Use of the SGLT-2 inhibitor dapagliflozin was associated with significant improvements in symptoms and physical limitations among patients with heart failure with preserved ejection fraction (HFpEF) according to results of the PRESERVED-HF trial presented at the Heart Failure Society of America (HFSA) Annual Scientific Meeting 2021.

Specifically, treatment with dapagliflozin resulted in clinically meaningful and statistically significant improvements in HF limitations measured by the Kansas City Cardiomyopathy Questionnaire clinical summary (KCCQ-CS) score and in exercise function as measured by 6-minute walking distance

“To our knowledge, PRESERVED-HF is the first trial to show compelling benefits of SGLT2 inhibitors on both patient-reported symptoms and physical limitations, as well as objectively measured physical function in individuals with HFpEF – outcomes of great importance to both patients and clinicians,” said Mikhail Kosiborod, MD, cardiologist at Saint Luke’s Mid America Heart Institute and Vice President of Research at Saint Luke’s Health System, in a St Luke's 

Kosiborod said the findings are particularly meaningful for HFpEF which he notes has been referred to as the “black hole” of cardiology because of the historic lack of effective treatments with disease modifying properties. “PRESERVED-HF,” he commented in the statement, “shows that dapagliflozin can enable individuals with HFpEF to feel better and do more within just 12 weeks.”

PRESERVED-HF, a multicenter, double-blind, randomized, placebo-controlled trial, assessed the use of dapagliflozin 10 mg vs matching placebo once daily for 12 weeks among 324 patients (162 in each arm) across 26 US sites. KCCQ clinical summary score at 12 weeks was the primary outcome of interest with 6-minute walking distance a key secondary endpoint.

Criteria for PRESERVED-HF inclusion were NYHA class II-IV symptoms, left ventricular ejection fraction (LVEF) of at least 45%, NTproBNP of ≥225 pg/mL, current diuretic therapy, and at least one of the following: recent HF hospitalization or urgent visit requiring IV diuretic, elevated filling pressures by right or left heart catheterization, or structural heart disease by echocardiography.

Average duration of HF was 3 years with median LVEF 60%. Mean age of study participants was 70 years; 57% were women, 30% were African American—both groups known to have high HFpEF symptom burden but traditionally to be under-represented in clinical trials, according to the St Lukes statement. Approximately half of participants had diabetes (56%) and atrial fibrillation (53%).

Investigators report that use of dapagliflozin was associated with significant improvements in symptoms and physical limitations measured by the KCCQ-CS—an increase of 5.8 points (95% CI, 2.3-9.2) at 12 weeks (

=.001) for total symptoms and increase of 5.3 points for physical limitations. Analysis for the secondary endpoint found dapagliflozin was associated with a significant improvement in 6-minute walking distance vs placebo—effect size, 20.1 meters (95% CI, 5.6-34.7; 

The study indicates the effect of dapagliflozin was consistent across subgroups, including those with type 2 diabetes, baseline LVEF, sex, race, and age.

No differences were observed between dapagliflozin and placebo groups in terms of natriuretic peptides, A1C, or systolic blood pressure. There was a modest weight reduction of 0.72 (95% CI, 0.01-1.42) kg observed with dapagliflozin versus placebo (

“Taken together with the results of previous studies, our findings further strengthen the notion that SGLT2 inhibitors represent a disease-modifying therapy, and thus an important new treatment option for HFpEF, which is a highly morbid condition,” stated Kosiborod. “This is great news for patients and clinicians. As a cardiologist and researcher, I am excited about the potential impact of PRESERVED-HF data on the management of this patient population.”

This study, “Effects of Dapagliflozin on Symptoms, Function and Quality of Life in Patients with Heart Failure and Preserved Ejection Fraction - Main Results from the PRESERVED-HF Trial,” was presented at HFSA 2021.

Articles

Dapagliflozin adds substantial improvements in symptoms, exercise function to demonstrated disease-modifying properties for patients with HFpEF.  

HFpEF News: Dapagliflozin Improves Symptoms, Exercise Function in PRESERVED-HF 

Opioid overdose death rates increased among non-Hispanic Black persons between 2018 and 2019 while rates for other race and ethnicity groups leveled off, according to new research published in the 

“These data add to the evidence of worsening disparities in opioid overdose deaths by race/ethnicity,” wrote authors led by Marc Larochelle, MD, MPH, internal medicine physician, Boston Medical Center

The research was conducted as part of the ongoing 

(HCS), the largest addiction implementation study to date that was launched by the National Institutes of Health (NIH) in partnership with the National Institute on Drug Abuse (NIDA).

"We must explicitly examine and address how structural racism affects health and leads to drug use and overdose deaths."

The objective of HCS is to reduce opioid overdose deaths through community engagement interventions such as overdose education, naloxone distribution, and enhanced delivery of medications for opioid use disorder.

"We must explicitly examine and address how structural racism affects health and leads to drug use and overdose deaths," said NIDA Director Nora D. Volkow, MD, who was not part of the current study, in an 

Systemic racism fuels the opioid crisis, just as it contributes mightily to other areas of health disparities and inequity, especially for Black people. We must ensure that evidence-based interventions, tailored to communities, are able to cut through the economic and social factors that drive disparities in substance use and addiction, to reach all people in need of services."

For the current study, Dr Larochelle and colleagues analyzed data from 2018-2019 death certificates for individuals aged ≥18 years across 67 communities disproportionally affected by opioid overdose deaths in 4 states (New York, Kentucky, Massachusetts, and Ohio) enrolled in HCS.

Researchers calculated opioid overdose death rates and trends overall and then stratified them by race/ethnicity (non-Hispanic White, non-Hispanic Black, Hispanic, other) and state. The total population across the 67 communities was approximately 8.3 million.

Across all 4 states, there was no significant change in opioid overdose deaths rates between 2018 and 2019 (rate ratio [RR]=1.03; 95% confidence interval [CI], 0.98-1.08).

Researchers observed a 38% overall increase in the opioid overdose death rate for non-Hispanic Black individuals from 2018 to 2019 (RR=1.38; 95% CI, 1.21-1.57) relative to non-Hispanic White individuals but no change overall among other racial and ethnic groups, according to the study.

Opioid overdose death rate increases among non-Hispanic Black individuals was observed in Kentucky (RR=1.46; 95% CI, 1.01-2.11) and Ohio (RR=1.45; 95% CI, 1.24-1.7), but no significant increase was observed in Massachusetts.

Researchers noted that while opioid overdose death rates were unchanged for non-Hispanic Black adults in New York (RR=1.03; 95% CI, 0.72-1.48), there was an 18% decline among non-Hispanic White adults (RR=0.82; 95% CI, 0.72-0.93).

“These data highlight the importance of timely, local data to inform an equitable approach for developing community-tailored strategies to reduce opioid overdose deaths,” concluded researchers. “An antiracist public health approach that explicitly examines the role of racism is urgently needed in research, public health, and policy approaches to address the crisis of opioid-related harms.”

Reference: Larochelle MR, Slavova S, Root ED, et al. 

Disparities in opioid overdose death trends by race/ethnicity, 2018–2019, from the HEALing Communities Study

. AJPH. Published online ahead of print September 9, 2021.

New research shows opioid overdose death rates increased among Black Americans between 2018 and 2019, despite having leveled off in other ethnic/racial groups.

Study: Opioid Overdose Death Rate Climbed Nearly 40% among Black Americans

How widespread is the Delta variant (B.1.617.2) in the US?

Centers for Disease Control and Prevention (CDC)

, as of September 14, 2021, the SARS-CoV-2 Delta variant made up 

The CDC estimates as of September 14, 2021, the 5 states with the highest unweighted proportion of new cases attributed to the SARS-CoV-2 Delta variant are:

How many people in the US have been vaccinated against COVID-19?

 as of today, September 17, 2021, at 2:49 PM, EDT:

The 5 states with the highest percentage of population fully vaccinated are:

How many cases of COVID-19 have been confirmed in the US?

, as of today, September 17, 2021 at 4:21 PM, EDT, there have been:

The 5 states with the highest total confirmed cases are:

 California has the highest number of deaths due to COVID-19

 with 67 763 reported fatalities, followed by 

How many cases of COVID-19 have been confirmed globally?

Data from the CDC on the Delta variant and US vaccination rates and from the Johns Hopkins COVID-19 interactive map on cases and deaths in the US and worldwide.

COVID-19 Updates: Delta Variant, US Vaccinations, & Global Data as of September 17, 2021

 as of today, September 16, 2021, at 3:00 PM, EDT:

, as of today, September 16, 2021 at 4:21 PM, EDT, there have been:

 with 67 439 reported fatalities, followed by 

COVID-19 Updates: Delta Variant, US Vaccinations, & Global Data as of September 16, 2021

Preventable hospitalizations of patients unvaccinated against SARS-CoV-2 infection from June through August 2021 have cost an estimated $5 billion according to a 

published by the Peterson Center on Healthcare and the Kaiser Family Foundation.

The hospitalizations are of course traumatic for patients and for their loved ones and the clinicians who care for them. In addition, study authors point out, US taxpayers, whether through publicly funded health plans or through increased rates of private insurance, are ultimately paying for the avoidable care. 

Despite the availability of safe and effective COVID-19 vaccines, US vaccination rates have lagged, particularly in some southern and western states and among younger people. As of early September 2021, 25% of adults over the age of 18 years in the US remain unvaccinated for COVID-19. As a result of the drop off in vaccinations and the rapid spread of the more infectious delta variant, COVID-19 cases, hospitalizations, and deaths are, once again, climbing.

The surge in COVID-19 hospitalizations also is putting financial strain on payers. As a result, insurers are beginning to reinstate cost-sharing for COVID-19 treatment, though patients still only pay a small share of the total costs. The study estimates that the average hospitalization for COVID-19 costs approximately $20,000, though the costs for those requiring a ventilator are much higher.

The study’s analysis of HHS and CDC data indicates there were 32 000 preventable COVID-19 hospitalizations in June, 68 000 in July, and another 187 000 among unvaccinated adults in the US in August—a total of 287 000 across the 3 months.

If each of these preventable hospitalizations cost roughly $20 000, on average, that would mean these largely avoidable hospitalizations have already cost more than $5 billion since the beginning of June.

The study authors say this figure is likely an understatement of the cost burden from preventable treatment of COVID-19 among unvaccinated adults, because it does not include the cost of outpatient treatment, which is likely substantial. They cite a Medicare study that found patients with COVID-related admissions had multiple outpatient visits (3.2 on average) that cost approximately $164 each (and this is only for those COVID-19 patients who were hospitalized at one point). 

An analysis of the privately insured found COVID-19 outpatient treatment costs can average $500-$1,000 per patient. There is also reason to believe that average costs for COVID-19 hospitalizations may be even higher than $20 000 based on other studies of privately insured patients and Medicare recipients. One study that has yet to be peer reviewed found that while the median hospitalization costs private payers $25 339, the mean cost was $42 200. Similarly, in their justification for charging higher medical insurance premiums to unvaccinated employees, Delta Airlines said their average hospitalization cost was $50 000 (though it is unclear if this is the median or mean cost).

Additionally, although breakthrough infections and hospitalizations are rare, unvaccinated people are also more likely to spread the virus to those who have taken measures to protect themselves and others, and those costs are not included in the estimate.

Avoidable COVID-19 hospitalizations for unvaccinated persons in the US have cost an estimated $5 billion since June, according to a new study. 

COVID-19 Hospitalizations for Unvaccinated Cost US Billions

It is no secret that the COVID-19 pandemic has profoundly impacted both 

 mental health. Although strides have been made in the US to mitigate the transmission of COVID-19, such as vaccination efforts and social distancing, the mental strain of COVID-19 will likely continue. For this reason, 

 recently examined the 50 states across 31 key metrics to determine which environmental factors are associated with a person's overall physical and mental wellbeing. The key metrics ranged from adult depression rate to divorce rate to amount of work hours. In the slides below, find which states ranked highest and lowest across each metric. 

Slideshows

What state has the lowest suicide rate? Which one has the highest share of adult depression? Find the answers and more insights from a nationwide analysis, here.

Mental Health in America: Which States are Happiest?

Elective orthopedic procedures are among the most commonly performed surgeries. Although there is usually identifiable pathology (eg, osteoarthritis, degenerative disc disease, spinal stenosis) that could be considered an indication or these procedures, most are usually performed to reduce or eliminate pain and improve function.

It could be assumed that the efficacy of these procedures has been supported by high quality evidence, particularly randomized controlled trials (RCTs), but a recent umbrella review published in the 

calls this into question. Researchers examined meta-analyses of RCTs or of other study designs in absence of RCTs to compare the effectiveness of the 10 most common elective orthopedic procedures with no treatment, placebo, or non-operative care. 

In the slides below, find a recap of the findings for each procedure and key takeaways for your clinical practice.

What does the evidence show for the clinical effectiveness of 10 of the most common elective orthopedic procedures? A recent umbrella review sheds light. 

Common Elective Orthopedic Procedures: Does Research Support Their Use?

 as of today, September 15, 2021, at 3:47 PM, EDT:

, as of today, September 15, 2021 at 4:21 PM, EDT, there have been:

COVID-19 Updates: Delta Variant, US Vaccinations, & Global Data as of September 15, 2021

Identification of white coat and masked hypertension among both treated and untreated individuals is strongly recommended by the landmark 

 for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults. The guideline also recommends that treatment decisions (initiation or intensification) should be based on out-of-office blood pressure measures obtained by ambulatory or home blood pressure monitoring.

Summarized in this short slide show are the 7 guideline recommendations on identification and management of the 2 dangerous hypertension phenotypes as well as the evidence in support of each.

 Whelton PK, Carey RM, Aronow WS, et al. 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/ APhA/ASH/ASPC/NMA/PCNA Guideline for the prevention, detection, evaluation, and management of high blood pressure in adults: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. 

Identifying white coat and masked hypertension is essential for prevention of CV morbidity and mortality. Review the ACC/AHA recommendations on how to detect and manage. 

White Coat Hypertension & Masked Hypertension: A Primary Care Primer 

Elevated levels of urinary stress hormones are associated with an increased risk for incident hypertension and cardiovascular events among adults free of hypertension, according to research results published online September 13, 2021, in the journal 

Study investigators, led by Kosuke Inoue, MD, PhD, from the UCLA Fielding School of Public Health in Los Angeles, point to the role of psychosocial stress in the pathogenesis of hypertension and CV disease. Inoue notes, in 

 from the American Heart Association, that previous research has focused “on the relationship between stress hormone levels and hypertension or cardiovascular events in patients with existing hypertension.” He notes the lack of studies that look prospectively at the relationship in adults without hypertension as impetus for his current work.  

“It is important to examine the impact of stress on adults in the general population because it provides new information about whether routine measurement of stress hormones needs to be considered to prevent hypertension and CVD events."

“It is important to examine the impact of stress on adults in the general population because it provides new information about whether routine measurement of stress hormones needs to be considered to prevent hypertension and CVD events," said Inoue in the AHA statement.

Inoue et al conducted a prospective cohort study involving 412 adults aged 48 to 87 years free of hypertension from a substudy of the Multi-Ethnic Study of Atherosclerosis (MESA). Participants had available measurements of urinary stress hormones (norepinephrine, epinephrine, dopamine, and cortisol). The adjusted hazard ratio (aHR) of incident hypertension and cardiovascular events was estimated according to urinary stress hormone levels.

Participants average age was 61.2 years; 50% were women; 54% were Hispanic, 22%, Black, and 24% White.

Median follow-up time was 6.5 years. Investigators report the risk for incident hypertension during that period was increased per doubling of norepinephrine (aHR, 1.31 [95% confidence interval [CI], 1.06–1.61]), epinephrine (aHR, 1.21 [95% CI, 1.03–1.41]), dopamine (aHR, 1.28 [95% CI, 1.00–1.64]), and cortisol (aHR, 1.23 [95% CI, 1.04–1.44]). Inoue and colleagues found that in general the associations were stronger among participants aged <60 years vs those ≥60 years and in particular for dopamine (

During a median follow-up of 11.2 years, there was an increased risk of incident cardiovascular events per doubling of cortisol (aHR, 1.90 [95% CI, 1.16–3.09]), but not for catecholamines.

"The next key research question is whether and in which populations increased testing of stress hormones could be helpful. Currently, these hormones are measured only when hypertension with an underlying cause or other related diseases are suspected," said Inoue in the AHA statement. "However, if additional screening could help prevent hypertension and cardiovascular events, we may want to measure these hormone levels more frequently."

Study limitations, according to authors, included the exclusion of individuals with hypertension at initiation of the study which would have created a larger participant population and also exclusive use of urinalysis for stress hormone measurement.

Urinary stress hormones, hypertension, and cardiovascular events: The Multi-Ethnic Study of Atherosclerosis.

 Published online ahead of print September 13, 2021.

Each doubling of levels of 4 stress hormones was associated with a 21-31% increase in risk of developing hypertension over a median 6.5-year follow-up.