Faculty Bibliography

BACKGROUND AND OBJECTIVES/OBJECTIVE:Whether prolonged dual antiplatelet therapy (DAPT) is more protective in patients with CKD and drug-eluting stents compared with shorter DAPT is uncertain. The purpose of this meta-analysis was to examine whether shorter DAPT in patients with drug-eluting stents and CKD is associated with lower mortality or major adverse cardiovascular event rates compared with longer DAPT. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS/METHODS:A Medline literature research was conducted to identify randomized trials in patients with drug-eluting stents comparing different DAPT duration strategies. Inclusion of patients with CKD was also required. The primary outcome was a composite of all-cause mortality, myocardial infarction, stroke, or stent thrombosis (definite or probable). Major bleeding was the secondary outcome. The risk ratio (RR) was estimated using a random-effects model. RESULTS:=0.66) in patients with CKD. CONCLUSIONS:Short DAPT does not appear to be inferior to longer DAPT in patients with CKD and drug-eluting stents. Because of imprecision in estimates (few events and wide confidence intervals), no definite conclusions can be drawn with respect to stent thrombosis.

AIMS/OBJECTIVE:Different prediction models have been established to estimate mortality in the dialysis population. This study aims to externally validate the different available mortality prediction models in an incident dialysis population. MATERIALS/METHODS:This was a retrospective cohort study of incident hemodialysis and peritoneal dialysis patients at two academic tertiary care centers. METHODS:Three previously published prediction models were used: the Liu index, the Urea5 score, and a predictive model estimating the survival probability by Hemke et al. [6]. Models were compared using the C-statistic, net reclassification index, and integrated discrimination improvement. Only the subgroup of 193 patients with enough data to be included in all models was used. RESULTS:377 patients were started on dialysis in both institutions between 2006 and 2011. Median follow-up was 787 days. 104 patients (27.6%) died during follow-up and 181 were admitted to the hospital (48.0%). All three models were predictive of mortality and hospital admissions. The survival probability model by Hemke et al. [6] performed better than the other two models for mortality (C-statistic 0.72). The Liu index had the highest performance for hospital admissions (C-statistic 0.65). Using reclassification statistics (reference = Urea5), the only model to improve discriminatory ability was the Liu index for the outcome of hospital admission. CONCLUSION/CONCLUSIONS:The survival probability model by Hemke et al. [6] may be preferred for mortality prediction in incident dialysis patients. The Liu index could be used to predict hospital admissions in the same population. Available models demonstrated only modest performance in predicting either outcome. Therefore, alternative models need to be developed.
.

Background: The relative efficacy and safety of apixaban compared with no anticoagulation for atrial fibrillation (AF) has not been studied in dialysis patients.
Method(s): This retrospective cohort study utilized 2012-2015 United States Renal Data System data. Dialysis patients with incident, non-valvular AF treated with apixaban (521 patients) were matched for relevant baseline characteristics with patients not treated with any anticoagulant agent (1561 patients). Competing risk survival models were used.
Result(s): Compared with no anticoagulation, apixaban was not associated with reduced risk of stroke or thromboembolism: HR 1.23, 95% CI 0.68-2.20, p=0.49. A significantly higher incidence of fatal or intracranial bleeding was observed with apixaban compared with no treatment: HR 2.48, 95% CI 1.25-4.90, p=0.009. A higher rate of stroke or systemic thromboembolism (Figure) and fatal or intracranial bleeding was seen in the subgroup of patients treated with the standard apixaban dose (5 mg twice daily) but not with the reduced apixaban dose (2.5 mg twice daily). A similar incidence of clinically significant bleeding events and major cardiovascular events was seen with apixaban compared with no treatment.
Conclusion(s): Randomized studies are needed to assess the efficacy of apixaban compared with no anticoagulation in chronic dialysis. Awaiting randomized data, prudence in prescribing apixaban to dialysis patients, especially at the standard dose, is warranted. Disclaimer The data reported here have been supplied by the United States Renal Data System (USRDS). The interpretation and reporting of these data are the responsibility of the authors and in no way should be seen as official policy or interpretation of the US government

Background: Prasugrel and ticagrelor have superior efficacy compared with clopidogrel in patients with preserved renal function. No randomized or cohort data exist with respect to their efficacy or safety in patients with end-stage renal disease (ESRD).
Method(s): This retrospective cohort study used United States Renal Data System data from 2012 to 2015. We identified all dialysis patients who received a drug-eluting stent (DES) and were alive at 90 days after DES insertion. Prasugrel or ticagrelor users were matched 1:3 to patients treated with clopidogrel according to a propensity score. Outcomes were ascertained at 12 months. Competing risk survival models were used.
Result(s): Compared with clopidogrel, prasugrel or ticagrelor use was not associated with reduced risk of the composite outcome of cardiovascular mortality, myocardial infarction, or stroke: adjusted hazard ratio (HR) 0.91, 95% confidence interval (CI) 0.80-1.02 for prasugrel and HR 0.93, 95% CI 0.82-1.07 for ticagrelor. Ticagrelor use was associated with lower all-cause mortality and prasugrel use was associated with lower incidence of stroke, compared with clopidogrel. There was no difference in the incidence of fatal/intracranial or clinically-significant bleeding with either of the newer antiplatelet agents, compared with clopidogrel (Table). Shorter duration of the antiplatelet agent and acute coronary syndrome at presentation were independently associated with worse prognosis.
Conclusion(s): This is the first study examining clinical outcomes with prasugrel or ticagrelor in ESRD. Although no major efficacy benefit was detected, both prasugrel and ticagrelor were well-tolerated in patients with ESRD and may be considered in selected cases. Disclaimer The interpretation and reporting of these data are the responsibility of the authors and in no way should be seen as official policy or interpretation of the US government. (Figure Presented)

BACKGROUND/AIMS/OBJECTIVE:Chronic kidney disease (CKD) is common among patients with heart failure with preserved ejection fraction (HFpEF) and is associated with worse clinical outcomes. This study aims to identify whether the association of CKD with HFpEF is independent of underlying echocardiographic abnormalities. MATERIALS/METHODS:We conducted a retrospective cohort study including patients without prevalent heart failure referred for echocardiography. Patients with serial echocardiograms, baseline left ventricular ejection fraction (LVEF) ≥50% and estimated glomerular filtration rate (eGFR) ≥90 mL/min/1.73 m2 were matched 1:1 with patients with eGFR <60 mL/min/1.73 m2 for age (±5 years), sex, history of hypertension or diabetes, use of renin-angiotensin inhibitors, and LVEF (±5%). A secondary analysis included patients with preserved LVEF and normal left ventricular mass index matched for the same parameters except use of renin-angiotensin inhibitors. RESULTS:Patients with CKD were at increased risk for HFpEF admission: crude hazard ratio (HR) 1.79 (95% confidence interval [CI] 1.38-2.32, p < 0.001) and adjusted HR (for coronary disease, loop diuretics, left atrial diameter) 1.64 (95% CI 1.22-2.21, p = 0.001). LVEF and left ventricular diameter decreased over time in both groups but no difference was observed in rate of dropping. Results were similar in the secondary analysis (crude HR 1.99, 95% CI 1.07-3.71, p = 0.03 and HR adjusted for left atrial diameter 1.98, 95% CI 1.05-3.75, p = 0.04). Rate of change was similar for LVEF, pulmonary artery pressure, and left ventricular mass index in both groups. CONCLUSION/CONCLUSIONS:CKD is independently associated with incident HFpEF despite a similar change in relevant echocardiographic parameters in patients with or without CKD.

BACKGROUND:Echocardiographic characteristics across the spectrum of chronic kidney disease (CKD) have not been well described. We assessed the echocardiographic characteristics of patients with preserved renal function and mild or moderate CKD referred for echocardiography and determined whether echocardiographic parameters of left ventricular (LV) and right ventricular (RV) structure and function were associated with changes in renal function and mortality. METHODS:This retrospective cohort study enrolled all adult patients who had at least one trans-thoracic echocardiography between 2004 and 2014 in our institution. The composite outcome of doubling of serum creatinine or initiation of maintenance dialysis or kidney transplantation was the primary outcome. Mortality was the secondary outcome. RESULTS:29,219 patients were included. Patients with worse renal function had higher prevalence of structural and functional LV and RV abnormalities. Higher estimated glomerular filtration rate (eGFR) was independently associated with preserved LV ejection fraction, preserved RV systolic function, and lower LV mass, left atrial diameter, pulmonary artery pressure, and right atrial pressure, as well as normal RV structure. 1041 composite renal events were observed. 8780 patients died during the follow-up. Pulmonary artery pressure and the RV, but not the LV, echocardiographic parameters were independently associated with the composite renal outcome. In contrast, RV systolic function, RV dilation or hypertrophy, LV ejection fraction group, LV diameter quartile, and pulmonary artery pressure quartile were independently associated with all-cause mortality. CONCLUSIONS:Echocardiographic abnormalities are frequent even in early CKD. Echocardiographic assessment particularly of the RV may provide useful information for the care of patients with CKD.

The study aimed to evaluate antiplatelet drug responsiveness in stable outpatients with cardiovascular disease and chronic kidney disease (CKD) and examine whether impaired antiplatelet drug responsiveness is associated with worse clinical outcomes in this population. Stable cardiovascular patients (n = 771) were enrolled at least one month after an acute ischemic atherothrombotic event. Antiplatelet drug responsiveness was assessed with specific assays (serum TxA₂ for aspirin, the VASP assay for clopidogrel) and other aggregation-based assays using different agonists. All patients were followed until the first occurrence of a major adverse cardiovascular event. The 133 CKD patients were found to have higher activity of von Willebrand factor and higher fibrinogen levels. After a median follow-up of 33 months, 88 events occurred in patients without CKD and 31 events in patients with CKD (5.0 events and 8.7 events per 100 patient years, respectively, HR = 1.75 (95% CI 1.16-2.63; p = 0.008). The prevalence of poor aspirin and clopidogrel responsiveness and high platelet reactivity as assessed with different aggregation-based assays was similar in patients with estimated GFR ≥ 60 ml/min, 45-59 ml/min, and < 45 ml/min. No significant interaction for CKD vs. non-CKD was observed for events occurrence in patients with or without high platelet reactivity on several assays, with the exception of collagen-induced aggregation. In stable cardiovascular patients, CKD is not associated with higher platelet reactivity. Decreased antiplatelet drug responsiveness is not associated with worse clinical outcomes in CKD patients.

Cardiovascular disease is the principal cause of morbidity and mortality in patients with diabetes mellitus. The incidence or progression of kidney disease is also common in these patients. Several clinical trials have established the efficacy of angiotensin receptor blockers for the prevention of adverse cardiovascular and renal outcomes in this population and are summarized in this review article. Head-to-head comparison of angiotensin receptor blockers with angiotensin-converting enzyme inhibitors has shown similar cardioprotective and renoprotective properties of both medication classes. However, angiotensin receptor blockers have an improved safety profile with fewer episodes of cough and angioedema and may be the agent of choice in patients with diabetes and hypertension. Novel therapeutic strategies, such as those that include a mineralocorticoid receptor blocker or a selective sodium-glucose cotransporter type 2 inhibitor, may further protect patients with diabetes from cardiovascular and renal complications.

OBJECTIVES:Regular exercise is known to reduce arterial stiffness (AS) in hemodialysis patients. However, the impact of a more realistic intradialytic form of exercise, such as pedaling, is unclear. We aimed to examine (i) the effect of intradialytic pedaling exercise on AS over 4 months and (ii) the longer term effect of pedaling on AS 4 months after exercise cessation. METHODS:Patients on stable in-center hemodialysis (3 x/week) were randomly assigned 1:1 to either intradialytic pedaling exercise (EX) or to a control group receiving usual hemodialysis (nonEX) for 4 months. At baseline and 4 months, peripheral and central blood pressure (BP) indices, heart rate (HR), augmentation index HR corrected (AIx75), and carotid-femoral pulse wave velocity (cfPWV) were assessed (applanation tonometry). Measurements were repeated in the EX group 4 months postexercise cessation. RESULTS:As per protocol analysis was completed in 10 EX group participants (58 ± 17 years, body mass index 26 ± 4 kg/m2) and 10 nonEX group participants (53 ± 15 years, body mass index 27 ± 6 kg/m2). Peripheral and central BP was unchanged in both groups. AIx75 was unchanged in the EX group, however, a significant median increase of 3.5% [interquartile range, IQR 1.0, 8.5] was noted in the nonEX group (P = 0.009). We noted a significantly greater absolute decrease in cfPWV in the EX group compared to controls: -1.00 [IQR -1.95, 0.05] vs. 0.20 [IQR -0.10, 0.90] (P = 0.033). Interestingly, the decrease in cfPWV observed in the EX group was partially reversed 4 months after exercise cessation. CONCLUSION:Intradialytic pedaling exercise has a beneficial impact on AS. This relationship warrants further investigation. CLINICAL TRIALS REGISTRATION:Trial Number #NCT03027778 (clinicaltrials.gov).