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.

Articles

AHA 2020

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.

Videos

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.

Check out this AHA 2020 video with John McMurray, MD, examining differences in HFpEF among men and women.

Of the 168 patients who had MINOCA, 21 had contraindications to OCT. Among the 147 who underwent OCT, 145 had adequate OCT for analysis and 116 underwent CMR (median 6 days from MI; IQR, 3-9).

When using OCT and cardiac MRI data, investigators were able to determine cause for MINOCA in 84% of patients. Imaging data determined 74 experienced myocardial infarction—the other diagnoses included myocarditis (17), Takotsubo Syndrome (n=4), and non-ischemic cardiomyopathy (n=3). OCT imaging tests led to the identification of a definite or possible culprit lesion in 46.7% of women (95% CI, 38.0-54.7%) with OCT imaging data and cardiac CMR was abnormal in 86 of the 116 women with available data (95% CI, 65.0-81.6%).

“Our findings demonstrate that even if the angiogram does not show substantial artery blockage, when women have symptoms and blood test findings consistent with a heart attack, it is likely a true heart attack and not heart inflammation,” Reynolds said. “Additional imaging tests can get to the root of the problem and help health care professionals make an accurate heart attack diagnosis for women and to ensure they receive timely treatment.”

Coronary Oct And Cardiac Mri To Determine Underlying Causes Of Minoca In Women

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

HARP-MINOCA Outlines Benefit of OCT, Cardiac CMR When Diagnosing Heart Attacks

Results of the RIVER trial suggest rivaroxaban (Xarelto) could be used instead of warfarin in patients with 

Presented at the American Heart Association (AHA) Scientific Sessions 2020, data from the trial indicated rivaroxaban 20 mg once daily was noninferior to warfarin for a primary endpoint of death, major cardiovascular events, and major bleeding—with a nonsignificant trend favoring rivaroxaban for most of the study’s secondary endpoints, including incidence of stroke.

“This is the largest trial designed to evaluate the safety and efficacy of direct oral anticoagulants in patients with bioprosthetic mitral valves and atrial fibrillation or flutter. Earlier trials of direct oral anticoagulants vs. warfarin for atrial fibrillation or flutter together included fewer than 200 patients with bioprosthetic mitral valves,” said lead investigator Otavio Berwanger, MD, PhD, a cardiologist and the director of the Research Institute Hcor at Hospital de Coracao in Sao Paulo, Brazil, in a 

With data suggesting off-label use of rivaroxaban and other direct oral anticoagulants in patients with bioprosthetic mitral valves who have atrial fibrillation or flutter, investigators designed the RIVER trial to further explore the potential safety and efficacy in this setting. Designed as a pragmatic, multicenter, open-label, randomized, noninferiority trial, RIVER was conducted across 49 sites and enrolled 1,005 patients.

Patients were considered eligible for inclusion in the trial at any time at least 48 hours after undergoing mitral valve surgery. Patients were excluded based on contraindications to either study drug, being at an extremely high risk of bleeding, transient atrial fibrillation caused by surgery, or if they received mechanical valves.

Patients included in the study were randomized in 1:1 ratio to receive either rivaroxaban or warfarin and followed for 12 months. Investigators pointed out patients with renal dysfunction were given 15 mg rivaroxaban and warfarin doses were titrated to maintain a target international normalized ratio (INR) between 2.0-3.0. The primary endpoint of the study was a composite of all-cause mortality, stroke, transit ischemic attack (TIA), major bleeding, valve thrombosis, systemic embolism not related to the central nervous system, or hospitalization for heart failure. Individual components of the primary endpoint, bleeding events, and venous thromboembolism as secondary endpoints for the trial.

In total, 505 patients were randomized to warfarin and 500 to rivaroxaban. The median age of study participants was 59.3 years, 60.4% were women, 60.7% had hypertension, 38.8% had heart failure, and 15.4% had a history of stroke or TIA. Additionally, investigates pointed out 95.6% of patients had atrial fibrillation and 4.3% had atrial flutter.

During the follow-up period, the mean time until a primary-outcome event occurred was 347.5 days in the rivaroxaban group and 340.1 days in the warfarin group (RMST difference: 7.4 days; 95% CI, -1.4 to 16.3; 

=.10 for superiority). Deaths from cardiovascular causes or thromboembolic events occurred among 3.4% of patients in the rivaroxaban group and in 5.1% of patients in the warfarin group (HR, 0.65; 95% CI, 0.35-1.20). Further analysis suggested stroke occurred in 0.6% of the rivaroxaban group and 2.4% in the warfarin group (HR, 0.25; 95% CI, 0.07-0.88).

Safety analyses indicated major bleeding occurred among 1.4% of patients in the rivaroxaban group and 2.6% of patients in the warfarin group (HR, 0.54; 95% CI, 0.21-1.35) and revealed a similar frequency not other serious adverse events among the study groups.

“The results from the RIVER Trial are consistent with previous research, including ROCKET and other pivotal trials of DOACs, and can inform clinical practice for patients with bioprosthetic mitral valves,” Berwanger added. “For a subgroup of patients with a mitral valve replacement within the last three months, rivaroxaban was statistically and clinically superior to warfarin.”

Rivaroxaban in Patients with Atrial Fibrillation and a Bioprosthetic Mitral Valve,

” was presented at AHA 2020 and simultaneously published in the 

Results of the RIVER trial suggest rivaroxaban was noninferior to warfarin for the study's composite endpoint of all-cause mortality, major cardiovascular events, and major bleeding.

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