Statin Use and Survival After Acute Kidney Injury

IntroductionThe incidence of acute kidney injury (AKI) in hospitalized patients is rising, and survivors are at high risk for cardiovascular events and mortality. Effective strategies that improve long-term outcomes of AKI are unknown.MethodsA retrospective cohort study was performed between 2008 and 2011. All subjects were followed until 31 March 2013, with a minimum follow-up of 2 years. Participants were adults 18 years of age or older, who developed AKI during a hospitalization and had chronic kidney disease (CKD) following discharge (n = 19,707 mean age 69.9 years, mean postdischarge estimated glomerular filtration rate (eGFR) 43.0 ml/min/1.73 m2). Exposure to statins was examined prior to the index hospitalization as well as within 2 years following hospital discharge. The primary outcome was mortality; secondary outcomes included all-cause re-hospitalization and cardiovascular events.ResultsWithin 2 years of discharge, only 38.3% of the participants were prescribed a statin. After adjustment for comorbidities, statin use prior to admission, demographics, baseline kidney function, and a number of other factors, statin use was associated with lower mortality (hazard ratio, 0.74; 95% confidence interval, 0.69, 0.79) in AKI survivors with CKD. Patients who received a statin also had a lower risk of all cause rehospitalization (adjusted hazarad ratio, 0.90; 95% confidence interval, 0.85, 0.94). Statin use was not associated with a reduction in cardiovascular events.DiscussionAmong AKI survivors with CKD, statin use was associated with a lower risk of mortality and rehospitalization rates. This finding suggests that there is an opportunity to improve postdischarge care in AKI survivors

Lack of association between dual antiplatelet therapy use and stent thrombosis between 1 and 12 months following resolute zotarolimus-eluting stent implantation

Aim The optimal duration of dual antiplatelet therapy (DAPT) following the use of new generation drug-eluting stents is unknown. Methods and results The association between DAPT interruption and the rates of stent thrombosis (ST) and cardiac death/target-vessel myocardial infarction (CD/TVMI) in patients receiving a Resolute zotarolimus-eluting stent (R-ZES) was analysed in 4896 patients from the pooled RESOLUTE clinical programme. Daily acetylsalicylate (ASA) and a thienopyridine for 6-12 months were prescribed. A DAPT interruption was defined as any interruption of ASA and/or a thienopyridine of >1 day; long interruptions were >14 days. Three groups were analysed: no interruption, interruption during the first month, and >1-12 months. There were 1069 (21.83%) patients with a DAPT interruption and 3827 patients with no interruption. Among the 166 patients in the 1-month interruption group, 6 definite/probable ST events occurred (3.61%; all long DAPT interruptions), and among the 903 patients in the >1-12 months (60% occurred between 6 and 12 months) interruption group, 1 ST event occurred (0.11%; 2-day DAPT interruption). Among patients with no DAPT interruption, 32 ST events occurred (0.84%). Rates of CD/TVMI were 6.84% in the 1-month long interruption group, 1.41% in the >1-12 months long interruption group, and 4.08% in patients on continuous DAPT. Conclusion In a pooled population of patients receiving an R-ZES, DAPT interruptions within 1 month are associated with a high risk of adverse outcomes. Dual antiplatelet therapy interruptions between 1 and 12 months were associated with low rates of ST and adverse cardiac outcomes. Randomized clinical trials are needed to determine whether early temporary or permanent interruption of DAPT is truly safe. Clinical Trials.gov identifiers NCT00617084; NCT00726453; NCT00752128; NCT0092794

Infrared imaging and spectral-domain optical coherence tomography findings correlate with microperimetry in acute macular neuroretinopathy: a case report

<p>Abstract</p> <p>Introduction</p> <p>Spectral-domain optical coherence tomography findings in a patient with acute macular neuroretinopathy, and correlation with functional defects on microperimetry, are presented.</p> <p>Case presentation</p> <p>A 25-year old Caucasian woman presented with bitemporal field defects following an upper respiratory tract infection. Her visual acuity was 20/20 in both eyes and a dilated fundus examination revealed bilateral hyperpigmentary changes in the papillomacular bundle. Our patient underwent further evaluation with spectral-domain optical coherence tomography, infrared and fundus autofluorescence imaging. Functional changes were assessed by microperimetry. Infrared imaging showed the classic wedge-shaped defects and spectral-domain optical coherence tomography exhibited changes at the inner segment-outer segment junction, with a thickened outer plexiform layer overlying these areas. Fluorescein and indocyanine green angiography did not demonstrate any perfusion defects or any other abnormality. Microperimetry demonstrated focal elevation in threshold correlating with the wedge-shaped defects in both eyes.</p> <p>Conclusion</p> <p>Spectral-domain optical coherence tomography findings provide new evidence of the involvement of the outer plexiform layer of the retina in acute macular neuroretinopathy.</p

Rationale and design of two randomized sham-controlled trials of catheter-based renal denervation in subjects with uncontrolled hypertension in the absence (SPYRAL HTN-OFF MED Pivotal) and presence (SPYRAL HTN-ON MED Expansion) of antihypertensive medications: a novel approach using Bayesian design.

BACKGROUND: The SPYRAL HTN clinical trial program was initiated with two 80-patient pilot studies, SPYRAL HTN-OFF MED and SPYRAL HTN-ON MED, which provided biological proof of principle that renal denervation has a blood pressure-lowering effect versus sham controls for subjects with uncontrolled hypertension in the absence or presence of antihypertensive medications, respectively. TRIAL DESIGN: Two multicenter, prospective, randomized, sham-controlled trials have been designed to evaluate the safety and efficacy of catheter-based renal denervation for the reduction of blood pressure in subjects with hypertension in the absence (SPYRAL HTN-OFF MED Pivotal) or presence (SPYRAL HTN-ON MED Expansion) of antihypertensive medications. The primary efficacy endpoint is baseline-adjusted change from baseline in 24-h ambulatory systolic blood pressure. The primary safety endpoint is incidence of major adverse events at 1 month after randomization (or 6 months in cases of new renal artery stenosis). Both trials utilize a Bayesian design to allow for prespecified interim analyses to take place, and thus, the final sample sizes are dependent on whether enrollment is stopped at the first or second interim analysis. SPYRAL HTN-OFF MED Pivotal will enroll up to 300 subjects and SPYRAL HTN-ON MED Expansion will enroll up to 221 subjects. A novel Bayesian power prior approach will leverage historical information from the pilot studies, with a degree of discounting determined by the level of agreement with data from the prospectively powered studies. CONCLUSIONS: The Bayesian paradigm represents a novel and promising approach in device-based hypertension trials. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02439749 (SPYRAL HTN-OFF MED Pivotal) and NCT02439775 (SPYRAL HTN-ON MED Expansion)

Rationale and design of two randomized sham-controlled trials of catheter-based renal denervation in subjects with uncontrolled hypertension in the absence (SPYRAL HTN-OFF MED Pivotal) and presence (SPYRAL HTN-ON MED Expansion) of antihypertensive medications: a novel approach using Bayesian design

Background The SPYRAL HTN clinical trial program was initiated with two 80-patient pilot studies, SPYRAL HTN-OFF MED and SPYRAL HTN-ON MED, which provided biological proof of principle that renal denervation has a blood pressure-lowering effect versus sham controls for subjects with uncontrolled hypertension in the absence or presence of antihypertensive medications, respectively. Trial design Two multicenter, prospective, randomized, sham-controlled trials have been designed to evaluate the safety and efficacy of catheter-based renal denervation for the reduction of blood pressure in subjects with hypertension in the absence (SPYRAL HTN-OFF MED Pivotal) or presence (SPYRAL HTN-ON MED Expansion) of antihypertensive medications. The primary efficacy endpoint is baseline-adjusted change from baseline in 24-h ambulatory systolic blood pressure. The primary safety endpoint is incidence of major adverse events at 1 month after randomization (or 6 months in cases of new renal artery stenosis). Both trials utilize a Bayesian design to allow for prespecified interim analyses to take place, and thus, the final sample sizes are dependent on whether enrollment is stopped at the first or second interim analysis. SPYRAL HTN-OFF MED Pivotal will enroll up to 300 subjects and SPYRAL HTN-ON MED Expansion will enroll up to 221 subjects. A novel Bayesian power prior approach will leverage historical information from the pilot studies, with a degree of discounting determined by the level of agreement with data from the prospectively powered studies. Conclusions The Bayesian paradigm represents a novel and promising approach in device-based hypertension trials. Clinical trial registration URL: https://www.clinicaltrials.gov. Unique identifier: NCT02439749 (SPYRAL HTN-OFF MED Pivotal) and NCT02439775 (SPYRAL HTN-ON MED Expansion)

In-vivo high resolution imaging of optic nerve head drusen using spectral-domain Optical Coherence Tomography

<p>Abstract</p> <p>Background</p> <p>Optic nerve head drusen (ONHD) are white calcareous deposits, seen either superficially on the optic nerve head or buried within it. Diagnosis of ONHD is made by one or more ways: clinical exam, autofluorescence, ultrasound of the optic nerve, CT scan and/or visual field examination. The present study describes features of ONHD based on another diagnostic modality, the spectral-domain OCT (Spectralis).</p> <p>Methods</p> <p>This is a retrospective case series of 5 patients with bilateral ONHD with a best-corrected visual acuity of 20/20 and no other posterior segment pathology. All the patients underwent fundus photography, fundus autofluorescence, B-scan ultrasonography, Spectralis OCT and Humphrey 30-2 threshold visual fields.</p> <p>Results</p> <p>All 5 patients had surface ONHD which were autofluorescent and echodense on B-scan ultrasonography. Spectralis OCT findings in the corresponding areas include 'scattered spots with high reflectivity' casting a shadow underneath. The reflectivity can be distinctly differentiated from the blood vessels on the optic nerve. Two patients had an arcuate scotoma on the Humphrey visual fields. No correlation was found between the changes on Spectralis OCT with that of visual field.</p> <p>Conclusions</p> <p>Spectralis OCT is another useful ancillary investigation in the diagnosis of ONHD and we describe the features in the present study.</p

A re-examination of the SPYRAL HTN-OFF MED Pivotal trial with respect to the underlying model assumptions

Background: The SPYRAL HTN-OFF MED Pivotal trial demonstrated that RDN was efficacious compared to a sham control. The underlying model was an extension of the analysis of covariance (ANCOVA) model, adjusted for baseline blood pressure (BP), and allowed borrowing of information from the previously reported feasibility study using a novel Bayesian method. Fundamental to the estimation of a treatment effect for efficacy are a multitude of statistical modelling assumptions, including the role of outliers, linearity of the association between baseline BP and outcome, and parallelism of the treatment effect difference over the baseline BP range. In this report, we examine the validity of these assumptions to verify the robustness of the treatment effect measured. Methods: We examined the requisite modelling assumptions of the ANCOVA model fitted to the SPYRAL HTN-OFF MED Pivotal trial using Bayesian methods. To address outliers, we fit a robust regression model (with heavy tailed errors) to the data with diffuse weakly informative prior distributions on the parameters. To address linearity, we replaced the linear baseline term by a natural spline term with 4 degrees of freedom. To address parallelism, we refit the ANCOVA model with an interaction term for treatment arm and baseline BP. Results: ANCOVA models were fitted to the trial data (pooled across the feasibility and pivotal cohorts) using Bayesian methodology with diffuse (non-informative) prior distributions. The modelling assumptions inherent to the ANCOVA models were shown to be broadly satisfied. A robust ANCOVA model yielded a posterior treatment effect of -4.1 mmHg (95% credible interval: -6.3 to -1.9) indicating the influence of outlier values was small. There was moderate evidence of an interaction term effect between baseline BP and treatment, but no evidence of gross violation of linearity in baseline BP. Conclusion: The posterior treatment effect estimate is shown to be robust to underlying model assumptions, thus further supporting the evidence of RDN to be an efficacious treatment for resistant hypertension

Long-term reduction in morning and nighttime blood pressure after renal denervation: 36-month results from SPYRAL HTN-ON MED trial.

Elevated morning and nighttime blood pressures (BP) are associated with increased risk of cardiovascular events such as stroke and myocardial infarction. We compared the long-term changes in morning and nighttime BP in patients with uncontrolled hypertension (office systolic BP between 150 and <180 mmHg/diastolic BP ≥ 90 mmHg; mean ambulatory systolic BP (SBP) between 140 and <170 mmHg; 1-3 prescribed antihypertensive medications). Eighty patients were randomized to RDN or sham control. In patients taking at least 3 antihypertensive medications at 36 months (N = 23 RDN group; N = 23 sham group), the 24 h ambulatory SBP as well as morning (7:00-9:00AM) and nighttime (1:00-6:00AM) ambulatory SBP were significantly lower for the RDN group compared to sham control (24 h SBP: -20.2 vs. -10.2, p = 0.0087; morning SBP: -23.9 vs. -8.0 mmHg, p = 0.029; nighttime SBP: -20.8 vs. -7.2 mmHg, p = 0.0011). At 36 months, 24 h SBP was controlled to <130 mmHg in 40% of RDN patients in the morning compared to 6% for the sham group; P = 0.021 and in 80% of the RDN patients at night compared to 39% in the sham group; P = 0.019. Major adverse events through 36 months were rare in both groups, and there were no renal artery re-interventions or vascular complications. Morning and nighttime SBP were significantly lower in patients prescribed at least 3 antihypertensive medications at 36 months in the SPYRAL HTN-ON MED trial for RDN compared with sham control. The results suggest RDN has significant benefit when the risk of cardiovascular events is highest

Polymer-based or polymer-free stents in patients at high bleeding risk

Background: polymer-free drug-coated stents provide superior clinical outcomes to bare-metal stents in patients at high bleeding risk who undergo percutaneous coronary intervention (PCI) and are treated with 1 month of dual antiplatelet therapy. Data on the use of polymer-based drug-eluting stents, as compared with polymer-free drug-coated stents, in such patients are limited. Methods: in an international, randomized, single-blind trial, we compared polymer-based zotarolimus-eluting stents with polymer-free umirolimus-coated stents in patients at high bleeding risk. After PCI, patients were treated with 1 month of dual antiplatelet therapy, followed by single antiplatelet therapy. The primary outcome was a safety composite of death from cardiac causes, myocardial infarction, or stent thrombosis at 1 year. The principal secondary outcome was target-lesion failure, an effectiveness composite of death from cardiac causes, target-vessel myocardial infarction, or clinically indicated target-lesion revascularization. Both outcomes were powered for noninferiority. Results: a total of 1996 patients at high bleeding risk were randomly assigned in a 1:1 ratio to receive zotarolimus-eluting stents (1003 patients) or polymer-free drug-coated stents (993 patients). At 1 year, the primary outcome was observed in 169 of 988 patients (17.1%) in the zotarolimus-eluting stent group and in 164 of 969 (16.9%) in the polymer-free drug-coated stent group (risk difference, 0.2 percentage points; upper boundary of the one-sided 97.5% confidence interval [CI], 3.5; noninferiority margin, 4.1; P = 0.01 for noninferiority). The principal secondary outcome was observed in 174 patients (17.6%) in the zotarolimus-eluting stent group and in 169 (17.4%) in the polymer-free drug-coated stent group (risk difference, 0.2 percentage points; upper boundary of the one-sided 97.5% CI, 3.5; noninferiority margin, 4.4; P = 0.007 for noninferiority). Conclusions: among patients at high bleeding risk who received 1 month of dual antiplatelet therapy after PCI, use of polymer-based zotarolimus-eluting stents was noninferior to use of polymer-free drug-coated stents with regard to safety and effectiveness composite outcomes. (Funded by Medtronic; ONYX ONE ClinicalTrials.gov number, NCT03344653.)