Faculty Bibliography

BACKGROUND:Patients with chronic kidney disease (CKD) and stable ischemic heart disease are at markedly increased risk of cardiovascular events. Prior trials comparing a strategy of optimal medical therapy (OMT) with or without revascularization have largely excluded patients with advanced CKD. Whether a routine invasive approach when compared with a conservative strategy is beneficial in such patients is unknown. METHODS:or on dialysis) and moderate or severe ischemia on stress testing. Participants were randomized in a 1:1 fashion to the invasive or a conservative strategy. The primary end point is a composite of death or nonfatal myocardial infarction. Major secondary endpoints are a composite of death, nonfatal myocardial infarction, hospitalization for unstable angina, hospitalization for heart failure, or resuscitated cardiac arrest; angina control; and disease-specific quality of life. Safety outcomes such as initiation of maintenance dialysis and a composite of initiation of maintenance dialysis or death will be reported. The trial is projected to have 80% power to detect a 22% to 24% reduction in the primary composite end point with the invasive strategy when compared with the conservative strategy. CONCLUSIONS:ISCHEMIA-CKD will determine whether an initial invasive management strategy improves clinical outcomes when added to OMT in patients with advanced CKD and stable ischemic heart disease.

Introduction: There are scant data on the use of P2Y12 antagonist therapy upstream of diagnostic angiography (DA), especially when administered in the ED for NSTEMI. We host a multicenter US registry to describe patterns of upstream P2Y12therapy and outcomes.
Method(s): UPSTREAM (NCT02271022) is an ongoing prospective, observational registry of consecutive NSTEMI patients, evaluated in an ED, who at the treating clinician's discretion are given a loading dose (LD) of ticagrelor, clopidogrel, or prasugrel 4 or more hrs prior to DA, which in turn is performed no more than 72 hrs after ED arrival. Data are collected on all patients through hospital discharge. Those patients receiving ticagrelor throughout the index hospitalization and at discharge are followed 30-40 days for vital status, rehospitalization, bleeding complications, and P2Y12 compliance. We report the in-hospital outcomes of the first 2512 NSTEMI patients studied at 54 hospitals.
Result(s): In this cohort over 3.5 years' enrollment, the P2Y12 upstream LD was clopidogrel in 53%, ticagrelor in 46%, and prasugrel in 1%, although agent switching during hospitalization and at discharge occurs. Overall, 1355 (54%) received at least one dose of ticagrelor? 697 (27.7%) were maintained on ticagrelor consistently and had 30-day follow-up completed. Patients had a mean age of 63 y? 19% are older than 75 y. Approximately 21% of patients had a documented prior MI, 26% had a prior stent, 15% had prior CABG, and 12% had documented CKD. The median (SD) time from ED arrival to LD was 6.4 (6.7) h, and time from LD to DA was 11.3 (9.5) h. DA was performed via femoral access in 57% of patients and radially in 43%. Post-DA management was 58% stent, 34% medical management, and 8% CABG. In-hospital CV events, including mortality, were infrequent (0.6%). Only 53 patients (31 [1.2%] CABG-related and 22 [0.9%] non-CABG) required RBC transfusion, while 23 (19 CABG-related) required a platelet transfusion. Six stent thrombosis events were recorded.
Conclusion(s): Upstream P2Y12therapy in NSTEMI patients undergoing an invasive strategy is associated with good clinical outcomes and minimal risk of bleeding. The most commonly used

Introduction: In patients presenting to non-PCI capable hospital with STEMI, the management options include transfer for primary PCI (PPCI) or administration of thrombolytics and transfer for PCI (lytics + PCI), a decision largely driven by the estimated door to device time. The 2013 AHA/ACC STEMI guidelines increased the door to device time for STEMI transfer patients from < 90 minutes to < 120 minutes. Whether this change has impacted management is not known.
Method(s): Patients in the New York (NY) State PCI Registry who underwent PCI (PPCI or lytics + PCI) for STEMI after being transferred from a non-PCI capable hospital in 2012 and 2014 were included in this study. Primary outcome was a change in the proportion of patients who underwent PPCI in relation to lytics + PCI in 2014 as compared with year 2012. Secondary outcomes were changes in transfer time (non-PCI capable transfer hospital door to PCI hospital door time), PCI hospital door to device time, transfer hospital door to device time in PPCI patients, and in-hospital mortality for all STEMI transfer patients who underwent PCI.
Result(s): There were 2019 and 1799 patients who underwent PCI (PCI or lytics +PCI) for a STEMI after presenting to a non-PCI capable hospital in NY State in 2012 and 2014 respectively. There was an increase in the proportion of patients receiving PPCI (vs lytics+ PCI) from 2012 to 2014 (74.15% to 78.32%, p = 0.0025). Moreover, in patients receiving PPCI, there was also a decrease in transfer time [median: 102 min (Q1:73, Q3162) to 97 min (Q1: 70, Q3:147),p = 0.005], PCI hospital door to device time [35 min (25,53) to 34 min (24, 51), p = 0.07), and transfer hospital door to device time [143 min (105, 220) to 134 min (102, 200), p = 0.005]. However, there was no change in mortality from 2012 to 2014 in all STEMI transfer patients who underwent PCI (2.13% vs 2.95%, p = 0.11).
Conclusion(s): Data from NY State indicates a significant increase in referral for PPCI in patients presenting with a STEMI to a non-PCI capable hospital with the change in guidelines increasing the door to device times for transfer patients. Whether such a strategy improves outcomes should be tested in further studies

There are no dedicated data to guide drug eluting stent (DES) versus bare metal stent (BMS) selection in patients with end stage renal disease undergoing dialysis (ESRD-D). It is unclear whether long-term benefits of a specific stent-type outweigh risks in this population at high risk for both bleeding and ischemic events. We performed a meta-analysis of non-randomized studies extracted from PubMed, Scopus, and EMBASE; assessing the safety and effectiveness of DES versus BMS in ESRD-D patients. Odds ratios (OR) and 95% confidence intervals (CI) were computed with the Mantel-Haenszel method. Random-effects model was used for all analyses. A total of 17 non-randomized studies (N=63,157; 41,621 DES and 21,536 BMS) met the inclusion criteria and were included for the final quantitative analysis; median follow-up of 1 year (range: 9 months - 6 years). The use of DES in ESRD-D patients was associated with lower all-cause mortality (OR 0.75, 95%CI 0.64-0.89, P<0.001) compared with BMS. The use of DES was also associated with lower rates of cardiovascular mortality (OR 0.75, 95%CI 0.60-0.99, P=0.047) and target lesion/vessel revascularization (TLR/TVR) (OR 0.78, 95%CI 0.64-0.94, P=0.01). However, there were no differences in non-cardiovascular mortality, myocardial infarction, stent thrombosis, stroke or major bleeding in DES versus BMS. In this largest meta-analysis of long-term outcomes following percutaneous coronary intervention in ESRD-D patients, DES was associated with lower rates of all-cause mortality, TLR/TVR, and cardiovascular death.

BACKGROUND:Some studies have shown that body weight variability is a risk factor for cardiovascular events, but this has not been studied in subjects with diabetes mellitus. METHODS AND RESULTS/RESULTS:We measured intraindividual variations in body weight from baseline and follow-up visits in 6408 subjects with type 2 diabetes mellitus from 3 clinical trials. The primary end point, any coronary event, was a composite of coronary heart disease death, myocardial infarction, resuscitated cardiac arrest, coronary revascularization, and unstable or new-onset angina. After adjustment for risk factors, baseline lipid levels, mean body weight, and weight change, each increase of 1 SD in body weight variability, measured as average successive variability and used as a time-dependent covariate, was associated with an increase in the risk of any coronary event (hazard ratio, 1.08; 95% CI, 1.01-1.14; P=0.017), major coronary event (hazard ratio, 1.12; 95% CI, 1.04-1.20; P=0.002), any cardiovascular event (hazard ratio, 1.08; 95% CI, 1.03-1.14; P=0.0015), and death (hazard ratio, 1.16; 95% CI, 1.10-1.22; P<0.0001). Among patients in the quintile with the highest variation in body weight compared with the lowest, the risk of any coronary event was 59% higher; the risk of a major coronary event, 82% higher; any cardiovascular event, 75% higher; death, 82% higher; myocardial infarction, 99% higher; and stroke, 92% higher in adjusted models. The results were consistent in a number of sensitivity analyses. CONCLUSIONS:Among subjects with type 2 diabetes mellitus, fluctuation in body weight was associated with higher mortality and a higher rate of cardiovascular events, independent of traditional cardiovascular risk factors. CLINICAL TRIAL REGISTRATION/BACKGROUND:URL: http://www.clinicaltrials.gov . Unique identifier: NCT00327691 and NCT00327418.

Background Standardization of evidence-based medical therapies has improved outcomes for patients with non- ST -segment-elevation myocardial infarction ( NSTEMI ). Although racial differences in NSTEMI management have previously been reported, it is uncertain whether these differences have been ameliorated over time. Methods and Results The ARIC (Atherosclerosis Risk in Communities) Community Surveillance study conducts hospital surveillance of acute myocardial infarction in 4 US communities. NSTEMI was classified by physician review, using a validated algorithm. From 2000 to 2014, 17 755 weighted hospitalizations for NSTEMI (patient race: 36% black, 64% white) were sampled by ARIC . Black patients were younger (aged 60 versus 66 years), more often female (45% versus 38%), and less likely to have medical insurance (88% versus 93%) but had more comorbidities. Black patients were less often administered aspirin (85% versus 92%), other antiplatelet therapy (45% versus 60%), β-blockers (85% versus 88%), and lipid-lowering medications (68% versus 76%). After adjustments, black patients had a 24% lower probability of receiving nonaspirin antiplatelets (relative risk: 0.76; 95% confidence interval, 0.71-0.81), a 29% lower probability of angiography (relative risk: 0.71; 95% confidence interval, 0.67-0.76), and a 45% lower probability of revascularization (relative risk: 0.55; 95% confidence interval, 0.50-0.60). No suggestion of a changing trend over time was observed for any NSTEMI therapy ( P values for interaction, all >0.20). Conclusions This longitudinal community surveillance of hospitalized NSTEMI patients suggests black patients have more comorbidities and less likelihood of receiving guideline-based NSTEMI therapies, and these findings persisted across the 15-year period. Focused efforts to reduce comorbidity burden and to more consistently implement guideline-directed treatments in this high-risk population are warranted.

Aims/UNASSIGNED:The association between depression care adequacy and the risk of subsequent adverse cardiovascular disease (CVD) outcomes among patients with a previous diagnosis of myocardial infarction (MI) or stroke is not well defined. Methods and Results/UNASSIGNED:This retrospective cohort study used commercial claims data (2010-2015) and included adults with newly diagnosed and treated MDD following an initial MI or stroke diagnosis. Depression care adequacy was assessed during the 3-month period following the MDD diagnosis index date using two measures: antidepressant dosage adequacy and duration adequacy. Cox models adjusted for the propensity of receiving adequate depression care were used to compare the risk of a composite CVD outcome (MI, stroke, congestive heart failure [CHF], and angina) as well as each individual CVD event between patients receiving adequate versus inadequate depression care. 1568 patients were included in the final cohort. Of these, 937 (59.8%) were categorized as receiving inadequate depression care based on at least 1 of the 2 treatment adequacy criteria. Propensity score adjusted Cox models showed that depression care inadequacy was associated with a significantly higher risk of the composite CVD endpoint (HR, 1.20; 95% CI, 1.04-1.39), stroke (HR 1.20, 95% CI, 1.02-1.42) and angina (HR 1.95, 95% CI, 1.21-3.16) with no significant interaction based on cohort included (MI vs. stroke) or the definition of inadequate depression (dose vs. duration inadequacy) (Pinteraction>0.05). Conclusions/UNASSIGNED:Inadequate MDD care was associated with a higher risk of adverse CVD events. These findings reveal a significant unmet clinical need in patients with post-MI or post-stroke MDD that may impact CVD outcomes.

OBJECTIVE:To analyze trends in the incidence, in-hospital management, and outcomes of acute myocardial infarction (AMI) complicating pregnancy and the puerperium in the United States. PATIENTS AND METHODS/METHODS:Women 18 years or older hospitalized during pregnancy and the puerperium were identified from the National Inpatient Sample database from January 1, 2002, to December 31, 2014. International Classification of Diseases, Ninth Revision diagnosis and procedure codes were used to identify AMI during pregnancy-related admissions. RESULTS:Overall, 55,402,290 pregnancy-related hospitalizations were identified. A total of 4471 cases of AMI (8.1 [95% CI, 7.5-8.6] cases per 100,000 hospitalizations) occurred, with 922 AMI cases (20.6%) identified in the antepartum period, 1061 (23.7%) during labor and delivery, and 2390 (53.5%) in the postpartum period. ST-segment elevation myocardial infarction occurred in 1895 cases (42.4%), and non-ST-segment elevation myocardial infarction occurred in 2576 cases (57.6%). Among patients with pregnancy-related AMI, 2373 (53.1%) underwent invasive management and 1120 (25.1%) underwent coronary revascularization. In-hospital mortality was significantly higher in patients with AMI than in those without AMI during pregnancy (adjusted odds ratio, 39.9; 95% CI, 23.3-68.4; P<.001). The rate of AMI during pregnancy and the puerperium increased over time (adjusted odds ratio, 1.25 [for 2014 vs 2002]; 95% CI, 1.02-1.52). CONCLUSION/CONCLUSIONS:In patients hospitalized during pregnancy and the puerperium, AMI occurred in 1 of every 12,400 hospitalizations and rates of AMI increased over time. Maternal mortality rates were high. Additional research on the prevention and optimal management of AMI during pregnancy is necessary.