Jamal S. Rana, MD, PhD, from Kaiser Permanente Northern California in Oakland, and colleagues examined whether or not heavy episodic drinking days (HED; i.e., “binge” drinking), in conjunction with habitual drinking, impacts CVD risk among US adults. The analysis included 697,985 adults (43% women) who, in 2014 to 2015, reported drinking alcohol as part of regular health care screening.

The researchers found that for men and women (aged 18 to 65 years), those with high total consumption (≥15 drinks/week for men; 8 or more drinks/week for women) had higher odds of CVD compared with those with moderate (3 to 14 drinks/week for men; 3 to 7 drinks/week for women) or low (1 to 2 drinks/week for men or women) consumption. Associations were stronger among those reporting any HED (5 or more drinks on any day in past 3 months for men and 4 or more for women; 20.8%). For men older than 65 years, CVD risk was not increased with or without HED. For women older than 65 years and HED, moderate and high total consumptions more than doubled the odds of CVD vs that seen with low consumption.

“Women feel they’re protected against heart disease until they’re older, but this study shows that even when you’re young or middle aged, if you are a heavy alcohol user or binge drink, you are at risk for coronary heart disease,” Rana said in a statement.

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Acoramidis is an orally-administered small molecule designed to stabilize tetrameric transthyretin (TTR). The NDA is supported by data from the randomized, double-blind, placebo-controlled phase 3 ATTRibute-CM trial (ClinicalTrials.gov Identifier: NCT03860935), which evaluated the efficacy and safety of acoramidis in 632 adults with symptomatic ATTR-CM. 

Study participants were randomly assigned 2:1 to receive acoramidis 800mg orally twice daily or placebo for 30 months. The primary endpoint of the study was a 4-step hierarchical combination of all-cause mortality, cumulative frequency of cardiovascular-related hospitalization, change from baseline in N-terminal pro–B-type natriuretic peptide (NT-proBNP), and change from baseline in 6-minute walk distance over a 30-month fixed treatment duration. 

Results showed a statistically significant improvement with acoramidis compared with placebo for the primary endpoint, with a win ratio of 1.8 (95% CI, 1.4-2.2; P <.0001). “Together, death from any cause and cardiovascular-related hospitalization contributed more than half the wins and losses to the win ratio (58% of all pairwise comparisons); NT-proBNP pairwise comparisons yielded the highest ratio of wins to losses (23.3% vs. 7.0%),” explained the study authors. Adverse events were found to be similar between the groups.

A Prescription Drug User Fee Act target date of November 29, 2024 has been set for the application.

Kim L. Feingold, PhD, from Northwestern University Feinberg School of Medicine in Chicago, and colleagues randomly assigned (1:1) patients undergoing primary valve surgery via sternotomy to acupuncture (51 individuals) or standard care (49 individuals). Daily inpatient acupuncture sessions started on postoperative day 1.

The researchers found that an average of 3.8 acupuncture sessions were delivered per patient during a mean hospital stay of 4.6 days. Acupuncture was associated with lower pain, nausea, stress, and anxiety after each session and across admission vs standard care. Additionally, acupuncture was associated with a lower incidence of postoperative atrial fibrillation (acupuncture, 13.7%; standard care, 32.7%), fewer discharges on amiodarone (acupuncture, 9.8%; standard care, 26.5%), and fewer hours in the intensive care unit (acupuncture, 30.3; standard care, 37.0).

“We learned that acupuncture after open heart surgery is feasible in this fast-paced environment, even in the intensive care unit the day after surgery, and was well tolerated by patients with no adverse effects,” Feingold said in a statement. “The majority of patients had no prior history with acupuncture, demonstrating their openness to receive integrative therapies after surgery. Overall, patients reported that it was a pleasant and positive aspect of their cardiovascular surgery recovery.”

Several authors disclosed ties to the medical technology industry.

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Rebecca C. Woodruff, PhD, MPH, from the US Centers for Disease Control and Prevention in Atlanta, and colleagues conducted a cross-sectional study examining surveillance data from the RSV Hospitalization Surveillance Network. To estimate the weighted period prevalence of acute cardiac events, cases of RSV infection in adults aged 50 years and older within 12 states over 5 RSV seasons were examined.

A total of 6248 hospitalized adults with laboratory-confirmed RSV infection were included. The researchers found that the weighted estimated prevalence of experiencing a cardiac event was 22.4%, with weighted estimated prevalence of 15.8, 7.5, 1.3, 1.1, and 0.6% for acute heart failure, acute ischemic heart disease, hypertensive crisis, ventricular tachycardia, and cardiogenic shock, respectively. The risk for experiencing an acute cardiac event was higher for adults with underlying cardiovascular disease (33.0 vs 8.5%; adjusted risk ratio [aRR], 3.51). Of the hospitalized adults with RSV infection, 18.6 and 4.9% required intensive care unit (ICU) admission and died, respectively; those who experienced an acute cardiac event had higher risks for ICU admission and in-hospital death (aRRs, 1.54 and 1.77, respectively).

“Acute cardiac events contribute substantially to the burden of RSV disease; whether RSV vaccination can prevent these complications is an important question as the impact of these vaccines is evaluated,” the authors write.

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In its new presidential advisory, the American Heart Association (AHA) has shined a spotlight on cardiovascular-kidney-metabolic (CKM) syndrome. CKM is a newly described multisystem syndrome highlighting the interactions among risk factors linked to poor health, organ damage, cardiovascular events, and early death. This includes obesity, type 2 diabetes and other metabolic abnormalities, chronic kidney disease (CKD), and cardiovascular disease risk.

According to the advisory, “rather than simply considering cardiorenal syndrome and cardiometabolic disease as separate entities, it is increasingly clear that we need to consider their overlap as a broader construct of CKM syndrome.

“Nearly every major organ system is affected as a consequence of CKM syndrome, with associated clinical challenges including kidney failure, premature cognitive decline, metabolic dysfunction-associated steatotic liver disease (previously nonalcoholic fatty liver disease), obstructive sleep apnea, and increased risk for cancer. However, the greatest clinical impact of CKM syndrome with regard to morbidity and premature mortality is through the disproportionate burden of [cardiovascular disease].”

More than 90 million adults, or 1 in 3 individuals, in the US have at least 3 risk factors for CKM syndrome, according to Chiadi Ndumele, MD, PhD, MHS, a cardiologist and member of the advisory writing committee. Social determinants of health and risk enhancers also play a role in who is prone to developing these risk factors and who receives adequate care, Dr Ndumele, an associate professor at Johns Hopkins University in Baltimore, Maryland, pointed out. Prevention efforts and early life screening for risk factors are major goals of this initiative, he said.

The advisory, published in Circulation, takes an interdisciplinary approach to preventing and managing CKM syndrome throughout a patient’s lifetime from youth to adulthood. It provides guidance on CKM syndrome prevention, staging, prediction, and approaches to holistic and equitable care.

CKM Syndrome Staging

The advisory details a CKM syndrome staging framework designed to help clinicians slow progression by considering the totality of patients’ individual risk exposures. The frequency and intensity of screening should increase with the CKM syndrome stage. The framework outlines how and when to use specific therapies.

• Stage 0 describes healthy adults with no risk factors whom clinicians can encourage to preserve cardiovascular health through AHA’s life’s essential 8: eating healthy, staying active, maintaining healthy weight, avoiding smoking, and maintaining normal range blood pressure, blood sugar, and lipids. Clinicians should screen these adults every 3 to 5 years to assess blood pressure, triglycerides, HDL cholesterol, and blood sugar. At every stage, clinicians should perform yearly measurement of waist circumference and body mass index and encourage healthy lifestyle behaviors.
• Stage 1 describes adults with excess or dysfunctional adipose tissue from overweight, obesity, abdominal obesity, and/or impaired glucose tolerance. (Women with gestational diabetes fall into this category.) Clinicians should screen every 2 to 3 years for blood pressure, triglycerides, cholesterol, and blood sugar. The goal is at least 5% weight loss, with treatment for glucose intolerance if needed.
• Stage 2 describes adults with metabolic risk factors or CKD. These individuals have type 2 diabetes, hypertension, hypertriglyceridemia, metabolic syndrome, and/or metabolic or nonmetabolic etiologies of CKD. Yearly assessment of blood pressure, triglycerides, cholesterol, and blood sugar is warranted. Kidney function should be assessed at least yearly and more frequently in those at risk for kidney failure. CKD screening should include blood and urine testing for estimated glomerular filtration rate (eGFR) and urinary albumin to creatinine ratio (UACR).

Stage 2 warrants intensified lifestyle medication and targeted therapies to control blood pressure, blood sugar, and cholesterol, protect kidney function, and reduce the risk of heart failure. Medications may include glucagon-like peptide 1 (GLP-1) receptor agonists or sodium glucose contransporter 2 inhibitors (SGLT2i).

• Stage 3 describes adults with subclinical atherosclerotic cardiovascular disease or subclinical heart failure. It also includes those with risk equivalents including patients with stage 4 to 5 CKD and those with high predicted cardiovascular risk.

The goal of care in stage 3 is increasing or changing medications or lifestyle efforts to prevent progression to symptomatic cardiovascular disease (eg, heart failure) and kidney failure. Regression may be possible. Clinicians should use coronary artery calcium screening to guide decisions about cholesterol-lowering statin therapy if necessary.

• Stage 4 describes patients with clinical cardiovascular disease including coronary heart disease, heart failure, atrial fibrillation, stroke, or peripheral arterial disease. People may have already had a heart attack or stroke. Stage 4b patients also have end-stage kidney disease (ESKD) and are therefore at the highest risk for cardiovascular events, hospitalizations, and premature death. The goal of management in stage 4 is individualized treatment to optimize care and secondary prevention.

Read more: Heart Failure Medications

Enhancing Risk Prediction With a New Tool

The AHA will be unveiling a new risk calculator that includes CKM components such as cardiovascular disease, CKD, and metabolic disorders. It will gauge an individual’s risk for heart failure in addition to heart attack and stroke.

The new tool – to be presented at AHA’s Scientific Sessions in Philadelphia, Pennsylvania on November 11-13, 2023 – goes beyond the current pooled cohort equation. It starts younger (at age 30 years) and reflects risk in various ethnicities. The calculator will include blood sugar measurement results, eGFR, UACR, and social determinants of health.

The risk calculator will calculate both 10-year and 30-year cardiovascular disease risk.

Risk-Enhancing Factors

The advisory noted specific factors and medical history that can increase the likelihood that CKM syndrome progresses to a more advanced stage. These factors might adversely affect predisposition, lifestyle behaviors, medication exposures, and more.

• Family history of diabetes or kidney failure
• High-sensitivity C-reactive protein of 2.0mg/L or higher
• Chronic inflammatory conditions such as lupus and HIV/AIDS
• High-risk demographic groups such as South Asians and individuals of low socioeconomic status
• Adverse social determinants of health (eg, economic instability, low education, poor health care access, under-resourced neighborhoods, and low social/community context due to racism, etc)
• Mental health disorders
• Sleep disorders
• Sex-specific factors (eg, erectile dysfunction, premature menopause, hypertensive disorders of pregnancy, preterm birth, polycystic ovarian syndrome)

Major goals are to find optimal strategies to support lifestyle change and weight loss at every stage, tailored approaches to selecting cardioprotective anti-hyperglycemic therapies in at-risk patients and those with existing cardiovascular disease, the use of lipid-lowering therapies beyond statins in those with diabetes and/or high risk for CKM syndrome, and management of cardiovascular disease in patients with CKD.

The call to action centers on addressing research gaps and improving patients’ social determinants of health, access to pharmacotherapies, CKM syndrome education, interdisciplinary care, obesity management, and community support.

“We actually now have therapies that converge together and meaningfully improve outcomes, whether from a metabolic, cardiovascular, or kidney perspective,” said Janani Rangaswamy, MD, a nephrologist and coauthor of the paper. She is also professor of medicine at the George Washington University School of Medicine in Washington, DC. Dr Rangaswamy mentioned, for example, that high-level evidence supports SGLT2i for cardio-kidney protection in patients who have CKD with and without diabetes across albuminuria categories and patients who have heart failure with preserved or reduced ejection fraction. Combined use of SGLT2i and GLP-1 RA may be considered for those with multiple CKM syndrome risk factors in the setting of high predicted cardiovascular risk. In patients with CKD and diabetes, finerenone, a nonsteroidal mineralocorticoid receptor antagonist, shows benefit on top of renin angiotensin aldosterone system inhibitors.

The advisory proposed value-based care whereby patients with at least 2 criteria for CKM syndrome see a multidisciplinary care team that includes representation from primary care, cardiology, nephrology, and endocrinology with oversight from a care coordinator. The goal is upfront, guideline-recommended treatment.

Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.

Yakubu Bene-Alhasan, MD, MPH, from Medstar Health in Baltimore, and colleagues used data from the National Institutes of Health “All of Us” Research Program to examine the association between the frequency of marijuana use and new-onset heart failure. The researchers found there were 2958 events within a median follow-up of 45 months from a final population of 156,999 patients. Daily marijuana use was associated with an increased risk for incident heart failure compared with never use (adjusted hazard ratio, 1.34; 95% CI interval, 1.04 to 1.72). After the addition of coronary artery disease diagnosis as a time-varying covariate in the main model, the association was attenuated and no longer significant (adjusted hazard ratio, 1.27; 95% CI, 0.99 to 1.62).

Avilash Mondal, MD, from Nazareth Hospital in Philadelphia, and colleagues examined the association between CUD in elderly nonsmokers with established cardiovascular disease risk and MACCE. The researchers found that 13.9% of 28,535 elderly cannabis users reported MACCE episodes. Compared with the non-CUD cohort, the CUD cohort reported higher MACCE (odds ratio, 1.20), all-cause mortality, dysrhythmia, acute myocardial infarction, transfer to other facilities, and home health care. In CUD users, chronic lung disease, renal disease, hypertension, and hyperlipidemia were predictors of MACCE episodes.

“The main public message is to be more aware of the increased risks and open the lines of communication so that cannabis use is acknowledged and considered,” Mondal said in a statement.

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Treatment with analog rather than human insulin may result in better clinical outcomes in patients with type 2 diabetes receiving maintenance hemodialysis (HD), investigators suggest.

In the multinational Analyzing Data, Recognizing Excellence and Optimizing Outcomes (ARO) ii study, investigators compared outcomes between 713 analog insulin and 733 human insulin users. In adjusted multivariable analyses, significantly lower proportions of the analog than human insulin group experienced major adverse cardiovascular events (MACE, 26.8% vs 35.9%), hospitalization (58.2% vs 75.0%), and all-cause mortality (22.0% vs 31.4%), James Fotheringham, PhD, of the University of Sheffield in Sheffield, UK, and colleagues reported in the American Journal of Kidney Diseases. Analog users had significant 18.3%, 24.3%, 19.2% lower risks for these outcomes, respectively. MACE was defined as hospitalization for coronary, cerebral, or peripheral arterial events, heart failure, or cardiac arrest.

Hypoglycemia (less than 3.0 mmol/L) occurred at comparable rates among analog and human insulin users: 14.1% vs 15.0%.

Insulin therapy is the “cornerstone” of antihyperglycemic treatment in kidney failure since these patients are ineligible for sodium-glucose contransporter 2 inhibitors, Dr Fotheringham’s team noted.

“Both long- and short-acting analogues, therefore, could significantly reduce glycemic variability, which has been linked to mortality in people on HD, without necessarily modifying HbA1c.”

Human insulin, they noted, has been linked with postprandial hyperglycemia followed by hypoglycemia and weight gain.

Since this was an observational study, residual confounding could not be ruled out, such as the cost and availability of each insulin type.

Disclosure: This research was supported by Amgen. Please see the original reference for a full list of disclosures.

HealthDay News — Aspirin is underused in secondary prevention of cardiovascular disease (CVD), according to a study published online August 22 in the Journal of the American Medical Association.

Sang Gune K. Yoo, MD, from Washington University in St. Louis, and colleagues reported and assessed aspirin use for secondary prevention of CVD in a cross-sectional analysis using data from 51 low-, middle-, and high-income countries. The overall pooled sample included 124,505 individuals aged 40 to 69 years.

The researchers found that 8.1% of the sample had a self-reported history of CVD. Aspirin use for secondary prevention among individuals with a history of CVD was 40.3% in the overall pooled sample. By income group, the estimates were 16.6, 24.5, 51.1, and 65.0% in low-, lower-middle, upper-middle, and high-income countries, respectively.

“In order to create interventions, we have to understand what is actually going on, which is what we’re trying to establish in this study,” Yoo said in a statement. “Then we can start to think about how to develop strategies to increase evidence-based aspirin use in order to save lives.”

Two authors disclosed ties to the pharmaceutical industry; one author reported that their employer has a patent and license, and a second author reported having a patent pending.

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The HeatRisk Forecast Tool is a joint effort between the CDC and the National Oceanic and Atmospheric Administration National Weather Service to give Americans a week-long heads-up that broiling temperatures are headed their way. It is all close at hand at the HeatRisk Dashboard online, just enter a zip code for the latest forecast and updates.

Climate change is making for more and longer periods of hot, humid weather. Emergency department visits for heat-related illness peaked in many regions of the country last summer, and working-age people who were forced to labor outside faced higher risks.

But extreme heat experienced without the help of air conditioning can also be hazardous to people with underlying health issues, the CDC added.

The new HeatRisk tool “identifies health and temperature data to deliver a seven-day outlook for hot weather,” the CDC explained. “The tool uses a five-level scale to indicate how risky the heat level is in a specific area.” The tool is calibrated to assess the unique risks from heat to health that might come in specific areas of the US.

“Pulling in data from the HeatRisk Forecast Tool, in the Dashboard people can enter their zip code and get personalized heat forecast information for their location alongside protective actions to take,” the CDC said. There is also information available on local area air quality, sourced from the US Environmental Protection Agency AIR NOW Air Quality Index.

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HealthDay News — For patients with chronic coronary artery disease, colchicine is associated with a reduced incidence of total knee replacement (TKR) and total hip replacement (THR) vs placebo, according to a study published online May 30 in the Annals of Internal Medicine.

Michelle W.J. Heijman, PhD, from Radboud University Medical Center in Nijmegen, Netherlands, and colleagues examined whether colchicine reduces TKRs and THRs in an exploratory analysis of the Low-Dose Colchicine 2 randomized trial involving 5522 patients with chronic coronary artery disease at 43 centers in Australia and the Netherlands. Participants were randomly assigned to 0.5mg colchicine or placebo once daily (2762 and 2760 patients) during a median follow-up of 28.6 months.

The researchers found that TKR or THR was performed in 2.5 and 3.5% of patients in the colchicine and placebo groups, respectively, during the trial (incidence rate, 0.90 vs 1.30 per 100 person-years; hazard ratio, 0.69). Similar results were obtained in sensitivity analyses when patients with gout at baseline were excluded and when joint replacements that occurred in the first three and six months of follow-up were not included.

“We showed that colchicine, 0.5mg daily, was associated with a lower incidence of TKR and THR compared with placebo in patients with chronic coronary artery disease,” the authors write. “This suggests that colchicine may slow the progression of osteoarthritis, but this needs to be confirmed in an appropriately designed prospective placebo-controlled trial.”

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Ylva Trolle Lagerros, MD, PhD, from the Karolinska Institutet in Stockholm, and colleagues used data from the Swedish Patient Register and the Prescribed Drug Register to examine the association between PDE5i treatment and cardiovascular outcomes in men with stable coronary artery disease treated with nitrate medication. Exposure was defined as 2 or more dispensed prescriptions of PDE5i.

The analysis included 55,777 men who were treated with nitrates and 5710 men treated with nitrates and a PDE5i. The researchers found that combined use of PDE5i treatment with nitrates was associated with increased mortality, cardiovascular mortality, noncardiovascular mortality, myocardial infarction, heart failure, cardiac revascularization, and major cardiovascular events (hazard ratios, 1.39, 1.34, 1.40, 1.72, 1.67, 1.95, and 1.70, respectively).

“Our goal is to underscore the need for careful patient-centered consideration before prescribing PDE5i medication to men receiving nitrate treatment,” senior author Daniel Peter Andersson, MD, PhD, from Stockholm University, said in a statement. “Furthermore, it justifies our efforts for continued research into the ambiguous effects of erectile dysfunction drugs on men with cardiovascular disease.”

One author disclosed ties to the pharmaceutical industry.

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Wenya Zhang, from the Chinese Academy of Medical Sciences & Peking Union Medical College in Beijing, and colleagues conducted a population-based cohort study using data from the UK Biobank to examine whether age at AF diagnosis is associated with risk of incident dementia and its subtypes. The main analysis included 433,746 participants.

The researchers found that compared to individuals without AF, the 30,601 with AF had increased risk of developing all-cause dementia and VD (adjusted hazard ratios, 1.42 and 2.06, respectively), but not AD. Younger age at AF onset was associated with increased risks of developing all-cause dementia, AD, and VD (adjusted hazard ratio per 10-year decrease, 1.23, 1.27, and 1.35, respectively). For developing all-cause dementia, the highest hazard ratio was seen for individuals with AF diagnosed before age 65 years, followed by AF diagnosed at age 65 to 74 years (adjusted hazard ratios, 1.82 and 1.47, respectively) after propensity-score matching; the hazard ratio for AF diagnosed at 75 years or older was not significant. Results were similar for AD and VD.

“The quantitative manifestation of the association between AF onset age and incident dementia highlights the importance of monitoring cognitive function among AF patients, especially those younger than 65 years at diagnosis,” the authors write.

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Samir Gupta, MD, from Sidra Medicine in Doha, Qatar, and colleagues conducted a multicenter, randomized, double-blind, placebo-controlled trial assessing early ibuprofen treatment (≤72 hours after birth) for a large PDA (diameter ≥1.5 mm with pulsatile flow) in extremely preterm infants. Overall, 326 and 327 infants were assigned to receive ibuprofen and placebo, respectively; 324 and 322 had data available for outcome analyses. A composite of death or moderate or severe bronchopulmonary dysplasia evaluated at 36 weeks of postmenstrual age was the primary outcome.

The researchers found that a primary outcome event occurred in 69.2 and 63.5% of infants in the ibuprofen and placebo groups, respectively (adjusted risk ratio, 1.09; 95% CI, 0.98 to 1.20; P =.10); 13.6 and 10.3 percent of infants, respectively, died (adjusted risk ratio, 1.32; 95% CI, 0.92 to 1.90). Moderate or severe bronchopulmonary dysplasia occurred in 64.2 and 59.3% of the ibuprofen and placebo groups, respectively, among the infants who survived to 36 weeks of postmenstrual age (adjusted risk ratio, 1.09; 95% CI, 0.96 to 1.23).

“Our results are broadly consistent with those of other studies of early targeted treatment of PDA with ibuprofen that have not shown a convincing benefit with respect to clinical outcomes,” the authors write.

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Researchers conducted the randomized, double-blind, double-dummy, controlled phase 3 ADVOCATE trial. They reported on the efficacy and safety profiles of avacopan for the treatment of adult patients with AAV receiving rituximab (RTX).

The randomization process was stratified based on vasculitis disease status (whether patients were newly diagnosed or experiencing relapse), ANCA status (positive for antiproteinase 3 [PR3] or anti-myeloperoxidase), and the type of immunosuppressive treatment (either cyclophosphamide or RTX).

The primary efficacy endpoints were the percentages of patients achieving disease remission by week 26 and maintaining remission by week 52, defined as a Birmingham Vasculitis Activity Score (BVAS) of 0 and not using GCs for at least 4 weeks prior to assessment.

The RTX arm encompassed 214 out of 330 patients, making up approximately 64.8% of the total cohort. Mean patient age was 60 years, a majority of patients had renal vasculitis (76% based on BVAS), around 46% were PR3-ANCA positive, and about 58% were newly diagnosed. 

The avacopan group consisted of 57% men, while the prednisone group was comprised of 48.6% men. Baseline mean eGFRs were 57.1±32.2 and 56.0±33.4 mL/min/1.73 m² among the avacopan and prednisone groups, respectively.

At week 26, the avacopan group demonstrated a remission rate of 77.6% while the prednisone group had a rate of 75.7%. Moreover, 71.0% of the avacopan group maintained remission at week 52, compared with 56.1% of the prednisone group, accounting for an estimated common difference of 16.5 percentage points (95% CI, 4.3-28.6).

Additionally, the avacopan group demonstrated improvements in relapse rates (8.7% vs 20.2%), albuminuria (geometric mean of urinary albumin:creatine ratio percent change at week 4, -43.4% vs 8.30%), and reduced GC-related toxicity (mean GC toxicity index cumulative worsening score at week 26, 36.8 vs 52.9), compared with the prednisone group. 

In terms of safety, 34.6% (n=37) of patients in the avacopan group experienced serious treatment-emergent AEs, totaling 62 events, while 39.3% (n=42) of patients in the prednisone group experienced 91 AEs.

The study authors concluded, “These results demonstrate the efficacy of avacopan for achieving and sustaining remission in patients with AAV treated with RTX.”

Disclosure: Multiple study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures. 

Justine Hugon-Rodin, MD, PhD, from the Hospital Saint Joseph in Paris, and colleagues conducted a prospective cohort study to define the time until normalization of the estrogen-related thrombotic biomarkers after CHC cessation. Women aged 18 to 50 years who had decided to stop their CHC were enrolled. The study started 6 weeks before CHC cessation and included 6 visits afterward up to 12 weeks after cessation.

The researchers found that from baseline to week 12, there were decreases in the average levels of normalized sensitivity ratios to activated protein C (4.11 to 1.27 nmol/L), thrombomodulin (2.53 to 1.11 nmol/L), and sex hormone-binding globulin (167 to 55.4 nmol/L) among 66 users of CHC. Overall, 85.8, 81.3, and 76.2% and 86.7, 85.5, and 87.8% of the decrease from baseline to week 12 was achieved at 2 and 4 weeks after CHC cessation, respectively. Among 28 control women, levels were not meaningfully modified throughout the study.

“It’s reassuring to know that that possible harm of the pill goes away rapidly when one stops taking it,” coauthor Marc Blondon, MD, from the University Hospitals of Geneva, said in a statement.

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Sameed Ahmed M. Khatana, MD, MPH, from the Perelman School of Medicine at the University of Pennsylvania in Philadelphia, and colleagues examined the burden of extreme heat-associated cardiovascular deaths in the US using data on cardiovascular deaths among adults and the number of extreme heat days in each county in the US from 2008 to 2019. County-level projected numbers of extreme heat days and populations under 2 scenarios were obtained for the midcentury period (2036 to 2065): shared socioeconomic pathways (SSP) 2 to 4.5 (representing demographic projections from a middle-of-the-road socioeconomic scenario and intermediate emission increase) and SSP5-8.5 (demographic projections in a fossil-fueled development-based economy and large increase in emissions). The association of cardiovascular mortality with extreme heat was estimated.

The researchers found that from 2008 to 2019, extreme heat was associated with 1651 excess cardiovascular deaths per year. Extreme heat is projected to be associated with 4320 and 5491 excess deaths annually by midcentury, representing increases of 162 and 233% under SSP2-4.5 and SSP5-8.5, respectively. In the SSP2-4.5 scenario, elderly adults are projected to have a 3.5 times greater increase in deaths compared with nonelderly adults, and non-Hispanic Blacks are projected to have a 4.6 times greater increase vs non-Hispanic Whites.

“Clinical and community-based mitigation strategies, along with global efforts to confront climate change, are needed to address this growing public health issue,” the authors write.

One author disclosed ties to Abiomed and Biosense Webster.

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The left-sided Impella heart pump is made by Abiomed, a subsidiary of Johnson & Johnson MedTech, and has already been linked to 129 injuries and 49 deaths.

“The FDA has identified this as a Class I recall, the most serious type of recall. Use of these devices may cause serious injuries or death,” the statement said, although it adds that “this recall is a correction, not a product removal.”

The advisory informs those implanting the Impella devices about revised instructions for use, including “carefully position the pump catheter during operative procedures.”

“During operations, the Impella device could cut through the wall of the left ventricle,” the company warned in its statement. “The use of the affected Impella pumps may cause serious adverse health consequences, including left ventricle perforation or free wall rupture, hypertension, lack of blood flow, and death.”

According to the latest Abiomed advisory, anyone undergoing a procedure using Impella left-sided blood pumps should be aware of the new instructions for use, especially people with heart disease, the elderly, and women.

But Public Citizen, a consumer advocacy group, issued a statement calling for a full ban on the devices. Despite dozens of severe injuries and deaths, “the FDA has allowed them to remain in use,” the group said. “Moreover, there are serious and ongoing concerns about whether there are clinically meaningful survival benefits that outweigh the risks of these left ventricular assist devices.”

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During its daylong meeting, the FDA Anesthesiology and Respiratory Therapy Devices Panel reviewed ways to better evaluate the accuracy of pulse oximeters in patients with darker skin. Although there is more work to be done when it comes to making pulse oximeters more accurate, panel member Jeffrey Feldman, MD, said the benefits of these devices still outweigh their limitations.

“This technology has and continues to save lives on a daily basis in this country. … It needs to be improved. We need to look at health disparities, and we need to do better,” he said after the meeting, CNN reported. “But we also need to recognize how valuable this technology is for patients every day, at home, and in the hospital.”

Precisely because the general public can use these devices at home to check their oxygen levels, the panel homed in on how to ensure the accuracy of pulse oximeters for all skin tones before they reach drugstore shelves. So, the panel focused on the structure of company trials testing the products.

Back in 2013, the FDA issued premarket guidance for developers of pulse oximeters, recommending that they have “a range of skin pigmentation” represented in their clinical studies of the devices, including at least two “darkly pigmented subjects or 15 percent of the study group,” whichever is larger.

Now, the FDA is weighing proposals to update these clinical trials to include more diverse groups of people, with at least 24 participants spanning the entire range of skin tones on the 10-shade Monk Skin Tone scale.

“There’s no question that more diversity needs to be a part of whatever new requirements that they would issue,” Feldman said. “The prior requirements in 2013 were small numbers and really not very diverse — the only requirement was for up to two patients of color — and so that I think has proven to be inadequate to predict real-world performance.”

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The Food and Drug Administration (FDA) has accepted for review the New Drug Application for eplontersen for the treatment of hereditary transthyretin-mediated amyloid polyneuropathy (ATTRv-PN).

Hereditary ATTR is a severe, progressive and life-threatening disease caused by the abnormal formation and aggregations of transthyretin (TTR) amyloid deposits in various tissues and organs. Eplontersen is an investigational ligand-conjugated antisense medicine designed to reduce the production of TTR protein.

The submission includes data from the phase 3 NEURO-TTRansform study, which compared the efficacy and safety of eplontersen to the historical placebo arm from the Tegsedi^® (inotersen) NEURO-TTR trial (ClinicalTrials.gov Identifier: NCT01737398).

Findings from the 35-week interim analysis showed that treatment with eplontersen led to a significant mean reduction in serum TTR concentration, as well as a significant treatment effect on the modified Neuropathy Impairment Score +7 (a measure of neuropathic disease progression), compared with the historical placebo arm (both P <.0001). Moreover, treatment with eplontersen improved patient-reported quality of life, as measured by the Norfolk Quality of Life Questionnaire-Diabetic Neuropathy (key secondary endpoint; P <.0001).

“Overall, the interim analysis demonstrated eplontersen has the potential to make a positive impact on disease progression and improve quality of life in a substantial number of patients,” said Eugene Schneider, MD, executive vice president and chief clinical development officer at Ionis.

The FDA has assigned a Prescription Drug User Fee Act action date of December 22, 2023 to the application.

Eplontersen is also being evaluated in the phase 3 CARDIO-TTRansform study (ClinicalTrials.gov Identifier: NCT04136171) for transthyretin amyloid cardiomyopathy.

Reference

Ionis announces FDA acceptance of New Drug Application for eplontersen for the treatment of hereditary transthyretin-mediated amyloid polyneuropathy (ATTRv-PN). News release. Ionis Pharmaceuticals. March 7, 2023. Accessed March 8, 2023. https://www.prnewswire.com/news-releases/ionis-announces-fda-acceptance-of-new-drug-application-for-eplontersen-for-the-treatment-of-hereditary-transthyretin-mediated-amyloid-polyneuropathy-attrv-pn-301764027.html.

Fixed-dose combination therapies including at least 2 antihypertensive drugs and a statin with or without the addition of aspirin reduce the risk for first cardiovascular events in patients with stage 3 to 4 chronic kidney disease (CKD), investigators report.

In a meta-analysis of 18,162 individuals from 3 clinical trials with no pre-existing cardiovascular disease, 3315 (18%) had an estimated glomerular filtration rate (eGFR) less than 60 mL/min/1.73m² at baseline. Over a median of 5 years, the primary composite cardiovascular outcome occurred in 232 (3%) of treated patients with normal eGFR compared with 339 (5%) of patients receiving placebo or minimal care (control group). Treated patients with normal eGFR had a significant 32% reduced risk of the primary outcome, which included time to first occurrence of a combination of cardiovascular death, myocardial infarction, stroke, or arterial revascularization.

Among patients with lower eGFR, the primary outcome occurred in 4% of the treatment group compared with 8% of the control group – a significant 51% reduced risk with fixed-dose combination therapy, Reza Malekzadeh, MD, of Tehran University of Medical Sciences in Tehran, Iran, and colleagues reported in the Clinical Journal of the American Society of Nephrology. The investigators adjusted results for sex, age, body mass index, diabetes, and smoking.

The number needed to treat to prevent the primary outcome within 5 years was 67 in the normal eGFR group and 25 in the low eGFR group. The absolute reduction in cardiovascular risk was greater with the addition of aspirin, regardless of kidney function, the investigators reported.

Dizziness was significantly more frequent in the polypill than control group (11% vs 8%), but other adverse events were comparable. The gastrointestinal bleeding rate did not differ significantly between those treated with vs without aspirin (0.43% vs 0.23%).

“Combining these treatments in a polypill would result in better adherence, and in secondary prevention this can translate into incremental benefits for reducing the risk of a future cardiovascular event,” Dr Malekzadeh’s team reported.

Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.

HealthDay News — Intake of food additive emulsifiers is associated with an increased risk for cardiovascular disease (CVD), according to a study published online September 6 in The BMJ.

Laury Sellem, PhD, from Université Sorbonne Paris Nord, and colleagues examined the associations between exposure to food additive emulsifiers (i.e., total modified starches, lecithins, xanthan gum, pectins, monoglycerides and diglycerides of fatty acids, carrageenan, and guar gum) and the risk for CVD in a prospective cohort study involving 95,442 adults without prevalent CVD. Participants included a cohort from the French NutriNet-Santé study launched in 2009.

The researchers found that 1995 incident CVD, 1044 coronary heart disease, and 974 cerebrovascular disease events were diagnosed during a median follow-up of 7.4 years. Higher intake of celluloses (E460 and E468) was positively associated with elevated risks for CVD (hazard ratio, 1.05 per one standard deviation) and coronary heart disease (hazard ratio, 1.07). Higher risks for CVD and coronary heart disease were seen in association with higher cellulose E460 intake (hazard ratios, 1.05 and 1.07, respectively) and with higher intake of carboxymethylcellulose (E466; (azard ratios, 1.03 and 1.04, respectively). Higher risks for all outcomes were seen in association with higher intakes of monoglycerides and diglycerides of fatty acids (E471 and E472). An increased risk for coronary heart disease was seen in association with high intake of trisodium phosphate (E339; hazard ratio, 1.06).

“Results from this large prospective cohort suggest that additive emulsifiers may be associated with an increased risk of CVD,” the authors write. “Despite the moderate magnitude of the associations, these findings may have important public health implications given that these food additives are used ubiquitously in thousands of widely consumed ultra-processed food products.”

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Although a recent meta-analysis suggested that gonadotropin-releasing hormone (GnRH) antagonists lead to fewer major adverse cardiovascular events (MACE) compared with luteinizing hormone-releasing hormone (LHRH) agonists, a new real-world study finds the opposite: higher MACE risk with GnRH antagonist use. Investigators presented the findings at the Society of Urologic Oncology 24th Annual Meeting in Washington, DC.

“Our analysis of data from [approximately] 45,000 PCa patients collected over the most recent decade likely reflects real-world outcome patterns,” according to Tanya Dorff, MD, of the City of Hope National Medical Center, Duarte, California, and colleagues.

The investigators examined MACE and all-cause mortality risk among men receiving at least 1 dose of an GnRH antagonist or LHRH agonist (99% from 2010-2020) from the Decision Resources Group database.

Based on data from 40,753 men, MACE risk was a significant 1.6-fold higher for GnRH antagonist recipients vs LHRH agonist recipients in an adjusted analysis, Dr Dorff reported on behalf of her team. Based on data from 41,765 men, all-cause mortality risk was a significant 1.8-fold higher for GnRH antagonist vs LHRH agonist users in an adjusted analysis.

Adjusted analyses accounted for age, body mass index, personal and family MACE history, statin use, tobacco history, history of diabetes and/or hypertension, antagonist vs agonist use, baseline PSA, oncology vs urology setting, and race and ethnicity. 

“In this real-world claims database, overall MACE and mortality risk both increased consistently by 4-5% per year during the first 4 years after ADT initiation,” Dr Dorff and colleagues reported. Due to the inherent limitations of retrospective observational studies, further detailed studies are needed to explain any differences in these risks for GnRH antagonist vs LHRH agonist users. ADT duration and concomitant use of androgen receptor pathway inhibitors are important factors.

The median age of the cohort was 75 years. Black and Asian men accounted for 12.7% and 1.3% of patients, respectively. The antagonist and agonist groups had comparable proportions of patients with MACE history (3.4% vs 3.0%). MACE incidence was higher among White than Black and Asian patients initiating androgen deprivation therapy (ADT): 4.0% vs. 2.4% vs 2.2%, respectively, at 1 year after ADT initiation and 21.0% vs 13.3% vs 11.7%, respectively, at 4 years.

“As patients initiating ADT likely have a high burden of underassessed and untreated CV risk factors, clinicians should focus on monitoring and treating comorbidities to reduce mortality risk in PCa patients on ADT,” the authors concluded in a poster presentation.

Disclosure: This research was supported by Tolmar inc. Please see the original reference for a full list of disclosures.

José A. Joglar, MD, from UT Southwestern Medical Center in Dallas, and colleagues conducted a comprehensive literature review and updated recommendations for the diagnosis and treatment of AF.

The authors developed new classifications of the stages of AF, which recognize AF as a disease continuum that requires a variety of strategies at the different stages. Lifestyle and risk factor modification is recognized as a pillar of AF management that can prevent onset, progression, and adverse outcomes; risk factor management is emphasized throughout the disease continuum, and the guideline offers more prescriptive recommendations, including obesity management, weight loss, physical activity, and smoking cessation. Recommendations for anticoagulation are made based on yearly thromboembolic event risk using a validated clinical risk score. Patients at intermediate-to-low (<2 percent) annual risk for ischemic stroke can benefit from consideration of factors that may modify their risk, including AF characteristics, sex, and blood pressure control. The importance of early and continued management of patients with AF, which should focus on maintaining sinus rhythm and minimizing AF burden, is emphasized in the guideline.

“The new guideline reinforces the urgent need to approach a-fib as a complex cardiovascular condition that requires disease prevention, risk factor modification, as well as optimizing therapies and patients’ access to care and ongoing, long-term management,” Joglar said in a statement.

The guideline was developed in collaboration with and endorsed by the American College of Clinical Pharmacy and the Heart Rhythm Society. Several committee members disclosed ties to the biopharmaceutical, medical technology, and publishing industries.

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