Capodanno, Davide

Background A contemporary, comprehensive risk score for the prediction of in‐hospital fatal and nonfatal adverse events after percutaneous coronary intervention has been recently developed, albeit its external validation in patients with acute coronary syndrome is lacking. The objective of this study is to validate the Mayo Clinic integer risk score in a large cohort of patients with acute coronary syndrome undergoing percutaneous coronary intervention from the MATRIX (Minimizing Adverse Haemorrhagic Events by Transradial Access Site and Systemic Implementation of Angiox) trial. Methods The risk score is composed of a common set of 23 clinical and procedural variables (model A) and 18 preprocedural variables (model B). The primary objective was to appraise the receiver‐operator characteristics of both models for in‐hospital mortality, bleeding, contrast‐associated acute kidney injury, and stroke. The impact of risk score categories on 1‐year outcomes was also investigated. Results Among the 6724 patients undergoing percutaneous coronary intervention in the MATRIX trial, the receiver‐operator characteristics—area under the curves for in‐hospital mortality, bleeding, contrast‐associated acute kidney injury, and stroke were 0.88 (95% CI, 0.85–0.91), 0.66 (95% CI, 0.63–0.69), 0.70 (95% CI, 0.67–0.72), and 0.65 (95% CI, 0.52–0.78) for model A and 0.88 (95% CI, 0.84–0.92), 0.63 (95% CI, 0.60–0.66), 0.66 (95% CI, 0.63–0.69), and 0.65 (95% CI, 0.52–0.78) for model B, respectively. Mortality (model A), bleeding, and stroke risks were well calibrated, whereas mortality (model B) and contrast‐associated acute kidney injury risk were underestimated. There was a gradual risk increase for 1‐year mortality and bleeding as a function of the risk score tertile using both models. Conclusions The risk score identifies patients with acute coronary syndrome at incremental risk of in‐hospital mortality, bleeding, contrast‐associated acute kidney injury, and stroke, representing a valuable tool for mitigation of modifiable risk factors. Registration URL: https://www.clinicaltrials.gov ; Unique Identifier: NCT01433627.

Antiplatelet therapy is the mainstay of pharmacologic treatment to prevent thrombotic or ischemic events in patients with coronary artery disease treated with percutaneous coronary intervention and those treated medically for an acute coronary syndrome. The use of antiplatelet therapy comes at the expense of an increased risk of bleeding complications. Defining the optimal intensity of platelet inhibition according to the clinical presentation of atherosclerotic cardiovascular disease and individual patient factors is a clinical challenge. Modulation of antiplatelet therapy is a medical action that is frequently performed to balance the risk of thrombotic or ischemic events and the risk of bleeding. This aim may be achieved by reducing (ie, de-escalation) or increasing (ie, escalation) the intensity of platelet inhibition by changing the type, dose, or number of antiplatelet drugs. Because de-escalation or escalation can be achieved in different ways, with a number of emerging approaches, confusion arises with terminologies that are often used interchangeably. To address this issue, this Academic Research Consortium collaboration provides an overview and definitions of different strategies of antiplatelet therapy modulation for patients with coronary artery disease, including but not limited to those undergoing percutaneous coronary intervention, and consensus statements on standardized definitions.

Background In TAILOR‐PCI, genotype‐guided selection of P2Y 12 inhibitors after percutaneous coronary intervention did not significantly reduce the risk of ischemic events at 12 months. The Age, Body Mass Index, Chronic Kidney Disease, Diabetes, and Genotyping (ABCD‐GENE) score identifies patients with high platelet reactivity on clopidogrel at increased risk of ischemic events. The aim of this study was to investigate the value of the ABCD‐GENE score for tailoring P2Y 12 inhibitor selection after percutaneous coronary intervention. Methods and Results In a post hoc analysis of the TAILOR‐PCI, outcomes were analyzed by ABCD‐GENE score and allocation to genotype‐guided or conventional P2Y 12 inhibitor selection. Primary (death, myocardial infarction, or stroke) and secondary (cardiovascular death, myocardial infarction, stroke, stent thrombosis, or severe recurrent ischemia) outcomes were assessed. Among 3883 patients discharged on clopidogrel in the genotype‐guided and conventional therapy groups, 15.8% and 84.2% had high (≥10 points) or low (<10) ABCD‐GENE scores, respectively. At 12 months, both the primary (5.2% versus 2.6%, P <0.001) and secondary outcomes (7.7% versus 4.6%, P =0.001) were significantly increased in patients with high ABCD‐GENE score. Among 4714 patients allocated to genotype‐guided or conventional therapy, the former did not significantly reduce the 12‐month risk of the primary and secondary outcomes in both the high and low ABCD‐GENE score groups (p interaction =0.48 and 0.27, respectively). Conclusions Among patients with percutaneous coronary intervention on clopidogrel, the ABCD‐GENE score was helpful in identifying those at higher risk. The ABCD‐GENE score may potentially enhance the precision of tailored selection of P2Y 12 inhibitors, which needs to be confirmed in prospective investigations. Clinical Trial Registration URL: http://www.clinicaltrials.gov . Unique Identifier: NCT01742117.

Abstract Aims Guidelines recommend the use of potent P2Y12 inhibitors over clopidogrel for the reduction of ischaemic events in patients with acute coronary syndrome (ACS). However, this comes at the expense of increased bleeding. A guided selection of P2Y12 inhibiting therapy has the potential to overcome this limitation. We aimed at evaluating the comparative safety and efficacy of guided vs. routine selection of potent P2Y12 inhibiting therapy in patients with ACS. Methods and results We performed a network meta-analysis of randomized controlled trials (RCTs) comparing different oral P2Y12 inhibitors currently recommended for the treatment of patients with ACS (clopidogrel, prasugrel, and ticagrelor). RCTs including a guided approach (i.e. platelet function or genetic testing) vs. standard selection of P2Y12 inhibitors among patients with ACS were also included. Incidence rate ratios (IRR) and associated 95% confidence intervals (CIs) were estimated. P-scores were used to estimate hierarchies of efficacy and safety. The primary efficacy endpoint was major adverse cardiovascular events (MACE) and the primary safety endpoint was all bleeding. A total of 61 898 patients from 15 RCTs were included. Clopidogrel was used as reference treatment. A guided approach was the only strategy associated with reduced MACE (IRR: 0.80, 95% CI: 0.65–0.98) without any significant trade-off in all bleeding (IRR: 1.22, 95% CI: 0.96–1.55). A guided approach and prasugrel were associated with reduced myocardial infarction. A guided approach, prasugrel, and ticagrelor were associated with reduced stent thrombosis. Ticagrelor was also associated with reduced total and cardiovascular mortality. Prasugrel was associated with increased major bleeding. Prasugrel and ticagrelor were associated with increased minor bleeding. The incidence of stroke did not differ between treatments. Conclusion In patients with an ACS, compared with routine selection of potent P2Y12 inhibiting therapy (prasugrel or ticagrelor), a guided selection of P2Y12 inhibiting therapy is associated with the most favourable balance between safety and efficacy. These findings support a broader adoption of guided approach for the selection of P2Y12 inhibiting therapy in patients with ACS. Study registration number This study is registered in PROSPERO (CRD42021258603). Key Question A guided selection of P2Y12 inhibiting therapy using platelet function or genetic testing improves outcomes among patients undergoing percutaneous coronary intervention. Nevertheless, the comparative safety and efficacy of a guided versus routine selection of potent P2Y12-inhibiting therapy in acute coronary syndrome has not been explored. Key Finding In a comprehensive network meta-analysis including the totality of available evidence and using clopidogrel as treatment reference, a guided approach was the only strategy associated with reduced major adverse cardiovascular events without any significant trade-off in bleeding. Prasugrel and ticagrelor increased bleeding and only ticagrelor reduced mortality. Take Home Message A guided selection of P2Y12-inhibiting therapy represents the strategy associated with the most favourable balance between safety and efficacy. These findings support a broader adoption of guided P2Y12 inhibiting therapy in patients with acute coronary syndrome.

Abstract A substantial number of chronic coronary syndrome (CCS) patients undergoing percutaneous coronary intervention (PCI) experience periprocedural myocardial injury or infarction. Accurate diagnosis of these PCI-related complications is required to guide further management given that their occurrence may be associated with increased risk of major adverse cardiac events (MACE). Due to lack of scientific data, the cut-off thresholds of post-PCI cardiac troponin (cTn) elevation used for defining periprocedural myocardial injury and infarction, have been selected based on expert consensus opinions, and their prognostic relevance remains unclear. In this Consensus Document from the ESC Working Group on Cellular Biology of the Heart and European Association of Percutaneous Cardiovascular Interventions (EAPCI), we recommend, whenever possible, the measurement of baseline (pre-PCI) cTn and post-PCI cTn values in all CCS patients undergoing PCI. We confirm the prognostic relevance of the post-PCI cTn elevation &gt;5× 99th percentile URL threshold used to define type 4a myocardial infarction (MI). In the absence of periprocedural angiographic flow-limiting complications or electrocardiogram (ECG) and imaging evidence of new myocardial ischaemia, we propose the same post-PCI cTn cut-off threshold (&gt;5× 99th percentile URL) be used to define prognostically relevant ‘major’ periprocedural myocardial injury. As both type 4a MI and major periprocedural myocardial injury are strong independent predictors of all-cause mortality at 1 year post-PCI, they may be used as quality metrics and surrogate endpoints for clinical trials. Further research is needed to evaluate treatment strategies for reducing the risk of major periprocedural myocardial injury, type 4a MI, and MACE in CCS patients undergoing PCI.

Abstract This Consensus Document is the first of two reports summarizing the views of an expert panel organized by the European Association of Percutaneous Cardiovascular Interventions (EAPCI) on the clinical use of intracoronary imaging including intravascular ultrasound (IVUS) and optical coherence tomography (OCT). The first document appraises the role of intracoronary imaging to guide percutaneous coronary interventions (PCIs) in clinical practice. Current evidence regarding the impact of intracoronary imaging guidance on cardiovascular outcomes is summarized, and patients or lesions most likely to derive clinical benefit from an imaging-guided intervention are identified. The relevance of the use of IVUS or OCT prior to PCI for optimizing stent sizing (stent length and diameter) and planning the procedural strategy is discussed. Regarding post-implantation imaging, the consensus group recommends key parameters that characterize an optimal PCI result and provides cut-offs to guide corrective measures and optimize the stenting result. Moreover, routine performance of intracoronary imaging in patients with stent failure (restenosis or stent thrombosis) is recommended. Finally, strengths and limitations of IVUS and OCT for guiding PCI and assessing stent failures and areas that warrant further research are critically discussed.