European Society of Cardiology Congress 2021

Every year, European Society of Cardiology (ESC) Congress offers clinicians and researchers a glimpse into the latest data from clinical trials. Our editorial staff's top picks for new trials from ESC Congress 2021 includes EMPEROR-Preserved, FIGARO-DKD, SSaSS, MASTER DAPT, and the LOOP Study.

Check out the slideshow below for more on each trial in our list of top 5 new trials presented at ESC Congress 2021. 


Top New Trials at ESC Congress 2021

Editor's note: Clicking in the center of a slide will open a new tab with our coverage of the highlighted study. 

Articles

Every year, ESC Congress provides clinicians and researchers with a glimpse into the latest data from clinical trials. Our editorial staff's top picks for new trials from ESC Congress 2021 conference includes EMPEROR-Preserved, FIGARO-DKD, SSaSS, MASTER DAPT, and the LOOP Study.

ESC Congress 2021: Top Trials Slideshow

Patrick Campbell is the senior editor of Practical Cardiology, as well as its sister publication Endocrinology Network. Prior to joining these brands, he led coverage of cardiology and diabetes with HCPLive. Before joining parent company MJH Life Sciences in 2019, he spent time as a beat reporter with the Pocono Record in Stroudsburg, PA and Star News Group in Manasquan, NJ. He also touts experience in multimedia, having spent time as a freelance multimedia specialist with NJ Advance Media and multimedia coordinator at the Pocono Record. In his free time, he enjoys traveling, sports, and exploring the great outdoors. Follow him on Twitter @RealPatCampbell or reach him via email at PCampbell@mjhlifesciences.com.

Presented at the European Society of Cardiology (ESC) Congress 2021, 

 demonstrated edoxaban was noninferior to warfarin for adverse events following transcatheter aortic valve implantation (TAVI) in patients with nonvalvular atrial fibrillation.

A 1426-patient trial with participants from 173 medical centers in 14 countries, results suggest edoxaban was noninferior to warfarin following TAVR in this patient population in regard to rate of adverse clinical events, but investigators also urge caution related to an association with an increased risk of major bleeding, which was driven by rates of gastrointestinal bleeding.

“Overall, this trial showed the noninferiority of edoxaban compared to warfarin (or similar analogues) with respect to the composite efficacy endpoint of adverse clinical events. On the other hand, we need to be attentive to the higher bleeding risks with edoxaban. Based on secondary analyses, it seems that lowering the edoxaban dosage when indicated and avoiding patients on mandatory antiplatelet therapy is reasonable safety advice from a clinical point of view. We will be conducting a detailed analysis on specific types of bleeding in the near future,” said principal investigator George Dangas, MD, PhD, professor of medicine and director of cardiovascular innovation at Icahn School Medicine at Mount Sinai, in 

For more insight into the results of ENVISAGE-TAVI AF and to learn about any forthcoming analyses of data from the trial, 

reached out to Dangas and that conversation is the subject of the following ESC Congress 2021 House Call.

This study was presented as “ENVISAGE-TAVI AF: edoxaban vs. vitamin K antagonists after TAVI in patients with atrial fibrillation“ at ESC Congress 2021 and simultaneously published as “

Edoxaban versus Vitamin K Antagonist for Atrial Fibrillation after TAVR,

Videos

George Dangas, MD, PhD, discusses the results of ENVISAGE-TAVI AF and provides perspective into the priorities of investigators as they plan and conduct additional analyses of the trial. 

ENVISAGE-TAVI AF: Clinical Implications and Next Steps, With George Dangas, MD, PhD

Cardiovascular disease remains the predominant cause of health-related morbidity and mortality worldwide.

 While some genetic factors contribute to both risk for and protection from cardiovascular disease (CVD), the European Society of Cardiology (ESC) estimates that up to 90% of heart attack, stroke, and peripheral arterial disease (PAD) risk can be attributed to smoking, poor diet, lack of physical activity, obesity, high blood pressure, raised blood lipids, diabetes, and alcohol consumption.

 The ESC considers promoting CVD prevention a priority and to that end presented updated guidelines at ESC Congress 2021.

Key to preventing CVD is the prevention of atherosclerotic build-up in the arterial system. Fatty atherosclerotic plaque is responsible for most cases of myocardial infarction (MI), stroke, PAD, and sudden cardiac death. The ESC believes that the best way to prevent serious cardiovascular events is through mitigating modifiable risk factors for CVD.

 It all starts with adopting a healthy lifestyle and maintaining it throughout a lifetime.

The ESC recommends that clinicians first identify who will benefit most from preventative treatments such as blood pressure medications and lipid-lowering therapies and considers this risk stratification the cornerstone of these guidelines.

 For patients at higher risk, such as those with high blood pressure, diabetes, and dyslipidemias, targets for all 3 should be set and treatment initiated with escalation as need to meet the needs of the individual patient.

 When patients already have such risk factors for CVD it is of utmost importance that those underlying conditions be treated aggressively.

In healthy people, especially young people who have not yet developed atherosclerotic disease, promoting a healthy lifestyle may stop CVD before it starts. Key to this approach is smoking cessation, maintaining a normal blood pressure, exercise and weight management as well as eating a balanced and healthy diet.

 Cardiologists and other clinicians can set targets for lifestyle modifications based on the 10-year risk for developing CVD using established risk measures.

Frank Visseren, MD, PhD, an epidemiologist and professor in vascular medicine at the University Medical Center in Utrecht, the Netherlands, is the chairperson for the guidelines task force. He underscores the importance of tailoring preventative and treatment strategies to each patient:

“Individualized decisions using risk estimation and a stepwise approach to therapies is more complex than a one-size-fits-all approach but reflects the diversity of patients and patient characteristics in everyday clinical practice, and is essential to give the right patient the right treatment.”

Five key modifiable risk factors were highlighted by the group: Smoking, exercise, nutrition, weight management, mental health, and population-level interventions.

The ESC believes that stopping smoking may be the most effective preventative measure of all with regards to CVD.1 All clinicians should encourage quitting at every visit. Guidelines now recommend smoking cessation regardless of weight gain.

With regards to exercise, the ESC guidelines taskforce recommends that adults avoid sedentary time and strive for at least 150-300 minutes of moderate-intensity, or 75-150 minutes of high intensity exercise each week.

 For the first time the task force has included the use of wearable activity trackers as potentially beneficial in promoting activity and maintaining a healthy weight.

Nutrition is a very important aspect of CVD prevention. The ESC task force recommends plant-based foods such as whole grains, fruits, vegetables, and nuts.

 New for the 2021 guideline is the recommendation that adopting a Mediterranean type of diet along with restricting alcohol intake should be suggested for all patients.

The prior two recommendations are closely related to maintaining appropriate body weight and composition. The ESC recommends that overweight and obese patients lose weight in an effort to lower blood pressure, blood lipids, and the risk of diabetes.

 New to the 2021 guidelines is the recommendation that weight reduction surgery (bariatric) be considered for obese patients with high risk for CVD.

Mental health has been linked to increase CVD risk.

 For the first time the ESC recommends we provide intensified support to patients with mental health problems while encouraging them to comply with lifestyle changes and medication therapy.

Finally, the ESC taskforce highlights the steps we can take on a global level to promote cardiovascular health and prevent CVD. These measures include reducing pollution through reduced fossil fuel use and placing limits on carbon dioxide emissions.

 Further, they recommend more outdoor recreational space, reductions in marketing unhealthy food and E-cigarettes to children, and labeling food and alcohol with nutritional content warnings.

Finally, the task force recommends that cardiovascular disease prevention should be an interdisciplinary effort with frontline clinicians, cardiologists, and other specialists working together to promote best practices and the implementation of these guidelines put forth by the European Society of Cardiology.

https://academic.oup.com/eurheartj/advance-article/doi/10.1093/eurheartj/ehab484/6358713

https://www.escardio.org/The-ESC/Press-Office/Press-releases/How-can-I-avoid-heart-disease-or-stroke

Gregory Weiss, MD, provides an overview of the updated cardiovascular disease prevention guidelines from the European Society of Cardiology, which were released at ESC Congress 2021. 

ESC Releases Updated Cardiovascular Disease Prevention Guidelines

An analysis of the TWILIGHT study presented at the 

European Society of Cardiology (ESC) Congress 2021 

suggests the benefits of ticagrelor monotherapy compared with DAPT with aspirin were consistent regardless of the stent type used.

Stratifying patients into 3 groups based on drug-eluting stent (DES) type, results of TWILIGHT-Stent indicate use of ticagrelor monotherapy after 3-month DAPT in patients undergoing PCI lowered bleeding complications without increasing risk of ischemic with no significant differences among DES types.

“We found that ticagrelor monotherapy was well tolerated and very successful in reducing bleeding and without a penalty in increasing ischemic endpoints. So high consistency regardless of the broader drug eluting stent type,” said George Dangas, MD, PhD, director of cardiovascular innovation at Icahn School of Medicine at Mount Sinai, in an interview with 

The current analysis was performed by TWILIGHT investigators out of an interest in describing the effects of ticagrelor monotherapy against ticagrelor plus aspirin according to type of newer generation stent used in the trial

For the purpose of analysis, patients were classified into 3 groups based on whether they received adurable polymer everolimus-eluting stents (DP-EES), durable polymer zotarolimus-eluting stents (DP-ZES), and biodegradable polymer DES (BP-DES). Investigators identified cohorts of 3014 with DP-EES, 1350 with DP-ZES, and 1405 with BP-DES.

Stent types included in the DP-EES group were: Promus Premier, Promuse Element, Xience Alpine, Xience Expedition, Xience Prime II, and Xience Pro. Stent types included in the DP-ZES group were: Onyx and Endeavor. Stent types included in the BP-DES group were: Orsiro, Ultimaster, Alex, Abluminus, Tetriflex, Supraflex, Yukon Choice Flex, Yukon Choice Elite, Biomime, Metafor, MiStent, Destiny, Firehawk, EUCATECH/eucaLimus, Bioss LIM C, XLIMUS, BuMA, TIVOLI, HELIOS, NOYA, Prolim, Cordimax, GuReater, Synergy, Tetrilimus, Biomatrix Flex, Biomatrix Alpha, and AXXESS.

The primary outcome of interest for the analysis was incidence of BARC 2, 3, or 5 bleeding from 0-12 months after randomization. The secondary outcome of interest was incidence of target lesion failure and incidence of major adverse cardiovascular or cerebral events (MACCE), including all-cause death, nonfatal myocardial infarction, and nonfatal stroke from 0-12 months after randomization.

Upon analysis, results indicated ticagrelor monotherapy was associated with significantly lower rates of BARC type 2, 3, or 5 bleeding, regardless of stent type (

 for interaction=.76). Additionally, results suggested use of ticagrelor monotherapy resulted in similar rates of MACCE in patients with DP-EES (4.2% vs 4.3%; HR: 0.97; 95% CI: 0.68-1.37); DP-ZES (4.1% vs. 3.1%; HR, 1.32 [95% CI, 0.75-2.33]), and BP-DES (3.9% vs 4.2%; 95% CI: 0.54-1.55; 

for interaction=0.60) when compared against ticagrelor plus aspirin. Investigators also pointed out no differences were observed in ischemic or bleeding complications according to DES type in both unadjusted and covariate-adjusted analyses.

“Comparing this among the 3 drug-eluting stent types, we found no major differences among them and, very importantly, rates of late stent thrombosis within each one of these buckets of drug-eluting stents were very, very low in the 0.5% range or lower sometimes,” Dangas added. “So, that indicates a tremendous I would say success, a clinical success with these type of stents in a population that regardless of randomization had to have 1 angiographic high-risk criteria, like a bifurcation, a double stent, a long stent, a left main, (or) CT coronary occlusion, and a clinical high-risk characteristic.”

This study “TWILIGHT-Stent: Ticagrelor Monotherapy According to Stent Type,” was presented at ESC Congress 2021.

Results of the TWILIGHT-Stent study provide insight into the impact of stent type on effects of ticagrelor monotherapy compared against ticagrelor plus aspirin among patients within the original TWILIGHT trial.

TWILIGHT-Stent: Results Consistent Regardless of Stent Type

Results of the Amulet IDE trial suggest the Amplatzer Amulet Left Atrial Appendage Occluder demonstrated superior left atrial appendage (LAA) closure and noninferior safety and effectiveness for stroke prevention in patients with nonvalvular 

Presented during as part of a late-breaking session at the 

European Society of Cardiology (ESC) Congress 2021

, the head-to-head trial provides clinicians with insights into results seen with the devices from Abbott and Boston Scientific as the popularity of LAA procedures continues to grow.

"Atrial fibrillation cases have increased in recent years as the world continues to age, making stroke risk more prevalent and resulting in higher usage of blood-thinning medication that can lead to bleeding and other complications," said principal investigator Dhanunjaya Lakkireddy, MD, Kansas City Heart Rhythm Institute at HCA Midwest Health, in 

. “Amulet demonstrated a clear benefit for people suffering from atrial fibrillation who are at risk of stroke and in need of LAA occlusion. The Amulet IDE trial data show that we can effectively treat these patients with Amulet and get them off blood thinners immediately following implantation."

With an interest in comparing the Amplatzer Amulet occluder against the Watchman occluder, Amulet IDE was designed as a multicenter randomized trial in patients 18 years of age or older with paroxysmal, persistent, or permanent nonvalvular atrial fibrillation, and at a high risk of stroke or systemic embolism. The trial was designed with a trio of primary endpoints, including a composite safety end point of procedure-related complications, all-cause death, or major bleeding at 12 months, a composite efficacy end point of ischemic stroke or systemic embolism at 18 months, and an additional end point assessing the rate of LAA occlusion at 45 days. Of note, the trial was sponsored by Abbott who was responsible for the design as well as selecting the monitoring sites.

A total of 2592 patients were screened for eligibility at 108 centers in the US and abroad from September 2016-March 2019. A cohort of 1878 was randomly assigned to receive an Amulet occluder or a Watchman device. In total, 934 patients were randomized to the Amulet occluder and 944 were randomized to the Watchman device.

Upon analysis, results indicated the Amulet occluder was noninferior to the Watchman device for the composite safety endpoint, with a primary safety event occurring among 14.5% of the Amulet occluder group and 14.7% in the Watchman group (difference=—.14 [95% CI, —3.42 to 3.13]; 

 <.001 for noninferiority). Further analysis revealed major bleeding (10.6% vs 10.0%) and all-cause mortality (3.9% vs 5.1%) were similar between those in the Amulet occluder and Watchman groups.

When assessing the primary efficacy end point, results suggested the Amulet occluder was noninferior to the watchman device and for a composite end point of stroke, systemic embolism, or cardiovascular/unexplained death (5.6% vs 7.7%; difference=—2.12 [95% CI, —4.45 to 0.21]; 

<.001 for noninferiority). Results also indicated the rate of major bleeding was similar between the groups, with a. Rate of 11.6% among the Amulet occluder group and 12.3% among the Watchman device group (difference=—0.71 [95% CI, —3.72 to 2.31]; 

=.32 for superiority). When assessing rates of occlusion at 45 days, results suggested occlusion was higher for the Amulet occluder group compared to the Watchman device group (98.9% vs 96.8%; difference=2.03 [95% CI, 0.41 to 3.66]; 

“The Amulet LAA occluder was superior with respect to LAA closure and noninferior with respect to safety and effectiveness for stroke prevention in patients with NVAF compared to the Watchman device,” Lakkireddy added in 

 
"The dual seal design of the Amulet LAA occluder helps to overcome the limitations of a single seal device, including but not limited to short LAA length, proximal lobes near the ostium, and very large ostia. In addition, immediate closure of the LAA with the Amulet disc allows some patients to be treated without the need for anticoagulation therapy after the procedure.”

This study was presented as “Amulet IDE: Amplatzer Amulet left atrial appendage occluder randomized controlled trial,” at ESC Congress 2021 and simultaneously published as “

Amplatzer Amulet Left Atrial Appendage Occluder Versus Watchman Device for Stroke Prophylaxis (Amulet IDE): A Randomized Clinical Trial,

The Amulet IDE Trial is the first trial to offer a head-to-head comparison of the Amplatzer Amulet occluder from Abbot against the Watchman device from Boston Scientific for left atrial appendage occlusion. 

Amplatzer Amulet Outperforms Watchman Device for LAA Occlusion in Head-to-Head Trial

A post hoc analysis of the TWILIGHT trial is providing clinicians with insight into the effects of ticagrelor monotherapy among patients with high bleeding risk (HBR) from the trial.

, results suggest ticagrelor monotherapy was associated with a lower risk of BARC 2, 3, or 5 bleeding compared to ticagrelor plus aspirin among patients meeting ARC-HBR criteria.

After identifying 1064 patients from the TWILIGHT trial meeting ARC-HBR criteria, investigates sought to assess the rates of different types of bleeding events among this patient population. Upon analysis, investigators found rates of BARC 2, 3, or 5 bleeding were significantly lower in the ticagrelor monotherapy group compared against ticagrelor plus aspirin in both HBR (6.3% vs 11.4%, 

Additionally, in HBR patients, ticagrelor monotherapy was associated with significant reductions in TIMI major bleeding as well as GUSTO moderate or severe bleeding compared to ticagrelor plus aspirin. Investigators also pointed out there was no difference observed in ischemic endpoints from the trial among HBR and non-HBR patients. 

For more on the results of this analysis, 

reached out to study investigator Davide Cao, MD, an interventional cardiology fellow at Icahn School of Medicine at Mount Sinai, and a transcription of that conversation can be found below.

Can you describe the results of TWILIGHT HBR?

Now, the TWILIGHT trial enrolled patients deemed to be at high risk for ischemic and bleeding events. However, the clinical and angiographic criteria that were used to define high-risk patients were developed nearly six years ago and, in the meantime, there have been a number of risk prediction models and risk- or consensus-based definitions that have been proposed to identify high bleeding risk (HBR) patients.

So, the purpose of the present study was to evaluate the treatment effects of ticagrelor monotherapy in a contemporary HBR population, as defined by the Academic Research Consortium criteria, which we know has a consensus-based definition, which identified 14 major criteria 6 minor criteria, and define HBR patients as those who fulfill at least 1 major or 2 minor criteria.

When we applied the ARC criterion HBR, we observed that 17.2% of patients met the ARC-HBR definitions and their results showed that withdrawing aspirin and continuing ticagrelor monotherapy after 3 months of dual antiplatelet therapy among patients who underwent PCI with a drug-eluting stent resulted in a lower incidence of BARC 2, 3, or 5 bleeding as well as BARC 3 or 5 bleeding consistently among HBR and non-HBR patients.

However, as I said, this analysis provided some additional insights. The most important insights are that HBR patients or into the higher-risk profile realized a significantly larger absolute risk reduction with respect to major BARC 3 or 5 bleeding as compared to non-HBR patients. This is particularly important when we evaluate the effectiveness of a new treatment strategy in terms for instance of number needed to treat and the impact on public health is obviously more important when we evaluate what is the absolute reduction in the risk of a patient rather than the relative reduction in the risk of a patient.

We’ve seen multiple subgroup analyses from TWILIGHT, what other analyses could provide additional clinical insight?

The reason we've run several additional subgroup analyses is because we wanted to focus on patients who are usually underrepresented in clinical trials and they generally tend to be underrepresented because they're at very high risk. In these patients, the level of evidence in support of guideline recommendations is relatively weak. This is the case for HBR patients, diabetic patients, patients with chronic kidney disease, women—all of these groups are largely underrepresented and these were obviously subgroup analyses of particular interest for us.

I would say that there are additional issues to examine from the TWILIGHT trial. I wouldn't name just a specific subgroup of patients, but there are certainly additional issues. An example of one may be examining the total number of bleeding and ischemic events and what are the treatment effects of ticagrelor monotherapy on the overall number of events as compared to a standard time-to-first-event analysis.

Another interesting topic would be the incidence rate of dyspnea among patients treated with ticagrelor. We know that this is reason for ticagrelor discontinuation in about 1 out of 5 patients on ticagrelor. This is, of course, an issue when it comes to patients on ticagrelor monotherapy because if they discontinue ticagrelor because of dyspnea, they don't have background antithrombotic therapy with aspirin. Finally, I would say that another very interesting analysis would be to investigate the tradeoff between ischemic and bleeding events among patients on ticagrelor monotherapy compared ticagrelor plus aspirin and the impact of bleeding and ischemic events on subsequent mortality.



Editor's note: This transcript has been edited for clarity and length. 

TWILIGHT-HBR suggests ticagrelor monotherapy could lower bleeding risk among patients meeting ARC-HBR criteria. Study presenter Davide Cao, MD, offers further perspective on results of the post hoc analysis.

Ticagrelor Monotherapy Reduces Bleeding Events vs DAPT with Aspirin in HBR Patients

A new analysis of the TWILIGHT trial examining the effects of ticagrelor in patients with concomitant diabetes and chronic kidney disease indicates ticagrelor monotherapy reduced risk of clinically relevant and major bleeding with no significant increase in ischemic events compared to ticagrelor plus aspirin.

Presented at the European Society of Cardiology (ESC) Congress 2021, the study outlines the increased risk of bleeding and ischemic outcomes in this patient population as well as the association of ticagrelor monotherapy with a more favorable net benefit than ticagrelor plus aspirin among patients in the trial.

With increasing rates of diabetes and chronic kidney disease in recent years, developing an understanding of best practices in anticoagulation among this patient population has the potential to reduce event rates and improve patient outcomes for a large patient population. With this in mind, TWILIGHT CKD-DM was designed to assess whether a short dual antiplatelet therapy course reduced BARC 2, 3, or 5 bleeding without increasing death, myocardial infarction, or stroke among patients in the trial with concomitant diabetes and chronic kidney disease.

Of the 7119 patients randomized in the TWILIGHT trial, 499 (8.0%) had concomitant diabetes and chronic kidney disease. For the purpose of analysis, patients were stratified according to diabetes status and presence of chronic kidney disease. These groups included 561 patients with chronic kidney disease but without diabetes, 1822 patients with diabetes but without chronic kidney disease, and 3391 patients without either diagnosis.

Upon analysis, results suggested ticagrelor monotherapy was associated with significant. Reductions in BARC 2, 3 or 5 and BARC 3 or 5 bleeding events, irrespective of diabetes and chronic kidney disease status. Investigators pointed out the results of this post hoc analysis are intended to be hypothesis-generating and larger studies are needed to confirm these findings.

out to study investigator Davide Cao, MD, an interventional cardiology at Icahn School of Medicine at Mount Sinai, and that conversation is the subject of this ESC Congress 2021 House Call.

This study, “Ticagrelor monotherapy after percutaneous coronary intervention in patients with concomitant diabetes mellitus and chronic kidney disease: a TWILIGHT substudy,” was presented at ESC Congress 2021.

A post hoc analysis of the TWILIGHT trial suggests the effects of ticagrelor monotherapy observed in the overall trial were consistent, irrespective of diabetes and chronic kidney disease status. 

TWILIGHT Analysis Suggests Ticagrelor Monotherapy Preferable in Concomitant Diabetes and CKD

The influenza (flu) vaccine has been around for a very long time. Even with highly variable efficacy from year to year, the flu vaccine is routinely recommended for everyone prior to the winter months and especially for high-risk patients. Over the years clinicians began to notice that during flu epidemics, more people were dying of cardiovascular causes than during non-epidemic periods.

Until recently, observational studies suggested that the influenza vaccine may have a protective effect with regards to cardiovascular events. These data were subsequently supported by small, randomized trials.

 While flu vaccination is currently recommended for patients with heart disease it is not the standard of care following myocardial infarction. More recently the Influenza Vaccination After Myocardial Infarction (IAMI) study was completed looking at flu vaccination after myocardial infarction (MI) or percutaneous coronary intervention (PCI) in high-risk patients. The results from this pivotal study were presented this month at the 2021 European Society of Cardiology (ESC) Congress.

The IAMI trial was the first randomized, placebo-controlled, double-blinded, multicenter trial to look at the flu vaccine in the setting of acute coronary syndromes (ACS) and MI.

Ole Frobert, MD, PhD, of Orebro University Hospital, Sweden presented the findings at the ESC congress meeting. The results of the trial were exciting to say the least. Frobert and colleagues found that flu vaccination early after an MI or in high-risk coronary heart disease resulted in a lower risk of all-cause death, MI, or stent thrombosis, as well as a lower risk of all-cause and cardiovascular death at 12 months compared with placebo.

“Our findings suggest that influenza vaccination should be considered as part of in-hospital treatment after myocardial infarction,” Frobert states

These results are very promising. The flu vaccines have become ubiquitous across the world with a long track record of safety. With cardiovascular disease continuing to rise worldwide prevention remains a mainstay of cardiovascular medicine. However, the IAMI study suggests that vaccinating patients hospitalized with ACS within 72 hours may dramatically reduce morbidity and mortality after MI.

Frobert and colleagues speculate that the protective effect from flu vaccination in this setting could be from anti-inflammatory effects from the vaccine and or prevention of acute influenza infection which may trigger acute coronary events.

The authors of the study did want to point out that the study was halted during the COVID-19 global pandemic but that the results remain robust with over 2,500 patients enrolled.

 These results underscore the importance of vaccination programs. The general public generally look at vaccines as a preventative measure when it comes to individual infections. However, the global COVID-19 pandemic has brought vaccines into specific relief these days. 

Frobert and colleagues have uncovered an important secondary preventative function of a well-known flu vaccine. While this study gives hope to many cardiologists and patients a war of information currently plagues the scientific community. This fact makes organizations like the ESC more important than ever. The 2021 ESC Congress is just the vehicle we need to disseminate fact through scientific rigor and a global presence. Moving forward, cardiologists can pass this information on to their patients with confidence rooted in strong consensus and pivotal research.

The IAMI study will have a lasting impact on cardiovascular care. Frobert and colleagues hope that the following take-home points will lead to a change in the acute management of myocardial infarction ultimately saving lives:

The flu vaccine saves lives and should be considered as part of 

 treatment after myocardial infarction (MI).

All patients with cardiovascular disease should get their yearly flu shot.

Influenza illness is linked to cardiovascular disease.

Evidence shows that a flu shot could prevent death caused by cardiovascular disease.

https://www.escardio.org/The-ESC/Press-Office/Press-releases/Flu-jab-after-heart-attack-should-become-standard-care

Phrommintikul A, Kuanprasert S, Wongcharoen W, 

. Influenza vaccination reduces cardiovascular events in patients with acute coronary syndrome. 

Frøbert O, Götberg M, Erlinge D, et al. Influenza Vaccination After Myocardial Infarction: A Randomized, Double-Blind, Placebo-Controlled, Multicenter Trial. 

Gregory Weiss, MD, reviews and offers perspective on a study presented at ESC Congress 2021 examining the association between influenza vaccines and improved outcomes in patients with cardiovascular disease.

Influenza Vaccines: Another Jab at Cardiovascular Disease

Although SGLT2 inhibitors have put the ‘flozins’ at centerstage at recent cardiology conferences, a unique newcomer to the group has been making waves since a pair of phase 3 trials were presented at the American Heart Association 2020 Annual Meeting.

A dual SGLT1/2 inhibitor, sotagliflozin made a splash in late 2020 with the SOLOIST-WHF and SCORED trials, which demonstrated the agent provided meaningful benefit in patients with diabetes and chronic kidney disease or heart failure. Despite impressive data from its phase 3 program, sotagliflozin has no existing FDA indications, unlike other SGLT2 inhibitors.

The subject of SLGT1/2 inhibition and its effect on cardiovascular and kidney endpoints was the subject of a late-breaking presentation led by principal investigator of the SOLOIST-WHF and SCORED trials Deepak Bhatt, MD, MPH, executive director of interventional cardiovascular programs at Brigham and Women’s Hospital, at the 

. With an interest in learning more about sotagliflozin and its potential for receiving an FDA indication in the future, we reached to Bhatt for more perspective and that conversation is the subject of this ESC Congress 2021 House Call.


Deepak Bhatt, MD, discusses a presentation he gave at ESC Congress 2021 on SGLT2, 1/2 inhibition and reflects on the potential for sotagliflozin to receive approval from the FDA based on data from SOLOIST-WHF and SCORED. 

The Future of Sotagliflozin With Deepak Bhatt, MD

Results of an open-label study conducted in villages across rural China indicate salt substitutes with reduced sodium levels and increased potassium levels could significantly reduce the 

Titled the Salt Substitute and Stroke Study (SSaSS), results indicate use of the salt substitute was associated with a lower rate of stroke, major adverse cardiovascular events, and death over a 5-year follow-up period, which investigators suggest could have global implications.

“This study provides clear evidence about an intervention that could be taken up very quickly at very low cost. A recent modelling study done for China projected that 365,000 strokes and 461,000 premature deaths could be avoided each year in China if salt substitute was proved to be effective. We have now showed that it is effective, and these are the benefits for China alone. Salt substitution could be used by billions more with even greater benefits,” said principal investigator Professor Bruce Neal, MBChB, PhD, executive director of the George Institute for Global Health in Sydney, Australia,

Despite the understanding of associations between increased levels of dietary sodium consumption and cardiovascular risk, few studies in the past have provided evidence of an effective solution for reducing sodium intake and whether these methods would subsequently reduce cardiovascular risk in these patients. SSaSS was designed as an open-label, cluster-randomized trial conducted in 600 villages in rural areas of 5 provinces in China. The trial enrolled more than 20,000 patients from April 2014-January 2015 and aimed to follow each participant for 5 years.

Patients included in the trial had to have a history of stroke or be at least 60 years of age or older and have hypertension. Villages included in the study were randomized in a 1:1 ratio to the intervention group or a control group. Patients randomized to the intervention group received a substitute that was 75% sodium chloride and 25% potassium chloride by mass and those in the control group continued to use regular salt.

The primary outcome of the trial was stroke. The trial also included multiple secondary outcomes, including a composite of major adverse cardiovascular events and death from any cause, and incidence of clinical hyperkalemia was used as the primary safety outcome.

From the 600 villages, a total of 20,995 patients were enrolled in the trial. Of these 10,504 were assigned to the salt-substitute group and 10,491 were assigned to the regular salt group. The study cohort had a mean age of 65.4 years, 49.5% were female, 72.6% had a history of stroke, and 88.4% had a history of hypertension. The mean duration of follow-up was 4.74 years.

Upon conclusion of the trial, results suggested use of a salt substitute was associated with a lower rate of stroke. Specifically, those randomized to the salt substitute had a stroke rate of 29.14 events per 1000 person-years compared to 33.65 events per 1000 person-years with regular salt (RR, 0.86 [95% CI,0.77-0.96]; 

=.006). Similarly, use of the salt substitute was also associated with lower rates of major adverse cardiovascular events, with an event rate of 49.09 events per 1000 person-years in the substitute group compared to 56.29 per 1000 person-years in the regular salt group (RR, 0.87 [95% CI, 0.87-0.94]; 

Investigators also pointed out a lower rate of death was observed in the salt substitute group, with an event rate of 39.28 per 1000 person-years compared to 44.61 per 1000 person-years in the regular salt group (RR, 0.88 [95% CI, 0.82-0.95]; 

 <.001). Results of a safety analysis suggested the rate of serious adverse events attributable to hyperkalemia was not significantly higher among those receiving salt substitute than those receiving regular salt, with an event rate of 3.35 per 1000 person-years with the salt substitute and 3.30 per 1000 person-years with regular salt (RR, 1.04 [95% CI, 0.80-1.37]; 

“The trial result is particularly exciting because salt substitution is one of the few practical ways of achieving changes in the salt people eat. Other salt reduction interventions have struggled to achieve large and sustained impact,” Neal added, in the aforementioned statement.

For more on the results of SSaSS and their implications on real-world risk reduction, check out this video interview with Neal.

This study was presented as “SSaSS: Salt Substitute and Stroke Study into the effect of salt substitutes on cardiovascular events and death,“ at ESC Congress 2021 and simultaneously published as “

Effect of Salt Substitution on Cardiovascular Events and Death

Data from the Salt Substitute and Stroke Study suggest switching from regular salt to a salt substitute could reduce the risk of stroke by 14% and investigators believe these results can be applied to patient populations across the world. 

Use of Salt Substitute Could Reduce Risk of Stroke, Cardiovascular Events, and Death

Boehringer Ingelheim and Eli Lilly and Company have announced the US Food and Drug Administration (FDA) granted Breakthrough Therapy designation for empagliflozin (Jardiance) as an investigational treatment for adult patients with 

heart failure with preserved ejection fraction (HFpEF).

, the Breakthrough Therapy designation was granted less than a month after empagliflozin received approval for use in patients with heart failure with reduced ejection fraction (HFrEF) and the designation is based on the results of the landmark EMPEROR-Preserved trial, which was presented at the European Society of Cardiology Congress 2021 and simultaneously published in the 

"This Breakthrough Therapy designation underscores the potential of Jardiance to help fill a critical need for a clinically proven treatment for people with this highly prevalent, difficult-to-treat condition," said Mohamed Eid, MD, MPH, MHA, vice president of Clinical Development & Medical Affairs, Cardio-Metabolism & Respiratory Medicine with Boehringer Ingelheim Pharmaceuticals, Inc, in the aforementioned statement. “Following the recent FDA approval of Jardiance for heart failure with reduced ejection fraction, this is another important milestone supporting the potential of Jardiance as the first therapy clinically proven to improve outcomes across the full heart failure spectrum."

 was hailed by sponsors Boehringer Ingelheim and Eli Lilly and Company as the first and only successful trial for HFpEF when the companies announced the trial had met its primary end point in July 2021. A phase 3 trial randomizing patients to empagliflozin 10 mg or placebo therapy in addition to guideline-directed medical therapy, EMPEROR-Preserved enrolled nearly 5988 patients with and without type 2 diabetes, with NYHA class II-IV heart failure, and an ejection fraction greater than 40%. With a median follow-up time of 26.2 months and a composite primary end point of time to first event of cardiovascular death or hospitalization for heart failure, results of the trial suggested use of empagliflozin was associated with a 21% reduction in the primary end point (HR, 0.79; 95% CI, 0.69-0.90; 

Further analysis of trial results indicated this effect was mainly driven by a lower risk of hospitalization (HR, 0.73; 95% CI, 0.61-0.88; 

 <.001), with investigators pointing out the reductions observed for cardiovascular death did not reach statistical significance (HR, 0.91; 95% CI, 0.75-1.09). Additionally, use of empagliflozin was associated with a slower rate of eGFR decline compared to use of placebo therapy (-1.25 vs -2.62 ml/min/1.73m2/year; 

"Given the scarcity of treatment options for this debilitating condition, the benefits demonstrated in the EMPEROR-Preserved trial constituted a major clinical breakthrough," said Jeff Emmick, MD, PhD, vice president, Product Development, Lilly. "Together with our Boehringer Ingelheim partners, we look forward to working closely with the FDA through this accelerated process to potentially bring Jardiance to adults with heart failure with preserved ejection fraction as soon as possible."

In their statement, Boehringer Ingelheim and Eli Lilly and Company noted empagliflozin is currently approved by the FDA for lowering blood sugar along with diet and exercise in adults with type 2 diabetes, reducing the risk of cardiovascular death in adults with type 2 diabetes with known cardiovascular disease, and reducing the risk of cardiovascular death and hospitalization for heart failure in adults with HFrEF.

For more on the results of EMPEROR-Preserved, check out our Q&A with principal investigator Javed Butler, MD, from ESC Congress 2021.

Announced by Boehringer Ingelheim and Eli Lilly and Company on September 9, the Breakthrough Therapy designation for empagliflozin is based on the results of the EMPEROR-Preserved trial. 

FDA Grants Empagliflozin Breakthrough Therapy Designation for HFpEF

: An elderly man is brought to the ED as a code STEMI from home for AMS and SOB. He recently recovered from pneumonia. He is too lethargic to give any meaningful history, but the wife says he has not been having any chest pain or other pain. He has a history of hypertension, treated with benazepril as well as a prior MI.

: Vital signs are normal except for pulse in the 110’s.

Computer Read: Sinus rhythm with first degree AB block, RBBB, Inferior MI, ***ACUTE MI***, QTc 410ms

Our latest cardiology case report from Brady Pregerson, MD, features an elderly man brought to the emergency department as a code STEMI from home for altered mental status and shortness of breath. Can you determine the correct diagnosis?

Cardiology Case Report: Altered Mental Status and Shortness of Breath

A new US Food and Drug Administration (FDA) approval could substantially broaden the utilization of donor hearts for transplantation in the US.

Announced in a statement from TransMedics Group, Inc. on September 7, the FDA has granted premarket approval to the OCS Heart System for the preservation of donor hearts deemed unsuitable for procurement and transplantation at initial evaluation due to limitations of prolonged cold status cardioplegic preservation from donors after brain death.

"The approval of this revolutionary technology marks a critical step forward for heart transplantation," said Jacob Schroder, MD, surgical director of heart transplantation at Duke University Medical Center and the principal investigator for the OCS Heart EXPAND Trial, in the 

. "The OCS Heart System allows surgeons to assess donor heart's viability in real time and minimizes the negative effects of cold storage. This will increase utilization of donor hearts that are rarely used due to limitations of cold storage preservation. By expanding the donor pool of acceptable hearts, the OCS will enable us to better meet the growing demand for heart transplantation in the U.S. and save lives."

A company specializing in technology for portable extracorporeal warm perfusion and assessment of donor organs for transplantation, the OCS Lung System from TransMedics Group received approval from the FDA in June 2019. According to TransMedics Group, the approval for the OCS Heart System is based on the results of the OCS Heart EXPAND Trial and a pair of associated trials.

The OCS Heart EXPAND trial assessed use of the OCS Heart System with unutilized donor hearts not meeting standard acceptance criteria for transplantation. The study enrolled 93 eligible donor hearts with a mean UNOS match run of 66 declines. Of the 93 hearts, 75 were successfully transplanted during the trial, which had a pair of primary effectiveness end points of patient survival at 30 days following transplantation and absence of severe primary heart graft dysfunction in the first 24 hours following transplantation. Results of the study indicated an incidence rate of primary heart graft dysfunction at 24 hours of 10.7% and a 30-day survival rate of 94.7%. Additionally, results indicated a 6-month survival rate for patients included in the study was 88%.

"We are honored and humbled that the OCS Heart System is now the only FDA approved device indicated for ex-vivo perfusion and assessment of both donor hearts and lungs as an alternative to the antiquated cold storage preservation. We take this responsibility very seriously, and we are looking forward to the next phase of commercial activities, the initiation of the OCS Heart Perfusion (OHP) Registry, and potentially expanding our clinical indications in the future,” said Waleed Hassanein, MD, President and Chief Executive Officer of TransMedics Group, 

Announced in a statement from TransMedics Group Inc. on September 7, premarket approval to the OCS Heart System could allow for broader utilization of donor hearts for transplantation in the US. 

FDA Approves OCS Heart System for Hearts from DBD Donors

This article was originally published on 

 report of a trial comparing semaglutide, a glucagon-like peptide-1 receptor agonist (GLP-1 RA), versus tirzepatide, a drug that has both GLP-1a and glucose-dependent insulinotropic polypeptide activity.

 GLP-1 RA’s stimulate insulin secretion during hyperglycemia and decrease glucagon secretion during euglycemia and hypoglycemia.GLP-1 RA’s also decrease gastric emptying thereby decreasing appetite and body weight. Tirzepatide has GLP-1 RA activity, but also stimulates insulin release and decreases glucagon levels during euglycemia and hypoglycemia via its glucose-dependent insulinotropic activity. This dual-action has theoretical advantages. The study compared semaglutide 1 mg SQ weekly, versus tirzepatide 5, 10, or 15 mg SQ weekly. Tirzepatide has not yet been FDA approved.

All 3 tirzepatide doses decreased mean hemoglobin A1c (A1c) by 2.01 to 2.3% versus 1.86% for semaglutide. Bodyweight decreased 1.9 to 5.5 kg more with tirzepatide than with semaglutide over the 40-week study. But this was not a fair comparison because STEP 2 or the Semaglutide Treatment Effect in People with Obesity study used a semaglutide dose of 2.4 mg weekly,

 and higher semaglutide doses probably would have reduced hemoglobin A1c and body weight more.

But here’s the real question. Why is a cardiologist (me) studying an article on new diabetes treatments? I remember similar thoughts about why cardiologists were interested in lipid metabolism when lovastatin was FDA approved in November 1987. And look where cardiologists are now in managing lipids using statins, PCSK9 inhibitors, ezetimibe, and bempedoic acid. Cardiologists, like all clinicians, get interested in problems they can fix easily. Metformin, sodium-glucose transport type 2 inhibitors (SGLT2i), and GLP-1 RAs (as the oral semaglutide, Rybelsus) are now all available orally. Even when using GLP1a’s as injection is not difficult. They are easy to use because they rarely cause hypoglycemia unless administered with insulin or a sulfonylurea. This means they are “smart drugs” in that their glucose-lowering effect dissipates as the glucose levels fall. All reduce A1c and reduce body weight, and the latter effect can make you a hero to your patients!

I’ll bet that our experience with LDL management, that “even lower is even better”, will also ultimately be applied to A1c management. The Fourier Trial demonstrated a 2% absolute risk reduction in cardiovascular events after only 3 years when high-risk coronary patients reduced their median LDL-C from 92 to 30 mg/dl using the PCSK-9 inhibitor, evolucamab.

 I realize that available diabetes trials show no difference in outcomes with A1c’s above or below 7%, but these trials used insulin to achieve the A1c levels, and insulin causes hypoglycemia and has many atherogenic properties. Furthermore, someone with “borderline diabetes” has already lost 50% of his/her insulin-secreting capacity. The Diabetes Prevention Program demonstrated that treating patients with prediabetes, defined as an oral glucose tolerance 2-hour value above 140 mg/dl, but less than 200 mg/dl, decreased the onset of diabetes by 31%.

 Hyperglycemia not only glycosylates hemoglobin, but also glycosylates proteins in the LDL particle making LDL more inflammatory and atherogenic. In the Early ACS Trial, among 879 patients with non-ST segment elevation MIs (NSTEMI), 32.5% had known diabetes, 12.2% had undiagnosed diabetes but fasting glucose values at or above 126 mg/dL or an A1c greater than 6.5%, and 8% had prediabetes diagnosed by a glucose of 110 to 126 mg/dL. 5Only 44.4% had normal glucose metabolism. Prediabetes is dangerous. It leads to diabetes and causes cardiac events along the way.

Maybe it’s time for cardiologists to know more, do more, and be more aggressive about treating diabetes, borderline or otherwise.

Frias JP, Davies MJ, Rosenstock J, et al. Tirzepatide versus Semaglutide Once Weekly in Patients with Type 2 Diabetes. N Engl J Med 2021;385:503-15.

Davies M, Faerch L, Jeppesen OK, et al. Semaglutide 2.4 mg once a week in adults with overweight or obesity, and type 2 diabetes (STEP 2): a randomised, double-blind, double-dummy, placebo-controlled, phase 3 trial. Lancet 2021;397:971-84.

Sabatine MS, Giugliano RP, Keech AC, et al. Evolocumab and Clinical Outcomes in Patients with Cardiovascular Disease. N Engl J Med 2017;376:1713-22.

Knowler WC, Barrett-Connor E, Fowler SE, et al. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med 2002;346:393-403.

Giraldez RR, Clare RM, Lopes RD, et al. Prevalence and clinical outcomes of undiagnosed diabetes mellitus and prediabetes among patients with high-risk non-ST-segment elevation acute coronary syndrome. Am Heart J 2013;165:918,925.e2.

Editorial advisory board member Dr. Paul Thompson reflects on how advances in diabetes management have impacted cardiovascular medicine and why staying abreast of these advances is essential to being a cardiologist in 2021. 

Paul Thompson, MD: Why Cardiologists Need to Be Diabetologists

 reached out to advisory board member Brett Nowlan, MD, a noninvasive cardiologist and board-certified lipidologist at a private practice in Connecticut, to take part in our coverage of the annual meeting. Nowlan’s personal experience provides a unique perspective on data from the ESC’s annual meeting. A practicing cardiologist in the US, Nowlan spent the early portion of his life, including attending medical school, in South Africa. With this additional perspective, Nowlan compiled a list and created a video detailing his picks for the top 5 studies from ESC Congress 2021.


Practical Cardiology editorial advisory board member Brett Nowlan, MD, compiled a top 5 list of studies he thought were noteworthy from ESC Congress 2021 and offers his perspective on why he chose each study. 

FDA Grants Empagliflozin Breakthrough Therapy Designation for HFpEF

Cardiology Case Report: Altered Mental Status and Shortness of Breath

FDA Approves OCS Heart System for Hearts from DBD Donors

Paul Thompson, MD: Why Cardiologists Need to Be Diabetologists

ESC Congress 2021 Expert Perspective: Top 5 Studies With Brett Nowlan, MD