Rate Of Recurrent Events Research Articles

Reduced Recurrent Ischemic Event Rate for Patients Undergoing Invasive Carotid Artery Intervention

Introduction - Patients with a symptomatic carotid artery stenosis risk a recurrent ischemic event during the waiting time to intervention or in the perioperative period. As the risk of recurrence is highest in the early phase after the presenting event, recent strategies recommend short delay to intervention but there are concerns that the possible benefit from early intervention may be counterbalanced by an increased perioperative complication rate. The aim of this national audit was to study the effects of more expedient carotid intervention on the risk of recurrent ischemic events. Methods - The Swedish Vascular Registry (Swedvasc) covers all centers in the country performing carotid interventions, and all registrations for symptomatic carotid artery stenosis from May 2008 to December 2015 were analyzed, focusing on recurrent ischemic events in the delay to surgical intervention and during the 30-day perioperative follow-up. The National Prescribed Drug Registry provided data on preventive medications prior to hospitalization for the carotid procedure. Results - In Swedvasc 6814 procedures for symptomatic carotid stenosis were registered during the time period. The mean age was 72 (±8) years and 68% were male. The presenting events were TIA in 58%, amaurosis fugax in 22% and stroke in 20%. Baseline demographic variables, comorbidities and secondary prevention pharmacotherapy when admitted for the procedure was similar during study period. The waiting time from the presenting neurological event to carotid intervention decreased from 13 (IQR 6-27) to 7 days (IQR 4-12) during the study period. Importantly, the proportion of recurrent ischemic events decreased over time from 30% (CI 28-33%) in 2008-2009 to 21% (CI 19–23%) in 2014-2015 (p< 0.01, χ2test). The perioperative stroke and/or death rate was 3.6%, with a decreasing trend during study period (5.3% 2008-2009 vs. 3.2% 2014-2015, p=0.05). Conclusion - In this population-based study, the overall risk for a recurrent ischemic event, from the presenting event until the 30-day follow-up, was markedly decreased during the time period. Efforts in reducing the delay to surgery were not counterbalanced by any increase in the perioperative complication rate.

Sex-discrete role of depressive symptomatology on 10-year first and recurrent cardiovascular disease incidence: results from ATTICA and GREECS prospective studies

ObjectiveThe sex-specific effect of depressive symptomatology on 10-year first and recurrent cardiovascular disease (CVD) events was evaluated. MethodsThe Greek samples from ATTICA (2002-2012, n = 845 free-of-CVD subjects) and GREECS (2004-2014, n = 2,172 subjects with acute coronary syndrome (ACS)) prospective epidemiological studies with baseline psychological assessments were used for the first and the recurrent event, respectively. Depressive symptomatology was assessed at baseline, through Zung Self-Rating Depression Scale in the ATTICA study, and through the Center for Epidemiological Studies-Depression scale in the GREECS study. ResultsACS as well as free-of-CVD women scored significantly higher for depressive symptomatology. Men scored higher than women against first (19.7% vs. 11.7%) and subsequent CVD events (38.8% vs. 32.9%). In participants with depressive symptoms man-to-woman first and recurrent CVD event rate ratio was below 1, confirming that depressive women were more likely to have a CVD event than depressive men. Multiadjusted analysis revealed that depressive symptomatology had an independent aggravating effect on the first (hazard ratio (HR) = 2.72, 95% confidence interval (95% CI) 1.50, 9.12) and recurrent (HR = 1.31, 95% CI 1.01, 1.69) CVD events only in women. Mediation analysis in women revealed that 35% (23%, 44%) of excess first-CVD-event risk of depressive symptoms was attributed to conventional risk factors. The respective number for recurrent CVD events was 46% (23%, 53%); different patterns of ranking regarding the mediating effect corresponding to each adjustment factor were observed. ConclusionsThe present work augments prior evidence that psychological stressors possess important drivers of CVD onset and progression mainly in women, while it gives rise to research toward unidentified paths behind this claim.

Poly (l-lactic acid) bioresorbable scaffolds versus metallic drug-eluting stents for the treatment of coronary artery disease: A meta-analysis of 11 randomized trials.

Bioresorbable vascular scaffolds (BVS) have been proposed for overcoming the long-term limitations of permanent metallic stents, while theoretically warranting similar advantages in plaque stabilization and anti-restenotic drug delivery in the early postrevascularization phase. However, increased rates of malapposition, restenosis, or thrombosis have emerged from initial trials with BVS, that were nevertheless underpowered for the evaluation of the real outcome benefits of these coronary devices. The recent completion of newer randomized clinical trials paves the way to the present meta-analysis, aiming at the comparison of Poly (l-Lactic acid) BVS (PLLA-BVS) versus metallic drug-eluting stents (DES) in the treatment of coronary stenoses. Literature and main scientific session abstracts were searched for randomized clinical trials (RCTs) comparing drug-eluting BVS versus metallic DES for the treatment of coronary artery disease (CAD). The primary efficacy endpoint was mortality, secondary endpoints were cardiovascular death, myocardial infarction, target lesion revascularization (TLR), stent thrombosis and the composite of device-oriented target lesion failure (TLF). We included 11 randomized trials, for a total population of 10,707 patients, 54.5% treated with BVS. The major indication for PCI was stable CAD, whereas acute coronary syndrome represented 30% of the patients. At a mean follow-up of 2.64 years (1-5 years), mortality occurred in 2.71% of the patients, with no difference according to the type of implanted stent (OR[95%CI] = 0.94 [0.74, 1.20], p = .62). No interaction was observed according to patients' risk profile or the rate of diabetes and ACS. However, a significant increase in myocardial infarction, stent thrombosis, TLR and TLF was observed with BVS as compared to DES. The present meta-analysis provides the most updated data on the use of PLLA-BVS for the treatment of CAD. We documented a poorer performance of these new coronary devices, as compared to new generation metallic DES, being associated with an increased rate of recurrent cardiovascular events. However, such ischemic complications did not impact on mortality, with a comparable survival independently from the type of stent.

Incidence and risk factors for recurrent cardiovascular disease in middle-eastern adults: a retrospective study

BackgroundIndividuals with established cardiovascular disease (CVD) and risk factors such as age, smoking, hypertension, and diabetes mellitus are at an increased risk of recurrent cardiovascular events and death. The incidence rate of recurrent CVD events varies between countries and populations. The United Arab Emirates (UAE) has one of the highest age-standardized death rates for CVD worldwide. The aim of our study was to estimate the incidence rates and determine the predictors of recurrent CVD events among UAE nationals.MethodsWe investigated an outpatient-based cohort of patients with a history of CVD visiting Tawam Hospital between April 1, 2008 and December 31, 2008. They were followed-up until July 31, 2018. Univariable and multivariable Cox proportional hazards regression models were used to determine the association between major CVD risk factors and the risk of CVD recurrence.ResultsA total of 216 patients (167 males, 49 females) with a history of CVD were included. They were followed for a median (interquartile range) of 8.1 (5.5–9.3) years, with a total of 1184 patient-years of follow-up. The overall incidence rate of recurrent CVD events was 92.1 per 1000 patient-years. The 8-year cumulative incidence was 73.7%. Age, female sex, and diabetes mellitus were significant predictors of recurrent CVD events, where females had a 1.96 times higher risk of recurrent CVD events than males.ConclusionSignificant predictors of recurrent CVD events are older age, female sex, and diabetes mellitus. The incidence rate of recurrent CVD events was 92.1 per 1000 patient-years. Preventive measures, based on international guidelines for CVD management, may improve CVD morbidity and mortality in the UAE population.

Penalized survival models for the analysis of alternating recurrent event data.

Recurrent event data are widely encountered in clinical and observational studies. Most methods for recurrent events treat the outcome as a point process and, as such, neglect any associated event duration. This generally leads to a less informative and potentially biased analysis. We propose a joint model for the recurrent event rate (of incidence) and duration. The two processes are linked through a bivariate normal frailty. For example, when the event is hospitalization, we can treat the time to admission and length-of-stay as two alternating recurrent events. In our method, the regression parameters are estimated through a penalized partial likelihood, and the variance-covariance matrix of the frailty is estimated through a recursive estimating formula. Moreover, we develop a likelihood ratio test to assess the dependence between the incidence and duration processes. Simulation results demonstrate that our method provides accurate parameter estimation, with a relatively fast computation time. We illustrate the methods through an analysis of hospitalizations among end-stage renal disease patients.

D-dimer testing, with gender-specific cutoff levels, is of value to assess the individual risk of venous thromboembolic recurrence in non-elderly patients of both genders: a post hoc analysis of the DULCIS study

Male patients, especially the young, are at a higher risk of recurrent venous thromboembolism (RVTE) than females. Recent scientific reports show the use of D-dimer does not help predict RVTE risk in males. In the present report, we reviewed the data obtained in the DULCIS study (main report published in Blood 2014), focusing on D-dimer results recorded in non-elderly patients of both genders included in the study, and their relationship with RVTE events occurring during follow-up. Using specifically designed cutoff values for positive/negative interpretation, serial D-dimer measurements (performed during warfarin treatment and up to 3 months after discontinuation of anticoagulation) in 475 patients (males 57.3%) aged ≤ 65 years were obtained. D-dimer resulted positive in 46.3% and 30.5% of males and females, respectively (p = 0.001). Following management procedure, anticoagulation was stopped in 53.7% of males and 69.5% of females, who had persistently negative D-dimer results. The rate of subsequent recurrent events was 1.7% (95% CI 0.5–4.5%) and 0.4% (95% CI 0–2.5%) patient-years in males and females, respectively, with upper limits of confidence intervals always below the level of risk considered acceptable by international scientific societies for stopping anticoagulation (< 5%). In conclusion, using sensitive quantitative assays with specifically designed cutoff values and serial measurements during and after discontinuation of anticoagulation, D-dimer testing is useful to predict the risk of RVTE and is of help in deciding the duration of anticoagulation in both male and female adult patients aged up to 65 years.

Modern opportunities for the diagnosis and treatment of vulvovaginal candidiasis (in aid of a practitioner)

Vulvovaginal candidiasis (VVC) is one of the most common vaginal infections, representing 40% to 50% of all cases of infectious vulvovaginitis. Between 70-75% of sexually active women experience at least one episode of VVC in their lifetime, and 8-10% of adult women have recurrent VVC. The treatment of VVC remains as one of the most pressing challenges of gynecology. The share of recurrent disease event rates remains high, despite the modern medicines used to treat various forms of VVC.

P3606Impact of diabetes mellitus on the selection of antiplatelet treatment and medium-term prognosis after acute coronary syndrome

Abstract Introduction Patients with diabetes mellitus (DM) have a higher atherothrombotic risk and higher rates of recurrent ischemic events compared with the non-diabetic population. Although current antiplatelet therapy strategies have been shown to be successful in improving outcomes in acute coronary syndrome (ACS), patients with DM continue to experience high rates of adverse cardiovascular events. Today, it is known that diabetic patients are characterized by a deregulation in different intracellular signaling pathways, which leads to an inadequate or suboptimal response to antiplatelets agents. The purpose of this study is to analyze the different therapeutic strategies, the use of new antiplatelet drugs and medium-term prognosis in diabetic patients compared with non-diabetic patients who have suffered an ACS. Methods It is an observational, prospective and multicenter registry of patients with ACS. The objective is to analyze the differences in the management of DM patients vs non-DM patients in the acute phase and their evolution during the first year after coronary event. Antiplatelet therapy administered will be evaluated, type of coronary injury and treatment performed, major adverse events as well as cardiovascular complications and mortality at one year of follow-up. Results Of a total of 1717 patients, 38% were diabetic. The diabetic population was older, with a higher prevalence of cardiovascular risk factors and higher rate of previous cardiovascular events (cerebrovascular, peripheral arterial disease and coronary disease). Patients with DM received less new antiplatelets drugs at admission (15.5% DM vs 26.5% non DM, p&lt;0.001) and less in-hospital switch to new antiplatelet agents was performed. They were subjected to a lower number of catheterizations and at the time of revascularization, the drug-eluting stent was of choice. During admission, they developed more complications, both ischemic (refractory angina, reinfarction or CVA) and hemorrhagic. Following one year, DM had higher major cardiovascular events (MACE) and higher mortality (7.72% vs 5.14%, p=0.0039). Non-coronary revascularization, renal failure, and reduced ejection fraction were predictive variables of death in diabetic population. Treatment with new antiplatelet drugs was associated with a statistically significant decrease in total mortality an MACE without differences in major bleeding. Conclusion More than a third of patients with ACS are diabetic. These patients present with more severe coronary disease associating a greater number of cardiovascular events and a higher mortality rate after one year of ACS. However, despite this, they undergo less invasive tests and they were undertreated with the new antiplatelets therapies. Acknowledgement/Funding SEC

P3709Risk of recurrent cerebral ischemia in young patients with cryptogenic ischemic stroke and patent foramen ovale

Abstract Background The cause of ischemic stroke (IS) remains often unclear in young patients. Relevant structural heart abnormities with known embolic potential may represent cause of IS also in young population. A persistent foramen ovale (PFO) is a known risk factor for paradoxical embolism, including ischemic stroke (IS). Aims The aims of our prospective study were to assess the rates of recurrent ischemic stroke events in young IS patients with PFO during a 35-month follow-up period (FUP) on effective antiplatelet therapy (OAT) and to evaluate a potential relationship with the presence of PFO on transesophageal echocardiography (TEE). Methods The study set consisted of young acute IS patients &lt;50 years enrolled in the prospective HISTORY (Heart and Ischemic STrOke Relationship studY) study, NCT01541163). In all patients, the brain ischemia was confirmed on CT or MRI. Admission ECG, serum specific cardiac markers, transesophageal echocardiography, 24-hour and 3-week ECG-Holter were performed in all patients. Results Out of 980 patients enrolled in the HISTORY study, 260 patients were younger than 50 years and 185 (56% males, mean age 41±8 years) patients were classified as cryptogenic IS in ASCOD classification. PFO was diagnosed in 60 patients (32%). Six new clinically apparent recurrent ischemic brain events were recorded during a 35-month FUP. No significant difference was found in the presence of IS recurrence between patient group with PFO and without PFO (2 [3.2% patients with PFO] versus 4 [3.2% without PFO] of young IS patients, P=0.99). Conclusion The presence of PFO was not associated with a higher risk of new brain ischemic lesions in young patients with with cryptogenic ischemic stroke during a 35-month follow-up period. Number of recurrent clinical IS is relatively small, thus achieved results may be not so robust. Acknowledgement/Funding Grant support IGA MZ CR NT/14288-3, AZV MZ CR 17-30101A, IGA LF UP Olomouc (2016-2018), FNOL SUG No. 87-85

5191Recurrent coronary heart disease in the year following myocardial infarction among US men and women between 2008 and 2015

Abstract Background Although the risk of recurrent events among adults with coronary heart disease (CHD) has declined considerably from the 1970's in the US and many Western countries, studies from the 2000's show that rates remain high. Women have lower rates of incident CHD but little is known about sex differences in recurrent events in adults with CHD. Purpose To examine trends in rates of recurrent myocardial infarction (MI), recurrent CHD, and all-cause mortality following a MI hospitalization between 2008 and 2015 among US men and women. Also, we compared sex differences in event rates among individuals with a MI hospitalization versus their counterparts without a history of CHD. Methods Data were used from 1,232,024 (53% women) US adults &lt;65 years of age with commercial health insurance in the MarketScan database and US adults ≥66 years of age with government health insurance through Medicare who had a MI hospitalization between January 1, 2008 and December 31, 2015. For each calendar year, age-standardized sex-specific rates of recurrent MI, recurrent CHD (i.e., recurrent MI or coronary revascularization), and all-cause mortality (in Medicare only) were calculated through 365 days following the hospital discharge date for MI. In a secondary analyses, we assessed the rate of recurrent MI, CHD events and all-cause mortality among women versus men with a history of MI (n=324,283) and without a history of CHD (n=1,297,132) in 2014–2015. For these analyses, adjusted hazard ratios (95% confidence intervals) were calculated using follow-up through December 31, 2016. Results From 2008 to 2015, age-standardized rates over 365 days of follow-up for recurrent MI declined by 15%, from 94 to 80 per 1000 person-years, in men and by 14%, from 89 to 77 per 1000 person-years, in women. Age-standardized recurrent CHD rates decreased by 16%, from 163 to 138 per 1000 person-years, in men and by 17%, from 142 to 118 per 1000 person-years, in women. In the Medicare population, age-standardized all-cause mortality rates following MI decreased by 6%, from 446 to 421 per 1000 person-years, in men and by 3%, from 412 to 398 per 1000 person-years, in women. In the secondary analyses, the women-to-men hazard ratios for those with a history of MI and those without prior CHD were 0.97 (0.94–0.99) and 0.67 (0.65–0.69), respectively, for MI, 0.89 (0.87–0.91) and 0.52 (0.51–0.54), respectively, for CHD, and 0.84 (0.83–0.85) and 0.74 (0.73–0.75) respectively, for all-cause mortality. Conclusion Reductions in rates of recurrent MI, recurrent CHD, and all-cause mortality within 365 days after hospitalization for MI have been similar for US women and men. The lower risk for events comparing women versus men without prior CHD is attenuated after a MI. Acknowledgement/Funding The design and conduct of the study was supported through a research grant from Amgen, Inc.

P1533The sex-based effect of skeletal muscle mass on 10-year cardiovascular disease prognosis of patients with acute coronary syndrome: the mediating effect of systemic inflammation

Abstract Background/Introduction Predictive and prognostic ability of muscle mass in CVD settings is increasingly discussed. Purpose The sex-specific effect of skeletal muscle mass index (SMI) on 10-year recurrent fatal/non fatal cardiovascular disease (CVD) event of acute coronary syndrome (ACS) patients was evaluated. Methods In 2006–2009, n=1,000 consecutive patients (n=222 females), hospitalized at a cardiology clinic with ACS diagnosis and with symptoms and left ventricular function indicative of heart failure were selected. SMI was created to reflect skeletal muscle mass through appendicular skeletal muscle mass (indirectly calculated through population formulas) divided by body mass index (BMI). Results In 10-year follow-up (2016), 55% of ACS patients exhibited recurrent fatal/non fatal CVD events (53% in females vs. 62% in males, p=0.04). Patients in 2nd SMI tertile (mostly overweight) had 10% lower risk for CVD recurrence (female:male rate ratio=0.87) over their counterparts at 1st (mostly normalweight) and 3rd tertile (mostly obese). Multivariate analysis revealed that ACS patients in 2nd SMI tertile presented 46% and 85% lower CVD event risk over their counterparts in 1st tertile (Hazard Ratio (HR)=0.54, 95% Confidence Interval (95% CI) 0.30, 0.96, p=0.002) and 3rd tertile (HR=1.85, 95% CI 1.05, 2.94, p=0.03). Sex-related sensitivity analyses revealed that even if U-shape association was retained in both males and females in crude and age- adjusted models, further adjustment for clinical, lifestyle and sociodemographic factors resulted in a significant trend only in females (HR=1.85, 95% CI 1.05, 2.94, p=0.03). Mean (95% confidence interval) survival (free-of-CVD) time (years) in females patients at 1st, 2nd and 3rd tertile was 7.4 (6.5, 8.2), 8.2 (7.1, 9.2) and 6.7 (5.5, 7.9), respectively. Inflammatory markers i.e. C-reactive protein (CRP) and white blood cells (WBC) had strong confounding effect on the association between SMI and 10-year recurrent CVD event rate in females. A significant inverse linear association between the examined factors was observed only in females (ρ(CRP)=-0.490, p&lt;0.001 &amp; ρ(WBC)=-0.380, p=0.05). Unadjusted analysis revealed that females of 2nd tertile had significantly lower mean values of inflammatory markers compared with their 1st tertile counterparts (all ps&lt;0.05). Additionally, females of 3rd tertile presented slightly higher inflammation levels compared with females of 2nd tertile yet this difference was not significant. In males no significant trend was observed. Conclusion AU-shape association between SMI and 10-year CVD event especially in females was highlighted. This work reveals sex-specific remarks for “obesity-lean paradox” in secondary prevention, implying that high muscle mass accompanied by obesity and excess adiposity may not guarantee better prognosis. Acknowledgement/Funding None

P4401Depressive symptomatology, sex and 10-year cardiovascular disease; revealing the mediation ranking of lifestyle, sociodemographic and clinical factors in primary and secondary prevention spectrum

Abstract Background/Introduction Brain and heart interplay is highly discussed in healthy yet even more in cardiac population with inconclusive evidence regarding the sex-related interactions. Purpose The sex-specific effect of depressive symptomatology (DS) on 10-year first and recurrent cardiovascular disease (CVD) events was evaluated. Methods The samples of two cohorts were used; n=845 free of CVD males and females (2002–2012) and n=2,172 males and females with acute coronary syndrome (ACS) (2004–2014) with baseline psychological assessments (Zung Self-Rating Depression Scale and Centre of Epidemiological Studies-Depressive symptoms scale, respectively) were used. The percentage of excess mediated risk (PEMR) and the corresponding 95% Confidence Interval (95% CI) were used to evaluate the mediating effect of various factors on the examined association. Results ACS as well as free-of-CVD females scored significantly higher for DS. Males exceeded females against first (19.7% vs. 11.7%, p&lt;0.001) and subsequent CVD events (38.8% vs. 32.9%, p=0.016) while in participants with DS a male-to-female first and recurrent CVD event rate ratio below -1- was noticed. Multivariate Cox regression analysis revealed that DS remained an independent aggravating factor for first (Hazard Ratio (HR) = 2.72, 95% Confidence Interval (95% CI) 1.50, 9.12, p=0.01) and recurrent (HR=1.31, 95% CI 1.01, 1.69, p&lt;0.001) CVD events only in females. Mediation analysis in females revealed that 35% (23%, 44%) of excess first-CVD-event risk of DS was attributed to lifestyle, sociodemographic, clinical, anthropometric factors as well as lipid and inflammatory markers. The respective number for recurrent events was 46% (23%, 53%). In free-of-CVD females, factors mostly accounted for excess DS risk, close to the overall, were C-reactive protein [38% (31%, 51%)], waist-to-hip ratio [35% (31%, 42%)] and diabetes [32% (27%, 36%)]. Among lipid markers, the biggest mediating effect was observed for high density lipoprotein [28% (25%, 32%)] and triglycerides [26% (22%, 33%)]. As for non-clinical factors, financial status [23% (15%, 31%)] presented the biggest mediating effect followed by educational status, adherence to Mediterranean diet and sleep duration. In ACS females, diabetes [40% (27%, 51%)] and adherence to medication [40% (29%, 53%)] had the biggest mediating effect followed by hypertension [38% (27%, 48%)]. Patients' CVD history and discharge status, presented a very low mediating effect size (∼10%). Among the examined lifestyle factors, current smoking was revealed the strongest mediator, accounting for 33% (19%, 39%) of DS aggravating effect. Anthropometric parameters in terms of body mass index seemed to modestly mediate the examined association (∼29%). Conclusions The present work augments prior evidence that psychological stressors possess important drivers of CVD onset and progression mainly in females while it gives rise to research towards unidentified paths behind this claim. Acknowledgement/Funding The ATTICA study is supported by research grants from the Hellenic Cardiology Society [HCS2002] and the Hellenic Atherosclerosis Society [HAS2003].

Long-Term Evolution of Premature Coronary Artery Disease

BackgroundThe long-term evolution of premature coronary artery disease (CAD) is unknown. ObjectivesThe objective of this study was to describe the evolution of coronary atherosclerosis in young patients and identify the risk factors of poor outcomes. MethodsParticipants age ≤45 years with acute or stable obstructive CAD were prospectively enrolled and followed. The primary endpoint was all-cause death, myocardial infarction (MI), refractory angina requiring coronary revascularization, and ischemic stroke. ResultsEight hundred-eighty patients with premature CAD were included. They were age 40.1 ± 5.7 years, mainly men, smokers, with a family history of CAD or hypercholesterolemia. At baseline presentation, 91.2% underwent coronary revascularization, predominantly for acute MI (78.8%). Over a follow-up of 20 years, one-third (n = 264) of patients presented with a total of 399 ischemic events, and 36% had at least a second recurrent event. MI was the most frequent first recurrent event (n = 131 of 264), mostly related to new coronary lesions (17.3% vs. 7.8%; p = 0.01; hazard ratio [HR]:1.45; 95% confidence interval [CI]: 1.09 to 1.93 for new vs. initial culprit lesion). All-cause death (n = 55; 6.3%) occurred at 8.4 years (median time). Ethnic origin (sub-Saharan African vs. Caucasian, adjusted hazard ratio [adjHR]: 1.95; 95% CI: 1.13 to 3.35; p = 0.02), inflammatory disease (adjHR: 1.58; 95% CI: 1.05 to 2.36; p = 0.03), and persistent smoking (adjHR: 2.32; 95% CI: 1.63 to 3.28; p < 0.01) were the strongest correlates of a first recurrent event. When considering all recurrent events, the same factors and Asian ethnicity predicted poor outcome, but persistent smoking had the greatest impact on prognosis. ConclusionsPremature CAD is an aggressive disease despite the currently recommended prevention measures, with high rates of recurrent events and mortality. Ethnicity and concomitant inflammatory disease are associated with poor prognoses, along with insufficient control of risk factors.

TCT-278 Clinical Outcomes of All-Comer Patients Presenting With Acute Coronary Syndrome Treated With the COMBO Stent: From the MASCOT and REMEDEE Registry

Acute coronary syndrome (ACS) is associated with higher rates of recurrent ischemic events, myocardial infarction (MI), and stent thrombosis (ST). The dual-therapy COMBO stent combines a sirolimus-eluting biodegradable polymer with anti-CD34+ antibodies promoting rapid endothelialization of the

Long-Term Corticosteroid-Sparing Immunosuppression for Cardiac Sarcoidosis.

BackgroundLong‐term corticosteroid therapy is the standard of care for treatment of cardiac sarcoidosis (CS). The efficacy of long‐term corticosteroid‐sparing immunosuppression in CS is unknown. The goal of this study was to assess the efficacy of methotrexate with or without adalimumab for long‐term disease suppression in CS, and to assess recurrence and adverse event rates after immunosuppression discontinuation.Methods and ResultsRetrospective chart review identified treatment‐naive CS patients at a single academic medical center who received corticosteroid‐sparing maintenance therapy. Demographics, cardiac uptake of 18‐fluorodeoxyglucose, and adverse cardiac events were compared before and during treatment and between those with persistent or interrupted immunosuppression. Twenty‐eight CS patients were followed for a mean 4.1 (SD 1.5) years. Twenty‐five patients received 4 to 8 weeks of high‐dose prednisone (>30 mg/day), followed by taper and maintenance therapy with methotrexate±low‐dose prednisone (low‐dose prednisone, <10 mg/day). Adalimumab was added in 19 patients with persistently active CS or in those with intolerance to methotrexate. Methotrexate±low‐dose prednisone resulted in initial reduction (88%) or elimination (60%) of 18‐fluorodeoxyglucose uptake, and patients receiving adalimumab‐containing regimens experienced improved (84%) or resolved (63%) 18‐fluorodeoxyglucose uptake. Radiologic relapse occurred in 8 of 9 patients after immunosuppression cessation, 4 patients on methotrexate‐containing regimens, and in no patients on adalimumab‐containing regimens.ConclusionsCorticosteroid‐sparing regimens containing methotrexate with or without adalimumab is an effective maintenance therapy in patients after an initial response is confirmed. Disease recurrence in patients on and off immunosuppression support need for ongoing radiologic surveillance regardless of immunosuppression regimen.

The impact of EGFR-TKI use on clinical outcomes of lung adenocarcinoma patients with brain metastases after Gamma Knife radiosurgery: a propensity score-matched analysis based on extended JLGK0901 dataset (JLGK0901-EGFR-TKI).

Recent advances in targeted therapy have prolonged overall survival (OS) for patients with lung cancer. The impact of epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKI) on brain metastases (BM) treated with stereotactic radiosurgery (SRS) has not, however, been fully elucidated. We investigated the influence of post-SRS EGFR-TKI use on the efficacy and toxicity of SRS for BM from lung adenocarcinoma. We used the updated dataset of the Japanese Leksell Gamma Knife (JLGK) 0901 study, which proved the efficacy of Gamma Knife SRS in patients with BM. Propensity score matching (PSM) analysis was employed to determine the impact of concurrent or post-SRS EGFR-TKI use on OS, neurological death, intracranial disease recurrence and SRS-related adverse events. Among 1194 patients registered in the JLGK0901 study, 608 eligible lung adenocarcinoma patients were identified and 238 (39%) had received EGFR-TKI concurrently or during the post-SRS clinical course. After PSM, there were 200 patient pairs with/without post-SRS EGFR-TKI use. EGFR-TKI use was associated with longer OS (median 25.5 vs. 11.0months, HR 0.60, 95% CI 0.48-0.75, p < 0.001), although the long-term OS curves eventually crossed. Distant intracranial recurrence was more likely in patients receiving EGFR-TKI (HR 1.45, 95% CI 1.12-1.89, p = 0.005). Neurological death, local recurrence and SRS-related adverse event rates did not differ significantly between the two groups. Although patients receiving EGFR-TKI concurrently or after SRS had significantly longer OS, the local treatment efficacy and toxicity of SRS did not differ between patients with/without EGFR-TKI use.

Cardiovascular Risk Factors and Secondary Events Among Acute and Chronic Stable Myocardial Infarction Patients: Findings from a Managed Care Database.

IntroductionLong-term risk for recurrent cardiovascular events among myocardial infarction (MI) patients in the acute versus chronic stable phase is not well characterized. This study was conducted to evaluate risk factors associated with all-cause mortality and cardiovascular (CVD) morbidity and to determine the transition period from the acute to chronic stable phase of disease.MethodsAdministrative claims data from a managed care database (2007–2012) were linked to the Social Security Death Index. Kaplan–Meier curves were generated over a 3-year period. The association between risk factors and clinical endpoints was assessed using Cox proportional hazard models. Poisson models estimated the ‘transition time’ from acute to chronic phase of disease.ResultsOn average, recurrent cardiovascular event rates were higher among acute MI patients in comparison to the chronic MI patients during the first 3 months of follow-up. Over the 3-year follow-up period, survival curves became parallel and for some outcomes (i.e., acute myocardial infarction and bleeding events), were not statistically significantly different between the two groups. In both the acute and chronic MI cohorts, diabetes, heart failure, and renal disease were consistently statistically significant and positively associated with greater risk of death and ischemic events. PAD was consistently associated with increased risk among the chronic cohort and composite endpoints among the acute patients.ConclusionsGreater understanding of differences in the CVD risk profiles and the transition from acute to chronic stable phase may help identify high-risk patients and inform clinical risk stratification and long-term disease management in MI patients.FundingMerck & Co., Inc., Kenilworth, NJ, USA.Electronic supplementary materialThe online version of this article (10.1007/s40119-019-00147-5) contains supplementary material, which is available to authorized users.

Sample size calculation for the Andersen-Gill model comparing rates of recurrent events.

Recurrent events arise frequently in biomedical research, where the subject may experience the same type of events more than once. The Andersen-Gill (AG) model has become increasingly popular in the analysis of recurrent events particularly when the event rate is not constant over time. We propose a procedure for calculating the power and sample size for the robust Wald test from the AG model in superiority, noninferiority, and equivalence clinical trials. Its performance is demonstrated by numerical examples. Sample SAS code is provided in the Supplementary Material.

Comparative Effectiveness and Safety of Ticagrelor versus Prasugrel in Patients with Acute Coronary Syndrome: A Retrospective Cohort Analysis.

To compare the effectiveness and safety of ticagrelor versus prasugrel in preventing recurrent cardiovascular disease (CVD) and major bleeding events in patients with acute coronary syndrome (ACS). Retrospective cohort analysis. Truven Commercial and Medicare Supplemental claims database (2011-2016). Study consisted of adults with ACS who newly initiated ticagrelor or prasugrel within 7days of their first ACS diagnosis and had no prior use for at least 12months; after propensity score matching, 10,073 patients were in each group. The primary study outcomes, first occurrence of a recurrent nonfatal CVD event (composite of myocardial infarction and stroke) and occurrence of a major bleeding event, were compared between the ticagrelor and prasugrel groups. Secondary outcomes included occurrence of minor bleeding events, defined based on the presence of bleeding events in outpatient claims. Cox proportional hazards models after propensity score matching were used to obtain the hazard ratio (HR) and 95% confidence interval (CI). In the Cox proportional hazards model, the use of ticagrelor was associated with a decreased risk of recurrent nonfatal CVD events (HR 0.80, 95% CI 0.70-0.92) and major bleeding events (HR 0.54, 95% CI 0.41-0.70) compared with prasugrel. Additionally, the use of ticagrelor was associated with a lower risk of minor bleeding events compared with prasugrel (HR 0.71, 95% CI 0.65-0.78). In this population-based cohort of incident ACS patients, ticagrelor was associated with a reduced rate of recurrent nonfatal CVD events, major and minor bleeding events compared with prasugrel.

Immediate Antihypertensive Treatment for Patients With Acute Ischemic Stroke With or Without History of Hypertension

Clinical trials have generally shown a neutral effect of early blood pressure (BP) decreases on clinical outcomes after acute ischemic stroke. Whether the effect of early antihypertensive therapy differs for patients with ischemic stroke with or without prior hypertension is unclear. To investigate the association between immediate antihypertensive treatment and patient outcomes according to the presence or absence of hypertension before stroke onset. This study was a prespecified subgroup analysis of the China Antihypertensive Trial in Acute Ischemic Stroke (CATIS), a multicenter, single-blind, blinded end-points randomized clinical trial of 4071 patients with acute ischemic stroke and elevated systolic BP. Patients were recruited from August 2009 to May 2013, and this statistical analysis was performed using the intention-to-treat population from January to October 2018. Participants were randomly assigned to receive antihypertensive treatment (aimed at decreasing systolic BP by 10%-25% within the first 24 hours after randomization, achieving systolic BP <140 mm Hg and diastolic BP <90 mm Hg within 7 days, and maintaining this level during hospitalization) or to the control arm (discontinued all antihypertensive medications). Primary outcome was a combination of death and major disability (modified Rankin Scale score ≥3; range 0-6, with higher values indicating greater disability) at 14 days or hospital discharge. In total, 2038 patients were randomized to receive antihypertensive treatment, and 2033 patients were randomized to the control group. The mean (SD) age was 62.0 (10.9) years, and 2604 participants (64.0%) were men. At day 14 or hospital discharge, the primary outcome was not different between the treatment and control groups among patients with or without prior hypertension (P = .97 for homogeneity): odds ratios (ORs) associated with treatment were 1.00 (95% CI, 0.87-1.16) for patients with prior hypertension and 1.00 (95% CI, 0.75-1.32) for patients without. Early antihypertensive treatment was associated with different rates of 3-month recurrent stroke (patients with hypertension: OR, 0.44; 95% CI, 0.25-0.77 vs without hypertension: OR, 3.43; 95% CI, 0.94-12.55; P = .005 for homogeneity) and vascular events (patients with hypertension: OR, 0.66; 95% CI, 0.43-1.02 vs those without hypertension: OR, 1.91; 95% CI, 0.75-4.83; P = .04 for homogeneity) by hypertension history. Among patients with acute ischemic stroke, early antihypertensive treatment was not associated with different death and major disability outcomes by hypertension history. However, early antihypertension therapy was associated with a decreased rate of recurrent stroke among patients with a history of hypertension and may inform future studies in the optimal approach to hypertension management in the setting of acute ischemic stroke. ClinicalTrials.gov identifier: NCT01840072.