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Background: In the ARCTIC trial (Assessment by a Double Randomization of a Conventional Antiplatelet Strategy Versus a Monitoring-Guided Strategy for Drug-Eluting Stent Implantation and of Treatment Interruption Versus Continuation One Year After Stenting), treatment adjustment following platelet function testing failed to improve clinical outcomes. However, high-on-treatment platelet reactivity (HPR) is considered as a predictor of poor ischemic outcome. This prespecified substudy evaluated clinical outcomes according to the residual platelet reactivity status after antiplatelet therapy adjustment. Methods: We analyzed the 1213 patients assigned to the monitoring arm of the ARCTIC trial in whom platelet reactivity was evaluated by the VerifyNow P2Y 12 test before percutaneous coronary intervention and during the maintenance phase (at 14 days). HPR was defined as platelet reaction unit≥235U. The primary ischemic end point, a composite of death, myocardial infarction, stent thrombosis, stroke, or urgent revascularization and the safety end point of major bleeding were assessed according to the platelet reactivity status. Results: Before percutaneous coronary intervention, 35.7% of patients displayed HPR (n=419). During the acute phase, between percutaneous coronary intervention and the 14-day platelet function testing, ischemic (adjusted hazard ratio, 0.94 [95% CI, 0.74–1.18]; P =0.58) and safety outcomes (hazard ratio, 1.28 [95% CI, 0.22–7.59]; P =0.78) were similar in HPR and non-HPR patients. During the maintenance phase, the proportion of HPR patients (n=186, 17.4%) decreased by 56%. At 1-year, there was no difference for the ischemic end point (5.9% versus 6.0%; adjusted hazard ratio, 0.79 [95% CI, 0.40–1.58]; P =0.51) and a nonsignificant higher rate of major bleedings (2.7% versus 1.0%, hazard ratio, 2.83 [95% CI, 0.96–8.41]; P =0.06) in HPR versus non-HPR patients. Conclusions: The proportion of HPR was halved after platelet function testing and treatment adjustment but without significant ischemic benefit at 1 year. HPR seems more as a modifiable risk marker than a risk factor of ischemic outcome. Clinical Trial Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT00827411.

Background: ST-segment–elevation myocardial infarction (STEMI) and non–ST-segment–elevation myocardial infarction (NSTEMI) management has evolved considerably over the past 2 decades. Little information on mortality trends in the most recent years is available. We assessed trends in characteristics, treatments, and outcomes for acute myocardial infarction in France between 1995 and 2015. Methods: We used data from 5 one-month registries, conducted 5 years apart, from 1995 to 2015, including 14 423 patients with acute myocardial infarction (59% STEMI) admitted to cardiac intensive care units in metropolitan France. Results: From 1995 to 2015, mean age decreased from 66±14 to 63±14 years in patients with STEMI; it remained stable (68±14 years) in patients with NSTEMI, whereas diabetes mellitus, obesity, and hypertension increased. At the acute stage, intended primary percutaneous coronary intervention increased from 12% (1995) to 76% (2015) in patients with STEMI. In patients with NSTEMI, percutaneous coronary intervention ≤72 hours from admission increased from 9% (1995) to 60% (2015). Six-month mortality consistently decreased in patients with STEMI from 17.2% in 1995 to 6.9% in 2010 and 5.3% in 2015; it decreased from 17.2% to 6.9% in 2010 and 6.3% in 2015 in patients with NSTEMI. Mortality still decreased after 2010 in patients with STEMI without reperfusion therapy, whereas no further mortality gain was found in patients with STEMI with reperfusion therapy or in patients with NSTEMI, whether or not they were treated with percutaneous coronary intervention. Conclusions: Over the past 20 years, 6-month mortality after acute myocardial infarction has decreased considerably for patients with STEMI and NSTEMI. Mortality figures continued to decline in patients with STEMI until 2015, whereas mortality in patients with NSTEMI appears stable since 2010.

Background: No randomized study has investigated the value of optical coherence tomography (OCT) in optimizing the results of percutaneous coronary intervention (PCI) for non–ST-segment elevation acute coronary syndromes. Methods: We conducted a multicenter, randomized study involving 240 patients with non–ST-segment elevation acute coronary syndromes to compare OCT-guided PCI (use of OCT pre- and post-PCI; OCT-guided group) to fluoroscopy-guided PCI (angiography-guided group). The primary end point was the functional result of PCI assessed by the measure of post PCI fractional flow reserve. Secondary end points included procedural complications and type 4a periprocedural myocardial infarction. Safety was assessed by the rate of acute kidney injury. Results: OCT use led to a change in procedural strategy in 50% of the patients in the OCT-guided group. The primary end point was improved in the OCT-guided group, with a significantly higher fractional flow reserve value (0.94±0.04 versus 0.92±0.05, P =0.005) compared with the angiography-guided group. There was no significant difference in the rate of type 4a myocardial infarction (33% in the OCT-group versus 40% in the angiography-guided group, P =0.28). The rates of procedural complications (5.8%) and acute kidney injury (1.6%) were identical in each group despite longer procedure time and use of more contrast medium in the OCT-guided group. Post-PCI OCT revealed stent underexpansion in 42% of patients, stent malapposition in 32%, incomplete lesion coverage in 20%, and edge dissection in 37.5%. This led to the more frequent use of poststent overdilation in the OCT-guided group versus the angiography-guided group (43% versus 12.5%, P P =0.01). Conclusions: In patients with non–ST-segment elevation acute coronary syndromes, OCT-guided PCI is associated with higher postprocedure fractional flow reserve than PCI guided by angiography alone. OCT did not increase periprocedural complications, type 4a myocardial infarction, or acute kidney injury. Clinical Trial Registration: URL: http://www.clinicaltrials.gov . Unique identifier: NCT01743274.

An asymptomatic and sedentary 58-year–old man with moderate overweight (body mass index, 29 kg/m2) and controlled hypertension was referred for a stress test. The patient had a highly positive stress test, with significant ST segment depression and tightening chest pain 2 minutes after the start of the exercise (40 Watts) followed by nonsustained ventricular tachycardia at rest. The physician hospitalized the patient into the coronary care unit for further evaluation. The echocardiogram was considered normal, without wall motion abnormalities, and serial troponin measurements remained normal. The patient was scheduled for next day coronary angiogram. In the morning, the laboratory evaluation included a fasting blood glucose value of 135 mg/dL, with a hemoglobin A1C of 7.4%, resulting in the likely diagnosis of previously unknown type 2 diabetes mellitus. Renal function was normal. The coronary angiogram showed a right-sided dominant coronary anatomy, with a focal lesion (75%) of the mid right coronary artery and with a fractional flow reserve (FFR) measured at 0.65. There were 2 focal and severe lesions in the left anterior descending artery (LAD), 1 proximal (95%) just before the first diagonal branch, which had also an intermediate ostial lesion, and 1 less tight lesion downstream (70%). FFR was not performed on the LAD because of the critical nature of the proximal lesion. The circumflex artery was a small artery without major branches. How would you manage this patient? ### Diabetes Mellitus and Coronary Artery Disease Cardiovascular disease is the leading cause of morbidity and mortality in people with diabetes mellitus. Patients with diabetes mellitus have a 2- to 4-fold increase in risk of developing cardiovascular disease than those without diabetes mellitus, and also a 2- to 5-fold increase in mortality attributable to cardiovascular disease when compared with age- and sex-matched nondiabetic persons.1 Accelerated atherogenesis, blood abnormalities (altered platelet function, inflammation, hypofibrinolysis, and hypercoagulability), …

Background— Allogenic platelet transfusions (PT) are administered to treat excessive bleeding in patients on P2Y 12 receptor inhibitors (RI). We assessed the effect of ex vivo and in vivo PT on platelet activation and aggregation in patients on dual antiplatelet therapy. Methods and Results— In the Antagonize P2Y 12 Treatment Inhibitors by Transfusion of Platelets in an Urgent or Delayed Timing After Acute Coronary Syndrome or Percutaneous Coronary Intervention Presentation-Acute Coronary Syndrome (APTITUDE-ACS) study, patients presenting with acute coronary syndrome or for elective percutaneous coronary intervention, receiving loading doses of clopidogrel (600 mg, n=13 or 900 mg, n=12), prasugrel 60 mg (n=10), or ticagrelor 180 mg (n=10) were included. PT was performed ex vivo by mixing platelet-rich plasma from blood sampling performed at baseline in increasing proportions with platelet-rich plasma sampled 4 hours after loading dose. The percentage restoration of residual platelet aggregation achieved with 80% proportion PT (residual platelet aggregation 80% PT mix/residual platelet aggregation baseline×100) significantly decreased with increasing potency of P2Y 12 RI (83.9±11%, 73±14%, 66.3±15%, 40.9±19% for clopidogrel 600 mg, clopidogrel 900 mg, prasugrel, and ticagrelor, respectively; P for trend 12 RI drug–effect, was assessed before and after in vivo PT administered for excessive bleeding in patients undergoing cardiac surgery while on a maintenance dose of aspirin and clopidogrel (n=45), prasugrel (n=6), or ticagrelor (n=3). When compared with baseline, there was a significant relative increase of 23.1% in platelet activation after PT transfusion (42.2±23.6% versus 56.6±18.2%; P =0.0008). Conclusions— PT restores platelet reactivity in patients with acute coronary syndrome/percutaneous coronary intervention and in patients undergoing cardiac surgery on P2Y 12 RI while bleeding with a less effect with increasing potency of P2Y 12 inhibition. Clinical Trial Registration— URL: http://www.recherche-biomedicale.sante.gouv.fr/pro/comites/coordonnees.htm and http://www.cnil.fr/ . Unique identifiers: No. 301111 and No. 1547216v0.

Background— Clopidogrel loading has mostly been studied in clopidogrel-naïve patients. Whether clopidogrel-treated patients readmitted for an acute coronary syndrome or percutaneous coronary intervention can benefit from a new load of clopidogrel and at what dose remain unknown. Our aim was to evaluate the impact of 3 different strategies of administration of a loading dose of 900 mg clopidogrel in patients already treated with a maintenance dose of 75 mg clopidogrel for at least 7 days on residual platelet aggregation. Methods and Results— Patients treated long term by clopidogrel 75 mg/d were assigned to receive a first loading dose of 300, 600, or 900 mg clopidogrel and 4 hours later a second loading dose of 600, 300, or 0 mg, respectively, to achieve a total loading dose of 900 mg in all patients. Platelet aggregation was evaluated at baseline, at 4 hours after the initial load (and before second load), and at 24 hours using light transmission aggregometry with 20 μmol ADP and the point-of-care assay VerifyNow P2Y 12 . The primary objective of the study was to evaluate the inhibition (relative change) of residual platelet aggregation (percentage of IRPA) between 600- and 900-mg first loading at 4 hours. IRPA at 24 hours also was evaluated as a secondary objective, as well as the rate of suboptimal response at 4 hours defined as IRPA P =0.0024). The difference in percentage IRPA at 4 hours was not significant between 300 and 600 mg but was significant between 600 and 900 mg and between 300 and 900 mg. Percentage IRPA assessed at 24 hours when all patients had received 900 mg did not differ between the 3 loading regimens. The rates of suboptimal response (IRPA P =0.02 for all). Conclusions— In patients treated long term with 75 mg clopidogrel, a new loading dose of 900 mg improves IRPA and reduces poor and/or slow response to clopidogrel significantly more than that obtained with 300 or 600 mg.

In this issue of Circulation: Cardiovascular Interventions , Wang et al1 publish on the real-world impact of platelet function testing where clinicians have direct access to point-of-care platelet function testing without protocol-mandated treatment strategies. Their hypothesis was that no-cost access to platelet function testing would increase treatment adjustment with P2Y12 receptor inhibitors and subsequently improve clinical outcomes of acute coronary syndrome (ACS) patients. Their conclusion is that access to no-cost platelet function testing had a modest impact on ADP receptor inhibitor selection and dosing and no impact on clinical outcome. Strikingly, switching from clopidogrel to more potent P2Y12 receptor inhibitor seemed to be independent of platelet function test results. The Treatment With Adenosine Diphosphate Receptor Inhibitors: Longitudinal Assessment of Treatment Patterns and Events After Acute Coronary Syndrome Prospective Open Label Antiplatelet Therapy (TRANSLATE-POPS) is a relevant study as it brings into light how evidence-based medicine is translated into the real-life setting.1 See Article by Wang et al This study first outlines the disproportionate relationship between knowledge and implementation into clinical practice. TRANSLATE-POPS was a prospective, cluster-randomized trial where participating centers were assigned access to no-cost platelet function testing versus usual care for ACS patients treated with PCI. Platelet function testing was performed only in two-third of patients treated in intervention sites. More importantly, treatment adjustments occurred in