Myocardial Metabolomics of Human Heart Failure With Preserved ...
SGLT2i Still Underprescribed In HFrEF, New US Analysis Confirms
Only one in five patients hospitalized for heart failure with reduced ejection fraction (HFrEF) receive a prescription for an SGLT2 inhibitor at discharge, according to a contemporary US analysis.
Among hospitals participating in the American Heart Association Get With The Guidelines–Heart Failure (GWTG-HF) registry, 74.6% of all sites discharged fewer than 25% of patients with prescriptions for SGLT2 inhibitors. Additionally, fewer than 10% of all individuals in the study received prescriptions for the quadruple combination of SGLT2 inhibitors, beta-blockers, mineralocorticoid receptor antagonists (MRAs), and an ARB or angiotensin receptor–neprilysin inhibitor (ARNI) as recommended in the most recent US And European guidelines.
"The good news is that the rate of SGLT2 inhibitor prescription at discharge was increasing over the 12-month study period, but use of SGLT2 inhibitors at discharge was still less than 30% among eligible patients during the latest months of our study from April to June 2022," senior study author Stephen J. Greene, MD (Duke Clinical Research Institute, Durham, NC), said in an email.
Greene presented the data at last month's European Society of Cardiology Heart Failure 2023 Congress. The study, with Greene as senior author and Jacob B. Pierce, MD, MPH (Duke University School of Medicine, Durham, NC), as first author, was published simultaneously in JAMA Cardiology.
Prescription Shortfalls
Pierce et al examined data on 49,399 patients (median age 67 years; 33.5% female) hospitalized for HFrEF between July 2021 and July 2022 at 489 registry hospitals.
Compared with those who did not receive a "gliflozin" prescription, those who did were more often younger, Black, diabetic, had private insurance or Medicaid, and had both diabetes and chronic kidney disease (CKD). Patients with lower ejection fraction, higher body mass index, or an implantable cardioverter-defibrillator also had higher rates of SGLT2 prescribing.
Having kidney insufficiency or anemia, or being a current smoker, were linked to lower likelihood of getting an SGLT2 inhibitor.
The next step is closing these gaps in quality of care and doing so with a sense of urgency. Stephen J. Greene
Among patients who received a gliflozin prescription, use of background triple therapy was higher than in those who did not (46.3% vs 27.6%; P < 0.001). Looking at the 461 individual hospitals with 10 or more eligible discharges, only 4% discharged half or more patients with a SGLT2 inhibitor prescription.
Hospital-level factors associated with not receiving a prescription at discharge included having fewer beds, a lack of interventional cardiac catheterization and heart transplantation services, being a nonteaching center, and being located in the western United States or in a rural area. However, in multivariable analyses, only the number of beds remained a predictor (OR 1.12; 95% CI 1.07-1.16).
Urgent Need to Close Care Gaps
Despite the low prescribing rates of SGLT2 inhibitors, the authors note that an overall rate of 20% in this contemporary cohort is actually not unique and represents higher uptake than might be expected for a new, evidence-based therapy. An analysis of the GWTG-HF registry following approval of ARNI for HFrEF in 2015, for example, found that only a little over 2% of hospitalized patients were receiving ARNI prescriptions at discharge.
Still, they say it "remains concerning that the vast majority of patients expected to derive benefit are not receiving this medication."
To TCTMD, Greene said many of the patient characteristics associated with discharge prescription for SGLT2 inhibitors were "unfortunate" but not surprising.
"Eligible females were less likely than eligible males to be prescribed an SGLT2i, showing a sex-based disparity," he noted. "Likewise, many of the relationships were consistent with the risk-treatment paradox we often see with heart failure therapies, where the patients at greatest risk and in greatest clinical need are less likely to receive appropriate therapy."
Although high drug costs remain a barrier, with a recent analysis suggesting that some Medicare patients end up paying over US $900 per year out of pocket for their SGLT2 inhibitor alone, Greene said the current study, looking specifically at prescribing patterns, adds to others suggesting out-of-pocket costs are not the dominant explanation for the widespread underuse of both branded and generic guideline-directed medical therapies, or for the magnitude of the prescribing gaps.
"We saw enormous hospital-level variation in discharge use of SGLT2i, with some hospitals discharging 100% of eligible patients on an SGLT2 inhibitor while others [were] discharging zero patients on an SGLT2 inhibitor. This variation persisted even after adjusting for characteristics of the patient population at those hospitals, including insurance status, and other hospital characteristics," he added. "In aggregate, these data strongly suggest a quality-of-care issue driving such large differences across US hospitals. I view this paper as really defining the scope of the problem. The next step is closing these gaps in quality of care and doing so with a sense of urgency."
What's The Difference Between Systolic And Diastolic Heart Failure?
In systolic heart failure, the heart cannot effectively contract with each heartbeat. In diastolic heart failure, your heart cannot relax between heartbeats. Both types can lead to right-sided heart failure.
Heart failure occurs when your heart is unable to pump the amount of blood your body needs to keep you healthy. It can occur on the left or right side of the heart or on both sides.
The left side is in charge of pumping oxygen-rich blood into your body, while the right side collects blood that's low in oxygen from your veins and sends it to your lungs to collect oxygen, after which it returns to the left side.
If you have left-sided heart failure, it means your heart is not pumping enough blood out to your body. Your heart may pump less efficiently when you're doing physical activity or feeling stressed.
Two types of heart failure can affect the left side of the heart: systolic and diastolic. The diagnosis depends on how well your heart can pump blood.
If you have systolic heart failure, it means your heart does not contract effectively with each heartbeat. If you have diastolic heart failure, it means your heart isn't able to relax normally between beats.
Both types of left-sided heart failure can lead to right-sided heart failure. Right-sided heart failure happens when the right ventricle functions poorly due to poor contraction or high pressure in the right side of the heart.
When it comes to diagnosing and managing these two types of heart failure, there are some similarities and some differences. Read on to find out what you need to know about systolic and diastolic heart failure.
If you have systolic or diastolic heart failure, you may experience symptoms such as shortness of breath after routine physical activity. Depending on the function of your heart, actions like climbing stairs or walking a short distance may cause these symptoms.
Symptoms of left-sided heart failure can include:
However, in the early stages of heart failure, you may not have any symptoms.
Doctors diagnose heart failure clinically at a patient's bedside. The diagnosis is confirmed based on the results from imaging tests, symptoms, and other lab tests, such as blood tests.
If doctors suspect you have heart failure, they may perform tests that can include:
Systolic heart failure happens when the left ventricle of your heart cannot contract completely. That means your heart will not pump forcefully enough to move your blood throughout your body in an efficient way.
It's also called heart failure with reduced ejection fraction (HFrEF).
Ejection fraction (EF) is a measurement of how much blood leaves a heart ventricle every time it pumps.
Doctors determine your EF as a percentage with an imaging test such as an echocardiogram. Between 50 and 70 percent EF is the typical range, according to the American Heart Association (AHA). It's still possible to have other types of heart failure, even if your EF is within that range.
If your EF is under 40 percent, you may have reduced ejection fraction or systolic heart failure.
Diastolic heart failure diagnosisDiastolic heart failure occurs when your left ventricle can no longer relax between heartbeats because the tissues have become stiff. When your heart cannot fully relax, it won't fill up again with blood before the next beat.
This type is also called heart failure with preserved ejection fraction (HFpEF).
For this type, your doctor may order an imaging test on your heart and determine that your EF looks fine.
Your doctor will then consider whether you have other symptoms of heart failure and if there's evidence from other tests that your heart is not functioning properly. If those criteria are met, you may be diagnosed with diastolic heart failure.
This type of heart failure most often affects older people and also affects more females than males. It typically occurs alongside other types of heart disease and other non-heart-related conditions such as cancer and lung disease.
Having high blood pressure, also called hypertension, is one of the most important risk factors. Another important risk factor is untreated sleep apnea.
There are different medications available to treat systolic heart failure. These can include:
Standard treatment can involve a combination of these medications, since each class of medication targets a different mechanism of heart failure.
A typical treatment regimen can include: ARNI, ARB, or ACE I along with a beta-blocker and an MRA. Diuretics may also be used for people who continue to have problems with urine retention despite other medical treatments and while following a low salt diet.
There is new evidence that SGLT2, originally a diabetes medication, can reduce the likelihood of death and re-hospitalization. It is now a standard part of heart failure treatment.
A review published in 2017 looked at 57 previous trials involving combination treatments. It found that people who took a combination of ACE inhibitors, BBs, and MRAs had a 56 percent reduced risk of death from systolic heart failure, compared with people who took a placebo.
People who took a combination of ARN inhibitors, BBs, and MRAs had a 63 percent reduced death rate compared with those who took a placebo.
Doctors may treat diastolic heart failure using many of the same medications that are options for systolic heart failure.
In general, the main approaches to treating diastolic heart failure with medication include:
Doctors may also recommend adopting a heart-healthy lifestyle as part of a cardiac rehabilitation program.
Recommendations can include:
For some people with left-sided heart failure, a device that is surgically implanted improves heart function. Types of devices can include:
In some cases, surgery may be recommended to treat left-sided heart failure. The two main types of surgery can include:
Systolic and diastolic heart failure both affect the left side of the heart. The left side of the heart is in charge of pumping oxygen-rich blood to the body. Having left-ventricle heart failure means that your heart is not able to efficiently pump all the blood that your body needs.
This can cause symptoms such as shortness of breath, fatigue, and weakness.
Doctors can diagnose left-ventricle heart failure as systolic, which means the heart is unable to contract well during heartbeats, or diastolic, which means the heart is unable to relax between heartbeats.
Both types of heart failure have treatment options, ranging from medication and adopting a heart-healthy lifestyle to implanted devices, surgery, and transplantation.
A primary care doctor provides overall healthcare and is your main point of contact for health concerns. They can refer you to a cardiologist, who specializes in heart disease.
A cardiologist may order tests to monitor your condition and recommend medication, certain procedures, surgery, or lifestyle changes. Both doctors often work with nurses and physician assistants.
A cardiac surgeon may perform coronary bypass surgery, heart valve repair, or other operations to treat underlying causes of heart failure. They may implant a device to help your heart work. Rarely, they may do a heart transplant. Their team may include nurses and physician assistants.
Cardiac rehabilitation includes lifestyle education, physical exercises, and psychosocial support. It can help strengthen your heart, improve your well-being, and reduce your risk of future heart problems. Your team may include nurses, occupational therapists, and physical therapists.
A balanced diet protects your heart and may help you lose weight. A registered dietitian can help you develop a sustainable, heart-healthy diet. You may need to adjust your intake of calories, saturated fat, sodium, or fluids.
Tobacco, alcohol, and other drugs can damage your heart and blood vessels. A smoking cessation or substance use counselor can help you stop using these substances if you find it hard to quit. They may prescribe medication and counseling.
Heart disease raises the risk of anxiety, depression, and post-traumatic stress disorder (PTSD), which can affect heart health.
A psychologist, clinical social worker, or licensed counselor may help treat mental health conditions with psychotherapy. A psychiatrist can prescribe medication if needed. Social workers can connect you with support services and assist with legal, financial, and insurance concerns.
Palliative care doctors and nurses provide care to ease heart failure symptoms and treatment side effects, such as fatigue and nausea. A palliative care social worker helps you and your family plan for the future. Palliative care may improve quality of life at any stage of heart failure.
It's common to have questions about medications, especially when they're first prescribed to you. Your pharmacist can help explain medication dosing and timing as well as check for interactions with other prescription drugs, foods, or supplements.
Dapagliflozin Therapy Not Linked To Renal Damage In Heart Failure Patients
A new study by Nakase and team showed that patients with heart failure with a reduced ejection fraction (HFrEF) who saw a brief drop in estimated glomerular filtration rate (eGFR) after starting dapagliflozin did not often have renal tubular damage, and the drop might have been caused by a hemodynamic change instead. The findings of this study were published in Internal Medicine.
Uncertainty exists regarding the connection between the early decline in glomerular filtration rate (GFR) following the start of sodium-glucose co-transporter 2 inhibitors (SGLT2) and renal tubular damage in patients with heart failure and a low ejection fraction. Therefore, this study looked at how dapagliflozin treatment in individuals with HFrEF affected changes in estimated GFR and urine N-acetyl-D-glucosaminidase (uNAG).
Researchers looked at 89 individuals with HFrEF who had recently begun using dapagliflozin 10 mg/day for this trial. After starting dapagliflozin, changes in the eGFR and uNAG-to-creatinine ratio (uNAG/Cre) were assessed after 2 weeks and 2 months.
The key findings of this study were:
1. At two weeks, the eGFR started to fall, but by two months, it hadn't dropped any lower.
2. The uNAG/Cre was raised at two weeks, but by two months, it had not gone up any more.
3. The eGFR alterations and the uNAG/Cre changes did not correlate.
4. The relative change in the eGFR was linked with the relative change in the systolic blood pressure, hematocrit, plasma volume, and N-terminal pro-brain natriuretic peptide (NT-proBNP).
5. In a multiple linear regression analysis, the proportional change in urine osmolality at two weeks and the usage of loop diuretics were both substantially correlated with the relative change in uNAG/Cre and the relative change in eGFR at two weeks, respectively.
A brief drop in the eGFR in individuals with HFrEF following the start of dapagliflozin was not linked to renal tubular damage as determined by the NAG/Cre and may have been caused by a hemodynamic change. Although the concurrent use of loop diuretics and higher urine osmolality might cause tubular damage in HFrEF patients, additional WRF is unlikely to develop.
Reference:
Nakase, M., Ninomiya, K., Horiuchi, Y., Sekiguchi, M., Watanabe, Y., Setoguchi, N., Asami, M., Yahagi, K., Yuzawa, H., Komiyama, K., Tanaka, J., Aoki, J., & Tanabe, K. (2023). Impact of dapagliflozin on the renal function and damage in patients with heart failure with a reduced ejection fraction. Internal Medicine (Tokyo, Japan). Https://doi.Org/10.2169/internalmedicine.1506-22
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