scholarly journals Ischemic and Bleeding Events of Ticagrelor Monotherapy in Korean Patients With and Without Diabetes Mellitus: Insights From the TICO Trial

2021 ◽  
Vol 11 ◽  
Author(s):  
Kyeong Ho Yun ◽  
Jae Young Cho ◽  
Seung Yul Lee ◽  
Sang Jae Rhee ◽  
Byeong Keuk Kim ◽  
...  

Background: Ticagrelor monotherapy after 3 months dual antiplatelet therapy (DAPT) with aspirin and ticagrelor can reduce bleeding without increasing ischemic events after percutaneous coronary intervention (PCI). However, the impact of this approach among the patient with diabetes remains unknown.Methods: This was a sub-analysis of the Ticagrelor Monotherapy after 3 months in the Patients Treated with New Generation Sirolimus Eluting Stent for Acute Coronary Syndrome (TICO) trial. After successful PCI, the patients were randomly assigned to ticagrelor monotherapy after 3-months DPAT or to ticagrelor-based 12-months DAPT. We compared ischemic events and bleeding events between the patients with diabetes and without diabetes for 12 months. Ischemic events were defined as death, myocardial infarction, ischemic stroke, transient ischemic attack, stent thrombosis, and any revascularizations. Bleeding events were defined according to the Thrombolysis in Myocardial Infarction (TIMI) criteria and Bleeding Academic Research Consortium (BARC) definition.Results: Between August 2015 and October 2018, 3,056 patients were enrolled in the TICO trial, of which 835 (27.3%) had diabetes mellitus. Diabetes mellitus was associated with all evaluated ischemic and bleeding events. No significant differences in any ischemic events were observed in patients with diabetes between ticagrelor monotherapy after 3-months DAPT and ticagrelor-based 12-months DAPT (hazard ratio [HR] 0.83, 95% confidence interval [CI] 0.45–1.52, p = 0.540). In patients with diabetes, the overall incidence of bleeding complications during the 12-months follow-up period did not differ between the two treatment groups (HR 0.83, 95% CI 1.48–1.43, p = 0.505). However, ticagrelor monotherapy was significantly reduced both any TIMI bleeding and BARC three or five bleeding events in diabetes patients in the 3-months landmark analysis, after 3-months DAPT period (HR 0.20, 95% CI 0.07–0.59, p = 0.003).Conclusion: In diabetic patients, ticagrelor monotherapy showed a lower incidence of bleeding complications after 3-months DAPT period, without increasing ischemic complications, compared with ticagrelor-based 12-months DAPT (ClinicalTrials.gov Identifier: NCT02494895).

2021 ◽  
Vol 9 (4) ◽  
pp. 511-520
Author(s):  
Z. Wang ◽  
E. A. Asaphyeva ◽  
T. I. Makeeva

Abstract. Recently, quantitative analysis of the level of the N-terminal prohormone of the brain naturetic peptide (NT-proBNP) has been widely used to diagnose heart failure (HF). A statistically significant correlation was found between the serum NT-proBNP concentration and HF stage. It was found that in patients with high cardiovascular risk, NT-proBNP has the highest predictive value in relation to mortality. In young and middle-aged patients with diabetes mellitus (DM) with myocardial infarction (MI) and stents of an infarct-associated artery, the frequency of unfavorable remodeling (UR) of the left ventricle (LV) in the long-term prognosis was studied. The frequency of atherosclerotic lesions of the coronary arteries (CA) in patients with diabetes in acute coronary syndrome (ACS) was determined, the results of echocardiographic parameters were presented in the follow-up dynamics, the value of serum NT-proBNP in predicting LV UR 12 months after myocardial infarction (MI) was determined.Aim of study. To assess the diagnostic capabilities of NT-proBNP in the long-term prediction of the development of LV infarction in patients with MI with diabetes in young and middle age after percutaneous coronary intervention (PCI).Design. Prospective controlled non-randomized trial. The patients were examined twice: on the first day of ACS after PCI with stenting of infarct-associated coronary artery and 12 months after AMI. The study included 191 patients with ACS with / without ST-segment elevation, who were divided into two groups. The main group included 76 patients with ACS with diabetes mellitus, the comparison group included 115 patients with ACS without diabetes mellitus. Patients in both groups were comparable in age, gender, comorbidity, and complications of AMI. The duration of diabetes was, on average, 6 years (from one to 12 years).Material and methods. All patients underwent electrocardiography, echocardiography, tests for the content of troponin I, NT-proBNP, glycosylated hemoglobin, lipids, determined the level of creatinine in the blood and the glomerular filtration rate according to the Modification of diet in renal disease (MDRD). All patients were examined twice: on the first day of ACS after PCI with stenting of infarct-associated coronary artery and 12 months later.Results. In 69% of diabetic patients with anterior myocardial infarction and in 63% of patients with posterolateral MI 12 months after PCI, signs of LV inferiority were revealed in the form of an increase in the indices of end-diastolic and systolic volumes of the LV and low ejection fraction (≤45%). In patients without diabetes, these figures were 18% and 31%, respectively. High concentrations of NT-proBNP on the first day of myocardial infarction after PCI were of the greatest value in the diagnosis and prognosis of LV UR after 12 months.Conclusion. The NT-proBNP level of more than 776 pg/ml on the first day after PCI is an indicator of an unfavorable long-term prognosis in patients with young and middle-aged diabetes in terms of the development of LV systolic dysfunction.


2021 ◽  
Vol 28 (Supplement_1) ◽  
Author(s):  
HY Wang ◽  
ZX Cai ◽  
D Yin ◽  
WH Song ◽  
L Feng ◽  
...  

Abstract Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): Chinese College of Cardiovascular Physicians, CS Optimizing Antithrombotic Research Fund (Grant No. BJUHFCSOARF201801-01), the National Key Research and Development Program of China (Grant No. 2018YFC1315602), the Beijing Municipal Health Commission (Grant No. 2020-1-4032), the Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences (Grant No. 2016-I2M-1-009), and the National Natural Science Foundation of China (Grant No. 81870277). Background Patients with diabetes mellitus (DM) are known to be at high-risk for both ischemic and bleeding complications post-percutaneous coronary intervention (PCI). The ischemic benefit versus bleeding risk associated with extended dual antiplatelet therapy (DAPT) in high-risk "TWILIGHT-like" patients with diabetes mellitus after PCI has not been established. Methods All consecutive high-risk patients fulfilling the "TWILIGHT-like" criteria undergoing PCI from January 2013 through December 2013 were identified from prospective Fuwai PCI Registry. High-risk "TWILIGHT-like" patients were defined by at least 1 clinical and 1 angiographic feature based on TWILIGHT trial selection criteria. The present analysis evaluated 3425 diabetics patients with concomitant high-risk angiographic features who were event-free at 1 year after PCI. Median follow-up was 2.4 years. The primary effectiveness endpoint was a composite of death, myocardial infarction, or stroke (termed major adverse cardiac and cerebrovascular events) and primary safety endpoint was clinically relevant bleeding according to Bleeding Academic Research Consortium type 2, 3, or 5. Results On inverse probability of treatment weighting (IPTW) analysis, prolonged-term (>1-year) DAPT with aspirin and clopidogrel decreased the risk of primary effectiveness endpoint compared with shorter (≤1-year) DAPT (1.8% vs. 4.3%; hazard ratio [HR]IPTW: 0.381; 95% confidence interval [CI]: 0.252-0.576; P < 0.001) and reduced cardiovascular death (0.1% vs. 1.8%; HRIPTW: 0.056 [0.016-0.193]). Prolonged DAPT was also associated with a reduced risk of definite/probable stent thrombosis (0.2% vs. 0.7%; HRIPTW: 0.258 [0.083-0.802]), and non-significantly lower rate of myocardial infarction (0.5% vs. 0.8%; HRIPTW: 0.676 [0.275-1.661]). There was no significant difference between groups in clinically relevant bleeding (1.1% vs. 1.1%; HRIPTW: 1.078 [0.519-2.241]; P = 0.840). Similar results were observed in multivariable Cox proportional hazards regression model. Conclusion Among high-risk PCI patients with diabetes mellitus without an adverse event through 1 year, extending DAPT > 1-year significantly reduced the risk of major adverse cardiac and cerebrovascular events without an increase in clinically relevant bleeding, suggesting that such high-risk diabetic patients may be good candidates for long-term DAPT. Abstract Figure.


2012 ◽  
Vol 2012 ◽  
pp. 1-18 ◽  
Author(s):  
Karthik Balasubramaniam ◽  
Girish N. Viswanathan ◽  
Sally M. Marshall ◽  
Azfar G. Zaman

Patients with diabetes mellitus presenting with acute coronary syndrome have a higher risk of cardiovascular complications and recurrent ischemic events when compared to nondiabetic counterparts. Different mechanisms including endothelial dysfunction, platelet hyperactivity, and abnormalities in coagulation and fibrinolysis have been implicated for this increased atherothrombotic risk. Platelets play an important role in atherogenesis and its thrombotic complications in diabetic patients with acute coronary syndrome. Hence, potent platelet inhibition is of paramount importance in order to optimise outcomes of diabetic patients with acute coronary syndrome. The aim of this paper is to provide an overview of the increased thrombotic burden in diabetes and acute coronary syndrome, the underlying pathophysiology focussing on endothelial and platelet abnormalities, currently available antiplatelet therapies, their benefits and limitations in diabetic patients, and to describe potential future therapeutic strategies to overcome these limitations.


2020 ◽  
Vol 7 ◽  
Author(s):  
Hao-Yu Wang ◽  
Zhong-Xing Cai ◽  
Dong Yin ◽  
Wei-Hua Song ◽  
Lei Feng ◽  
...  

Background: Patients with diabetes mellitus (DM) are known to be at high-risk for both ischemic and bleeding complications post-percutaneous coronary intervention (PCI). The ischemic benefit vs. bleeding risk associated with extended dual antiplatelet therapy (DAPT) in high-risk “TWILIGHT-like” patients with diabetes mellitus after PCI has not been established.Methods: All consecutive high-risk patients fulfilling the “TWILIGHT-like” criteria undergoing PCI from January 2013 through December 2013 were identified from the prospective Fuwai PCI Registry. High-risk “TWILIGHT-like” patients were defined by at least one clinical and one angiographic feature based on the TWILIGHT trial selection criteria. The present analysis evaluated 3,425 diabetic patients with concomitant high-risk angiographic features who were event-free at 1 year after PCI. Median follow-up was 2.4 years. The primary effectiveness endpoint was a composite of death, myocardial infarction, or stroke (termed major adverse cardiac and cerebrovascular events), and primary safety endpoint was clinically relevant bleeding according to the Bleeding Academic Research Consortium types 2, 3, or 5.Results: On inverse probability of treatment weighting (IPTW) analysis, prolonged-term (>1-year) DAPT with aspirin and clopidogrel decreased the risk of primary effectiveness endpoint compared with shorter ( ≤ 1-year) DAPT [1.8 vs. 4.3%; hazard ratio (HR)IPTW: 0.381; 95% confidence interval (CI): 0.252–0.576; P < 0.001] and reduced cardiovascular death [0.1% vs. 1.8%; HRIPTW: 0.056 (0.016–0.193)]. Prolonged DAPT was also associated with a reduced risk of definite/probable stent thrombosis [0.2 vs. 0.7%; HRIPTW: 0.258 (0.083–0.802)] and non-significantly lower rate of myocardial infarction [0.5 vs. 0.8%; HRIPTW: 0.676 (0.275–1.661)]. There was no significant difference between groups in clinically relevant bleeding [1.1 vs. 1.1%; HRIPTW: 1.078 (0.519–2.241); P = 0.840). Similar results were observed in multivariable Cox proportional hazards regression model.Conclusion: Among high-risk PCI patients with diabetes mellitus without an adverse event through 1 year, extending DAPT >1-year significantly reduced the risk of major adverse cardiac and cerebrovascular events without an increase in clinically relevant bleeding, suggesting that such high-risk diabetic patients may be good candidates for long-term DAPT.


2021 ◽  
Vol 15 (8) ◽  
pp. 2017-2019
Author(s):  
Rao Salman Aziz ◽  
Usman Saeed ◽  
Nasim Aslam Ghumman ◽  
Muhammad Arshad ◽  
Asif Sohail ◽  
...  

Background: Diabetes is a complicated disease requires continuous clinical care, to govern blood sugar. Aim: To decides the impact of management of L carentin to diabetics at the lipid profile. Methods: This study turned into performed on 120 diabetic Patients had been decided on from endocrinology and diabetes, inside decided on standards. The Patients distributed into three Strata (1st Strata of healthy population and two Strata of patients with diabetes who were on metformin and glibenclamide, one Strata took a L carnitine in a dose of 1000 mg TDS and a Strata dealing with a placebo for a period of ninety days). Results: It is observed those who are on Lcarnitine, confirmed a large discount (p <0.05) with inside the triglyceride level, at the same time as no large adjustments had been located withinside the level of cholesterol and HDL and LDL. Conclusion: These study outcomes that management of L carentin improved profile of lipid in type-2diabetic Patients. Keyword: Dyslipidemia, Diabetes mellitus (DM), l-carnitine (LC).


2020 ◽  
Vol 19 (1) ◽  
Author(s):  
T. M. Hommels ◽  
R. S. Hermanides ◽  
B. Berta ◽  
E. Fabris ◽  
G. De Luca ◽  
...  

Abstract Background Several studies compared everolimus-eluting bioresorbable scaffolds (EE-BRS) with everolimus-eluting stents (EES), but only few assessed these devices in patients with diabetes mellitus. Aim To evaluate the safety and efficacy outcomes of all-comer patients with diabetes mellitus up to 2 years after treatment with EE-BRS or EES. Methods We performed a post hoc pooled analysis of patient-level data in diabetic patients who were treated with EE-BRS or EES in 3 prospective clinical trials: The ABSORB DM Benelux Study (NTR5447), TWENTE (NTR1256/NCT01066650) and DUTCH PEERS (NTR2413/NCT01331707). Primary endpoint of the analysis was target lesion failure (TLF): a composite of cardiac death, target vessel myocardial infarction or clinically driven target lesion revascularization. Secondary endpoints included major adverse cardiac events (MACE): a composite of all-cause death, any myocardial infarction or clinically driven target vessel revascularization, as well as definite or probable device thrombosis (ST). Results A total of 499 diabetic patients were assessed, of whom 150 received EE-BRS and 249 received EES. Total available follow-up was 222.6 patient years (PY) in the EE-BRS and 464.9 PY in the EES group. The adverse events rates were similar in both treatment groups for TLF (7.2 vs. 5.2 events per 100 PY, p = 0.39; adjusted hazard ratio (HR) = 1.48 (95% confidence interval (CI): 0.77–2.87), p = 0.24), MACE (9.1 vs. 8.3 per 100 PY, p = 0.83; adjusted HR = 1.23 (95% CI: 0.70–2.17), p = 0.47), and ST (0.9 vs. 0.6 per 100 PY, p > 0.99). Conclusion In this patient-level pooled analysis of patients with diabetes mellitus from 3 clinical trials, EE-BRS showed clinical outcomes that were quite similar to EES.


2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
P M Haller ◽  
J T Neumann ◽  
N A Soerensen ◽  
T S Hartikainen ◽  
A Gossling ◽  
...  

Abstract Background Patients with diabetes mellitus (DM) may have elevated levels of high-sensitive cardiac troponin (hs-Tn) despite acute myocardial ischemia being present. However, it is unclear whether this constrains diagnostic strategies in patients with suspected acute myocardial infarction (MI). Purpose We aimed to assess the diagnostic performance of the European Society of Cardiology (ESC) 0/1 hour (h) and 0/3h-algorithms comparing patients with and without DM and to derive optimized cut-offs. Methods We prospectively enrolled patients with symptoms suggestive of MI in two large clinical cohorts and measured hs-TnI at admission (baseline) and 1 (cohort A) and 3h (cohort A+B) thereafter. Patients with ST-elevation MI were excluded. Patients were stratified based on a diagnosis of DM at baseline. Final diagnoses were adjudicated independently by two cardiologists using all clinically available information, including hs-TnT, but blinded to hs-TnI values. Our primary outcomes of interest were safety of rule-out (defined by sensitivity and negative predictive value [NPV]), accuracy of rule-in (defined by specificity and positive predictive value [PPV]) and the overall performance (% of patients adjudicated to either rule-out or -in). For optimized cut-offs, a NPV >99.0% and a PPV >75.0% were targeted. Results DM was prevalent in 563 (15.29%) of 3683 included patients. MI was more prevalent among patients with DM (137 [24.3%] vs. 498 [16.0%], p<0.001). Using the ESC 0/1h-algorithm (Figure), rule-out was safe in diabetics (p for sensitivity = 1.00) with higher NPV in non-diabetics (p<0.001), while the proportion of patients ruled-out was smaller in diabetics (22.3% vs. 41.8%). Accuracy of rule-in was significantly lower in diabetics (specificity p=0.0035, PPV p=0.48), with a higher rule-in rate of patients with DM (29.5% vs. 21.8%). Using the ESC 0/3h-algorithm, safety of rule-out was lower in both groups compared to the ESC 0/1h-algorithm, with again higher NPV for non-DM (sensitivity p=0.18, NPV p<0.001) and a higher proportion of non-DM ruled-out (65.9% vs. 75.2%). Accuracy of rule-in was significantly lower for patients with DM (specificity p=0.0094, PPV p=0.87). Cut-off adjustment to yield pre-defined accuracy measures resulted in: 4ng/L at baseline or 6ng/L with a delta of 2ng/l for rule–out and 90ng/L or a delta of 10ng/L for rule-in with the ESC 0/1h algorithm; for the ESC 0/3h-algorithm cut-offs were 5ng/L with a delta of 20% for rule-out and 50ng/L with a delta of 20% for rule-in. Conclusion Application of the ESC 0/1h- and 0/3h-algorithms in diabetic patients provided reduced safety and accuracy for rule-out and rule-in of MI, respectively. Use of alternative cut-offs resulted in improved diagnostic safety and accuracy. Acknowledgement/Funding Abbott Diagnostics, German Center of Cardiovascular Research, German Heart Foundation, Else-Kröhner-Stiftung angegeben


2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
K Matsushita ◽  
B Marchandot ◽  
S Hess ◽  
M Kibler ◽  
C Sato ◽  
...  

Abstract Introduction Patients with atrial fibrillation (AF) are likely to have multiple co-morbidities and receive anticoagulants after TAVR, which lead to a poor prognosis including bleeding events. Closure time adenosine diphosphate (CT-ADP) is a primary hemostasis point-of-care test used as a surrogate marker of high molecular weight (HMW) multimers defect of Von Willebrand factor (VWF). Our prior studies suggest that prolongation of CT-ADP (&gt;180 seconds) after TAVR is a major determinant of early and late major/life-threatening bleeding complications (MLBCs). Purpose To evaluate the impact of post-procedural CT-ADP &gt;180sec on bleeding events in AF patients. Methods We included 878 patients from our prospective TAVR registry between 2010 and 2019. Bleeding complications were assessed according to the VARC-2 (Valve Academic Research Consortium-2) criteria. Major adverse cardiac and cerebrovascular events (MACCE) was defined as a composite of all-cause death, myocardial infarction, stroke, and heart failure hospitalization within 1-year after TAVR. Ongoing primary haemostasis disorder was defined by post-procedure CT-ADP &gt;180sec. Primary endpoint was the occurrence of MLBCs during the first year and the second endpoint was 1-year MACCE. Results Patients with AF had a higher incidence of all-cause mortality (15% vs. 8%, p=0.002), MACCE (29% vs. 20%, p=0.002), and MLBCs (20% vs. 12%, p=0.001) within 1-year compared to non-AF patients. When the cohort was split into 4 subgroups according to AF and CT-ADP &gt;180sec, patients with AF and CT-ADP &gt;180sec had the highest risk of MLBCs (log-rank test; p&lt;0.001) (Figure). Multivariate Cox regression analysis confirmed that the patients with AF and CT-ADP &gt;180sec had 4.6-fold higher risk of MLBCs within 1 year compared to non-AF patients with CT-ADP ≤180sec (hazard ratio: 4.60; 95% confidence interval: 2.18 - 9.68; p&lt;0.001). Conclusion Among TAVR patients, AF with post-procedural CT-ADP &gt;180 sec was identified as a strong independent predictor of MLBCs at 1-year follow-up. Our study suggest that persistent primary haemostasis disorders contribute to a higher risk of bleeding events particularly in AF patients and may be considered for a tailored and risk-adjusted antithrombotic therapy after TAVR. FUNDunding Acknowledgement Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): Dr Matsushita received a grant from Edwards Lifesciences.


Author(s):  
Dr. Abdulwahab Abuderman

<p>Sudden death with myocardial infarction has always<br />been a challenging issue for the investigators and<br />forensic pathologists. When a person suffering from<br />angina or myocardial infarction is simultaneously<br />suffering from diabetes mellitus issue becomes even<br />more complex for the investigators as usual signs &amp;<br />symptoms of MI may not manifest so as to rouse a<br />suspicion of MI. This study will help the pathologists to<br />understand the microscopic changes of diabetic<br />cardiomyopathy better in a case having MI with<br />diabetes. This study was done in 47 cases to know the<br />pathology of microvasculature and cardiomyocytes in<br />myocardial tissue of diabetic patients and expression of<br />angiogenic factors.</p>


2014 ◽  
Vol 111 (02) ◽  
pp. 273-278 ◽  
Author(s):  
Marc Laine ◽  
Corinne Frere ◽  
Richard Toesca ◽  
Julie Berbis ◽  
Pierre Barnay ◽  
...  

SummaryOptimal P2Y12 receptor blockade is critical to prevent ischaemic recurrence in patients undergoing percutaneous coronary intervention (PCI). We aimed to compare the level of platelet reactivity (PR) inhibition achieved by prasugrel and ticagrelor loading dose (LD) in diabetic acute coronary syndrome (ACS) patients undergoing PCI. We performed a single-center prospective open-label randomised trial. Patients with diabetes mellitus undergoing PCI for an ACS were randomised to receive prasugrel 60 mg or ticagrelor 180 mg. The primary endpoint of the study was the level of platelet reactivity (PR) assessed between 6 and 18 hours post-LD using the VASP index. We randomised 100 diabetic patients undergoing PCI for an ACS. No difference was observed in baseline characteristics between the two groups. In particular, the rate of patient receiving insulin therapy was identical (25 vs 28.6%; p =0.7). Ticagrelor achieved a significantly lower PR compared to prasugrel loading dose (17.3 ± 14.2 vs 27.7 ± 23.3%; p=0.009). In addition the rate of high on-treatment platelet reactivity, defined by a VASP ≥50%, tend to be lower in the ticagrelor group although the difference did not reach statistical significance (6 vs 16%; p=0.2). The rate of low on treatment PR was identical (60 vs 54%; p=0.8). The present study demonstrates that ticagrelor LD is superior to prasugrel LD to reduce PR in ACS patients with diabetes mellitus. Whether the higher potency of ticagrelor could translate into a clinical benefit should be investigated.


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