Faculty Bibliography

BACKGROUND:Describing the antihypertensive medication regimens used in the SPRINT (Systolic Blood Pressure Intervention Trial) would contextualize the standard and intensive systolic blood pressure (SBP) interventions and may inform future implementation efforts to achieve population-wide intensive SBP goals. METHODS:We included SPRINT participants with complete medication data at the prerandomization and 12-month visits. Regimens were categorized by antihypertensive medication class. Analyses were stratified by treatment group (standard goal SBP <140 mm Hg versus intensive goal SBP <120 mm Hg). RESULTS:<0.001). Prerandomization, angiotensin-converting enzyme inhibitor (ACE), or angiotensin-II receptor blocker (ARB) monotherapy was the most common regimen in the intensive and standard groups (12.6% versus 12.2%). At 12-months, ACE/ARB monotherapy was still the most common regimen among standard group participants (14.7%) and was used by 5.3% of intensive group participants. Multidrug regimens used by the intensive and standard participants at 12 months were as follows: an ACE/ARB with thiazide (12.2% and 7.9%); an ACE/ARB with calcium channel blocker (6.2% and 6.8%); an ACE/ARB, thiazide, and calcium channel blocker (11.4% and 4.3%); and an ACE/ARB, thiazide, calcium channel blocker, and beta-blocker (6.5% and 1.2%). CONCLUSIONS:SPRINT investigators favored combining ACEs or ARBs, thiazide diuretics, and calcium channel blockers to target SBP <120 mm Hg, compared to ACE/ARB monotherapy to target SBP <140 mm Hg. REGISTRATION/BACKGROUND:URL: https://clinicaltrials.gov; Unique identifier: NCT01206062.

BACKGROUND:Patient awareness, clinician detection, and management of chronic kidney disease remain suboptimal, despite clinical practice guidelines and diverse education programs. OBJECTIVE:This protocol describes a study to develop and investigate the impact of the National Kidney Foundation Kidney Score Platform on chronic kidney disease awareness, communication, and management, by leveraging the Behavior Change Wheel, an implementation science framework that helps identify behavioral intervention targets and functions that address barriers to behavior change. METHODS:We interviewed 20 patients with chronic kidney disease and 11 clinicians to identify patient and clinician behaviors suitable for intervention and barriers to behavior change (eg, limited awareness of chronic kidney disease clinical practice guidelines within primary care settings, limited data analytics to highlight chronic kidney disease care gaps, asymptomatic nature of chronic kidney disease in conjunction with patient reliance on primary care clinicians to determine risk and order kidney testing). Leveraging the Behavior Change Wheel, the Kidney Score Platform was developed with a patient-facing online Risk Calculator and a clinician-facing Clinical Practice Toolkit. The Risk Calculator utilizes risk predictive analytics to provide interactive health information tailored to an individual's chronic kidney disease risk and health status. The Clinical Practice Toolkit assists clinicians in discussing chronic kidney disease with individuals at risk for and with kidney disease and in managing their patient population with chronic kidney disease. The Kidney Score Platform will be tested in 2 Veterans Affairs primary health care settings using a pre-post study design. Outcomes will include changes in patient self-efficacy for chronic kidney disease management (primary outcome), quality of communication with clinicians about chronic kidney disease, and practitioners' knowledge of chronic kidney disease guidelines. Process outcomes will identify usability and adoption of different elements of the Kidney Score Platform using qualitative and quantitative methods. RESULTS:As of September 2020, usability studies are underway with veterans and clinicians to refine the patient-facing components of the Kidney Score Platform before study initiation. Results and subsequent changes to the Kidney Score Platform will be published at a later date. The study is expected to be completed by December 2021. CONCLUSIONS:Results of this study will be used to inform integration of the Kidney Score Platform within primary care settings so that it can serve as a central component of the National Kidney Foundation public awareness campaign to educate, engage, and empower individuals at risk for and living with chronic kidney disease. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID)/UNASSIGNED:PRR1-10.2196/22024.

Chronic kidney disease (CKD) is a potentially progressive disease that culminates in end-stage renal disease (ESRD) and has substantial morbidity. ESRD patients on hemodialysis (HD) are at high risk of hepatitis B (HBV) infection given prolonged vascular access, and person-to-person transmission via contaminated machines and personnel hands. Once patients have reached ESRD, they often fail to have adequate antibody response to HBV vaccination; whereas patients with CKD stage 4-5 NOT on HD have a higher antibody response. In a study of 68 patients, Fraser et al. found that after a 4-dose series, the seroprotection rate in adult pre-HD patients with serum creatinine levels of <=4 mg/dL was 86%, compared with 37% in patients with serum creatinine levels > 4 mg/dL, of whom 88% were on HD. Data was mined from the electronic medical record of all patients with CKD 4 and 5 seen in the Renal clinic at the Manhattan Campus of the VA NY Harbor Health Care System in July 2019 and their HBV immunity status confirmed by chart review. Barriers to vaccinating were identified through interviews with physician and patients. Several barriers were identified such as lack of housestaff education leading to not understanding the importance of checking HBV labs; delay in obtaining labs/or results, vaccination myths and inadequate follow-up. Countermeasures were developed for these barriers. We created and implemented a protocol for testing for HBV immunity and for immunization as appropriate. We are educating our fellows and ancillary staff. We also created a patient education flyer to increase CKD patients' awareness of HBV that would indirectly increase compliance with testing and adherence to the immunization schedule. Data collection for Sept-Oct 2019 prior to implementing the protocol, after only increased physician awareness, showed a decline in the percent of CKD 4-5 patients with insufficient or unknown immunity from 97.8% to 80%. The project is ongoing, and we are expecting that the results will be more robust as patient and staff education are emphasized; and patients complete their individualized vaccination schedules as appropriate.
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Total medication burden (antihypertensive and nonantihypertensive medications) may be associated with poor systolic blood pressure (SBP) control. We investigated the association of baseline medication burden and clinical outcomes and whether the effect of the SBP intervention varied according to baseline medication burden in SPRINT (Systolic Blood Pressure Intervention Trial). Participants were randomized to intensive or standard SBP goal (below 120 or 140 mm Hg, respectively); n=3769 participants with high baseline medication burden (≥5 medications) and n=5592 with low burden (<5 medications). Primary outcome: differences in SBP. Secondary outcomes: 8-item Morisky Medication Adherence Scale and modified Treatment Satisfaction Questionnaire for Medications measured at baseline and 12 months and incident cardiovascular disease events and serious adverse events throughout the trial. Participants in the intensive group with high versus low medication burden were less likely to achieve their SBP goal at 12 months (risk ratio, 0.91; 95% CI, 0.85-0.97) but not in the standard group (risk ratio, 0.98; 95% CI, 0.93-1.03; P_interaction<0.001). High medication burden was associated with increased cardiovascular disease events (hazard ratio, 1.39; 95% CI, 1.14-1.70) and serious adverse events (hazard ratio, 1.34; 95% CI, 1.24-1.45), but the effect of intensive versus standard treatment did not vary between medication burden groups ( P_interaction>0.5). Medication burden had minimal association with adherence or satisfaction. High baseline medication burden was associated with worse intensive SBP control and higher rates of cardiovascular disease events and serious adverse events. The relative benefits and risks of intensive SBP goals were similar regardless of medication burden. Clinical Trial Registration- URL: http://www.clinicaltrials.gov . Unique identifier: NCT01206062.

Objective/UNASSIGNED:Despite numerous interventions to address adherence to antihypertensive medications, continued high rates of uncontrolled blood pressure (BP) suggest a need to better understand patient factors beyond adherence associated with BP control. We examined how patients' BP-related beliefs, and aspects of life context affect BP control, beyond medication adherence. Methods/UNASSIGNED:We conducted a cross-sectional telephone survey of primary care patients with hypertension between 2010 and 2011 (N=103; 93 had complete data on all variables and were included in the regression analyses). We assessed patient sociodemographics (including race/ethnicity), medication adherence, BP-related beliefs, aspects of life context, and used clinical BP assessments. Results/UNASSIGNED:Regression models including sociodemographics, medication adherence, and either beliefs or context consistently predicted BP control. Adding context after beliefs added no predictive value while adding beliefs after context significantly predicted BP control. Practical Implications/UNASSIGNED:Results suggest that when clinicians must choose a dimension on which to intervene, focusing on beliefs would be the most fruitful approach to effecting change in BP control.

BACKGROUND AND OBJECTIVES/OBJECTIVE:In people with type 2 diabetes, aggressive control of glycemia, BP, and lipids have resulted in conflicting short-term (<5 years) kidney outcomes. We aimed to determine the long-term kidney effects of these interventions. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS/METHODS:primary composite kidney outcome was defined as incident macroalbuminuria, creatinine doubling, need for dialysis, or death by any cause. Cox proportional hazards regression estimated the effect of each intervention on the composite outcome and individual components. In secondary outcome analyses, competing risk regression was used to account for the risk of death in incident kidney outcomes. Analyses were adjusted for sociodemographics, randomization groups, and clinical factors. RESULTS:There were 988 cases of incident macroalbuminuria, 954 with doubling of creatinine, 351 requiring dialysis, and 1905 deaths. Hazard ratios (HRs) for the composite outcome with intensive glycemic, BP control, and fenofibrate use compared with standard therapy were 0.92 (95% confidence interval [95% CI], 0.86 to 0.98), 1.16 (95% CI, 1.05 to 1.28), and 1.16 (95% CI, 1.06 to 1.27). Multivariable, secondary outcome analyses showed that in the glycemia trial, only macroalbuminuria was significantly decreased (HR, 0.68; 95% CI, 0.59 to 0.77). In the BP and lipid trials, only creatinine doubling was affected (HR, 1.64; 95% CI, 1.30 to 2.06 and HR, 2.00; 95% CI, 1.61 to 2.49, respectively). CONCLUSIONS:In people with type 2 diabetes at high risk for cardiovascular disease, intensive glycemic control may result in a long-term reduction in macroalbuminuria; however, intensive BP control and fenofibrates may increase the risk for adverse kidney events.

BACKGROUND:Treating to a lower blood pressure (BP) may increase acute kidney injury (AKI) events. STUDY DESIGN/METHODS:Data for AKI resulting in or during hospitalization or emergency department visits were collected as part of the serious adverse events reporting process of the Systolic Blood Pressure Intervention Trial (SPRINT). SETTING & PARTICIPANTS/METHODS:9,361 participants 50 years or older with 1 or more risk factors for cardiovascular disease. INTERVENTIONS/METHODS:Participants were randomly assigned to a systolic BP target of <120 (intensive arm) or <140mmHg (standard arm). OUTCOMES & MEASUREMENTS/METHODS:Primary outcome was the number of adjudicated AKI events. Secondary outcomes included severity of AKI and degree of recovery of kidney function after an AKI event. Baseline creatinine concentration was defined as the most recent SPRINT outpatient creatinine value before the date of the AKI event. RESULTS:There were 179 participants with AKI events in the intensive arm and 109 in the standard arm (3.8% vs 2.3%; HR, 1.64; 95% CI, 1.30-2.10; P<0.001). Of 288 participants with an AKI event, 248 (86.1%) had a single AKI event during the trial. Based on modified KDIGO (Kidney Disease: Improving Global Outcomes) criteria for severity of AKI, the number of AKI events in the intensive versus standard arm by KDIGO stage was 128 (58.5%) versus 81 (62.8%) for AKI stage 1, 42 (19.2%) versus 18 (14.0%) for AKI stage 2, and 42 (19.2%) versus 25 (19.4%) for AKI stage 3 (P=0.5). For participants with sufficient data, complete or partial resolution of AKI was seen for 169 (90.4%) and 9 (4.8%) of 187 AKI events in the intensive arm and 86 (86.9%) and 4 (4.0%) of 99 AKI events in the standard arm, respectively. LIMITATIONS/CONCLUSIONS:Trial results are not generalizable to patients with diabetes mellitus or without risk factors for cardiovascular disease. CONCLUSIONS:More intensive BP lowering resulted in more frequent episodes of AKI. Most cases were mild and most participants had complete recovery of kidney function. TRIAL REGISTRATION/BACKGROUND:Registered at ClinicalTrials.gov with study number NCT01206062.

The appropriate target for BP in patients with CKD and hypertension remains uncertain. We report prespecified subgroup analyses of outcomes in participants with baseline CKD in the Systolic Blood Pressure Intervention Trial. We randomly assigned participants to a systolic BP target of <120 mm Hg (intensive group; n=1330) or <140 mm Hg (standard group; n=1316). After a median follow-up of 3.3 years, the primary composite cardiovascular outcome occurred in 112 intensive group and 131 standard group CKD participants (hazard ratio [HR], 0.81; 95% confidence interval [95% CI], 0.63 to 1.05). The intensive group also had a lower rate of all-cause death (HR, 0.72; 95% CI, 0.53 to 0.99). Treatment effects did not differ between participants with and without CKD (P values for interactions >/=0.30). The prespecified main kidney outcome, defined as the composite of >/=50% decrease in eGFR from baseline or ESRD, occurred in 15 intensive group and 16 standard group participants (HR, 0.90; 95% CI, 0.44 to 1.83). After the initial 6 months, the intensive group had a slightly higher rate of change in eGFR (-0.47 versus -0.32 ml/min per 1.73 m2 per year; P<0.03). The overall rate of serious adverse events did not differ between treatment groups, although some specific adverse events occurred more often in the intensive group. Thus, among patients with CKD and hypertension without diabetes, targeting an SBP<120 mm Hg compared with <140 mm Hg reduced rates of major cardiovascular events and all-cause death without evidence of effect modifications by CKD or deleterious effect on the main kidney outcome.

OBJECTIVE: We sought to understand barriers to hypertension self-management in patients with hypertension and comorbidities. METHODS: We conducted semi-structured, qualitative interviews with 48 patients with uncontrolled hypertension and at least one comorbidity to learn about beliefs and behaviors that might affect hypertension self-management. Using a grounded theory strategy, we analyzed interview transcripts detailing patients' hypertension self-management behaviors vis-a-vis a framework including Explanatory Models-a patient's understanding of the pathophysiology, cause, course, treatment, and severity of an illness, such as hypertension. RESULTS: We identified four factors that interfered with hypertension self-management. (1) Interdependence: Participants saw hypertension as interconnected to their comorbidities and subsequently had difficulty separating information about their illnesses. (2) Low priority: Compared to other conditions, participants assigned hypertension a lower priority. (3) Conflicts: Participants struggled with conflicts between hypertension self-management practices and those for comorbidities. (4) Managing multiple medications: Polypharmacy led to patients' confusion and concern about taking medications as prescribed. DISCUSSION: Participants did not experience hypertension as a discreet clinical condition; rather, they self-managed hypertension concurrently with other conditions, leading to a breakdown in hypertension self-management. We provide strategies to address each of the four barriers to better equip providers in addressing their clinically salient concerns.