Pharmacodynamic study of prasugrel or clopidogrel in non-ST-elevation acute coronary syndrome with CYP2C19 genetic variants undergoing percutaneous coronary intervention (PRAISE-GENE trial)

Jin, Cai; Kim, Moo Hyun; Guo, Long; Jin, Enze; Shin, Eun Seok; Ann, Soe Hee; Cho, Young‐Rak; Park, Jong Sung; Kim, Soo Jin; Lee, Michael S.

doi:10.1016/j.ijcard.2020.01.058

Cited by 6 publications

(4 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It is evident that although high-dose clopidogrel reduces platelet reactivity more than standard-dose clopidogrel, [116][117][118][119][120][121][122][123][124]138 prasugrel and ticagrelor are more potent platelet inhibitors than highdose clopidogrel. 18,[23][24][25]27,[128][129][130][131][132][133][134][135][136][137] However, there may be a tradeoff between efficacy and bleeding with these more potent agents. 139 The only study directly comparing prasugrel with ticagrelor in CYP2C19 LOF carriers showed no difference in the degree of platelet inhibition achieved between these 2 drugs.…”

Section: Summary Of Observational Studies Rcts and Meta-analysesmentioning

confidence: 99%

“…Data to date evaluating platelet function testing during oral P2Y12 inhibition strategies based on CYP2C19 genetic testing include 20 RCTs, 7 observational studies, and 1 meta-analysis, presented in Supplemental Table 4. 18,23–25,27,115–137 These studies have compared the pharmacodynamics profiles of standard-dose clopidogrel (75 mg daily) with that of high-dose clopidogrel (600/900 mg loading dose or 150 mg/d maintenance), cilostazol, prasugrel, or ticagrelor in CYP2C19 LOF carriers. Only 1 RCT has directly compared the effect of prasugrel and ticagrelor on platelet aggregation.…”

Section: Individualizing Oral P2y12 Inhibition With Cyp2c19 Genetic T...mentioning

confidence: 99%

See 1 more Smart Citation

CYP2C19 Genetic Testing for Oral P2Y12 Inhibitor Therapy: A Scientific Statement From the American Heart Association

Pereira,

Cresci,

Angiolillo

et al. 2024

Circulation

View full text Add to dashboard Cite

There is significant variability in the efficacy and safety of oral P2Y12 inhibitors, which are used to prevent ischemic outcomes in common diseases such as coronary and peripheral arterial disease and stroke. Clopidogrel, a prodrug, is the most used oral P2Y12 inhibitor and is activated primarily after being metabolized by a highly polymorphic hepatic cytochrome CYP2C219 enzyme. Loss-of-function genetic variants in CYP2C219 are common, can result in decreased active metabolite levels and increased on-treatment platelet aggregation, and are associated with increased ischemic events on clopidogrel therapy. Such patients can be identified by CYP2C19 genetic testing and can be treated with alternative therapy. Conversely, universal use of potent oral P2Y12 inhibitors such as ticagrelor or prasugrel, which are not dependent on CYP2C19 for activation, has been recommended but can result in increased bleeding. Recent clinical trials and meta-analyses have demonstrated that a precision medicine approach in which loss-of-function carriers are prescribed ticagrelor or prasugrel and noncarriers are prescribed clopidogrel results in reducing ischemic events without increasing bleeding risk. The evidence to date supports CYP2C19 genetic testing before oral P2Y12 inhibitors are prescribed in patients with acute coronary syndromes or percutaneous coronary intervention. Clinical implementation of such genetic testing will depend on among multiple factors: rapid availability of results or adoption of the concept of performing preemptive genetic testing, provision of easy-to-understand results with therapeutic recommendations, and seamless integration in the electronic health record.

show abstract

Section: Summary Of Observational Studies Rcts and Meta-analysesmentioning

confidence: 99%

Section: Individualizing Oral P2y12 Inhibition With Cyp2c19 Genetic T...mentioning

confidence: 99%

CYP2C19 Genetic Testing for Oral P2Y12 Inhibitor Therapy: A Scientific Statement From the American Heart Association

Pereira,

Cresci,

Angiolillo

et al. 2024

Circulation

View full text Add to dashboard Cite

show abstract

“…15,28,31 Therefore, these drugs are currently the preferred choice for patients presenting with acute coronary syndrome. Genetic variants of CYP2C19 might affect the platelet-inhibiting effects of prasugrel, 35 and relevant interactions between ticagrelor and CYP3AA inhibitors have been described, resulting in suppressed metabolism and consecutively prolonged half-life of ticagrelor. 36 According to some expert opinions, discontinuation of clopidogrel for 5-to-7 days before surgery does not seem to confer increased risk of ischemic coronary events.…”

Section: Aspirinmentioning

confidence: 99%

Point-of-Care Platelet Function Monitoring: Implications for Patients With Platelet Inhibitors in Cardiac Surgery

Bolliger

Lancé

Siegemund

2021

Journal of Cardiothoracic and Vascular Anesthesia

View full text Add to dashboard Cite

Although most physicians are comfortable managing the limited anticoagulant effect of aspirin, the recent administration of potent P2Y 12 receptor inhibitors in patients undergoing cardiac surgery remains a dilemma. Guidelines recommend discontinuation of potent P2Y 12 inhibitors 5-to-7 days before surgery to reduce the risk of postoperative hemorrhage. Such a strategy might not be feasible before urgent surgery, due to ongoing myocardial ischemia or in patients at high risk for thromboembolic events. Recently, different point-of-care devices to assess functional platelet quality have become available for clinical use. The aim of this narrative review was to evaluate the implications and potential benefits of platelet function monitoring in guiding perioperative management and therapeutic options in patients treated with antiplatelets, including aspirin or P2Y 12 receptor inhibitors, undergoing cardiac surgery. No objective superiority of one point-of-care device over another was found in a large meta-analysis. Their accuracy and reliability are generally limited in the perioperative period. In particular, preoperative platelet function testing has been used to assess platelet contribution to bleeding after cardiac surgery. However, predictive values for postoperative hemorrhage and transfusion requirements are low, and there is a significant variability between and within these tests. Further, platelet function monitoring has been used to optimize the preoperative waiting period after cessation of dual antiplatelet therapy before urgent cardiac surgery. Furthermore, studies assessing their value in therapeutic decisions in bleeding patients after cardiac surgery are scarce. A general and liberal use of perioperative platelet function testing is not yet recommended.

show abstract

“…Compared with clopidogrel, a lower dose of prasugrel (20/3.75 mg) in the PRASFIT-ACS trial [ 6 ] provided a favorable risk/benefit profile without increased bleeding, whereas standard-dose ticagrelor in the PHILO and TICAKOREA trials was associated with increased risk of adverse outcomes, including major bleeding, cardiac death, MI, or stroke [ 7 , 8 ]. For low-dose loading and maintenance doses of prasugrel for high platelet reactivity (HPR) and CYP2C19 polymorphic patients, we previously reported that half-dose prasugrel achieved a lower rate of HPR and a higher therapeutic window range (30 days) in Korean PCI patients [ 9 , 10 ]. The optimal dose for potent P2Y12 inhibitors in East Asians with ACS appears to be different with non-East Asians in daily practice.…”

Section: Introductionmentioning

confidence: 99%

Pharmacodynamics and Outcomes of a De-Escalation Strategy with Half-Dose Prasugrel or Ticagrelor in East Asians Patients with Acute Coronary Syndrome: Results from HOPE-TAILOR Trial

Jin

Kim

Song

et al. 2021

JCM

Self Cite

View full text Add to dashboard Cite

East Asians treated with potent P2Y12 inhibitors (prasugrel or ticagrelor) generally experience more intense platelet inhibitory responses resulting in an increased risk of major bleeding. Whether a half-dose de-escalation strategy improves the net clinical benefit in Korean patients with acute coronary syndrome (ACS) remains uncertain. A total of 120 patients were pragmatically randomized to either prasugrel (n = 39, 60 mg loading dose (LD)/10 mg maintenance dose (MD)), ticagrelor (n = 40, 180 mg LD/90 mg MD), or clopidogrel (n = 41, 600 mg LD/75 mg MD) followed by a half-dose reduction at 1 month, or conventional dose 75 mg clopidogrel. The primary endpoint was the incidence of optimal platelet reactivity (OPR), defined as a P2Y12 reaction unit (PRU) value between 85 and 208 (by VerifyNow) at 3 months. Ticagrelor treatment achieved a significantly lower PRU compared with prasugrel and clopidogrel (31.0 ± 34.5 vs. 93.2 ± 57.1 vs. 153.1 ± 69.4), resulting in the lowest rate of OPR (12.5% vs. 48.7% vs. 63.4%). At 9 months, the minor bleeding was significantly higher with potent P2Y12 inhibitors than with clopidogrel (31.6% vs. 12.2%; HR, 2.93; 95% CI, 1.12–7.75). Only a few patients experienced ischemic complications. In Korean ACS patients, a de-escalation strategy with half-dose ticagrelor and prasugrel from standard dose increased the OPR rate significantly. Half-dose ticagrelor had a lower OPR rate and greater platelet inhibition compared with half-dose prasugrel as well as conventional-dose clopidogrel. Optimal dose reduction strategies for potent P2Y12 inhibitors require further investigation to balance safety and efficacy.

show abstract

Pharmacodynamic study of prasugrel or clopidogrel in non-ST-elevation acute coronary syndrome with CYP2C19 genetic variants undergoing percutaneous coronary intervention (PRAISE-GENE trial)

Cited by 6 publications

References 40 publications

CYP2C19 Genetic Testing for Oral P2Y12 Inhibitor Therapy: A Scientific Statement From the American Heart Association

CYP2C19 Genetic Testing for Oral P2Y12 Inhibitor Therapy: A Scientific Statement From the American Heart Association

Point-of-Care Platelet Function Monitoring: Implications for Patients With Platelet Inhibitors in Cardiac Surgery

Pharmacodynamics and Outcomes of a De-Escalation Strategy with Half-Dose Prasugrel or Ticagrelor in East Asians Patients with Acute Coronary Syndrome: Results from HOPE-TAILOR Trial

Contact Info

Product

Resources

About