Research Spotlight

Posted July 15th 2021

Regional and ethnic influences on the response to empagliflozin in patients with heart failure and a reduced ejection fraction: the EMPEROR-Reduced trial.

Milton Packer M.D.

Milton Packer M.D.

Lam, C.S.P., Ferreira, J.P., Pfarr, E., Sim, D., Tsutsui, H., Anker, S.D., Butler, J., Filippatos, G., Pocock, S.J., Sattar, N., Verma, S., Brueckmann, M., Schnee, J., Cotton, D., Zannad, F. and Packer, M. (2021). “Regional and ethnic influences on the response to empagliflozin in patients with heart failure and a reduced ejection fraction: the EMPEROR-Reduced trial.” Eur Heart J Jun 29;ehab360. [Epub ahead of print].

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AIMS: The aim of this article is to explore the influence of region and race/ethnicity on the effects of empagliflozin in the Empagliflozin Outcome Trial in Patients with Chronic Heart Failure and a Reduced Ejection Fraction (EMPEROR-Reduced) trial. METHODS AND RESULTS: Of 3730 patients, 1353 (36.3%) were enrolled in Europe, 1286 (34.5%) in Latin America, 425 (11.4%) in North America, and 493 (13.2%) in Asia; 2629 (70.5%) were White, 257 (6.9%) Black, and 672 (18.0%) Asian. Placebo event rates (per 100 patient-years) for cardiovascular death or heart failure (HF) hospitalization varied by region (Asia 27.7, North America 26.4, Latin America 21.4, and Europe 17.5) and race/ethnicity (Black 34.4, Asian 24.3, and White 18.7); driven by differences in HF hospitalization. The ratio of total HF hospitalization to cardiovascular death varied from 5.4 in Asia and 4.8 in North America to 2.1 in Europe; and from 4.8 in Black and 4.2 in Asian to 2.2 in White patients. Groups with the highest ratio had the greatest reduction in the primary outcome with empagliflozin. Inclusion of outpatient worsening HF episodes added more events in Europe vs. other regions; enhanced the placebo event rates in Europe vs. other regions; and increased the relative risk reduction with empagliflozin in Europe from 6% to 26%. CONCLUSIONS: There were notable differences in the placebo event rates for major HF events across diverse regions and race/ethnic groups. The benefit of empagliflozin was most pronounced in groups with the highest ratio of HF hospitalization to cardiovascular death. Regional differences were attenuated when the definition of HF events was expanded to include outpatient worsening HF events.


Posted July 15th 2021

Monotherapy Anticoagulation to Expedite Home Treatment of Patients Diagnosed With Venous Thromboembolism in the Emergency Department: A Pragmatic Effectiveness Trial.

John S. Garrett M.D.

John S. Garrett M.D.

Kline, J.A., Adler, D.H., Alanis, N., Bledsoe, J.R., Courtney, D.M., d’Etienne, J.P., Diercks, D.B., Garrett, J.S., Jones, A.E., Mackenzie, D.C., Madsen, T., Matuskowitz, A.J., Mumma, B.E., Nordenholz, K.E., Pagenhardt, J., Runyon, M.S., Stubblefield, W.B. and Willoughby, C.B. (2021). “Monotherapy Anticoagulation to Expedite Home Treatment of Patients Diagnosed With Venous Thromboembolism in the Emergency Department: A Pragmatic Effectiveness Trial.” Circ Cardiovasc Qual Outcomes Jun 21;CIRCOUTCOMES120007600. [Epub ahead of print]. Circoutcomes120007600.

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BACKGROUND: The objective was to test if low-risk emergency department patients with vitamin K antagonist (venous thromboembolism [VTE]; including venous thrombosis and pulmonary embolism [PE]) can be safely and effectively treated at home with direct acting oral (monotherapy) anticoagulation in a large-scale, real-world pragmatic effectiveness trial. METHODS: This was a single-arm trial, conducted from 2016 to 2019 in accordance with the Standards for Reporting Implementation Studies guideline in 33 emergency departments in the United States. Participants had newly diagnosed VTE with low risk of death based upon either the modified Hestia criteria, or physician judgment plus the simplified PE severity index score of zero, together with nonhigh bleeding risk were eligible. Patients had to be discharged within 24 hours of triage and treated with either apixaban or rivaroxaban. Effectiveness was defined by the primary efficacy and safety outcomes, image-proven recurrent VTE and bleeding requiring hospitalization >24 hours, respectively, with an upper limit of the 95% CI for the 30-day frequency of VTE recurrence below 2.0% for both outcomes. RESULTS: We enrolled 1421 patients with complete outcomes data, including 903 with venous thrombosis and 518 with PE. The recurrent VTE requiring hospitalization occurred in 14/1421 (1.0% [95% CI, 0.5%-1.7%]), and bleeding requiring hospitalization occurred in 12/1421 (0.8% [0.4%-1.5%). The rate of severe bleeding using International Society for Thrombosis and Haemostasis criteria was 2/1421 (0.1% [0%-0.5%]). No patient died, and serious adverse events occurred in 2.5% of venous thrombosis patients and 2.3% of patients with PE. Medication nonadherence was reported by patients in 8.0% (6.6%-9.5%) and was associated with a risk ratio of 6.0 (2.3-15.2) for VTE recurrence. Among all patients diagnosed with VTE in the emergency department during the period of study, 18% of venous thrombosis patients and 10% of patients with PE were enrolled. CONCLUSIONS: Monotherapy treatment of low-risk patients with venous thrombosis or PE in the emergency department setting produced a low rate of bleeding and VTE recurrence, but may be underused. Patients with venous thrombosis and PE should undergo risk-stratification before home treatment. Improved patient adherence may reduce rate of recurrent VTE. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03404635.


Posted July 15th 2021

Cost-Related Nonadherence to Medications Among US Adults With Chronic Liver Diseases.

Sumeet K. Asrani M.D.

Sumeet K. Asrani M.D.

Lago-Hernandez, C., Nguyen, N.H., Khera, R., Loomba, R., Asrani, S.K. and Singh, S. (2021). “Cost-Related Nonadherence to Medications Among US Adults With Chronic Liver Diseases.” Mayo Clin Proc Jun 10;S0025-6196(21)00255-X. [Epub ahead of print].

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OBJECTIVE: To estimate the prevalence, risk factors, and consequences of cost-related medication nonadherence (CRN) in individuals with chronic liver diseases (CLDs) in the United States. PATIENTS AND METHODS: Using the National Health Interview Survey from January 1, 2014, to December 31, 2018, we identified individuals with CLDs. Using complex weighted survey analysis, we obtained national estimates and risk factors for CRN and its association with cost-reducing behaviors and measures of financial toxicity. We evaluated the association of CRN with unplanned health care use, adjusting for age, sex, race/ethnicity, insurance, income, education, and comorbid conditions. RESULTS: Of 3237 respondents (representing 4.6 million) US adults with CLDs, 813 (representing 1.2 million adults, or 25%; 95% CI, 23% to 27%) reported CRN, of whom 68% (n=554/813) reported maladaptive cost-reducing behaviors. Younger age, female sex, low income, and multimorbidity were associated with a higher prevalence of CRN. Compared with patients without CRN, patients experiencing CRN had 5.1 times higher odds of financial hardship from medical bills (adjusted odds ratio [aOR], 5.05; 95% CI, 3.73 to 6.83) and 2.9 times higher odds of food insecurity (aOR, 2.85; 95% CI, 2.02 to 4.01). The CRN was also associated with 1.5 times higher odds of emergency department visits (aOR, 1.46; 95% CI, 1.11 to 1.94). CONCLUSION: We observed a high prevalence of CRN and associated consequences such as high financial distress, financial hardship from medical bills, food insecurity, engagement in maladaptive cost-reducing strategies, increased health care use, and work absenteeism among patients with CLD. These financial determinants of health have important implications in the context of value-based care.


Posted July 15th 2021

Feasibility of an Internet-Based Intervention to Promote Exercise for People With Spinal Cord Injury: Observational Pilot Study.

Katherine Froehlich-Grobe Ph.D.

Katherine Froehlich-Grobe Ph.D.

Ochoa, C., Cole, M. and Froehlich-Grobe, K. (2021). “Feasibility of an Internet-Based Intervention to Promote Exercise for People With Spinal Cord Injury: Observational Pilot Study.” JMIR Rehabil Assist Technol 8(2): e24276.

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BACKGROUND: People with spinal cord injury (SCI) are less likely to be physically active and have higher chronic disease risk than those in the general population due to physical and metabolic changes that occur postinjury. Few studies have investigated approaches to promote increased physical activity (PA) for people with SCI despite evidence that they face unique barriers, including lack of accessible transportation and exercise equipment. To address these obstacles, we adapted an evidence-based phone-delivered intervention that promoted increased PA among people with SCI into a web-based platform, titled the Workout on Wheels internet intervention (WOWii). The adapted program provides participants with weekly skill-building information and activities, basic exercise equipment, and ongoing support through weekly group videoconferencing. OBJECTIVE: This pilot study was conducted to assess the feasibility of using a web-based and virtual format to deliver the WOWii program in a randomized controlled trial. METHODS: We assessed the feasibility of the web-based program by delivering an abbreviated, 4-week version to 10 participants with SCI. Rates of weekly videoconference attendance, activity completion, and exercise activity as tracked by an arm-based activity monitor were recorded for all participants. RESULTS: Participants averaged 3.3 of 4 (83%) weekly group videoconferences attended, 3.4 of 4 (85%) web-based module activities completed, and 2.3 of 4 (58%) weeks of using the arm-based activity monitor. The majority of the sample (9/10, 90%) synced their arm-based PA monitor at least once, and overall engagement as an average of each component across the 4 weeks was 75%. CONCLUSIONS: The intervention had sufficiently high levels of engagement to be used in a full randomized controlled trial to test its effectiveness in improving levels of PA among people with SCI. The knowledge we gained from this pilot study informed improvements that were made in the full randomized controlled trial.


Posted July 15th 2021

Impact of bariatric surgery on gastroesophageal reflux disease and esophageal motility.

Anh Nguyen, M.D.

Anh Nguyen, M.D.

Nguyen, A.D. (2021). “Impact of bariatric surgery on gastroesophageal reflux disease and esophageal motility.” Curr Opin Gastroenterol 37(4): 364-371.

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PURPOSE OF REVIEW: Obesity is rapidly increasing in prevalence, and bariatric surgery has become a popular treatment option that can improve all-cause mortality in obese individuals. Gastroesophageal reflux disease (GERD) and esophageal motility disorders are common in the obese population, and the effects of bariatric surgery on these conditions differ depending on the type of bariatric surgery performed. RECENT FINDINGS: Laparoscopic adjustable gastric banding has declined in popularity due to its contributions to worsening GERD symptoms and the development of esophageal dysmotility. Although laparoscopic sleeve gastrectomy (LSG) is the most popular type of bariatric surgery, a comprehensive assessment for acid reflux should be performed as LSG has been linked with worsening GERD. Novel methods to address GERD due to LSG include magnetic sphincter augmentation and concomitant fundoplication. Due to the decreased incidence of postoperative GERD and dysmotility compared to other types of bariatric surgeries, Roux-en-Y gastric bypass should be considered for obese patients with GERD and esophageal dysmotility. SUMMARY: Bariatric surgery can affect esophageal motility and contribute to worsening or development of GERD. A thorough workup of gastrointestinal symptoms before bariatric surgery should be performed with consideration for formal testing with high-resolution manometry and pH testing. Based on these results, the choice of bariatric surgery technique should be tailored accordingly to improve clinical outcomes.