[62] CARDIOVASCULAR DEATH AND NONFATAL MYOCARDIAL INFARCTION IN ACUTE CORONARY SYNDROME PATIENTS ARE PREDICTED BY RESIDUAL PLATELET REACTIVITY TO ADP IN THE ABSENCE OF CYP2C19*2 ALLELE: BEYOND GENETIC SCREENING

Abstract Introduction The myocardial-ischemic-injury-index (MI3) is a promising machine learned algorithm that predicts the likelihood of myocardial infarction in patients with suspected acute coronary syndrome. Whether this algorithm performs well in unselected patients or predicts recurrent events is unknown. Methods In an observational analysis from a multi-centre randomised trial, we included all patients with suspected acute coronary syndrome and serial high-sensitivity cardiac troponin I measurements without ST-segment elevation myocardial infarction. Using gradient boosting, MI3 incorporates age, sex, and two troponin measurements to compute a value (0–100) reflecting an individual's likelihood of myocardial infarction, and estimates the negative predictive value (NPV) and positive predictive value (PPV). Model performance for an index diagnosis of myocardial infarction, and for subsequent myocardial infarction or cardiovascular death at one year was determined using previously defined low- and high-probability thresholds (1.6 and 49.7, respectively). Results In total 20,761 of 48,282 (43%) patients (64±16 years, 46% women) were eligible of whom 3,278 (15.8%) had myocardial infarction. MI3 was well discriminated with an area under the receiver-operating-characteristic curve of 0.949 (95% confidence interval 0.946–0.952) identifying 12,983 (62.5%) patients as low-probability (sensitivity 99.3% [99.0–99.6%], NPV 99.8% [99.8–99.9%]), and 2,961 (14.3%) as high-probability (specificity 95.0% [94.7–95.3%], PPV 70.4% [69–71.9%]). At one year, subsequent myocardial infarction or cardiovascular death occurred more often in high-probability compared to low-probability patients (17.6% [520/2,961] versus 1.5% [197/12,983], P<0.001). Conclusions In unselected consecutive patients with suspected acute coronary syndrome, the MI3 algorithm accurately estimates the likelihood of myocardial infarction and predicts probability of subsequent adverse cardiovascular events. Performance of MI3 at example thresholds Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): Medical Research Council

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On-ticagrelor platelet reactivity and clinical outcome in patients undergoing percutaneous coronary intervention for acute coronary syndrome

Thrombosis and Haemostasis ◽

10.1055/a-1326-5110 ◽

2020 ◽

Author(s):

marc laine ◽

Vassili PANAGIDES ◽

Corinne Frère ◽

thomas cuisset ◽

Caroline Gouarne ◽

...

Keyword(s):

Myocardial Infarction ◽

Percutaneous Coronary Intervention ◽

Acute Coronary Syndrome ◽

Clinical Outcome ◽

Platelet Reactivity ◽

Coronary Intervention ◽

Coronary Syndrome ◽

Percutaneous Coronary ◽

The Relationship

Background: A strong association between on-thienopyridines platelet reactivity (PR) and the risk of both thrombotic and bleeding events in acute coronary syndrome (ACS) patients undergoing percutaneous coronary intervention (PCI) has been demonstrated. However, no study has analyzed the relationship between on-ticagrelor PR and clinical outcome in this clinical setting. Objectives: We aimed to investigate the relationship between on-ticagrelor PR, assessed by the vasodilator-stimulated phosphoprotein (VASP) index, and clinical outcome in patients with ACS undergoing PCI. Methods: We performed a prospective, multicenter, observational study of patients undergoing PCI for ACS. PR was measured using the VASP index following ticagrelor loading dose. The primary study endpoint was the rate of Bleeding Academic Research Consortium (BARC) type ≥2 at 1 year. The key secondary endpoint was the rate of major cardiovascular events (MACE) defined as the composite of cardiovascular death, myocardial infarction and urgent revascularization. Results: We included 570 ACS patients, among whom 33.9% had ST-elevation myocardial infarction. BARC type ≥ 2 bleeding occurred in 10.9% and MACE in 13.8%. PR was not associated with BARC ≥ 2 or with MACE (p=0.12 and p=0.56, respectively). No relationship between PR and outcomes was observed, neither when PR was analyzed quantitatively nor qualitatively (low on-treatment PR (LTPR) vs no LTPR). Conclusion: On-ticagrelor PR measured by the VASP was not associated with bleeding or thrombotic events in ACS patients undergoing PCI. PR measured by the VASP should not be used as a surrogate endpoint in studies on ticagrelor.

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Platelet reactivity and clinical outcomes in acute coronary syndrome patients treated with prasugrel and clopidogrel: a pre-specified exploratory analysis from the TROPICAL-ACS trial

European Heart Journal ◽

10.1093/eurheartj/ehz202 ◽

2019 ◽

Vol 40 (24) ◽

pp. 1942-1951 ◽

Cited By ~ 16

Author(s):

Dániel Aradi ◽

Lisa Gross ◽

Dietmar Trenk ◽

Tobias Geisler ◽

Béla Merkely ◽

...

Keyword(s):

Acute Coronary Syndrome ◽

Clinical Outcomes ◽

Independent Predictor ◽

Platelet Reactivity ◽

Academic Research ◽

Study Groups ◽

Cardiovascular Death ◽

Control Group ◽

Coronary Syndrome ◽

Increased Risk

Abstract Aims The value of platelet function testing (PFT) in predicting clinical outcomes and guiding P2Y12-inhibitor treatment is uncertain. In a pre-specified sub-study of the TROPICAL-ACS trial, we assessed ischaemic and bleeding risks according to high platelet reactivity (HPR) and low platelet reactivity (LPR) to ADP in patients receiving uniform prasugrel vs. PFT-guided clopidogrel or prasugrel. Methods and results Acute coronary syndrome patients with PFT done 14 days after hospital discharge were included with prior randomization to uniform prasugrel for 12 months (control group, no treatment modification) vs. early de-escalation from prasugrel to clopidogrel and PFT-guided maintenance treatment (HPR: switch-back to prasugrel, non-HPR: clopidogrel). The composite ischaemic endpoint included cardiovascular death, myocardial infarction, or stroke, while key safety outcome was Bleeding Academic Research Consortium (BARC) 2–5 bleeding, from PFT until 12 months. We identified 2527 patients with PFT results available: 1266 were randomized to the guided and 1261 to the control group. Before treatment adjustment, HPR was more prevalent in the guided group (40% vs. 15%), while LPR was more common in control patients (27% vs. 11%). Compared to control patients without HPR on prasugrel (n = 1073), similar outcomes were observed in guided patients kept on clopidogrel [n = 755, hazard ratio (HR): 1.06 (0.57–1.95), P = 0.86] and also in patients with HPR on clopidogrel switched to prasugrel [n = 511, HR: 0.96 (0.47–1.96), P = 0.91]. In contrast, HPR on prasugrel was associated with a higher risk for ischaemic events in control patients [n = 188, HR: 2.16 (1.01–4.65), P = 0.049]. Low platelet reactivity was an independent predictor of bleeding [HR: 1.74 (1.18–2.56), P = 0.005], without interaction (Pint = 0.76) between study groups. Conclusion Based on this substudy of a randomized trial, selecting prasugrel or clopidogrel based on PFT resulted in similar ischaemic outcomes as uniform prasugrel therapy without HPR. Although infrequent, HPR on prasugrel was associated with increased risk of ischaemic events. Low platelet reactivity was a strong and independent predictor of bleeding both on prasugrel and clopidogrel.

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Long versus short dual antiplatelet therapy in acute coronary syndrome patients treated with prasugrel or ticagrelor and coronary revascularization: Insights from the RENAMI registry

European Journal of Preventive Cardiology ◽

10.1177/2047487319836327 ◽

2019 ◽

Vol 27 (7) ◽

pp. 696-705 ◽

Cited By ~ 9

Author(s):

Fabrizio D'Ascenzo ◽

Maurizio Bertaina ◽

Francesco Fioravanti ◽

Federica Bongiovanni ◽

Sergio Raposeiras-Roubin ◽

...

Keyword(s):

Myocardial Infarction ◽

Percutaneous Coronary Intervention ◽

Acute Coronary Syndrome ◽

Propensity Score ◽

Dual Antiplatelet Therapy ◽

Coronary Intervention ◽

Cardiovascular Death ◽

Coronary Syndrome ◽

Increased Risk ◽

Percutaneous Coronary

Introduction The benefits of short versus long-term dual antiplatelet therapy (DAPT) based on the third generation P2Y12 antagonists prasugrel or ticagrelor, in patients with acute coronary syndromes treated with percutaneous coronary intervention remain to be clearly defined due to current evidences limited to patients treated with clopidogrel. Methods All acute coronary syndrome patients from the REgistry of New Antiplatelets in patients with Myocardial Infarction (RENAMI) undergoing percutaneous coronary intervention and treated with aspirin, prasugrel or ticagrelor were stratified according to DAPT duration, that is, shorter than 12 months (D1 group), 12 months (D2 group) and longer than 12 months (D3 group). The three groups were compared before and after propensity score matching. Net adverse clinical events (NACEs), defined as a combination of major adverse cardiac events (MACEs) and major bleedings (including therefore all cause death, myocardial infarction and Bleeding Academic Research Consortium (BARC) 3–5 bleeding), were the primary end points, MACEs (a composite of all cause death and myocardial infarction) the secondary one. Single components of NACEs were co-secondary end points, along with BARC 2–5 bleeding, cardiovascular death and stent thrombosis. Results A total of 4424 patients from the RENAMI registry with available data on DAPT duration were included in the model. After propensity score matching, 628 patients from each group were selected. After 20 months of follow up, DAPT for 12 months and DAPT for longer than 12 months significantly reduced the risk of NACE (D1 11.6% vs. D2 6.7% vs. D3 7.2%, p = 0.003) and MACE (10% vs. 6.2% vs. 2.4%, p < 0.001) compared with DAPT for less than 12 months. These differences were driven by a reduced risk of all cause death (7.8% vs. 1.3% vs. 1.6%, p < 0.001), cardiovascular death (5.1% vs. 1.0% vs. 1.2%, p < 0.0001) and recurrent myocardial infarction (8.3% vs. 5.2% vs. 3.5%, p = 0.002). NACEs were lower with longer DAPT despite a higher risk of BARC 2–5 bleedings (4.6% vs. 5.7% vs. 6.2%, p = 0.04) and a trend towards a higher risk of BARC 3–5 bleedings (2.4% vs. 3.3% vs. 3.9%, p = 0.06). These results were not consistent for female patients and those older than 75 years old, due to an increased risk of bleedings which exceeded the reduction in myocardial infarction. Conclusion In unselected real world acute coronary syndrome patients treated with percutaneous coronary intervention, DAPT with prasugrel or ticagrelor prolonged beyond 12 months markedly reduces fatal and non-fatal ischaemic events, offsetting the increased risk deriving from the higher bleeding risk. On the contrary, patients >75 years old and female ones showed a less favourable risk–benefit ratio for longer DAPT due to excess of bleedings.

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Elevated Cardiac Troponin in Acute Stroke without Acute Coronary Syndrome Predicts Long-Term Adverse Cardiovascular Outcomes

Stroke Research and Treatment ◽

10.1155/2014/621650 ◽

2014 ◽

Vol 2014 ◽

pp. 1-6 ◽

Cited By ~ 4

Author(s):

Farhan Raza ◽

Mohamad Alkhouli ◽

Paul Sandhu ◽

Reema Bhatt ◽

Alfred A. Bove

Keyword(s):

Myocardial Infarction ◽

Acute Coronary Syndrome ◽

Acute Stroke ◽

Cardiac Troponin ◽

Troponin I ◽

Nonfatal Myocardial Infarction ◽

Coronary Syndrome ◽

Baseline Characteristics

Background. Elevated cardiac troponin in acute stroke in absence of acute coronary syndrome (ACS) has unclear long-term outcomes.Methods. Retrospective analysis of 566 patients admitted to Temple University Hospital from 2008 to 2010 for acute stroke was performed. Patients were included if cardiac troponin I was measured and had no evidence of ACS and an echocardiogram was performed. Of 200 patients who met the criteria, baseline characteristics, electrocardiograms, and major adverse cardiovascular events (MACE) were reviewed. Patients were characterized into two groups with normal and elevated troponins. Primary end point was nonfatal myocardial infarction during follow-up period after discharge. The secondary end points were MACE and death from any cause.Results. For 200 patients, 17 patients had positive troponins. Baseline characteristics were as follows: age63.1±13.8, 64% African Americans, 78% with hypertension, and 22% with previous CVA. During mean follow-up of 20.1 months, 7 patients (41.2%) in elevated troponin and 6 (3.3%) patients in normal troponin group had nonfatal myocardial infarction (P=0.0001). MACE (41.2% versus 14.2%,P=0.01) and death from any cause (41.2% versus 14.5%,P=0.017) were significant in the positive troponin group.Conclusions. Elevated cardiac troponin in patients with acute stroke and no evidence of ACS is strong predictor of long-term cardiac outcomes.

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