Benefit of Switching Dual Antiplatelet Therapy After Acute Coronary Syndrome According to On-Treatment Platelet Reactivity: The TOPIC-VASP Pre-Specified Analysis of the TOPIC Randomized Study.

OBJECTIVES: This study sought to evaluate the impact of initial platelet reactivity on the benefit of switched strategy. BACKGROUND: TOPIC (Timing Of Platelet Inhibition after acute Coronary Syndrome) study suggested that switched dual antiplatelet therapy (DAPT) could improve net clinical benefit after acute coronary syndrome by preventing bleeding. METHODS: Acute coronary syndrome patients, 1 month after coronary stenting and event free, were randomly assigned to aspirin and clopidogrel (switched DAPT) or continuation of drug regimen (unchanged DAPT). All patients underwent platelet function testing at this time and were classified as low on-treatment platelet reactivity (LTPR) (platelet reactivity index vasodilator-stimulated phosphoprotein ≤20%) or non-LTPR (platelet reactivity index vasodilator-stimulated phosphoprotein >20%). The primary endpoint aimed to evaluate the impact of platelet reactivity on clinical outcomes and benefit of switched DAPT strategy. RESULTS: A total of 645 patients were included, 305 (47%) of whom were classified as LTPR. LTPR patients were less often diabetic (p = 0.01), had lower body mass index (p < 0.01), and were more often on ticagrelor (p < 0.01). Patients defined as LTPR and randomized to unchanged DAPT were at the highest risk of primary endpoint occurrence (31%; p < 0.01). Conversely, in the switched arm, LTPR patients had no significant difference in primary outcome incidence compared with non-LTPR patients (hazard ratio [HR]: 0.78; 95% confidence interval [CI]: 0.40 to 1.49; p = 0.45). The switched strategy was associated with important reduction in primary endpoint incidence in LTPR patients (HR: 0.29; 95% CI: 0.17 to 0.51; p < 0.01) and only numerically lower incidence in non-LTPR patients (HR: 0.79; 95% CI: 0.46 to 1.35; p = 0.39). CONCLUSIONS: Switched DAPT was superior regardless of initial platelet reactivity but the benefit was greater in LTPR patients. Indeed, the switched strategy was highly effective in this group, which had impaired prognosis with unchanged DAPT but similar prognosis after switching.

Association of Posterior Reversible Encephalopathy Syndrome and Transient Apical Ballooning Syndrome (Takotsubo): First Case Report of a Man and Review of the Literature.

INTRODUCTION: An association of posterior reversible encephalopathy syndrome (PRES) and takotsubo is rare. We present the first case of a male patient. CASE REPORT: A 69-year-old man presented to the hospital in a persistent comatose state following a generalized tonic-clonic seizure with high blood pressure. The electrocardiogram revealed transient left bundle branch block. Troponin and BNP were elevated. Cardiac ultrasound showed large apical akinesia with altered left ventricular ejection fraction, and the left ventriculogram showed characteristic regional wall motion abnormalities involving the mid and apical segments. Brain MRI showed bilateral, cortical, and subcortical vasogenic edema predominant in the posterior right hemisphere. The lumbar puncture and cerebral angiography were normal. Paraclinical abnormalities were reversible within 2 weeks with a clinical recovery in 3 months, confirming the takotsubo and the PRES diagnoses. DISCUSSION: Several theories hypothesize the underlying pathophysiology of takotsubo or PRES. Circulating catecholamines are up to 3 times higher in patients with takotsubo causing impaired microcirculation and apical hypokinesia. An association of both takotsubo and asthma crisis and PRES and asthma crisis underlines the role of catecholamines in the occurrence of these disorders. CONCLUSION: Early recognition of this rare association, in which heart and neurological damage may require rapid intensive care support, is needed.

Benefit of switching dual antiplatelet therapy after acute coronary syndrome: the TOPIC (timing of platelet inhibition after acute coronary syndrome) randomized study.

AIMS: Newer P2Y12 blockers (prasugrel and ticagrelor) demonstrated significant ischaemic benefit over clopidogrel after acute coronary syndrome (ACS). However, both drugs are associated with an increase in bleeding complications. The objective of the present study was to evaluate the benefit of switching dual antiplatelet therapy (DAPT) from aspirin plus a newer P2Y12 blocker to aspirin plus clopidogrel 1 month after ACS. METHODS AND RESULTS: We performed an open-label, monocentric, and randomized trial. From March 2014 to April 2016, patients admitted with ACS requiring coronary intervention, on aspirin and a newer P2Y12 blocker and without adverse event at 1 month, were assigned to switch to aspirin and clopidogrel (switched DAPT) or continuation of their drug regimen (unchanged DAPT). The primary outcome was a composite of cardiovascular death, urgent revascularization, stroke and bleeding as defined by the Bleeding Academic Research Consortium (BARC) classification ≥2 at 1 year post ACS. Six hundred and forty six patients were randomized and 645 analysed, corresponding to 322 patients in the switched DAPT and 323 in the unchanged DAPT group. The primary endpoint occurred in 43 (13.4%) patients in the switched DAPT group and in 85 (26.3%) patients in the unchanged DAPT (HR 95%CI 0.48 (0.34-0.68), P < 0.01). No significant differences were reported on ischaemic endpoints, while BARC ≥ 2 bleeding occurred in 13 (4.0%) patients in the switched DAPT and in 48 (14.9%) in the unchanged DAPT group (HR 95%CI 0.30 (0.18-0.50), P < 0.01). CONCLUSION: A switched DAPT is superior to an unchanged DAPT strategy to prevent bleeding complications without increase in ischaemic events following ACS.

Is platelet inhibition correlated with time from last intake on P2Y12 blockers after an acute coronary syndrome? A pilot study.

Delay from the last intake of drug could be an important and unexplored variable in the biological response to antiplatelet agents after acute coronary syndrome (ACS) discharge. The objective was to define the impact of the delay from P2Y12 blocker intake on the platelet inhibition level. We compared ticagrelor-, prasugrel-, and clopidogrel-treated patients. All consecutive patients, who had been addressed between 2013 and 2014 for ACS, treated with aspirin and a P2Y12 blocker as maintenance dose, were eligible. One month after discharge, blood sample and a questionnaire were proposed to the patient by a nurse blinded to the protocol. On this questionnaire, three questions about name of the drug, regularity of the intakes, and hour of the last intake were collected. The response to antiplatelet therapy was assessed using platelet reactivity index vasodilator-stimulated phosphoprotein (PRI VASP) and % of adenosine-5'-diphosphate-induced aggregation (%ADP).The primary objective of this study was to evaluate the correlation between platelet inhibition and delay from drug intake. We enrolled 474 ACS treated with clopidogrel 75 mg in 182 cases (38% patients), prasugrel in 190 cases (40%), or ticagrelor in 102 patients (22%). We observed a significant correlation between delay from intake and PRI VASP and %ADP for ticagrelor (r = 0.25, p = 0.01; r = 0.21, p = 0.03; respectively). On clopidogrel (r = 0.09, p = 0.24; r = 0.02, p = 0.80; respectively) and prasugrel (r = 0.02, p = 0.82; r = 0.11, p = 0.12 respectively), no correlation exists. In conclusion, ticagrelor, unlike thienopyridines, is associated with a significant correlation between delay from the last intake and platelet inhibition.

Percutaneous closure of a poorly tolerated post-transcatheter aortic valve implantation ventricular septal defect.

We report the case of a 78-year-old woman with severe aortic valve stenosis that was successfully treated with transcatheter aortic valve implantation, with initial good hemodynamic results and clinical improvement of the patient. After 3 weeks, her clinical condition worsened, with progressive heart failure. Transthoracic echocardiography revealed an iatrogenic large subaortic ventricular septal defect with important left-to right shunt (Qp/Qs 3:1). The patient underwent successful transcatheter closure of the ventricular septal defect with a 14-mm Amplatzer mVSD Occluder (AGA Medical, Plymouth, MN), resulting in dramatic clinical improvement.

Impact of obesity and the metabolic syndrome on response to clopidogrel or prasugrel and bleeding risk in patients treated after coronary stenting.

This study aimed to analyze the impact of body mass index (BMI) and the metabolic syndrome (MS) on responses to clopidogrel or prasugrel and bleeding risk after acute coronary syndrome. The study included 1,542 consecutive patients who underwent coronary stenting (287 clopidogrel 75 mg, 868 clopidogrel 150 mg, and 387 prasugrel 10 mg). Platelet reactivity was assessed 1 month after discharge using platelet reactivity index vasodilator stimulated phosphoprotein (PRI VASP). Three hundred thirty-six patients (21.8%) were obese (BMI ≥30), and we observed higher platelet reactivity associated with higher BMI across thienopyridine regimens. Incidence of high on-treatment platelet reactivity (PRI VASP >50%) was higher in obese than nonobese patients (p <0.05 for all regimens). Conversely, incidence of low on-treatment platelet reactivity with prasugrel therapy (PRI VASP <20%) was lower in obese than nonobese patients: 13% (12 of 93) versus 33% (97 of 294); odds ratio 0.30, 95% confidence interval 0.16 to 0.58; p <0.001. Accordingly, incidence of Bleeding Academic Research Consortium bleeding complications was higher in nonobese than in obese patients: 10% (119 of 1,206) versus 6% (20 of 336); odds ratio 1.7, 95% confidence interval 1.1 to 2.8; p = 0.03. This impaired response was only observed in obese patients with the MS, and obese with the MS had significantly higher platelet reactivity than other obese patients with all regimens (p <0.01). Obese patients without the MS had no significant difference in platelet reactivity compared with nonobese patients. In conclusion, the present study confirmed that BMI has a strong impact on response to clopidogrel and prasugrel with higher incidence of high on-treatment platelet reactivity, lower incidence of low on-treatment platelet reactivity, and lower bleeding complication in obese patients. However, among obese patients, the presence of the MS strongly affects response to antiplatelet agents, indicating that the metabolic status might be a better predictor of platelet inhibition than BMI.

Clinical implications of very low on-treatment platelet reactivity in patients treated with thienopyridine: the POBA study (predictor of bleedings with antiplatelet drugs).

OBJECTIVES: This study was designed to define the hyperresponse to thienopyridine (very low on-treatment platelet reactivity [VLTPR]) as the most predictive threshold value of platelet reactivity index vasodilator-stimulated phosphoprotein (PRI VASP) for the prediction of non-access site-related bleeding events. We also aimed to identify predictors of bleeding and VLTPR in patients treated with thienopyridines. BACKGROUND: New P2Y12 blockers and platelet monitoring has been proposed to optimize platelet inhibition after acute coronary syndromes and improve ischemic outcomes. However, bleeding complications remain the Achilles' heel of antiplatelet therapy, and platelet monitoring could be useful to evaluate this risk. METHODS: A total of 1,542 consecutive patients undergoing coronary stenting for ACS were included in the present study (287 taking clopidogrel 75 mg, 868 taking clopidogrel 150 mg, and 387 taking prasugrel 10 mg). RESULTS: During 6-month follow-up, 9% of patients (n = 139) experienced nonaccess site-related Bleeding Academic Research Consortium bleeding complications. These patients were more often women and nondiabetic and had lower PRI VASP values than others (p < 0.001). Receiver-operating characteristic curve analysis (0.71, p < 0.01) identified a threshold value for VLTPR of PRI VASP ≤10% to predict bleeding events with a sensitivity of 17% and a specificity of 97%. Although prasugrel was the main predictor of VLTPR in the whole population (odds ratio: 10.2, 95% confidence interval: 3.0 to -34.2; p < 0.001), VLTPR was the strongest and independent predictor of bleeding (odds ratio: 4.7, 95% confidence interval: 2.7 to 8.3; p < 0.001). CONCLUSIONS: The present study identified VLTPR (PRI VASP ≤10%) as the strongest predictor of bleeding complications in patients treated with thienopyridines. This marker could be useful for tailored therapy and bleeding prevention.

Three-dimensional transesophageal echocardiography assessment of a successful transcatheter mitral valve in valve implantation for degenerated bioprosthesis.

Reoperation for degenerated mitral bioprosthesis is considered a high risk procedure. Transcatheter mitral valve in valve implantation has emerged as an off-label alternative for patients contra-indicated to surgery. We report a 46-year-old man, with a 29 mm mitral bioprosthesis since 2002, who was admitted for acute heart failure because of a severe intra-prosthetic regurgitation. His recent medical history revealed a fast growing cavum carcinoma. In view of generally poor prognosis, the heart team decided to perform a transcatheter mitral valve in valve implantation by transapical approach. Live three-dimensional TEE was used during the implantation for sizing, device positioning, and hemodynamic assessment.