Guided P2Y 12 inhibitor therapy after percutaneous coronary intervention

• Published in: The Lancet (British edition) 2021-04, Vol.397 (10283), p.1423
• Main Authors: Sibbing, Dirk, Kastrati, Adnan
• Format: Article
• Language: English
• Subjects: Acute coronary syndromes; Adverse events; Alleles; Angioplasty; Antiplatelet therapy; Bleeding; Diabetes mellitus; Genotypes; Health services; Implants; Patients; Renal insufficiency; Risk; Side effects; Subgroups; Therapy; Thromboembolism; Thrombosis
• ISSN: 0140-6736; 1474-547X
• DOI: 10.1016/S0140-6736(21)00728-5

[...]determination of a single genotype is only a small extract from the entire genetic basis that determines drug response.11 Other factors including age, bodyweight, diabetes, and renal insufficiency can contribute to drug response and integration of these clinical variables with genetic data might enhance the accuracy by which drug response is determined. [...]CYP2C19 genotype data have taught us that heterozygous loss-of-function (CYP2C19*2) allele carriers show a broad distribution of drug response ranging from enhanced to low responders.12 Second, the timepoint for testing is set in a randomised trial, but the optimal timing for testing in a real-life setting could differ across clinical scenarios (eg, escalation vs de-escalation, acute coronary syndrome vs chronic coronary syndromes) and patient subgroups. While escalation of dual antiplatelet therapy usually requires early testing after the index procedure when the risk of stent thrombosis or reinfarction is highest, a de-escalation strategy may take place early but also in distance to PCI. [...]de-escalation of dual antiplatelet therapy may follow (1) a proactive approach (in line with clinical trial designs) with treatment de-escalation before the occurrence of a bleeding event in patients with a presumed high bleeding risk, or (2) a reactive approach with a change of treatment in reaction to the occurrence of adverse events (eg, side-effects on ticagrelor or prasugrel or bleeding). [...]any desired guided de-escalation of dual antiplatelet therapy entails the risk that test results with confirmation of either high on-treatment platelet reactivity or CYP2C19*2 allele carriage might consequently lead to an escalation back to potent P2Y12 inhibitors.