Abstract 15091: Significant Reductions in Both Adjudicated and Investigator-Reported Ischemic Events in REDUCE-IT

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Deepak L Bhatt ◽  
Robert Giugliano ◽  
Philippe G Steg ◽  
Michael Miller ◽  
Eliot A Brinton ◽  
...  
Keyword(s):  
Primary Endpoint ◽  
Coronary Revascularization ◽  
Hazard Ratio ◽  
Secondary Endpoint ◽  
Icosapent Ethyl ◽  
Clinical Events ◽  
High Degree ◽  
Ischemic Events ◽  
Fatal Myocardial Infarction

Introduction: REDUCE-IT was an event-driven trial that randomized 8,179 statin-treated patients with controlled LDL-C and moderately elevated triglycerides to icosapent ethyl (IPE) 4g daily or placebo, with a median of 4.9 years of follow-up. There was a significant reduction in the prespecified adjudicated rates of the primary endpoint (cardiovascular [CV] death, non-fatal myocardial infarction [MI], non-fatal stroke, coronary revascularization, and unstable angina requiring hospitalization) and of the key secondary endpoint (CV death, MI, stroke), as well as in all the primary endpoint components. We sought to determine the effect of IPE on investigator-reported events. Methods: The Clinical Endpoint Committee (CEC) blindly adjudicated investigator-reported events according to a prespecified charter. Medical records and reports were also reviewed to assess for clinical events not reported by investigators. An endpoint management team compiled and electronically provided event packets to the CEC via an adjudication database. The CEC Chair provided final adjudication if the two primary adjudicators could not reach consensus. Results: IPE significantly reduced the rate of the primary endpoint (hazard ratio 0.74, p=0.0000000002) and the key secondary endpoint (hazard ratio 0.75, p=0.000007) as reported by the site investigators, with consistent benefits in each component of the primary endpoint (Table). There was a high degree of concordance between investigator-reported and adjudicated endpoints. Conclusions: Icosapent ethyl significantly reduced multiple types of ischemic events, both by independent, blinded adjudication as well as by investigator-reported assessment. These results underscore the robustness of the benefits of icosapent ethyl seen in REDUCE-IT.

REDUCE-IT: total ischemic events reduced across the full range of baseline LDL cholesterol and other key subgroups

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
D Bhatt ◽  
M Miller ◽  
P.G Steg ◽  
E.A Brinton ◽  
T.A Jacobson ◽  
...  
Keyword(s):  
Primary Endpoint ◽  
Negative Binomial ◽  
Absolute Risk ◽  
Full Range ◽  
Secondary Endpoint ◽  
Nonfatal Stroke ◽  
Funding Source ◽  
Icosapent Ethyl ◽  
Prescription Form ◽  
Ischemic Events

Abstract Background REDUCE-IT (Reduction of Cardiovascular Events with Icosapent Ethyl-Intervention Trial), a study of 8,179 randomized statin-treated patients with elevated triglycerides (TG) and increased cardiovascular (CV) risk followed for a median of 4.9 years, demonstrated robust results. Icosapent ethyl (IPE), a pure and stable prescription form of eicosapentaenoic acid, 4g/day reduced both time-to-first and total primary endpoint ischemic events (CV death, nonfatal myocardial infarction [MI], nonfatal stroke, coronary revascularization, or hospitalization for unstable angina) by 25% (HR 0.75; 95% CI 0.68–0.83; p<0.0001) and 30% (rate ratio 0.70; 95% CI 0.62–0.78; p<0.0001), respectively. Similar substantial reductions in first and total key secondary endpoint ischemic events (composite of CV death, nonfatal MI, or nonfatal stroke) were also observed. Demographic and baseline disease characteristics were generally balanced across treatment groups. Time-to-first event analyses showed robust and generally consistent benefit across subgroups. Previous total event analyses by baseline TG demonstrated large, consistent, statistically significant reductions across tertiles, suggesting the CV benefit of IPE is tied primarily to non-TG factors. Purpose Further explore the extent to which IPE reduced total primary and key secondary events across prespecified baseline demographic, disease, treatment, and lipid/lipoprotein/inflammatory biomarker subgroups. Methods Total events across subgroups were assessed with the prespecified negative binomial regression method. Main outcomes were total (first and subsequent) primary and key secondary composite endpoint events. Results Median baseline LDL-C levels in ascending tertiles were 58, 76, and 96 mg/dL; there were large, significant relative reductions in total primary endpoint events with IPE across tertiles (35%, 28%, and 27%, respectively; interaction p=0.62), with parallel substantial absolute risk reductions. Similar, significant relative reductions of 33%, 28%, and 24% in total key secondary endpoint events were observed, along with substantial absolute risk reductions. Total events analyses of prespecified subgroups also demonstrated robust and generally consistent findings for the primary and key secondary composite endpoints. Conclusion REDUCE-IT demonstrated substantial reductions in first and total primary and key secondary endpoint ischemic events, with robust and generally consistent results across baseline TG and LDL-C levels, as well as other prespecified baseline biomarker, demographic, disease, and treatment subgroups. These analyses provide useful insights for clinicians considering the range of patients who may benefit from IPE therapy and suggest that mechanisms beyond the lipid/lipoprotein/inflammatory pathways tested, including mechanisms beyond the LDL receptor pathways, may contribute to the observed substantial reductions in total ischemic burden with IPE therapy. Funding Acknowledgement Type of funding source: Other. Main funding source(s): The study was funded by Amarin Pharma, Inc.

Abstract 12811: Clinical Outcomes and Prognostic Impact of Triglyceride Deposit Cardiomyovasculopathy Among Hemodialysis Patients Suspected of Coronary Artery Disease

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Tomohiro Onishi ◽  
Yusuke Nakano ◽  
Ken-ichi Hirano ◽  
Yasuyuki Nagasawa ◽  
Atomu Tajima ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Primary Endpoint ◽  
Cardiovascular Mortality ◽  
Cardiovascular Death ◽  
Hazard Ratio ◽  
Secondary Endpoint ◽  
Fatal Stroke ◽  
Artery Disease

Introduction: Hemodialysis (HD) has been reported as a strong prognostic factor in patients with cardiovascular disease. It is unknown how much triglyceride deposit cardiomyovasculopathy (TGCV), a novel identified rare cardiovascular disorder, is associated with cardiovascular mortality among HD patients. Hypothesis: We hypothesized that comorbidity of TGCV in HD patients who suspected of CAD plays a critical role for cardiovascular outcomes in this population. Methods: We examined the data obtained from 83 consecutive HD patients suspected of coronary artery disease who underwent both [123I]-β-methyl-iodophenyl-pentadecanoic acid (BMIPP) scintigraphy and subsequent coronary angiography (CAG). The primary endpoint was a composite of cardiovascular death, non-fatal myocardial infarction (MI), or non-fatal stroke up to 5 years of follow-up. The key secondary endpoint was a composite of cardiovascular death, non-fatal MI, non-fatal stroke, target vessel revascularization, or any hospitalization for heart failure. Results: A total of 83 HD patients were grouped into either the definite TGCV (17 patients), the probable TGCV (22 patients), or the non-TGCV control group (44 patients). At the end of the follow-up period for a median of 4.7 years, a primary endpoint event occurred in 58.8% of the definite TGCV patients (hazard ratio, 8.06; 95% confidence interval [CI], 2.52-25.8, Log-rank p<0.001) and 27.3% of the probable TGCV patients, as compared to 9.1% of the non-TGCV control patients; the corresponding rates of the key secondary endpoint were 88.2% for the definite TGCV patients (hazard ratio, 6.36; 95% CI, 2.89-14.0, Log-rank p<0.001) and 59.1% for the probable TGCV patients. In the multivariate Cox proportional hazard analyses after adjustment for confounding factors, various variables related to mortality on HD patients, or variables known as a classical cardiovascular risk, the definite TGCV was significantly and independently associated with cardiovascular mortality and outcomes in any of the three models. Conclusions: Comorbidity of TGCV in patients on HD was associated with increased risk of cardiovascular events including cardiovascular death, which might highlight the potential therapeutic target.

REDUCE-IT: outcomes by baseline statin type

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
D Bhatt ◽  
M Miller ◽  
P.G Steg ◽  
E.A Brinton ◽  
T.A Jacobson ◽  
...  
Keyword(s):  
Statin Therapy ◽  
Risk Reduction ◽  
Coronary Revascularization ◽  
Secondary Endpoint ◽  
Nonfatal Stroke ◽  
Funding Source ◽  
Icosapent Ethyl ◽  
Prescription Form ◽  
One Year ◽  
The Impact

Abstract Background REDUCE-IT (Reduction of Cardiovascular Events with Icosapent Ethyl-Intervention Trial) randomized 8,179 statin-treated patients with elevated triglycerides and increased cardiovascular (CV) risk to either icosapent ethyl (IPE), a pure, stable prescription form of eicosapentaenoic acid, 4g/day or placebo. IPE significantly reduced time to first occurrence of the primary composite endpoint of major adverse CV events (CV death, nonfatal myocardial infarction [MI], nonfatal stroke, coronary revascularization, or hospitalization for unstable angina) (HR 0.75, CI 0.68–0.83) and key secondary endpoint events (composite of CV death, nonfatal MI, or nonfatal stroke) (HR 0.74, CI 0.65–0.83) versus placebo (all p&lt;0.0001). A modest reduction in placebo-corrected LDL-C was observed (−6.6%; p&lt;0.0001). The mechanisms for the CV benefit of icosapent ethyl are not fully understood. Purpose Explore the impact of statin type and lipophilic/lipophobic category on outcomes, and on LDL-C, to further consider the possible relevance of LDL-C pathways to the observed CV benefit of icosapent ethyl. Methods Primary and key secondary endpoint analyses and LDL-C changes from baseline were explored by individual statin type (atorvastatin, simvastatin, rosuvastatin, or pravastatin) at baseline, and then by categorizing these statins into lipophilic (i.e., hydrophobic: atorvastatin, simvastatin) and lipophobic (i.e., hydrophilic: rosuvastatin, pravastatin) statin groups; 96.1% of patients fell within these individual statin groups. Results CV outcomes were similar across statin types (interaction p=0.61) and lipophilic/lipophobic categories (interaction p=0.51) (Figure). Statin type and category had a similar lack of meaningful impact on the modest placebo-corrected median LDL-C changes from baseline to one year, which ranged from −5.8 to −8.4% (all p≤0.0003). Conclusion No meaningful treatment differences in the primary or key secondary endpoints across statin type or lipophilic/lipophobic category were observed. A similar lack of treatment difference was observed in LDL-C changes from baseline to one year. Therefore, the LDL-C changes and CV risk reduction in REDUCE-IT appear independent of the type of concomitant statin therapy. These data provide clinicians with additional insight regarding concomitant statin therapy considerations when prescribing icosapent ethyl and suggest there are important mechanisms of action for the substantial CV risk reduction observed with icosapent ethyl that are distinct from the LDL receptor pathway. Funding Acknowledgement Type of funding source: Other. Main funding source(s): The study was funded by Amarin Pharma, Inc.

P5639Risk stratification for mortality using electrocardiographic markers based on 24-hour holter recordings: the JANIES-SHD study

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
T Kinoshita ◽  
K Hashimoto ◽  
K Yoshioka ◽  
Y Miwa ◽  
K Yodogawa ◽  
...  
Keyword(s):  
Heart Disease ◽  
Risk Stratification ◽  
Primary Endpoint ◽  
Left Ventricular ◽  
Hazard Ratio ◽  
Secondary Endpoint ◽  
Cardiac Mortality ◽  
Holter Ecg ◽  
All Cause Mortality ◽  
Holter Recordings

Abstract Background Recent guidelines have stated that reduced left ventricular ejection fraction (LVEF) is the gold standard marker for identifying patients at risk for cardiac mortality. Although reduced LVEF identifies patients at an increased risk of cardiac arrest, sudden cardiac deaths (SCDs) occur considerably more often in patients with relatively preserved LVEF. Current guidelines on SCD risk stratification do not adequately cover this general population pool. Several noninvasive electrocardiographic (ECG) risk stratifiers that reflect depolarization abnormality, repolarization abnormality, and autonomic imbalance have been evaluated so far. With current therapeutic advances using new medicines or devices, an LVEF is often preserved in patients with structural heart disease (SHD). However, the usefulness of noninvasive ECG markers for risk stratification in such a patient population has not yet been elucidated. Purpose This study aimed to assess clinical indices and ECG markers based on 24-hour Holter ECG recordings for predicting cardiac mortality in patients with SHD who have left ventricular dysfunction (LVD) but relatively preserved LVEF. Methods In total, 1,829 patients were enrolled into the Japanese Multicenter Observational Prospective Study (JANIES study). In this study, we analyzed data of 719 patients (569 men, age 64±13 years) with SHD including mainly ischemic heart disease (65.8%). As ECG markers based on 24-hour Holter recordings, nonsustained ventricular tachycardia (NSVT), ventricular late potentials, and heart rate turbulence (HRT) were assessed. The primary endpoint was all-cause mortality, and the secondary endpoint was fatal arrhythmic events. Results During a mean follow-up of 21±11 months, all-cause mortality was eventually observed in 39 patients (5.4%). Among those patients, 32 patients (82%) suffered from cardiac causes such as heart failure and arrhythmia. Multivariate Cox regression analysis showed that after adjustment for age and LVEF, documented NSVT (hazard ratio=2.82, 95% confidence interval [CI]: 1.38–5.76, P=0.005) and abnormal HRT (hazard ratio=2.31, 95% CI: 1.15–4.65, P=0.02) were significantly associated with the primary endpoint. These two ECG markers also had significant predictive values with the secondary endpoint. The combined assessment documented NSVT and abnormal HRT improved predictive accuracy. Conclusion This study demonstrated that combined assessment of documented NSVT and abnormal HRT based on 24-hour Holter ECG recordings are recommended for predicting future serious events in SHD patients who have relatively preserved LVEF. Acknowledgement/Funding Grants-in-Aid (21590909, 24591074, and 15K09103 to T.I.) for Scientific Research from the Ministry of Education, Culture, Sports, Science, and Technol

Predictive Value of Methods Measuring Platelet Activation for Ischemic Events in Patients Receiving Clopidogrel: A Systematic Review and Meta-analysis

2019 ◽  
Vol 24 (44) ◽  
pp. 5313-5333 ◽  
Author(s):  
Zhe Wang ◽  
Qiufen Xie ◽  
Qian Xiang ◽  
Yanjun Gong ◽  
Jie Jiang ◽  
...  
Keyword(s):  
Predictive Value ◽  
Light Transmission ◽  
Meta Analysis ◽  
Coronary Intervention ◽  
Clinical Events ◽  
Percutaneous Coronary ◽  
Light Transmission Aggregometry ◽  
Ischemic Events ◽  
Higher Sensitivity

This study investigates the efficiency and predictive value of light-transmission aggregometry (LTA), vasodilator-stimulated phosphoprotein (VASP) and VerifyNow for ischemia in patients undergoing percutaneous coronary intervention (PCI). Studies that used LTA, VASP or VerifyNow to predict ischemia were included, and their quality and efficiency were analyzed using Review Manager 5.3. The sensitivity and specificity of subgroup studies based on the outcome, cut-off value, and follow-up days were calculated and the summary ROC (sROC) curves were compared after having been fitted. Thirty-one studies including a total of 17,314 participants were analyzed. LTA, VASP and VerifyNow presented a considerable efficiency in predicting ischemic clinical events. In the subgroup analysis, the sensitivities of LTA, VASP and VerifyNow in predicting cardiac death, all-cause death, myocardial infarction, stent thrombosis, stroke, and revascularization were 0.40/0.63/0.62, 0.47/0.56/0.39, 0.40/0.48/0.60, 0.44/0.58/0.70, 0.29/not applicable/0.60 and 0.44/0.57/0.37, respectively and the specificities of LTA, VASP, and VerifyNow were 0.85/0.48/0.63, 0.73/0.52/0.63, 0.74/0.55/0.64, 0.75/0.47/0.61, 0.72/not applicable/ 0.61, and 0.70/0.47/0.67, respectively. LTA showed a higher sensitivity in predicting the outcomes over six months than those within six months, while VerifyNow prediction sensitivity was found to be higher within six months. Meanwhile, VerifyNow showed no statistically significant higher AUC of sROC in comparison to LTA and VASP in predicting ischemic events in patients undergoing clopidogrel treatment. The cut-off values of LTA, VASP and VerifyNow were suggested to be 56%, 50% and 235 respectively according to our study.

scholarly journals The impact of catheter ablation for patients with asymptomatic atrial fibrillation: subanalysis of kansai plus atrial fibrillation (kpaf) registry

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
M Pak ◽  
A Kobori ◽  
S Shizuta ◽  
Y Sasaki ◽  
T Toyota ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Catheter Ablation ◽  
Primary Endpoint ◽  
Hazard Analysis ◽  
Secondary Endpoint ◽  
Asymptomatic Patients ◽  
Significant Difference ◽  
Secondary Endpoints ◽  
The Impact

Abstract Background Catheter ablation (CA) of atrial fibrillation (AF) for symptomatic patients improves the quality of life and prognosis of patients with heart failure. However, the impact of CA for asymptomatic patients is still controversial. Purpose We aimed to investigate the clinical outcomes of CA of AF for asymptomatic patients compared to those for symptomatic patients. Methods A total of 5,013 patients from the Kansai Plus Atrial Fibrillation (KPAF) Registry who underwent CA were screened. The patients were divided into three groups by type of AF; paroxysmal (PAF), persistent (PEAF) and long standing (LSAF) and the patients in each type of AF were divided into two groups: asymptomatic and symptomatic. The primary endpoint was recurrent supraventricular tachyarrhythmias lasting for more than 30 seconds during follow-up 4 years after CA. The secondary endpoint was a composite of cardiovascular, cerebral, and gastrointestinal events during follow-up 4 years after CA. The incidence of complications related to CA between asymptomatic and symptomatic patients was also evaluated. Kaplan–Meier analysis was employed to estimate the primary and secondary endpoints. The statistical differences in primary and secondary endpoints between asymptomatic and symptomatic patients were evaluated using a log–rank test. The impact of symptom due to AF on the primary and secondary endpoint was evaluated using a Cox hazard analysis. The difference in incidence of complications between asymptomatic and symptomatic patients was evaluated using a chi–square test. Results In this study population, PAF was the most frequent at 64.4%, followed by PEAF (22.7%) and LSAF (13.0%). There were some significant differences in the baseline characteristics between asymptomatic and symptomatic patients in each type of AF. The proportion of male was significantly higher in asymptomatic patients than symptomatic patients in PAF (81.2% versus 67.2%, p&lt;0.001) and PEAF (86.4% versus 74.3%, p&lt;0.001). Left atrial diameter was larger in asymptomatic patients than symptomatic patients only in PAF (40±6mm versus 38±6mm, p&lt;0.001). In all types of AF, there was no significant difference in primary endpoint between asymptomatic and symptomatic patients as follows: 37.5% versus 40.6% (p=0.6) in PAF, 45.2% versus 55.1% (p=0.09) in PEAF and 59.3% versus 63.6% (p=1.0) in LSAF. There was also no significant difference in secondary endpoint between asymptomatic and symptomatic patients: 7.1% versus 6.8% (p=0.7) in PAF, 5.4% versus 8.7% (p=0.3) in PEAF and 4.4% versus 5.1% (p=0.5) in LSAF. In a Cox hazard analysis, the symptom did not affect both of the primary and secondary endpoints in each type of AF. In regard to the incidence of complications related to CA, there was no significant difference between asymptomatic and symptomatic patients in each type of AF. Conclusion CA of AF for asymptomatic patients can be safe and can lead to equivalent outcomes as well as symptomatic patients. Funding Acknowledgement Type of funding source: None

scholarly journals Prevalence and clinical outcomes of triglyceride deposit cardiomyovasculopathy among haemodialysis patients

Heart ◽  
2020 ◽  
Vol 107 (2) ◽  
pp. 127-134 ◽  
Author(s):  
Tomohiro Onishi ◽  
Yusuke Nakano ◽  
Ken-ichi Hirano ◽  
Yasuyuki Nagasawa ◽  
Toru Niwa ◽  
...  
Keyword(s):  
Primary Endpoint ◽  
Cardiovascular Death ◽  
Suspected Coronary Artery Disease ◽  
Control Group ◽  
Multivariate Models ◽  
Potential Therapeutic Target ◽  
Increased Risk ◽  
Artery Disease ◽  
Fatal Myocardial Infarction

ObjectiveTo evaluate the effect of triglyceride deposit cardiomyovasculopathy (TGCV) on the cardiovascular outcomes in haemodialysis (HD) patients with suspected coronary artery disease (CAD).MethodsThis retrospective single-centre observational study included data from the cardiac catheter database of Narita Memorial Hospital between April 2011 and March 2017. Among 654 consecutive patients on HD, the data for 83 patients with suspected CAD who underwent both [123I]-β-methyl-iodophenyl-pentadecanoic acid scintigraphy and coronary angiography were analysed. Patients were divided into three groups: definite TGCV (17 patients), probable TGCV (22 patients) and non-TGCV control group (44 patients). The primary endpoint was a composite of cardiovascular death, non-fatal myocardial infarction and non-fatal stroke assessed for up to 5 years of follow-up.ResultsThe prevalence of definite TGCV was approximately 20% and 2.6% among consecutive HD patients with suspected CAD and among all HD patients, respectively. At the end of the median follow-up period of 4.7 years, the primary endpoint was achieved in 52.9% of the definite TGCV patients (HR, 7.45; 95% CI: 2.28 to 24.3; p<0.001) and 27.3% of the probable TGCV patients (HR, 3.28; 95% CI: 0.93 to 11.6; p=0.066), compared with that in 9.1% of the non-TGCV control patients. Definite TGCV was significantly and independently associated with cardiovascular mortality and outcomes among HD patients in all multivariate models.ConclusionsTGCV is not uncommon in HD patients and is associated with an increased risk of cardiovascular events including cardiovascular death. Thus, TGCV might be a potential therapeutic target.

Long-Term Prognostic Value of Stress Cardiovascular Magnetic Resonance–Related Coronary Revascularization to Predict Death: A Large Registry With >200 000 Patient-Years of Follow-Up

2021 ◽  
Author(s):  
Théo Pezel ◽  
Thierry Unterseeh ◽  
Philippe Garot ◽  
Thomas Hovasse ◽  
Francesca Sanguineti ◽  
...  
Keyword(s):  
Lower Incidence ◽  
Prognostic Value ◽  
Coronary Revascularization ◽  
Hazard Ratio ◽  
Gadolinium Enhancement ◽  
Inducible Ischemia ◽  
Stress Cmr ◽  
Stress Cardiovascular Magnetic Resonance

Background: Although the benefit of coronary revascularization in patients with stable coronary disease is debated, data assessing the potential interest of stress cardiovascular magnetic resonance (CMR) to guide coronary revascularization are limited. We aimed to assess the long-term prognostic value of stress CMR-related coronary revascularization in consecutive patients from a large registry. Methods: Between 2008 and 2018, a retrospective cohort study with a median follow-up of 6.0 years (interquartile range, 5.0–8.0) included all consecutive patients referred for stress CMR. CMR-related coronary revascularization was defined by any coronary revascularization performed within 90 days after CMR. The primary outcome was all-cause death based on the National Death Registry. Results: Among the 31 762 consecutive patients (mean age 63.7±12.1 years and 65.7% males), 2679 (8.4%) died at 206 453 patient-years of follow-up. Inducible ischemia and late gadolinium enhancement by CMR were associated with death (both P <0.001). In multivariable Cox regression, inducible ischemia and late gadolinium enhancement were independent predictors of death (hazard ratio, 1.61 [99.5% CI, 1.41–1.84]; hazard ratio, 1.62 [99.5% CI, 1.41–1.86], respectively; P <0.001). In the overall population, CMR-related coronary revascularization was an independent predictor of greater survival (hazard ratio, 0.58 [99.5% CI, 0.46–0.74]; P <0.001). In 1680, 1:1 matched patients using a limited number of variables (840 revascularized, 840 nonrevascularized), CMR-related revascularization was associated with a lower incidence of death in patients with severe inducible ischemia (≥6 segments, P <0.001) but showed no benefit in patients with mild or moderate ischemia (<6 segments, P =0.109). Using multivariable analysis in the propensity-matched population, CMR-related revascularization remained an independent predictor of a lower incidence of all-cause mortality (hazard ratio, 0.66 [99.5% CI, 0.54–0.80], P <0.001). Conclusions: In this large observational series of consecutive patients, stress perfusion CMR had important incremental long-term prognostic value to predict death over traditional risk factors. CMR-related revascularization was associated with a lower incidence of death in patients with severe ischemia.

Association of thrombelastographic parameters with post-stenting ischemic events

2015 ◽  
Vol 9 (2) ◽  
pp. 192-195 ◽  
Author(s):  
Bo Wang ◽  
Xiao-Qing Li ◽  
Ning Ma ◽  
Dapeng Mo ◽  
Feng Gao ◽  
...  
Keyword(s):  
Platelet Function ◽  
Primary Endpoint ◽  
Characteristic Curve ◽  
Fibrin Clot ◽  
Intracranial Artery ◽  
Ischemic Cerebrovascular Disease ◽  
Intracranial Artery Stenosis ◽  
Ischemic Attack ◽  
Ischemic Events

Background and purposeThrombelastography (TEG) is widely used for the measurement of platelet function. However, few studies have investigated the TEG parameters in patients receiving extracranial or intracranial artery stenting for ischemic cerebrovascular disease. This study sought to describe the association of TEG parameters before the procedure with post-procedural ischemic events after extracranial or intracranial artery stenting.MethodsPatients in whom stenting was performed for extracranial or intracranial artery stenosis (70–99%) were recruited into the study. Blood samples were obtained for TEG to assess platelet function before stenting. The primary endpoint was ischemic stroke or transient ischemic attack in the territory of the stented artery.ResultsA total of 218 patients were included in the study. During a mean follow-up period of 132 days (range 98–226 days), 18 (8.3%) primary endpoint events were recorded. Compared with patients without ischemic events, the ADP-induced platelet-fibrin clot strength (MAADP) was significantly higher (41.57±15.10 vs 33.50±13.86, p=0.020) and the ADP inhibition rate (ADP%) was significantly lower in patients with ischemic events (39.54±23.15 vs 55.29±24.43, p=0.009). Multivariate analysis identified MAADP and ADP% as significant independent predictors of subsequent ischemic events with HRs of 1.036 and 0.965, respectively. From receiver operating characteristic curve analysis, MAADP >49.95 mm had the best predictive value of ischemic events.ConclusionsOur study suggests that TEG parameters MAADP and ADP% are associated with subsequent ischemic events in patients with extracranial or intracranial stents.Clinical trial numberNCT01925872.

Pembrolizumab versus placebo as post-nephrectomy adjuvant therapy for patients with renal cell carcinoma: Randomized, double-blind, phase III KEYNOTE-564 study.

2021 ◽  
Vol 39 (18_suppl) ◽  
pp. LBA5-LBA5
Author(s):  
Toni K. Choueiri ◽  
Piotr Tomczak ◽  
Se Hoon Park ◽  
Balaji Venugopal ◽  
Tom Ferguson ◽  
...  
Keyword(s):  
High Risk ◽  
Adjuvant Therapy ◽  
Primary Endpoint ◽  
Immune Therapy ◽  
Secondary Endpoint ◽  
Phase Iii ◽  
Statistical Hypothesis ◽  
Attractive Potential ◽  
Meaningful Improvement

LBA5 Background: Relapse after surgery for high-risk clear cell RCC (ccRCC) is associated with shortened life expectancy. Effective perioperative therapy to reduce this risk remains an unmet need. Adjuvant immune therapy is an attractive potential strategy for these pts. We conducted the KEYNOTE-564 trial to evaluate pembro vs placebo as adjuvant therapy for pts with RCC. Methods: KEYNOTE-564 is a phase III multicenter trial of pembro vs placebo in pts with histologically confirmed ccRCC, with intermediate-high risk (pT2, Gr 4 or sarcomatoid, N0 M0; or pT3, any Gr, N0 M0), high risk (pT4, any Gr, N0 M0; or pT any stage, any Gr, N+ M0), or M1 NED (no evidence of disease after primary tumor + soft tissue metastases completely resected ≤1 year from nephrectomy) (Leibovich et al, 2003; Fuhrman et al, 1982). Pts had undergone surgery ≤12 wks prior to randomization; had no prior systemic therapy; had ECOG PS 0 or 1. Study treatment was given for up to 17 cycles (≈1 yr). The primary endpoint was disease-free survival (DFS) per investigator assessment in all randomized pts (ITT population). Overall survival (OS) was a key secondary endpoint. Safety/tolerability were secondary endpoints, assessed in all treated pts. Results: Between Jun 30, 2017 and Sept 20, 2019, 994 pts were randomized 1:1 to pembro (n=496) or placebo (n=498). As of data cutoff date of Dec 14, 2020, median (range) follow-up, defined as time from randomization to data cutoff, was 24.1 (14.9−41.5) mo. No pts remain on study treatment. Baseline characteristics were generally balanced between arms. At first prespecified interim analysis, the primary endpoint of DFS was met (median not reached [NR] for both arms, HR 0.68, 95% CI 0.53−0.87; P=0.0010 [one-sided]). The estimated DFS rate at 24 mo was 77.3% with pembro vs 68.1% with placebo. Overall, DFS benefit was consistent across subgroups. A total of 51 OS events were observed (18 in the pembro arm, 33 in the placebo arm). Median OS was NR for both arms (HR 0.54, 95% CI 0.30−0.96; P=0.0164 [one-sided]); the p-value did not cross the statistical hypothesis testing boundary. The estimated OS rate at 24 mo was 96.6% with pembro vs 93.5% with placebo. 470 pts (96.3%) and 452 pts (91.1%) experienced ≥1 all-cause adverse events (AEs) with pembro vs placebo, respectively. Grade 3-5 all-cause AEs occurred in 158 pts (32.4%) with pembro and 88 pts (17.7%) with placebo. No deaths related to pembro occurred. Conclusions: Pembro demonstrated a statistically significant and clinically meaningful improvement in DFS vs placebo in pts with intermediate-high, high risk or M1 NED RCC. Additional follow-up is planned for the key secondary endpoint of OS. KEYNOTE-564 is the first positive phase III study with a checkpoint inhibitor in adjuvant RCC, and these results support pembro as a potential new standard of care for pts with RCC in the adjuvant setting. Clinical trial information: NCT03142334.

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