Coverage of the annual AHA Scientific Sessions

AHA Scientific Sessions 2020

I saw a patient years ago (August 2002) for triglycerides (TG) of 759 mg/dL despite pravastatin 20 mg daily. I started him on fenofibrate 145 mg daily, and he decreased his TGs to 300 mg/dL. The TGs got even better with high dose atorvastatin. He recently returned to see me prior to a lung transplant for advanced pulmonary fibrosis, but he had not yet been accepted for the transplant because his creatinine was 1.4 mg/dL. I stopped his fenofibrate and his creatinine decreased to 1.1 mg/dL 3 weeks later.

Many clinicians are unaware that fenofibrate can cause a reversible increase in creatinine because it interferes with creatinine excretion in the kidney. Creatinine values in the 5-year Fenofibrate Intervention and Event Lowering in Diabetes or FIELD study increased 12% soon after fenofibrate was started.

 A substudy of 661 FIELD participants demonstrated that creatinine increased when study drug was started in both groups, remained high in the fenofibrate group but fell promptly in the fenofibrate group when fenofibrate was stopped at the end of the 5-year study. The creatinine was actually lower in the fenofibrate group after the study demonstrating that fenofibrate improves renal function in diabetics. What a paradox…higher creatinine levels on the drug, but ultimately better renal function.

Fenofibrate is not the only lipid-lowering agent that raises creatinine. The new LDL cholesterol lowering drug, bempedoic acid, also increases creatinine by interfering with the organic anion transporter or OAT in the kidney. Bempedoic acid increases uric acid as well by a similar mechanism.

Please remember this increase in creatinine with fenofibrate and now with bempedoic acid. I have seen multiple patients over the years, who were told they were headed for dialysis, whose creatinine normalized after stopping the fenofibrate.

Some may ask why I use fenofibrate at all because the FDA now requires that the package insert for fenofibrate products state: “The effect of (fenofibrate) on coronary heart disease morbidity and mortality and non-cardiovascular mortality has not been established”.

 This is based primarily on the results of the Action to Control Cardiovascular Risk in Diabetes or ACCORD Trial.

ACCORD assigned statin-treated diabetics to either fenofibrate or placebo. There was no significant reduction in cardiovascular events with fenofibrate, but my gripe with ACCORD is that the subjects’ median baseline TG level was 162 with an interquartile mean of 113-229 mg/dl. I would not have treated many of these subjects with fenofibrate because their TGs were not high enough. If you look at the subgroup with TGs >203 and HDL-C’s <35 mg/dl, however, there was a reduction in events, but the 

-value was “not statistically significant” at 0.06, so not below the vaulted 0.05.

Concentrated fish oil is my first choice for treating TGs because the Cardiovascular Risk Reduction with Icosapent Ethyl for Hypertriglyceridemia or REDUCE-IT trial demonstrated a 4.8% absolute reduction in cardiovascular events with icosapent ethyl,

 but I still use fenofibrate for very high (fasting TGs >500 mg/dl) in combination with concentrated fish oil. Also, fenofibrate may have small vessel benefits, at least in diabetics. In FIELD, fenofibrate reduced amputations especially minor amputations, such as toes, and especially in individuals without large-vessel disease suggesting a small vessel benefit.

 (I would not consider losing my toes minor, but that’s their definition.) Similar to the reduced reduction in GFR noted above for FIELD, fenofibrate reduced both the need for first eye laser treatments and the progression of diabetic retinopathy in FIELD and ACCORD, respectively.

 Perhaps fenofibrate has a small (vessel) story to tell.

Articles

Dr. Paul D. Thompson tackles the topic of whether use of fenofibrate helps or harms kidney function. 

Does Fenofibrate Help or Hurt Renal Function? 

This series is being hosted by Practical Cardiology's sister publication, 

The idea of a cardiometabolic health specialty is a notion most likely born out of the best intentions but has since become a topic of controversy. In the year 2000, the thought of somebody besides an endocrinologist taking lead in the treatment of diabetes might have been a laughable notion, but now it is a serious discussion with input from a slew of parties.

As it stands, endocrinologists are in short supply, they treat dozens of conditions, and the number of patients with diabetes is growing. Just based on this alone, some would suggest an intervention, such as the creation of a new subspecialty, is already overdue. However, many endocrinologists would argue they are still the best equipped to treat these patients and arguing for the creation of a cardiometabolic subspecialty only detracts from endocrinology as a field.

In this 3-part feature series, we attempt to tackle to topic from the perspective of the 3 specialists most often to be included in the conversation: an endocrinologist, a cardiologist, and an internal medicine practitioner. With their own unique viewpoints, each approaches the discussion from the outlook of specialists in their field and whether the creation of a cardiometabolic subspecialty would help in the management of these patients.


Cardiometabolic Health Fellowships: The Answer or Part of the Problem?

Gregory Weiss, MD: Has the Time Come for a Cardiometabolic Subspecialty?

Simon Murray, MD: Who Should Be Treating Patients with Diabetes?

In this 3-part feature series, an endocrinologist, a cardiologist, and an internist tackle the topic of who should be in charge of treating patients with diabetes and whether the creation of a cardiometabolic specialty is a worthwhile endeavor.

Cardiometabolic Health: Future of Care or Detracting from Endocrinology?

A new analysis of data from the Women’s Health Initiative is offering further insight into the impact of increased sedentary behavior on 

Results suggest women spending 9.5 hours or more sitting or lying down each day had a 42% higher risk of being hospitalized with heart failure than women who spent 6.5 hours or less engaged in sedentary behavior, underlining the importance of emphasizing physical activity in aging patients.

"For heart failure prevention, we need to promote taking frequent breaks from prolonged sitting or lying down, in addition to trying to achieve guideline levels of physical activity, such as those recommended by the American Heart Association," said lead investigator Michael LaMonte, PhD, MPH, research associate professor of epidemiology in the School of Public Health and Health Professions at the University at Buffalo, in a 

statement from the American Heart Association

. "Very few studies have been published on sedentary time and heart failure risk, and even fewer have focused on older women in whom both sedentary behavior and heart failure are quite common."

With a knowledge gap related to associations of heart failure and sedentary behavior in older patient populations, LaMonte and a team of colleagues from institutions across the US designed their study with the aim of determining the impact of sedentary behaviors on heart failure risk in older women. Investigators designed their study as a prospective analysis of data from the Women’s Health Initiative, which contains data on more than nearly 90,000 postmenopausal women.

Eliminating women with heart failure at enrollment and those with the inability to walk one block without assistance, investigators identified a cohort of 80,982 women aged 50-79 years for inclusion in their analysis. Women included in the study were also required to have completed questionnaires, which included assessments of sedentary behavior, at baseline and years 3, 6, and 9.

Sedentary behavior was assessed using 2 questions. The first question assessed how many hours per day were spent sitting, including time at work, sitting at the table eating, driving or riding a car or bus, and sitting up watching TV or talking. The second question assessed how many hours per day were spent lying down or with their feet up, including time spent sleeping or trying to sleep at night, resting or napping, and lying down watching TV. Respondents were given 8 response options ranging from less than 4 hours to 16 or more hours per day.

The mean age of the study cohort was 63 years, 84.9% were White, 45% reported menopausal therapy use, and the mean reported time spent engaging in sedentary behavior per day was 7 hours. Investigators pointed out 11% of patients reported no recreational physical activity. A total of 1402 incident cases of heart failure hospitalization were observed over a mean follow-up of 9 years.

For the purpose of analysis, women were categorized according to sedentary time. These groups were defined as having less than 6.5, 6.6-9.5, or more than 9.5 hours per day of time spent sitting or lying down and, for additional analysis, as 4.5 or less, 4.6-8.5, or more than 8.5 hours per day spent sitting. Of note, the groups spending less than 6.5 hours per day sitting or lying down and those spending 4.5 or less hours per day sitting were used as reference groups.

When controlling for confounding factors, including age, race-ethnicity, education, income, smoking, alcohol, menopausal hormone therapy, and hysterectomy status, results of the analysis indicated heart failure risk increased across incremental trestles of total sedentary behavior ([6.6-9.5 hours: HR, 1.15; 95% CI, 1.01-1.31], [More than 9.5 hours: HR, 1.42; 95% CI, 1.25-1.61], 

 for trend <.001) and sitting time ([4.6-8.5 hours: HR, 1.14; 95% CI, 1.01-1.28], [More than 8.5 hours: HR, 1.54; 95% CI, 1.34-1.78], 

for trend<.001) compared to reference groups.

Further analysis indicated these trends remained significant after adjusting for additional factors, such as time-varying myocardial infarction and coronary revascularization (Total sedentary behavior HRs, 1.00, 1.11, 1.27; sitting HRs, 1.00, 1.09, 1.37; trend 

<.001 each) and for baseline physical activity (Total sedentary behavior HRs, 1.00, 1.10, 1.24; sitting HRs, 1.00, 1.08, 1.33; trend 

<.001 each). Investigators pointed out associations with sedentary behavior exposures did not differ based on age, race-ethnicity, BMI, physical activity, physical functioning, diabetes, hypertension, or coronary heart disease.

"These findings are consistent with other studies confirming that people with more daily sedentary time are more likely to develop chronic health conditions such as diabetes, high blood pressure, heart attack, stroke and premature death from heart disease and other causes," LaMonte added.

Association of Sedentary Time and Incident Heart Failure Hospitalization in Postmenopausal Women,

An analysis of data from the Women's Health Initiative details the detrimental impact of sedentary behavior on the risk of heart failure in older women. 

Too Much Sitting, Lying Down Could Increase Heart Failure Risk by 42% in Older Women

The Kardia AI V2 algorithm suite from AliveCor has received 510(k) clearance from the US Food and Drug Administration (FDA), according to a 

The new technology, which works in conjunction with the KardiaMobile and KardiaMobile 6L devices, along with the Kardia app, allows users to take a 30-second ECG and receive instant determinations of multiple cardiac conditions, such as a sinus rhythm with premature ventricular contractions (PVC), a sinus rhythm with supraventricular ectopy (SVE), as well as a sinus rhythm with wide QRS.

"Kardia AI V2 is the most sophisticated AI ever brought to personal ECG," said Priya Abani, CEO of AliveCor. "This suite of algorithms and visualizations will provide the platform for delivery of new consumer and professional service offerings beyond AFib, by allowing a much wider range of cardiac conditions to be determined on a personal ECG device."

According to the release, the algorithm suite boasts improved sensitivity and specificity on the company’s “Normal” and “Atrial Fibrillation” algorithms, leading to fewer false positives and false negatives. The suite also provides new visualizations on average beat, PVC identification, and a tachogram.

The release went on to note AliveCor hopes this new technology will augment remote and telehealth cardiological services for a majority of cases. They also noted plans to use this AI as a foundation for additional services in personal and professional environments, including advanced ECG determination services within KardiaCare; the Kardia Heart Health Report (HHR), a cardiologist-backed patient heart risk assessment report; a professional ambulatory monitoring service; as well as chronic heart disease management, which consists of combined human-backed and digital care plans for high-risk employees.

AliveCor expects the technology to become available for use in 2021.

AliveCor announced the US FDA has granted 510(k) clearance to Kardia AI V2 algorithm suite. 

AliveCor's Kardia AI V2 Algorithm Suite Receives FDA Clearance

This article was originally published on EndocrinologyNetwork.com.

An analysis of data from the SUSTAIN 6 and PIONEER 6 trials indicates use of semaglutide was associated with consistent reductions in major adverse cardiovascular events regardless of baseline triglyceride levels in patients with 

The analysis, which was conducted by investigators from St. Michael’s Hospital in Toronto and Brigham and Women’s Hospital, aggregated data from the SUSTAIN 6 and PIONEER 6 trials and concluded semaglutide reduced the risk of major adverse cardiovascular events across multiple levels of baseline triglycerides.

“We found that the incidence rate for MACE in the placebo arm increased across increasing triglyceride levels as evaluated categorically in this analyses. Semaglutide generally reduced the risk of MACE and its components versus placebo across all triglyceride groups,” said Subodh Verma, MD, PhD, a cardiac surgeon-scientist at St. Michael’s Hospital, in his AHA 2020 presentation. “Results were consistent when evaluating triglycerides categorically or as a continuous variable.”

Presented at the American Heart Association’s (AHA) Scientific Sessions 2020, the current study was designed as a posthoc analysis of the trials to assess effects of semaglutide on MACE and its components across triglyceride levels. Briefly, SUSTAIN 6 enrolled 2735 patients and randomized to either 0.5 or 1g semaglutide once weekly or placebo therapy and PIONEER 6 enrolled 3183 and randomized them to daily oral semaglutide or placebo.

The main outcome of interest for the analysis was change in triglyceride levels over time with semaglutide versus placebo in both trials. Additionally, Investigators hoped to determine the risk of first MACE and its components by baseline triglyceride levels and time to first MACE by triglyceride levels at baseline for semaglutide and placebo when pooling data from both trials.

Upon analysis, investigators identified 6417 patients from the trials with information related to baseline triglyceride measurements, These groups were defined as triglycerides 151 mg/dL or less, 151 mg/dL to 205 mg/dL, and more than 205 mg/dL. Results indicated the mean triglycerides for each of the 3 groups were 107.3 (26.0), 176.6 (15.6), and 326.5 (197.1) mg/dL, respectively.

Investigators estimated the effect of semaglutide versus placebo on primary endpoints using Cox regression by triglyceride level categorically and continuously when adjusted for baseline triglycerides and HDL cholesterol. Investigators also noted the analysis was designed to assess impact of statin treatment in these patients as well.

After analysis, investigators determined semaglutide reduced triglycerides versus placebo by 5% in the SUSTAIN 6 trial and 6% in the PIONEER 6 trial (

 <.01). Further analysis indicated the incidence of MACE with placebo increased across the increasing triglyceride groups. In comparison, semaglutide generally reduced the risk of MACE and its components across all triglyceride groups versus placebo. Additionally, results appeared to be consistent when evaluating triglycerides as a continuous variable and regardless of statin treatment among patients.

“This posthoc analysis of SUSTAIN 6 and PIONEER 6 trials pooled demonstrated that semaglutide reduced triglyceride levels versus placebo in both trials, in which over half of the patients had elevated levels at baseline,” Verma added.

Semaglutide Reduces Mace Consistently Across Baseline Triglyceride Levels in Patients With Type 2 Diabetes: A Post Hoc Analysis of the Sustain 6 and Pioneer 6 Trials

An analysis of data from a pair of major trials indicates use of semaglutide was associated with a reduction in MACE regardless of a patient's baseline triglyceride levels. 

Analysis Indicates Semaglutide Reduces MACE Regardless of Triglyceride Levels

While the American Heart Association Scientific Sessions 2020 was filled with noteworthy studies, a pair of phase 3 trials examining sotagliflozin in patients with type 2 diabetes may be the most impactful. Presented during a late-breaking session, the SCORED and SOLOIST trials demonstrated the effects of the dual SGLT1/SGLT2 inhibitor in patients with chronic kidney disease and worsening heart failure.

Despite both trials being cut short due to a lack of funding during the COVID-19 pandemic, results from both trials left many impressed and carry multiple implications for clinical practice. While the results have implications for sotagliflozin, which results indicate could lower the risk of stroke, they also offer further insight into the effects of the SGLT2 inhibitor class.

For further perspective on the trials, check out this video with Muthiah Vaduganathan, MD, MPH, a cardiologist at Brigham and Women’s Hospital, titled: “4 Takeaways from SOLOIST & SCORED”.

 and hear more from study chair Deepak Bhatt, MD, MPH, executive director of interventional cardiovascular programs at Brigham and Women’s Hospital, in an interview with 

Videos

A cardiologist from Brigham and Women's Hospital offers his thoughts on the results of phase 3 SCORED and SOLOIST trials, which examined use of sotagliflozin in patients with type 2 diabetes.

Muthiah Vaduganathan, MD: Key Takeaways from Sotagliflozin Data

Obesity may be the most detrimental health problem of the modern era. Over the past half-century, the global burden of obesity and its effect on global health, in particular, the growing incidence of cardiovascular disease (CVD) has increased exponentially.

Beyond the direct association between obesity and CVD, it is known to be linked to other major risk factors such as hyperlipidemia, insulin resistance, and hypertension.

 The ultimate goal for both primary and secondary prevention of CVD in obese patients is weight reduction. The three major methods for weight loss are: pharmacologic or medical treatments, dietary and lifestyle modifications, and bariatric or weight loss surgery.

To spite a reasonable body of evidence that bariatric surgery works, controversy remains. After the initial weight loss, do patients realize long-lasting reductions in CV risk? Many clinicians believe that the way to meaningful and long-term weight loss is through putting in the work rather than cutting corners with a fast fix and there may be something to be said for developing healthy, long-lasting habits. Thankfully data exist that answers these questions.

Weight loss in the obese population has been studied extensively. While strong evidence exists, that bariatric surgery is a more reliable method of weight reduction than either pharmacological or lifestyle methods interest has now shifted to whether or not weight reduction surgery leads to long-term reductions in obesity-related comorbidities.

In a recent nested cohort study performed by Osama Moussa and colleagues in the United Kingdom a clear association was found between bariatric surgery with lower long-term risk for major cardiovascular events (MACE) and heart failure in obese patients.

In another retrospective, matched, controlled cohort study Dr. Singh and colleagues, also in the UK, looked at specific risk factors for CVD after bariatric surgery and found a reduced risk of hypertension, heart failure, and mortality when compared to medical management.

 Singh further found that patients with type 2 diabetes mellitus who underwent bariatric surgery also had a lower incidence of atrial fibrillation.

 In yet another recent study published in Current Opinion in Lipidology, Zohaib Iqbal, a biologist in Manchester, UK found that bariatric surgery led to improvements in obesity-related metabolic comorbidities including dyslipidemia, HDL functionality, hypertension, type 2 diabetes mellitus, insulin resistance, and inflammation.

A major study out of the Cleveland Clinic sought to put to rest further questions about the efficacy of weight reduction surgery and the long-term implications with regards to MACE. Ali Aminian, MD, reports in the Journal of the American Medical Association that among patients with type 2 diabetes and obesity, bariatric surgery led to a significantly lower risk of incident MACE when compared to non-surgical treatment.

 An interesting caveat to these data appeared in another prominent article published this year in The American Journal of Cardiology showing that while MACE is reduced both short-term and long-term in the general bariatric population, obese patients with concomitant coronary artery disease (CAD) that underwent weight reduction surgery realized an increase in MACE events over time.

From these data, it is clear that bariatric surgery offers lasting benefits to obese patients, especially those suffering from type 2 diabetes with regards to CV risk reduction and long-term MACE. However, do the benefits outweigh the risks of surgery? Here are some statistics. The average three-year weight loss following bariatric surgery is 62% of excess weight.

 Short-term and long-term mortality rates are 0.5% and 5% respectively.

 In a landmark study known as the Swedish Obese Subjects (SOS) study, more than 2000 patients undergoing bariatric surgery with more than 20 years of follow-up realized a 29% reduction in mortality irrespective of the amount of weight lost.

The verdict is in. While more prospective randomized studies may be needed the available evidence suggests that there are undeniable, substantial, and sustainable benefits to weight reduction surgery over traditional weight-loss strategies in obese patients with regards to long-term cardiovascular risk and the incidence of MACE. Armed with this information clinicians can have a frank discussion with patients about weight reduction surgery and if it is right for them.

Dr. Gregory Weiss reflects on data related to bariatric surgery and its subsequent impact on cardiovascular health. 

Is it Time to Consider Bariatric Surgery for Primary Prevention?

This year clinicians and researchers across all disciplines of medicine have witnessed many firsts. As we navigate a perilous landscape dominated by the global COVID-19 pandemic, we have seen an extraordinary adaptation in the academic community. Science, medicine, and humanity itself must go on.

In keeping with this idea, the American Heart Association (AHA) has just completed its first virtual annual meeting from which the global academic community has introduced the latest research and insight in the field of cardiovascular science. In light of the incredible strain the pandemic has had on the global economy we present four sessions from the AHA Scientific Sessions 2020 highlighting the cost versus benefit of the latest drugs that treat type II diabetes mellitus that are also known to reduce cardiovascular (CV) risk.

On November 13th, 2020, Joseph Azuri, MD, and colleagues from Tel Aviv, Israel presented, in session P2007, a comparison between empagliflozin, an inhibitor of the sodium-glucose cotransporter 2 (SGLT2) and oral semaglutide, the first oral glucagon-like peptide 1 (GLP-1) receptor agonist. In keeping with the AHA strategic goal of reducing cardiovascular mortality by 20% these two drugs have been shown to significantly reduce the incidence of CV mortality in patients with type 2 diabetes mellitus and known CVD.

In light of the potential cost burden adding a new drug to a diabetes treatment regimen creates, Azuri sought to determine which drug would be most cost-effective while still reducing CV risk in type 2 diabetics. The research team went on to calculate the cost needed to treat (CNT) and prevent one case of CV mortality using either drug. They found the annual costs for empagliflozin and semaglutide were $4,572 and $6,680, respectively.

 In light of the similarity between the drugs with regards to efficacy and CV risk reduction, Azuri’s team recommends empagliflozin as the more cost-effective treatment.

In a second session on November 13th, 2020, P2013, Azuri and colleagues went on to compare three popular GLP-1 receptor agonists. With regards to semaglutide, dulaglutide, and liraglutide, the American Diabetes Association recommends providing one of these GLP-1 therapies to patients with type 2 diabetes and established CVD regardless of glycemic control.

 Concerned about the staggering costs associated with these new drugs Azuri sought to compare the 3 drugs for cost-effectiveness.

Azuri again calculated the annual cost needed to prevent one major adverse cardiovascular event (MACE) utilizing each of the three drugs in patients with type 2 diabetes and established CVD. The relative costs were $557,000 for semaglutide, $1,179,360 for liraglutide and $1,605,904 for dulaglutide.2 The research team concluded that, for secondary prevention of MACE in patients with type 2 diabetes and established CVD, semaglutide provides more value than the other two medications.

In session P1146 on November 13th, a colleague of Azuri’s, Ronen Arbel, PhD, further breaks down the cost effectiveness of two different preparations of the GLP-1 drug semaglutide. With an oral preparation of semaglutide now available, Arbel imagined that patients may prefer it over a subcutaneous injection for prevention of MACE in patients with type 2 diabetes.

Following the previous model, Arbel calculated the average annual cost for both preparations needed to prevent one MACE. The research team found that the average costs per year were $641,823 and $855,040 for the subcutaneous and oral preparations respectively.

 They further looked at the cost relationship between the two preparations and the endpoints of MACE versus cardiovascular mortality (CVM) alone. They concluded that the subcutaneous preparation of semaglutide was more cost-effective for the prevention of MACE in patients with type 2 diabetes but that for the prevention of CVM the oral preparation provided a significantly better monetary value.

Finally, in session MP463, also on November 13th, Arbel and colleagues looked at the cost-effectiveness of icosapent ethyl, a prescription omega-3 fatty acid supplement known to aid in prevention of MACE in patients with hypertriglyceridemia. The team looked specifically at the difference in cost when used for secondary prevention in diabetic patients with known CVD and for primary prevention in those with risk factors for CVD.

Arbel analyzed the cost of icosapent ethyl to prevent one MACE per year when prescribed for either primary or secondary prevention. The average cost of icosapent ethyl annually was $874,500 versus $206,965 when used for primary and secondary prevention respectively.

 The team found that the cost needed to treat was four times higher in the primary prevention group when compared to the secondary prevention group concluding that prescribing icosapent ethyl for diabetic patients with known CVD is significantly more cost effective.

We as clinicians often overlook the cost of the therapies we prescribe focusing solely on the most effective and proven treatments for our specific patients. These reports show that, when given choices between equally efficacious treatments, cost can play a significant role in our decision making and should. Of final note, we should all consider the enormous monetary amounts reported above. Reread those annual costs and consider the relative burdens such numbers place on patients and the health care system overall. A discussion for another time.

Gregory Weiss, MD, examines 4 studies presented at AHA Scientific Sessions 2020 comparing the cost-effectiveness of antidiabetic agents for reducing cardiovascular events. 

Comparing Cost-Effectiveness of Antidiabetic Therapies with Cardiovascular Benefit

With the efficacy and safety of SGLT2 inhibitors well-established, focus has now shifted to understanding the real-world use and applicability of these revolutionary agents. Among the multitude of ongoing programs and studies examining these topics is TRANSLATE-HF, which is a program commissioned by the American Heart Association (AHA) in collaboration with AstraZeneca focused on optimizing evidence-based treatment for patients with heart failure.

, which is composed of 6 studies in total, investigators sought to evaluate the generalizability of DAPA-HF eligibility and the US FDA label for dapagliflozin to heart failure patients in the US. Using these criteria and applying them to the AHA’s Get With the Guidelines-Heart Failure Registry, investigators determined 4 of 5 heart failure patients met criteria for receiving dapagliflozin. Presented at the 

, results of this study confirmed what many had already suspected—a large percentage of patients could benefit from receiving an SGLT2 inhibitor.

While the first study provides valuable insight, it has also bolstered interest in TRANSLATE-HF and the remaining data to come from the program. For more information on TRANSLATE-HF, the results of the first study presented at AHA 2020, and what tells us about SGLT2 inhibitor use, 

reached out to the study’s lead investigator Muthiah Vaduganathan, MD, MPH, a cardiologist at Brigham and Women’s Hospital, to take part in AHA 2020 House Call.

Timestamps:
What is TRANSLATE-HF? - 0:10 

Were you surprised by the results? - 2:10

Can you share details on upcoming studies? - 3:30

Generalizability of the US FDA Label for Dapagliflozin to Patients With Heart Failure With Reduced Ejection Fraction in the GWTG-HF Registry

TRANSLATE-HF is a collaborative effort between the AHA and AstraZeneca with the goal of increasing and optimizing SGLT2 inhibitor use in US patients. Hear further insight lead author from the first of 6 TRANSLATE-HF studies, which was presented at AHA 2020.

AHA & AstraZeneca Push for Uptake of SGLT2 Inhibitors with TRANSLATE-HF Program

The STRENGTH trial has drawn a slew of reactions from cardiologists and while they examined different agents, some have used the data to draw comparisons and question the results of the REDUCE-IT trial. After a slide from the presentation of the STRENGTH trial questioned the results of REDUCE-IT based on the results of their own trial examining AstraZeneca’s omega-3 CA (Epanova), it sparked an ongoing debate among cardiologists.

Since the presentation, the subject of mineral vs corn oil placebos, DHA vs EPA, and the overall designs of both the STRENGTH and REDUCE-IT trials have become topics of discussion. Among those taking to social media to share their thoughts on the debate was principal investigator from the REDUCE-IT trial, Deepak Bhatt, MD, MPH, executive director of interventional cardiovascular programs at Brigham and Women’s Hospital. To learn more about the differences between the combined EPA-DHA agent examined in STRENGTH and icosapent ethyl, we reached out to Bhatt and that conversation is the subject of the most recent AHA 2020 House Call.

Deepak Bhatt, MD, MPH, offers his thoughts on the most important REDUCE-IT analyses released in 2020 and why he disagrees with the notion results of the STRENGTH trial somehow impact the use of icosapent ethyl in clinical settings.

Deepak Bhatt, MD: STRENGTH, REDUCE-IT, and DHA

Among the thousands of studies presented at the American Heart Association’s Scientific Sessions 2020 were a pair of late-breaking studies presented by Deepak Bhatt, MD, MPH, executive director of interventional cardiovascular programs at Brigham and Women’s Hospital. Titled 

, the pair of phase 3 trials examined use of sotagliflozin in patients with type 2 diabetes and worsening heart failure or chronic kidney disease.

While diabetes medications have stolen headlines at major cardiovascular meetings in the past few years, sotagliflozin sets itself apart from dapagliflozin and empagliflozin as the only dual SGLT2/1 inhibitor currently in development for treatment of type 1 and type 2 diabetes. As part of Practical Cardiology’s coverage of the annual conference, we reached out to Bhatt for further insight into the results of SOLOIST and SCORED—that conversation Is the subject of this special edition AHA 2020 House Call.

Deepak Bhatt, MD, MPH, offers his thoughts on the results of SCORED and SOLOIST as well as diving deeper into the implications of the data for sotagliflozin and SGLT2 inhibitors moving forward. 

Deepak Bhatt, MD: Sotagliflozin and Phase 3 Data from AHA 2020

After making a splash with the overall results at the American Society of Nephrology’s Kidney Week 2020, new data from an analysis of cardiovascular outcomes from 

 is shedding additional light on the cardiorenal protection seen with finerenone.

Presented at the American Heart Association (AHA) Scientific Sessions 2020, results suggest the nonsteroidal, selective mineralocorticoid receptor antagonist finerenone was associated with a 14% reduction in negative cardiovascular outcomes and this effect was consistent regardless of baseline history of cardiovascular disease.

With a recent explosion in interest around antidiabetic agents with cardiorenal benefits, the results of the latest analysis highlight the potential of finerenone to fit into treatment algorithms.

A randomized, double-blind, placebo-controlled trial, FIDELIO-DKD enrolled more than 5600 patients with type 2 diabetes and meeting the criteria for chronic kidney disease and randomized them in 1:1 ratio to finerenone or placebo therapy. These patients were followed for a median of 2.6 years and overall results indicated finerenone lowered risk of worsening CKD by 18% (HR, 0.82; 95% CI, 0.73-0.93; 

=.001) while also providing a 16%(HR, 0.86; 95% CI, 0.75-0.99; 

=.034) reduction in a secondary endpoint of composite cardiovascular outcomes.

For the AHA 2020 analysis, investigators hoped to compare the effect of finerenone on individual cardiovascular outcomes of the study in those with and without cardiovascular disease at baseline. Of the 5674 patients randomized in the study, 2605 had cardiovascular disease at baseline—1303 randomized to finerenone and 1302 randomized to placebo. The composite cardiovascular outcome for the study included time to cardiovascular death, myocardial infarction, stroke, or hospitalization for heart failure.

Results of the analysis suggested use of finerenone was associated with reductions in risk of cardiovascular death (4.5% vs 5.3%; HR, 0.86; 95% CI, 0.68-1.08), nonfatal myocardial infarction (2.5% vs 3.1%; HR, 0.80; 95% CI, 0.68-1.08), and hospitalizations for heart failure (2.5% vs 3.1%; HR, 0.80; 95% CI, 0.58-1.09) when compared against placebo. Investigators pointed out a nonfatal stroke in 3.2% of finerenone patients and 3.1% of placebo patients (HR, 1.03; 95% CI, 0.76-1.38).

When comparing those with and without a history of cardiovascular disease, investigators found the effect of finerenone was not modified by prior cardiovascular disease (

 for interaction=.85). Among those with cardiovascular disease, finerenone use was associated with a 15% reduction in risk of the composite cardiovascular outcome with an incidence rate of 7.18 per 100 patient-years versus 8.5 per 100 patients-years seen with placebo therapy (HR, 0.85; 95% CI, 0.71-1.01). Among those without cardiovascular disease, finerenone was associated with a 14% reduction in risk of the composite cardiovascular outcome with an incidence rate of 3.43 per 100 patient-years versus 3.92 per 100-patients years seen with placebo therapy (HR, 0.86; 95% CI, 0.68-1.08).

For more on the result of this analysis, we reached out to FIDELIO-DKD investigator George Bakris, MD, professor of medicine at the University of Chicago Medicine and member of Practical Cardiology’s editorial advisory board, to take part in an AHA 2020 House Call.

Finerenone and cardiovascular outcomes in patients with chronic kidney disease and type 2 diabetes

,” was presented at AHA 2020 and simultaneously published in 

George Bakris, MD, offers further insight into the cardiovascular outcomes analysis of FIDELIO-DKD presented at AHA 2020. 

George Bakris, MD: Cardiovascular Benefits of Finerenone in FIDELIO-DKD

This article was originally published on Endocrinology Network.

A pair of late-breaking studies presented at AHA 2020 signal a new diabetes medication with cardiorenal benefits could soon make its name for itself.

Data from the phase 3 SOLOIST-WHF and SCORED trials suggest sotagliflozin was associated with significant reductions in death from cardiovascular disease in patients with worsening heart failure and significant reductions in blood glucose levels among patients with moderate to severe kidney impairment.

"With the results of these large two trials, adding to other recent data about drugs in this class, it is now clear that most patients with type 2 diabetes and either kidney disease or heart failure should be on an SGLT2 inhibitor," said Deepak Bhatt, MD, MPH, the executive director of Interventional Cardiovascular Programs at Brigham and Women’s Hospital, 

. "SCORED provides further randomized clinical trial evidence that SGLT2 inhibitors should be part of the standard of care for patients with type 2 diabetes mellitus and kidney disease. And SOLOIST demonstrates that early, in-hospital initiation of SGLT2 inhibitors is safe, effective, and should become the standard of care in patients with type 2 diabetes mellitus and heart failure."

Developed by Sanofi Inc. and transferred to Lexicon Pharmaceuticals, sotagliflozin is the the first dual SGLT2/1 inhibitor being developed for the treatment of type 1 and type 2 diabetes. With the recent increase in interest related to the cardiorenal protection seen with SGLT2 inhibitors, investigators sought to explore use of sotagliflozin in specific diabetic populations.

SOLOIST-WHF was designed as a multicenter, double-blind trial of patients with type 2 diabetes who were recently hospitalized for worsening heart failure. The trial randomized 1222 patients in a 1:1 ratio to sotagliflozin or placebo. The primary endpoint of the trial was the total number of deaths from cardiovascular causes and hospitalizations and urgent visits for heart failure. Of the 608 patients in the sotagliflozin group, 48.8% received the first dosage before discharge and the remaining 51.2% received the first dose a median of 2 days after discharge.

Of note, SOLOIST-WHF was ended early due to a lack of funding from the sponsor during the COVID-19 pandemic and the median follow-up time was 9.0 months.

SCORED was similar in design, but enrolled patients with type 2 diabetes, chronic kidney disease, and risks for cardiovascular disease. This trial enrolled 10,584 patients in a 1:1 ratio and patients were followed for a median of 16 months. The primary endpoint of the trial was a composite of the total number of deaths from cardiovascular causes, hospitalizations for heart failure, and urgent visits for heart failure. SCORED was also ended early due to a lack of funding during the pandemic.

Results of SOLOIST-WHF suggested sotagliflozin was associated with fewer primary endpoint events (245 vs 355) compared to placebo and a lower rate of primary endpoint events (51.0 vs. 76.3; HR, 0.67; 95% CI, 0.52-0.85; 

<.001) compared to placebo. Results from this trial also suggested sotagliflozin was associated with a lower rate of death from cardiovascular causes (HR, 0.84; 95% CI, 0.58-1.22) and rate of all-cause mortality (HR, 0.82; 95% CI, 0.59-1.14). Additionally, investigators found these results were consistent regardless of when first dose was administered.

Results of SCORED indicated sotagliflozin was associated with a lower rate of primary endpoint events HR, (0.74; 95% CI, 0.63-0.88; 

<.001) anda lower rate of deaths from cardiovascular causes (HR, 0.90; 95% CI, 0.73-1.12; 

=.35). Results also suggested sotagliflozin was associated with a reduction in first occurrence of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke (HR, 0.84; 95% CI, 0.72-0.99) and the first occurrence of death from cardiovascular causes or hospitalization for heart failure, which were the original coprimary endpoints of the trial.

"Sotagliflozin is the first SGLT2 inhibitor to show a beneficial effect on stroke among patients with diabetes, suggesting that it may also affect atherosclerosis, or plaque build-up in the coronary and brain arteries,” added Bhatt. “SCORED is also the first trial to show the benefits of SGLT2 inhibitors across the full range of albuminuria, or leakage of protein in the urine, which is common in people with Type 2 diabetes.”

The Effect of Sotagliflozin on Cardiovascular Events in Patients With Type 2 Diabetes Post Worsening Heart Failure (SOLOIST-WHF)

Effect of Sotagliflozin on Cardiovascular and Renal Events in Patients With Type 2 Diabetes and Moderate Renal Impairment Who Are at Cardiovascular Risk (SCORED)

,” were presented at AHA 2020 and simultaneously published in 

Data from the phase 3 SOLOIST-WHF and SCORED trials suggest sotagliflozin was associated with significant reductions in death from CVD in patients with worsening heart failure and significant reductions in blood glucose levels among patients with moderate to severe kidney impairment.

Sotagliflozin, a Dual SGLT2/1 Inhibitor, Shows Promise in Phase 3 Trials

A new therapy that shows promise for treating refractory 

 could be coming to the lipidologist’s armamentarium, according to the results of a phase 2 study presented at the American Heart Association (AHA) Scientific Sessions 2020.

Results from the double-blind trial suggest patients with refractory hypercholesterolemia receiving evinacumab, in both intravenous and subcutaneous doses, significantly reduced low density lipoprotein (LDL) cholesterol by more than 50% versus placebo therapy and that evinacumab generally well-tolerated among study participants.

“Our study assessing the safety and efficacy of evinacumab shows that it can lower LDL cholesterol by half in patients unable to attain target guidelines despite maximally tolerated lipid lowering therapy,” said lead investigator Robert Rosenson, MD, professor of medicine and director of Cardiometabolic Disorders at the Icahn School of Medicine at Mount Sinai, in a statement. “Evinacumab is a fully human monoclonal antibody that inhibits angiopoietin like protein 3 (ANGPLT3) and lowers LDL cholesterol through an LDL receptor independent pathway. Genetic studies have shown that people who are missing or have low levels of ANGPTL3 are known to have very low lifelong levels of LDL cholesterol and rarely suffer from atherosclerotic cardiovascular disease.”

The trial was designed with the aim of evaluating the safety and efficacy of evinacumab in patients with refractory hypercholesterolemia despite use of a PCSK9 inhibitor and maximally tolerated statin and ezetimibe. For inclusion in the study, patients needed to be 18-80 years at screening, have a primary diagnosis of hypercholesterolemia, either HeFH or non-HeFH with clinical ASCVD,and an LDL-C of 70 mg/dL or greater or 100 mg/dL or greater for those with and without clinical ASCVD, respectively.

In total, 272 patients were selected for inclusion and underwent randomization in the trial. For those in the subcutaneous portion of the trial, patients were randomized to receive either subcutaneous evinacumab at a dose of 450 mg weekly (n=40), 300 mg weekly (n=43), or 300 mg every 2 weeks (n=39) or placebo therapy (41 patients).In the intravenous portion of the trial, patients were randomized to intravenous evinacumab at a dose of 15 mg per kilogram of body weight every 4 weeks (n=39) or 5 mg per kilogram every 4 weeks (n=36) or placebo (n=34). The primary end point of the trial was the percent change in LDL-C levels from baseline to week 16 with evinacumab compared to placebo.

Results at week 16 indicated the differences in least-squares mean change from baseline in LDL-C level between groups assigned to receive subcutaneous evinacumab at a dose of 450 mg weekly, 300 mg weekly, or 300 mg every 2 weeks and placebo therapy were -56.0, -52.9, and -38.5 percentage points, respectively (

 <.001 for all comparisons). In the intravenous evinacumab groups, investigators noted differences of -50.5 (

 <.001) and -24.2 percentage points among patients receiving doses of 15 mg per kilogram and 5 mg per kg, respectively, versus the placebo group.

Additionally, investigators pointed out the responses to treatment could be observed as early as the first post-baseline lipid assessment and these were maintained through week 16. The safety analysis of trial data indicated the incidence of serious adverse events during the treatment period ranged from 3-16% among the trial groups.

“Our study demonstrates that a regimen of either subcutaneous or intravenous evinacumab can have a significant impact on LDL cholesterol,” Rosenson added. “If approved for use in this setting, evinacumab could potentially arm cardiologists with a major new add-on therapy to bring patients with HeFH to or closer to their cholesterol-lowering goal.”

Evinacumab in Patients with Refractory Hypercholesterolemia

,” was presented at AHA 2020 and simultaneously published in the 

Data from a phase 2 trial suggests evinacumab, in both subcutaneous and intravenous doses, were effective at lowering LDL-C in patients with refractory hypercholesterolemia. 

Phase 2 Trial Suggests Evinacumab Cuts LDL-C by 50% in Refractory Hypercholesterolemia 

Data from the EARLY-AF trial suggests first-line therapy with ablation could help maintain sinus rhythm better than traditional antiarrhythmic agents for patients with 

Results of the randomized trial indicate first-line ablation was linked to significant reductions arrhythmia outcomes including total AF burden and days with AF, suggesting initial treatment with ablation could be a more effective approach than first-line treatment with antiarrhythmic drugs, which is the current recommendation in contemporary guidelines.

“In this randomized trial involving patients with untreated paroxysmal atrial fibrillation, catheter cryoballoon ablation resulted in a significantly lower rate of recurrence of atrial tachyarrhythmia, as assessed by continuous cardiac rhythm monitoring, than antiarrhythmic drug therapy,” wrote study investigators.

To compare first-line approaches with cryoablation versus antiarrhythmic drugs, EARLY-AF was designed as a multicenter, open-label, randomized trial with blinded endpoint adjudication and conducted across 18 centers in Canada. Enrolling patients 18 and older with symptomatic AF and at least one episode of AF within 24 months before randomization, investigators enrolled a cohort of 303 patients for inclusion in their trial.

Patients were excluded from the study if they had a history of regular use of a class I or class III antiarrhythmic drug. Patients included in the study were randomized in 1:1 ratio to an initial strategy of catheter cry-balloon ablation or antiarrhythmic drug therapy. All patients in the study underwent insertion of an implantable cardiac monitor following enrollment with the goal of using this data to quantify AF burden.

The primary end point of the study was the first documented recurrence of any atrial tachyarrhythmia, between 91 and 365 days after catheter ablation or the initiation of an antiarrhythmic drug. Secondary endpoints included free from symptomatic arrhythmia, AF burden, and quality of life. The total follow-up period lasted 12 months.

Upon analysis, investigators found first-line ablation was associated with a 52% reduction in the recurrence of atrial tachyarrhythmia at 1 year—with events occurring among 66 of 154 patients randomized to undergo ablation and among 101 of 149 patients randomized to antiarrhythmic drug (HR, 0.48; 95% CI, 0.35-0.66; 

 <.001). Further analysis indicated symptomatic atrial tachyarrhythmia had recurred in 11% of patients randomized to ablation and 26.2% randomized to arrhythmic drug s (HR, 0.39; 95% CI, 0.22-0.68).

The analysis also suggested patients in the ablation group had a lower median percentage of time in atrial fibrillation than those receiving antiarrhythmic drugs (ablation: 0%, IQR, 0-0.08; antiarrhythmic drugs: 0.13%, IQR, 0-1.60). The trial’s safety analysis indicated serious adverse events occurred in 3.2% of those who underwent ablation compared to 4.0% of those who received antiarrhythmic drugs.

During his presentation at the American Heart Association Scientific Sessions 2020, Jason Andrade, MD, pointed out first-line ablation was associated with significant reductions in time to first recurrence of any atrial fibrillation, time to first recurrence of symptomatic atrial fibrillation, total AF burden, and days with AF.

Cryoablation or Drug Therapy for Initial Treatment of Atrial Fibrillation”

 was presented at AHA 2020 and simultaneously published in the 

Results of the EARLY-AF study suggest first-line ablation may be a better approach for patients with symptomatic atrial fibrillation than first-line antiarrhythmic drugs. 

First-Line Ablation More Effective than Antiarrhythmic Drugs for Atrial Fibrillation

New research from a study of more than 300 women is underlining the potential benefit of combining diagnostic imaging methods when treating 

 with non-obstructive coronary arteries (MINOCA).

Results of the HARP-MINOCA, which were presented at the American Heart Association’s (AHA) Scientific Sessions 2020, suggest use of coronary optical coherence tomography (OCT) and cardiac magnetic resonance imaging (MRI) explained why women presented with symptoms and had blood tests consistent with heart attack in 84% of the study cohort.

“Our findings are important because women (or men) with MINOCA have historically been told that since the angiogram is OK, they never had a heart attack. This is entirely wrong for about two-thirds of the women who had both imaging tests, and misleading for one-quarter of the women because we found they had another problem that was not related to blood flow and could be diagnosed via cardiac MRI,” said lead investigator Harmony Reynolds, MD, director of New York University Langone's Sarah Ross Soter Center for Women’s Cardiovascular Research and an associate professor in the department of medicine at NYU Grossman School of Medicine, in a 

Funded by the AHA, HARP-MINOCA was designed as a prospective, multicenter, international, diagnostic observational study and enrolled women with MI who did not have prior obstructive coronary artery disease (CAD) with the aim of evaluate the mechanisms of MINOCA and to identify cause of the heart attack in these patients. Among 301 women enrolled across 15 sites, investigators determined 168 had MINOCA—the patient population had a median age of 60 years and 50% were non-Hispanic whites.

Patients included in the study underwent multivessel OCT followed by CMR if invasive coronary angiography showed less than 50% stenosis in all major vessels. Investigators noted angiography, OCT, and CMR, were evaluated at blinded, independent core labs.

Data from HARP-MINOCA suggests use of OCT and cardiac CMR could help determine cause of symptoms in women presenting with MINOCA. 