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

Abstract

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...

Efficacy and Safety of Low-Dose Prasugrel Versus Clopidogrel in Patients With Acute Coronary Syndrome or Patients Undergoing Percutaneous Coronary Intervention: A Systematic Review and Meta-Analysis

“…We judged the risk of bias as high in one RCT (16.7%) due to inadequate information about allocation concealment in the randomization process [30]. The risk of bias in three observational studies (50.0%) was considered moderate [12,13,35], and the other three studies (50.0%) were considered to have serious risk of bias due to the existence of possible confounds ( Figure S1) [32][33][34], MACE MACE was reported in six RCTs (n = 6020) [10,11,[28][29][30][31], and ve observational studies (n = 7081) [13,[32][33][34][35]. There was no difference in the risk of MACE between patients receiving low-dose prasugrel and patients receiving clopidogrel (RR 1.02, 95%CI 0.91 to 1.14; Fig.…”

Antithrombotic Strategy for Patients with Acute Coronary Syndrome: A Perspective from East Asia

“…This is in line with our previous report that patients undergoing PCI in Japan were of advanced age and had a lower BMI than those in the United States [ 29 ]. Despite these modifications in the HBR criteria, prasugrel has been predominantly used in Japan (approximately 70–80% of patients with ACS undergoing PCI) [ 30 , 31 ].…”

“…As in Western countries, clopidogrel, in addition to aspirin, has been traditionally used after stent implantation in East Asian patients with ACS [ 32 , 33 , 34 ]. More recently, prasugrel and ticagrelor have also been introduced as potent P2Y12 inhibitors [ 30 , 31 , 35 ]. Clinical studies regarding the selection of P2Y12 inhibitors among patients with ACS conducted in East Asian countries are summarized in Table 2 .…”

“…Two retrospective studies were recently performed to address this issue. In a Japanese contemporary multicenter PCI registry (JCD-KiCS registry), Shoji et al [ 30 ] demonstrated that administration of low-dose prasugrel was significantly associated with a higher risk of short-term bleeding events than was clopidogrel (odds ratio [OR]: 2.91; 95% CI: 1.63–5.18; p < 0.001) after propensity score matching (901 pairs) in Japanese patients with ACS who underwent PCI. However, there was no significant difference in the incidence of composite ischemic events between the two groups (OR: 1.42; 95% CI: 0.90–2.23).…”

“…However, some studies showed that the use of prasugrel, even at a lower dose, was associated with an increased risk of bleeding compared with clopidogrel [ 30 , 31 ], raising questions regarding whether prasugrel administration should be restricted to patients at low bleeding risk or whether prasugrel should not be used before diagnostic angiography. Further studies regarding the timing and safety of prasugrel administration are warranted to assess the optimal timing of pretreatment with P2Y12 inhibitors for East Asian patients who present with NSTE-ACS.…”