)–antagonistic activity and are widely used in clinics for the prevention of ischemic events in patients with ST‐segment‐elevated and non‐ST‐segment‐elevated myocardial infarction (STEMI and NSTEMI, respectively) who are undergoing percutaneous coronary intervention (PCI) 1, 2, 3. Rapid, potent, and consistent inhibition of platelet aggregation is important in patients with acute STEMI undergoing PCI 4, 5.…”

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confidence: 99%

The Pharmacokinetics and Pharmacodynamics of Prasugrel and Clopidogrel in Healthy Japanese Volunteers

Umemura

Iwaki

2016

Clinical Pharm in Drug Dev

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The dosing regimen of prasugrel adjusted for Japanese patients was compared with that of clopidogrel by analyzing the pharmacokinetics and pharmacodynamics in 40 healthy Japanese subjects in a randomized, single‐blind crossover study. In period 1, the subjects received either 300 mg clopidogrel or 20 mg prasugrel; after a >2‐week interval (period 2), the drug was switched. Blood samples of 36 of the 40 subjects were collected for analysis of pharmacokinetics, pharmacodynamics, and CYP2C19 genotypes. The plasma concentration of the active metabolite of prasugrel increased rapidly and reached its peak 30 minutes postadministration, whereas that of the active metabolite of clopidogrel reached its peak 1 hour postadministration. The mean AUC and Cmax of the active metabolite of clopidogrel, but not those of prasugrel, were CYP2C19 genotype dependent. Prasugrel rapidly inhibited platelet aggregation, reaching its maximum effect 1 hour postadministration. Clopidogrel, on the other hand, showed maximum inhibition 2 hours postadministration. Platelet aggregation inhibition by clopidogrel was significantly lower in the poor‐metabolizer subjects than in the extensive‐metabolizer subjects. Overall, prasugrel inhibited platelet aggregation more rapidly and more effectively in healthy Japanese subjects than was observed for clopidogrel.

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Ischemic and Bleeding Events Among Patients With Acute Coronary Syndrome Associated With Low-Dose Prasugrel vs Standard-Dose Clopidogrel Treatment

et al. 2020

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IMPORTANCE Prasugrel was approved at a lower dose in 2014 in Japan than in the West because East Asian patients are considered more susceptible to bleeding than Western patients. However, real-world outcomes with low-dose prasugrel treatment remain unclear. OBJECTIVE To investigate the association of low-dose prasugrel vs standard-dose clopidogrel administration with short-term outcomes among patients with acute coronary syndrome undergoing percutaneous coronary intervention (PCI). DESIGN, SETTING, AND PARTICIPANTS This study used data from the Japan Cardiovascular Database-Keio Interhospital Cardiovascular Studies registry, a large, ongoing, multicenter, retrospective cohort of consecutive patients who underwent PCI. The present cohort study evaluated 2770 patients with acute coronary syndrome who underwent PCI and received either low-dose prasugrel (loading dose, 20 mg; maintenance dose, 3.75 mg) or clopidogrel (loading dose, 300 mg; maintenance dose, 75 mg) in combination with aspirin between 2014 and 2018. Propensity score-matching analysis was conducted to balance the baseline characteristics of patients receiving low-dose prasugrel and those receiving clopidogrel. Data analysis was conducted in June 2019. EXPOSURES Prescription of either low-dose prasugrel or standard-dose clopidogrel prior to PCI. MAIN OUTCOMES AND MEASURES Primary ischemic events (in-hospital death, recurrent myocardial infarction, and ischemic stroke) and primary bleeding events, defined as bleeding complications within 72 hours after PCI consistent with the National Cardiovascular Data Registry CathPCI Registry definition. RESULTS Of 2559 patients included in the study, the mean (SD) age was 67.8 (12.7) years, and 78.2% were male. In total, 1297 patients (50.7%) received low-dose prasugrel, and 1262 patients (49.3%) received clopidogrel. After propensity score matching, primary ischemic events among patients receiving low-dose prasugrel and those receiving clopidogrel were comparable (odds ratio [OR], 1.42; 95% CI, 0.90-2.23), but primary bleeding events were significantly higher among patients receiving prasugrel (OR, 2.91; 95% CI, 1.63-5.18). This increase in bleeding events was associated with the presence of a profile of high-bleeding risk (Ն75 years of age, body weight <60 kg, or history of stroke or transient ischemic attack) (OR, 4.08; 95% CI, 1.86-8.97), being female (OR, 3.84; 95% CI, 1.05-14.0), or the presence of ST-segment elevation myocardial infarction (OR, 2.07; 95% CI, 1.05-4.09) or chronic kidney disease (OR, 4.78; 95% CI, 1.95-11.7). CONCLUSIONS AND RELEVANCE Since its approval, low-dose prasugrel has been used by nearly 80% of patients who undergo PCI. Despite the modified dose, bleeding events were higher among patients receiving low-dose prasugrel than among patients receiving clopidogrel, with no difference (continued) Key Points Question Are there differences in ischemic and bleeding outcomes among East Asian patients with acute coronary syndrome who undergo percutaneous coronary intervention associated with admin...

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Efficacy and Safety of Adjusted-Dose Prasugrel Compared With Clopidogrel in Japanese Patients With Acute Coronary Syndrome

Cited by 283 publications

References 11 publications

World Heart Federation expert consensus statement on antiplatelet therapy in East Asian patients with ACS or undergoing PCI

World Heart Federation expert consensus statement on antiplatelet therapy in East Asian patients with ACS or undergoing PCI

The Pharmacokinetics and Pharmacodynamics of Prasugrel and Clopidogrel in Healthy Japanese Volunteers

Ischemic and Bleeding Events Among Patients With Acute Coronary Syndrome Associated With Low-Dose Prasugrel vs Standard-Dose Clopidogrel Treatment

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