Can we offer tailor-made pharmacological treatment of patients with acute coronary syndrome?

Platelet inhibition is a cornerstone in the treatment of the acute coronary syndrome (ACS).1–4 Dr Lewis and co-workers assessed the impact of 31 candidate gene polymorphisms on ADP-stimulated platelet reactivity in clopidogrel-treated coronary artery disease (CAD) patients of the International Clopidogrel Pharmacogenomics Consortium (ICPC). The influence of these polymorphisms on cardiovascular events (CVEs) was tested in 2134 ICPC patients. The authors concluded that several polymorphisms impact clopidogrel response. However, whereas no individual variant was associated with CVEs, generation of a pharmacogenomic polygenic response score revealed that patients who carried a greater number of alleles associated with increased on-treatment platelet reactivity were more likely to experience CVEs. In a Chinese study, Dr Xie and co-workers used a new platelet function test to guide antiplatelet therapy in stable CAD patients after percutaneous coronary intervention (PCI). The study was a randomized controlled trial of 2237 patients with stable CAD. The patients were randomized to be administered personalized antiplatelet therapy (personalized group; n = 1123) or standard antiplatelet treatment (standard group; n = 1114). The authors report that personalized antiplatelet therapy according to the maximum aggregation rate can significantly improve the net clinical benefit at a 180-day follow-up after PCI. Dr Serruys et al. report data from the GLOBAL LEADERS trial.5,6 The aim of the study was to evaluate long-term safety and efficacy of ticagrelor monotherapy in patients undergoing PCIs in relation to chronic obstructive pulmonary disease (COPD) at baseline and the occurrence of dyspnoea reported as an adverse event (AE) that may lead to treatment non-adherence.7,8 The study was a non-pre-specified, post-hoc analysis of the randomized GLOBAL LEADERS trial (n = 15 991), comparing the experimental strategy of 23-month ticagrelor monotherapy following 1-month dual antiplatelet therapy (DAPT) after PCI with the reference strategy of 12-month DAPT followed by 12-month aspirin monotherapy. The authors conclude that COPD negatively impacted long-term prognosis after PCI. Despite a higher incidence of dyspnoea in the experimental arm, in particular among COPD patients, the safety of the experimental treatment strategy appeared not to be affected. In Japan, reduced-dose prasugrel (loading/maintenance dose, 20/3.75 mg) has been approved for use in ACS patients undergoing PCI, due to higher bleeding risk recognized amongst East Asian patients. Dr Inohara and co-workers have evaluated the comparative effectiveness and safety of reduced-dose prasugrel vs. standard-dose clopidogrel in patients with ACS undergoing PCI. The authors used the nationwide Japanese PCI registry, and identified ACS patients undergoing PCI who were treated with either reduced-dose prasugrel or standard-dose clopidogrel in addition to aspirin. The primary outcome was in-hospital mortality following PCI. The authors concluded that in Japanese ACS patients undergoing PCI, the risk of bleeding is higher when using reduced-dose prasugrel than when using standard-dose clopidogrel, while there is no significant difference in in-hospital mortality and incidence of stent thrombosis between antiplatelet regimens. We also publish in this issue two Current Opinion papers. DNA polymorphisms can modulate the individual CV risk, as well as the response to drug therapy; however, pharmacogenomics is still not a reality in the clinical market. Dr Benincasa and co-workers from Italy propose a clinical perspective where epigenetics integrated with imaging tools and network medicine could help to refine the assessment of CV risk, leading to personalized therapy of diabetic patients. In the second Current Opinion paper, Dr Battistoni and Dr Volpe from Italy discuss whether renin–angiotensin system blockers9,10 might play a role in the COVID-19 pandemic. We have also decided to publish several interesting Letters to the Editor/Commentaries on the subject of COVID.