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Late-Breaking Science Presented at AHA20

For this blog dedicated to #AHA20,  I decided to put together a list of majority of American Heart Association (AHA) late-breaking study presentations at the 2020 Virtual AHA meeting from Day 1 to Day 3. So far, the late-breaking studies at AHA have covered a wide range of topics from heart failure, cardiovascular prevention focusing on a statin, newer LDL lowering therapies, Omge-3 fatty acid supplements, to polypills and imaging in women with MINOCA. Day 4 and Day 5 will cover multiple trials on atrial fibrillation, dual SGLT inhibitor, COVID, and Telemedicine.

Day 1

Name Trials Study Population Results Conclusion
GALACTIC HF

cardiac myosin activator Omecamtiv Mecarbil In Chronic Heart Failure with Reduced Ejection Fraction: The Global Approach to Lowering Adverse Cardiac Outcomes Through Improving Contractility In Heart Failure

Inclusion Criteria

Patients 18-85 years of age with CHF and NYHA class II, III, or IV symptoms

LVEF ≤35% and pro-BNP ≥400 pg/ml

 

N= 8256

Follow up= 21.8 months

Mean Age= 65 years

Primary Outcome=

cardiovascular death or CHF event

 

 

Mean LVEF: 27%

ACEi/ARNI  87%

Beta-blocker: 94%

Aldactone 78%

SGLT2iinhibitor: 2.5%

Primary Outcome

37.0% of the omecamtiv mecarbil group compared with 39.1% of the placebo group (p = 0.03).

 

Among patients with HFrEF on GDMT, the selective cardiac myosin activator omecamtiv mecarbil was superior to placebo. It was associated with a reduction in the primary composite outcome; however, no benefit in outcomes of CV Death, all cause death, or change in KCCQ total symptoms score.

 

AFFIRM-AHF

Ferric Carboxymaltose In Iron Deficient Patients Admitted for Acute Heart Failure

 

Inclusion Criteria

Hospitalization for CHF, and iron deficiency anemia- Serum ferritin <100 ng/ml or serum ferritin 100-299 ng/ml and transferrin saturation <20%, LVEF <50%

 

N= 1132

Follow up= 52 weeks

Mean Age= 71 yrs

Primary Outcome=

total heart failure hospitalizations and cardiovascular death

 

Primary Outcome

52.5% of the ferric carboxymaltose group compared with 67.6% of the placebo group (p = 0.059).

 

Among patients with CHF with iron deficiency, intravenous ferric carboxymaltose was associated with a numerical reduction in total heart failure hospitalizations and cardiovascular death.

 

VITAL

Omega-3 Fatty Acid and Vitamin D Supplementation In The Primary Prevention Of CV or cancer events

Inclusion Criteria

Men >50 years or women >55 years without any known known cardiovascular disease or cancer

N= 25,871

Follow up= 5.3 yrs

Mean Age= 67.1 yrs

Primary Outcome= CV death, nonfatal myocardial infarction (MI), or stroke

 

Primary Outcome

The primary CV outcome of CV death, nonfatal myocardial infarction (MI), or stroke, for vitamin D3 vs. placebo, was 3.1% vs. 3.2%, hazard ratio (HR) 0.97, 95% confidence interval (CI) 0.85-1.1, p = 0.69.

 

The results of this trial indicate that supplementation with either n–3 fatty acid at a dose of 1 g/day or vitamin D3 at a dose of 2000 IU/day was not effective in prevention of CV or cancer events

 

TIPS-3

A Polypill For Primary Prevention Of Cardiovascular Disease In Intermediate Risk People: Results Of The International Polycap Study

 

Inclusion Criteria

Target CV disease (CVD) risk: >1.0%/year

Men ≥50 years and women ≥55 years with an INTERHEART Risk Score (IHRS) of ≥10, or men and women ≥65 years with an IHRS of ≥5

 

N= 5713

Follow up= 4.6 yrs

Mean Age= 63.9 yrs

Primary Outcome= CV death, myocardial infarction (MI), stroke, heart failure (HF), cardiac arrest, revascularization

Primary Outcome

Polypill vs placebo

4.4% vs. 5.5% (hazard ratio [HR] 0.79

 

 

Once-daily polypill (fixed-dose combination of simvastatin, atenolol, ramipril, HCTZ) was superior to placebo in reducing systolic BP, LDL-C, and nonfatal CV events at approximately 5 years among intermediate CV risk patients, mostly in Southeast Asia

 

Day 2-3

 

Name Trials Topic of Interest Hypothesis Results
ALPHEUS

Ticagrelor Versus Clopidogrel In Elective Percutaneous Coronary Intervention

 

Inclusion Criteria

Patients undergoing nonemergent PCI

At least one high-risk criteria: age >75 years, renal insufficiency, diabetes, body mass index >30 kg/m2, ACS in last year, LVEF <40% and/or prior episode of heart failure, multivessel disease, need for multiple stents, left main, bifurcation or complex PCI

N= 1910

Follow up= 30 days

Mean Age= 66 yrs

Primary Outcome=

Primary Outcome

MI ype 4a, 4b (stent thrombosis) or major myocardial injury at 48 hours

 

Among patients undergoing elective and planned PCI, ticagrelor loading was not superior to clopidogrel loading. Ticagrelor failed to reduce the incidence of periprocedural myocardial infarction. Major bleeding was also similar between the groups, although an increase in nuisance or minor bleeding with ticagrelor.

 

HARP-MINOCA

Coronary OCT and Cardiac MRI to Determine Underlying Causes of Minoca in Women

 

Inclusion Criteria

prospective, multicenter, international, observational study, women with a clinical diagnosis of MI were enrolled

N= 170

145 with OCT;

116 with CMR

 

46% pts with culprit lesion on OCT.

Abnormal CMR in 74% pts, ischemic pattern in 53%, nonischemic pattern in 20.7%,

 

Multi-modality imaging with coronary OCT and CMR identified potential mechanisms in 84.5% of women with a diagnosis of MINOCA, three-quarters of which were ischemic and one-quarter of which were non-ischemic, alternate diagnoses to MI

 

RIVER 

Rivaroxaban Versus Warfarin In Patients With Bioprosthetic Mitral Valves And Atrial Fibrillation Or Flutter: Primary Results From The RIVER Randomized Trial

 

 

Inclusion Criteria

≥18 years with bioprosthetic MV + AF/AFl without any contraindication to the AC

 

N= 1005

Follow up= 1 yr

Mean Age= 59.3 yrs

Primary Outcome= death, major adverse cardiac events, major bleeding

Mean CHAD2vASC score= 2.6, HAS-Bled Score =1.6, 18% <3 months from MV surgery, 31% >5 yrs

Primary Outcome

The mean time to the primary outcome for rivaroxaban vs. warfarin was 347.5 vs. 340.1 days (p < 0.0001 for noninferiority, p = 0.1 for superiority).

 

 

rivaroxaban is noninferior to warfarin for prevention of thromboembolic events among patients with AF/AFL and a bioprosthetic mitral valve. All strokes were lower with rivaroxaban.

 

STRENGTH

Cardiovascular Outcomes with Omega-3 Carboxylic Acids (Epanova) In Patients With High Vascular Risk And Atherogenic Dyslipidemia

 

Inclusion Criteria

Statin-treated patients ≥18 yrs with or at high risk for cardiovascular disease and TG 180-500 mg/dl, HDL <42 mg/dl (men) or 47 mg/dl (women)

 

N= 13,078

Follow up= 42M

Mean Age= 63Yrs

Omega-3 CA Dose: 4 g/day

Primary Outcome=

cardiovascular death, MI, CVA, coronary revascularization, or hospitalization for unstable angina

 

Primary Outcome met in

12.0% of the omega-3 CA group compared with 12.2% of the placebo group (p = 0.84).

 

Among statin-treated patients with dyslipidemia and high cardiovascular risk, omega-3 CA was not superior compared to placebo.

 

OMEMI

Effects Of N-3 Fatty Acid Supplements on Clinical Outcome After Myocardial Infarction In The Elderly: Results Of The Omemi Trial

 

 

 

 

 

 

 

Inclusion Criteria

Patients 70-82 years of age

With Myocardial infarction 2-8 weeks prior to randomization

 

N=1,027

Follow up= 24M

Mean Age= 74Yrs

PUFA dose: 930g EPA+ 660g DHA

Primary Outcome=

all-cause death, nonfatal MI, revascularization, CVA, or hospitalization for heart failure

 

Primary Outcome

21.0% of the PUFA group compared with 19.8% of the placebo group (p = 0.62).

 

Among elderly patients with recent myocardial infarction, PUFA was not beneficial.

 

SAMSON

A Three-arm N-of-1 Trial with Statin, Placebo And Tablet Free Periods, To Verify Side Effects And Identify Their Cause

Inclusion Criteria

Patients with any adverse event within 2 weeks of starting a previous statin

N= 60

Follow up= 12 months

Primary Outcome:

placebo symptoms divided by statin symptoms= termed nocebo ratio

 

Nocebo ratio was 0.90- meaning 90% of symptoms elicited by placebo tablets Patients with previous adverse event to statin, 90% of the symptoms could be attributed to the nocebo effect
 

EVINACUMAB

The Efficacy and Safety Of angiopoietin-like 3 (ANGPTL3) inhibitor

-Evinacumab In Patients With Refractory Hypercholesterolemia

 

Inclusion Criteria

Diagnosis of primary hypercholesterolemia (either heterozygous familial hypercholesterolemia [HeFH] or non-HeFH) with clinical atherosclerotic cardiovascular disease (ASCVD) with statin (± ezetimibe) at the maximum tolerated dose, PCSK9 inhibitor for at least 8 weeks with LDL-C ≥70 mg/dl or 100 mg/dl with or without clinical ASCVD, respectively

 

N= 160 (SC), 106 (IV)

Follow up= 16 weeks

Mean Age= 54 years

Primary Outcome=

Primary Outcome

percent change in LDL-C from baseline

 

Phase II trial

small and underpowered for clinical outcomes

 

Evinacumab is superior to placebo in reducing LDL-C among patients with refractory hypercholesterolemia despite being on statins, ezetimibe, and PCSK9 inhibitors (baseline LDL-C: ~150 mg/dl)

 

SHORT-DAPT

One Month Dual Antiplatelet Therapy Followed By Aspirin Monotherapy After Drug Eluting Stent Implantation

Inclusion Criteria

Patients ≥19 years of age

undergoing PCI for stable or unstable ischemic heart disease

AMI excluded

 

N= 3020

Follow up= 12 months

Mean Age= 67 yrs

Primary Outcome=

cardiac death, nonfatal myocardial infarction, target-vessel revascularization, stroke, or major bleeding at 12 months

 

Primary Outcome

5.9% of the 1-month DAPT group compared with 6.5% of the 6- to 12-month DAPT group (p for noninferiority < 0.001; p for superiority = 0.48).

 

Among patients undergoing PCI for stable or unstable coronary artery disease, 1 month of DAPT was noninferior to 6-12 months of DAPT

 

 

“The views, opinions and positions expressed within this blog are those of the author(s) alone and do not represent those of the American Heart Association. The accuracy, completeness and validity of any statements made within this article are not guaranteed. We accept no liability for any errors, omissions or representations. The copyright of this content belongs to the author and any liability with regards to infringement of intellectual property rights remains with them. The Early Career Voice blog is not intended to provide medical advice or treatment. Only your healthcare provider can provide that. The American Heart Association recommends that you consult your healthcare provider regarding your personal health matters. If you think you are having a heart attack, stroke or another emergency, please call 911 immediately.”

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Deep Dive in HARP Trial

“Coronary Optical Coherence Tomography (OCT) and Cardiac Magnetic Resonance (CMR) Imaging to Determine Underlying Causes of MINOCA in Women” was presented on day 2 of AHA by Dr. Harmony R. Reynolds, MD during the late-breaking trial session. The trial is also simultaneously published in Circulation(1).

MINOCA (Myocardial Infarction with Nonobstructive Coronary Arteries) is quite a contemporary diagnosis. The term was initially coined by Dr. Beltram in an editorial, in response to a Swedish paper that described the cardiac magnetic resonance imaging findings in patients that had presented with myocardial infarction however did not have any significant coronary artery disease on cardiac catheterization(2).  MINOCA affects 6-15% of the patients presenting with MI and disproportionately affects women(1). In 2017, The European Society of Cardiology developed the first international position article on MINOCA and proposed the following MINOCA criteria: (a) AMI criteria as defined by the “Third Universal Definition of Myocardial Infarction”; (b) nonobstructive coronary arteries as per angiographic guidelines, with no lesions ≥50% in a major epicardial vessel; and (c) no other clinically overt specific cause that can serve an alternative cause for the acute presentation (3). Fundamental to the definition of MINOCA is the diagnosis of AMI with an elevated cardiac biomarker, typically a cardiac troponin >99th percentile with a rise or fall in the level on serial assessment. Although elevated troponin levels are indicative of myocyte injury with the release of this intracellular protein into the systemic circulation, the process is not disease-specific and can result from either ischemic or nonischemic mechanisms. MINOCA thus, becomes a working diagnosis. The role of CMR is crucial to establish the etiology in these patients. In 2019, an AHA statement paper on MINOCA, presented a stepwise diagnostic approach to evaluate the etiology(4). This paper proposed the use of coronary imaging after the CMR diagnosis of MI was established to further evaluate coronary etiology in absence of significant atherosclerotic disease. Earlier this year, ESC NSTEMI guidelines suggested class IB indication to perform CMR in patients with MINOCA, recommended use of traffic light diagnostic algorithm, and mentioned the use of OCT for the detection of unrecognized causes at coronary angiography, especially in suspected cases of thrombus, plaque rupture or erosion or SCAD(5).

 

The goal of the Women’s Heart Attack Research Program (HARP) was to implement an imaging protocol to evaluate the underlying causes of MINOCA, in order to guide clinical practice.

They enrolled 301 women presenting with a diagnosis of MI before the coronary angiography was done, in a prospective manner.  170 patients were diagnosed with MINOCA, out of which 145 had OCT imaging while 116 underwent CMR. The study established the cause of MINOCA in 84.5% of the women who underwent multi-modality imaging (98/116), compared with either OCT or CMR alone. OCT was able to identify culprit lesion in 46% of the patient while 74% of the patients had abnormal CMR. 53% of the patients had late gadolinium enhancement or edema in the coronary territory and ischemic pattern while almost 21% of patients were found to have myocarditis, stress-induced cardiomyopathy, or other nonischemic cardiomyopathies. Almost 15.5% of patients had no identifiable mechanism by OCT or CMR. Half of the patients with ischemic patterns on CMR didn’t have any culprit lesion on OCT. Alternative mechanisms of MI like coronary spasm or thromboembolism leading to MI are suggested in those patients. The study however didn’t perform any provocative testing to induce spasm. Similarly, 40% of the patients with normal CMR had culprit lesion on the OCT. This is lower compared to the latest CMR MINOCA studies where a diagnosis was established up to 87% of the cases(6). Whether these findings are due to shorter duration of ischemic injury or due to longer time between diagnosis of MI and CMR or maybe due to overestimation of the prevalence of abnormalities on OCT given the blinded core laboratory review, remains the point of discussion.

The authors conclude that the Multi-modality imaging with coronary OCT and CMR identified potential mechanisms in 84.5% of women with a diagnosis of MINOCA in this observational study.  The study was not designed to test the outcomes and further research is needed to establish if the OCT improves outcomes in patients with a working diagnosis of MINOCA. I am not certain if the trial will impact any OCT recommendation class in future guidelines given the absence of the outcome data and observational nature of the trial. The trial also suggested simultaneous use of OCT and CMR in cases of MINOCA however perhaps establishing the diagnosis MI with CMR, excluding myocarditis and nonischemic cardiomyopathy, in cases with a working diagnosis of MINOCA remains the key. As suggested by the diagnostic algorithm in the guidelines, once the MI diagnosis is established, OCT may be used to evaluate coronary mechanisms, however till the outcome data with OCT is available, this will probably depend on the preference of the clinical cardiologist and local availability. Given more than half of the patients with ischemic pattern on CMR had no culprit lesion on OCT in this trial, we may need more data before recommending regular simultaneous use of OCT and CMR.

 

References:

  1. Coronary Optical Coherence Tomography and Cardiac Magnetic Resonance Imaging to Determine Underlying Causes of MINOCA in Women | Circulation [Internet]. [cited 2020 Nov 15]. Available from: https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.120.052008
  2. Beltrame JF. Assessing patients with myocardial infarction and nonobstructed coronary arteries (MINOCA). Journal of Internal Medicine. 2013;273(2):182–5.
  3. Agewall S, Beltrame JF, Reynolds HR, Niessner A, Rosano G, Caforio ALP, et al. ESC working group position paper on myocardial infarction with non-obstructive coronary arteries. Eur Heart J. 2017 Jan 14;38(3):143–53.
  4. Contemporary Diagnosis and Management of Patients With Myocardial Infarction in the Absence of Obstructive Coronary Artery Disease: A Scientific Statement From the American Heart Association | Circulation [Internet]. [cited 2020 Nov 15]. Available from: https://www.ahajournals.org/doi/full/10.1161/CIR.0000000000000670
  5. 2020 ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation | European Heart Journal | Oxford Academic [Internet]. [cited 2020 Nov 15]. Available from: https://academic.oup.com/eurheartj/advance-article/doi/10.1093/eurheartj/ehaa575/5898842
  6. Troponin-positive chest pain with unobstructed coronary arteries: incremental diagnostic value of cardiovascular magnetic resonance imaging | European Heart Journal – Cardiovascular Imaging | Oxford Academic [Internet]. [cited 2020 Nov 15]. Available from: https://academic.oup.com/ehjcimaging/article/17/10/1146/2197117

“The views, opinions and positions expressed within this blog are those of the author(s) alone and do not represent those of the American Heart Association. The accuracy, completeness and validity of any statements made within this article are not guaranteed. We accept no liability for any errors, omissions or representations. The copyright of this content belongs to the author and any liability with regards to infringement of intellectual property rights remains with them. The Early Career Voice blog is not intended to provide medical advice or treatment. Only your healthcare provider can provide that. The American Heart Association recommends that you consult your healthcare provider regarding your personal health matters. If you think you are having a heart attack, stroke or another emergency, please call 911 immediately.”