Journal Wrap

The hottest research from various peer-reviewed journals – handpicked weekly by the ACC.org Editorial Board led by Kim Eagle, MD, MACC.

Study Finds CV, Renal Effects of Canagliflozin Consistent Across Different Levels of Kidney Function

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The cardiovascular and renal effects of the sodium glucose cotransporter-2 (SGLT-2) inhibitor canagliflozin are consistent across different levels of kidney function in people with type 2 diabetes who have or are at high risk of cardiovascular disease, according to a study published in Circulation.

For the study, Brendon L. Neuen, MBBS, et al., conducted a secondary analysis of the CANVAS trial, analyzing the effects of canagliflozin on cardiovascular, renal and safety outcomes in participants with and without chronic kidney disease (CKD) (defined as <60 and ≥60 mL/min/1.73m2) and for all outcomes using four categories for estimated glomerular filtration rate (eGFR) (<45, 45-<60, 60-<90, and ≥90 mL/min/1.73 m2).

The CANVAS trial enrolled 10,142 participants with type 2 diabetes and high cardiovascular risk who were followed for a mean of 188 weeks. At baseline, 2,039 participants (20.1 percent) had CKD. Of the patients with CKD, 71.6 percent had a history of cardiovascular disease. Read More >>>

According to the results, the risk reduction in the primary outcome was similar across the four eGFR categories and for participants with and without CKD. The overall effect of canagliflozin on fatal and nonfatal myocardial infarction and hospitalization for heart failure were consistent across the four eGFR categories; however, heterogeneity was observed for the effect on fatal and nonfatal stroke.

The same effect was observed for participants with and without CKD. In terms of renal outcomes, using eGFR as a continuous variable, the renoprotective effect of canagliflozin suggested a benefit at all levels of kidney function. In addition, the effects of canagliflozin on safety outcomes were consistent across all eGFR categories.

According to the authors, the relative effects of canagliflozin on most cardiovascular outcomes were consistent across different levels of kidney function, with the exception of heterogeneity for fatal and nonfatal stroke. The researchers concluded that approval of canagliflozin for patients with CKD “may allow additional individuals to benefit from this therapy.”


Neuen BL, Ohkuma T, Neal B, et al. Circulation 2018;June 25:[Epub ahead of print].

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Does Nurse-Led Medication Management Lower BP?

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The use of electronic health record (EHR)-based medical management tools in addition to nurse-led self-management education may lower blood pressure (BP), when compared with using EHR tools alone. This also may improve understanding of medication instructions and dosing, according to a study published in JAMA Internal Medicine.

Stephen D. Persell, MD, MPH, et al., looked at 794 patients with hypertension who self-reported using three or more medications concurrently. Patients were randomly assigned to three groups: EHR-alone group (comprised of medication review sheets at check-in and post-visit medication information sheets); EHR plus education group (comprised of EHR tools plus nurse-led medication management support); or usual care. Read More >>>

Results showed that after 12 months, the primary outcome of systolic BP was greater in the EHR-alone group compared with the usual care group by 3.6 mm Hg. Systolic BP in the EHR plus education group was not significantly lower compared with the usual care group (difference, −2.0 mm Hg), but was lower compared with the EHR-alone group (−5.6 mm Hg).

In addition, hypertension medication reconciliation was improved in both the EHR-alone group and the EHR plus education group compared with usual care. Further, understanding of medication instructions and dosing was greater in the EHR plus education group vs. the usual care group.

The authors add that moving forward, “self-administration errors, medication discrepancies, and incomplete adherence were common, leaving much room for improvement.”


Persell SD, Karmali KN, Lazar D, et al. JAMA Intern Med 2018;July 9:[Epub ahead of print].

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Mid-Life Hypertension Associated with Dementia

Systolic blood pressure (SBP) ≥130 mm Hg at age 50 is associated with increased risk of dementia, according to research in the European Heart Journal. This excess risk is independent of cardiovascular disease.

Data from the Whitehall II cohort study were used for the present analysis. SBP and diastolic blood pressure (DBP) were measured in 1985, 1991, 1997 and 2003. Whitehall II is an ongoing study of 6,895 men and 3,413 women, aged 35-55 years in 1985. Follow-up examinations were conducted in 1991 (n=8,815), 1997 (n=7,870), 2003 (n=6,967), 2007 (n=6,967), 2012 (n=6,318) and 2015 (n=5,632), with each wave taking two years to complete. Both SBP and DBP were measured at each visit. The primary outcome, dementia incidence, was ascertained through electronic health records through 2017. Read More >>>

A total of 8,639 adults (32.5 percent women) were included in the analysis. Dementia was identified through electronic health records in 385 participants. Mean age at dementia diagnosis was 75.2 (standard deviation, 5.4) years. Incidence of dementia was associated with lower education, higher BP, and comorbidities. SBP ≥130 mm Hg at age 50 was associated with an increased risk for dementia. However, SBP ≥130 mm Hg at age 60 or 70 was not associated with dementia.

After adjustment for factors including sociodemographic characteristics, health behaviors and time-varying chronic conditions a SBP ≥130 mm Hg increased the risk for dementia significantly (hazard ratio [HR], 1.38) compared with SBP <130 mm Hg. DBP was not associated with dementia. Participants with longer exposure to hypertension (SBP ≥130 mm Hg) between mean ages of 45 and 61 years had an increased risk of dementia compared with those with no or low exposure to hypertension (HR, 1.29). In multi-state models, SBP ≥130 mm Hg at 50 years of age was associated with greater risk of dementia in those free of cardiovascular disease over the follow-up (HR, 1.47).

“The findings of this longitudinal observational study of over 8,000 men and women support the hypothesis that hypertension in mid-life but not late life is associated with increased risk of dementia,” the authors write. “These findings, highlighting the importance of elevated systolic pressure at age 50 as a risk factor for dementia need to be replicated in larger studies to allow elaboration of evidence based prevention.”


Abell JG, Kivimaki M, Dugravot A, et al. Eur Heart J 2018;Jun 12:[Epub ahead of print].

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Is There an Association Between Participation in the BPCI Initiative and Medicare Payments?

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Hospital participation in five common medical bundles under the Bundled Payments for Care Improvement (BPCI) initiative, when compared with nonparticipation, may not be associated with changes in Medicare payments, clinical complexity, length of stay, emergency department use, hospital readmission or mortality, according to an article published in the New England Journal of Medicine.

BPCI, a voluntary episode-based payment program, was launched by the Center for Medicare and Medicaid Innovation (CMMI) in 2013. Karen E. Joynt Maddox, MD, MPH, et al., used Medicare claims from 2013 through 2015 to identify admissions for the five most commonly selected medical conditions within BPCI — congestive heart failure, pneumonia, chronic obstructive pulmonary disease, sepsis and acute myocardial infarction — and assessed changes in standardized Medicare payments per episode of care for these conditions at BPCI hospitals and matched control hospitals. Read More >>>

The authors found no significant changes in total or component Medicare episode payments and found no significant overall differences between BPCI hospitals and control hospitals in the change from baseline to the intervention period for length of stay, emergency department visits or readmissions within 30 or 90 days after discharge, or mortality within 30 or 90 days after admission.

Regarding changes in Medicare payments, at baseline, the average Medicare payment per episode of care observed for BPCI hospitals was $24,280, decreasing to $23,993 during the intervention period (p=0.41). Control hospitals had an average payment for all episodes of $23,901, which decreased to $23,503 during the intervention period (p=0.08).

The authors explain that a possibility for the failure of BPCI hospitals to reduce allowed payments is a lack of ability to influence care provided by skilled nursing facilities, inpatient rehabilitation facilities, long-term care hospitals or home health agencies, as hospitals may have little say in what happens to patients once they enter a post-acute care setting.

Moving forward, the authors called for further innovation within bundled-payment models. “Bundling of services to encourage more efficient care has great face validity and enjoys bipartisan support,” write Maddox et al. “For such bundling to work for medical conditions, however, more time, new care strategies and partnerships, or additional incentives may be required.”


Maddox KEJ, Orav EJ, Zheng J, Epstein AM. N Engl J Med 2018;379:260-9.

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Do Pooled Cohort Equations Overestimate ASCVD Risk?

Without including surveillance for atherosclerotic cardiovascular disease (ASCVD) events from the Centers for Medicare and Medicaid Services (CMS), observed risks may be lower than predicted by pooled cohort equations, according to a study published in JAMA Internal Medicine.

Samia Mora, MD, MHS, FACC, et al., sought to evaluate the predictive accuracy of the pooled risk equation using data from the Women’s Health Initiative (WHI), a multiethnic cohort of contemporary U.S. postmenopausal women. They evaluated a diverse group of 19,995 women aged 50 to 79 years. Read More >>>

Results showed a total of 1,236 ASCVD events occurred over 10 years. The authors found that the observed (predicted) risks for baseline 10-year risk categories of less than 5 percent, 5 percent to less than 7.5 percent, 7.5 percent to less than 10 percent, and 10 percent or more were 1.7 (2.8), 4.4 (6.2), 5.3 (8.7) and 12.4 (18.2), respectively. Small changes were noted after adjusting for time-dependent changes in statin and aspirin use.

Additionally, the authors found that while WHI-adjudicated risks were lower than predicted among women 65 years or older enrolled in Medicare, observed (predicted) risks became aligned after including events ascertained by linking with CMS for additional surveillance for events: 3.8 (4.3), 7.1 (6.4), 8.3 (8.7) and 18.9 (18.7), respectively, for the four risk categories. They add that similar results were seen across ethnic and racial groups.

In an accompanying editorial comment, Gregory D. Curfman, MD, FACC, notes that “the central message of the study by Mora, et al., is that accurate measurement of ASCVD risk in populations depends on comprehensive surveillance of events, but whether this provides a complete explanation of the overestimation of risk by the pooled cohort equation remains uncertain.”


Mora S, Wenger NK, Cook NR, et al. JAMA Intern Med 2018;July 23:[Epub ahead of print].

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Clinical Topics: Dyslipidemia, Heart Failure and Cardiomyopathies, Prevention, Lipid Metabolism, Nonstatins, Novel Agents, Statins, Acute Heart Failure, Hypertension, Sleep Apnea

Keywords: ACC Publications, Cardiology Magazine, Aspirin, Aspirin, Blood Pressure, Cardiovascular Diseases, Centers for Medicare and Medicaid Services (U.S.), Cohort Studies, Comorbidity, Dementia, Diabetes Mellitus, Type 2, Electronic Health Records, Emergency Service, Hospital, Episode of Care, Follow-Up Studies, Glomerular Filtration Rate, Health Behavior, Health Expenditures, Heart Failure, Home Care Agencies, Hospitalization, Hospitals, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Hypertension, Incidence, Inpatients, Length of Stay, Longitudinal Studies, Long-Term Care, Medicaid, Medicare, Medication Reconciliation, Motivation, Myocardial Infarction, Patient Discharge, Patient Readmission, Pneumonia, Postmenopause, Pulmonary Disease, Chronic Obstructive, Renal Insufficiency, Chronic, Reproducibility of Results, Risk Factors, Risk Reduction Behavior, Self Administration, Self Report, Self Care, Sepsis, Skilled Nursing Facilities, Sodium-Glucose Transport Proteins, Stroke, Subacute Care


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