late breaking science

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Late-Breaking Highlights: “To Screen Or Not To Screen And Then What? Studies of Detection and Treatment of AF”

Zain Ul Abideen Asad, MD, MBBS

This was an exciting session at AHA 2020 which focused on clinical trials of screening, monitoring, and early intervention in Atrial Fibrillation (AF). Screening of AF is a controversial topic and for individuals >65 years, current AHA guidelines give a Grade 2a recommendation for screening whereas USPSTF guidelines suggest that there is insufficient evidence for screening. In this article, I will be discussing studies that addressed AF screening and their implications on clinical practice with Dr. Stavros Stavrakis who is an electrophysiologist and Associate Professor at the University of Oklahoma Health Sciences Center, Oklahoma City.

Question: What are the important goals when we think about screening for AF?

Dr. Stavrakis: The important goals for screening in AF are to establish a diagnosis of new AF in patients at high risk of stroke so they can be anticoagulated, ultimately reducing the risk of stroke.

There were 3 important trials that addressed AF screening in different patient populations.

SEARCH AF

  • In patients who have undergone cardiac surgery and have a higher risk of stroke but no history of pre-operative or pre-discharge AF, what is the risk of developing AF/Aflutter in the sub-acute post discharge period?
  • 336 post-cardiac surgery patients (median CHADS2Vasc Score 4) but with little or no AF in the post-operative period (<24 hours of AF but no intent to anticoagulate at discharge) were randomized to continuous cardiac rhythm monitoring vs usual care during the sub-acute post discharge period.
  • In the enhanced cardiac rhythm monitoring group 19.6% participants developed AF/Aflutter as compared with 1.7% in the usual care group with an absolute rate difference 17.9% (p<0.001, NNS=6).

Question: What are the implications of this trial on clinical practice?

Dr. Stavrakis: Risk of POAF, although peaking at 48-72hours post-op, is not confined to the index hospitalization, continuous monitoring for POAF can identify AF in a significant proportion of patients (20%) that may need treatment with anticoagulation. Whether anticoagulation improves outcomes in these patients, remains to be determined.

VITAL-AF Trial

  • Among older adults (age>65) presenting to primary care visits, does point of care rhythm assessment with a single lead ECG result in increased diagnosis of AF?
  • 30,722 patients were randomized to screening vs control.
  • Screening did not significantly affect AF diagnosis in the overall study sample (1.74% vs 1.60%, p=0.33)
  • Increased likelihood of AF diagnosis at primary care encounter (p<0.02)
  • Effectiveness of screening varied by age with effective screening in age>85 (risk difference 1.88%, NNS=53)
  • Overall no difference in the initiation of anticoagulation

Question: What are the implications of this trial on clinical practice?

Dr. Stavrakis: There are 2 important implications from this trial.

  1. Screening everyone age>65 for AF at a single time point is not an efficient way to detect AF, especially if the usual care is very good in detecting AF by pulse palpation or BP device.Screening at age>85 may be more effective than usual care to identify silent AF, but it is uncertain if it changes management or outcomes

mSTOPS

  • Can screening for AF by wearing an ECG patch improve clinical outcomes at 3-years?
  • 1718 actively monitored participants vs 3371 matched observational controls with analysis of 3-year clinical outcomes.
  • Mean duration of follow-up was 29 months
  • 11.4% of actively monitored patients developed AF vs 7.3% of matched controls
  • No difference in anticoagulation prescription between both arms (45.2% vs 44%, p=0.84)
  • 3-year Primary combined end point (death, stroke, systemic embolism or MI) for entire cohort was 4.5 vs 5.5 per 100 person-year (HR 0.79, p<0.01) and for diagnosed AF patients it was 8.4 vs 13.8 per 100 person-year (HR 0.53, p<0.01).

Question: What are the implications of this trial on clinical practice?

Dr. Stavrakis: Clinical outcomes can be improved with AF screening provided these patients are followed up for extended periods of time. However, this was not a randomized trial and unknown confounders may have influenced the outcome.

Question: What are 3 important unanswered questions pertinent to screening of AF?

  1. What is the impact of AF screening on clinical outcomes? Large studies, adequately powered to detect clinical outcomes, are underway (SAFER, HEARTLINE, GUARD-AF).
  2. What is the optimal screening intensity that identifies AF which would benefit from anticoagulation?
  3. What is the minimum AF burden that, if identified with screening, would benefit from anticoagulation?

“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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Late-Breaking Science Presented at AHA20

Purvi Parwani, MBBS, MPH

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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Can Fish Oil Supplements Help Your Heart? Consumer Discretion is Advised

Huan Wang, PhD

The health benefits of fish oil, particularly omega-3 long-chain polyunsaturated fatty acids (n-3 LC-PUFAs) have been studied for decades. The key discoveries regarding the beneficial effects of n-3 LC-PUFAs include anti-inflammation, lowering blood lipid levels, anti-thrombotic effects, and possibly anti-arrhythmia (Mason, Libby, and Bhatt 2020). The market size of fish oil supplements expands rapidly in recent years and is estimated to reach USD 4.5 billion by 2027 (REPORTS AND DATA 2020). In many European nations, omega-3-acid ethyl esters have been prescribed to patients to reduce blood lipid levels for at least a decade and they also obtained US FDA approval in 2004 (Bays et al. 2008). However, not all news is encouraging. The findings of anti-arrhythmia effects of fish oil are mixed, with some trials demonstrating beneficial outcomes (Fig 1) and others finding no significant effects (Mozaffarian and Wu 2011; Reiffel and McDonald 2006).

Fig1. Physiological effects of n-3 PUFA that might influence cardiovascular risk.

The results of REDUCE-IT clinical trial published in 2019 promised a bright future for cardiovascular risk reduction using omega-3 fatty acids (Bhatt et al. 2019). In AHA 2020 late-breaking science session: “Fish Oil, Fancy Drugs, and Frustrations in Lipid Management”, Drs. A Michael Lincoff, Are Annesoenn Kalstad and Alberico Catapano presented compelling evidence on surprising neutral effects with omega-3 carboxylic acids supplement in two clinical trials. These controversial results provide an interesting argument on whether or not to take fish oil supplements for cardiovascular health protection.

Dr. Lincoff presented recent results about the effects of high-dose omega-3 fatty acids from the STRENGTH clinical trial (Nicholls et al. 2020). Despite moderate improvements in the blood lipid levels, patients with omega-3 supplementation have significantly increased risks of atrial fibrillation. The net outcome of omega-3 fatty acid supplementation is not beneficial. One of the possible explanations for this controversial result is using corn oil as a control condition instead of mineral oil–the control treatment in REDUCE-IT trial. Mineral oil treatment caused adverse effects, and corn oil had neutral effects on patients. Dr. Kalstad shared results from another clinical trial which showed similar findings (the OMEMI clinical trial) (Kalstad et al., n.d.). The overall effects of omega-3 fatty acids were neutral with an increased risk of atrial fibrillation. To bring together what we have learned, a summary was presented by Dr. Catapano to further evaluated the STRENGTH and OMEMI clinical trials. He thoughtfully discussed the discrepancies in REDUCE-IT, STRENGTH, and OMEMI trials, and provided several explanations such as the biochemical nature of DHA and EPA, different control conditions, and treatment dosage discrepancies.

Regardless of the discrepancies between STRENGTH and OMEMI trials, one thing is common, the increased risk of atrial fibrillation. So, if you are elderly with high cardiovascular risk, please think twice and monitor your response closely when taking fish oil as a dietary supplement. The frustrating results from STRENGTH and OMEMI trials don’t necessarily negate the beneficial effects in other aspects of the physiological benefits of fish oil (Fig 1) (Mozaffarian and Wu 2011). More research studies are needed in the future to better understand the effects and mechanisms of fish oil supplementation.

Reference

REPORTS AND DATA. 2020. Omega-3 Market To Reach USD 4.50 Billion By 2027 | CAGR: 7.2% | Reports And Data. Aug 10. https://www.prnewswire.com/news-releases/omega-3-market-to-reach-usd-4-50-billion-by-2027–cagr-7-2–reports-and-data-301109147.html.

Bays, Harold E., Ann P. Tighe, Richard Sadovsky, and Michael H. Davidson. 2008. “Prescription Omega-3 Fatty Acids and Their Lipid Effects: Physiologic Mechanisms of Action and Clinical Implications.” Expert Review of Cardiovascular Therapy. https://doi.org/10.1586/14779072.6.3.391.

Bhatt, Deepak L., P. Gabriel Steg, Michael Miller, Eliot A. Brinton, Terry A. Jacobson, Steven B. Ketchum, Ralph T. Doyle, et al. 2019. “Cardiovascular Risk Reduction with Icosapent Ethyl for Hypertriglyceridemia.” New England Journal of Medicine. https://doi.org/10.1056/nejmoa1812792.

Kalstad, Are Annesønn, Peder Langeland Myhre, Kristian Laake, Sjur Hansen Tveit, Erik Berg Schmidt, Pal Smith, Dennis Winston Trygve Nilsen, et al. n.d. “Effects of N-3 Fatty Acid Supplements in Elderly Patients after Myocardial Infarction: A Randomized Controlled Trial.” Circulation 0 (0). https://doi.org/10.1161/CIRCULATIONAHA.120.052209.

Mason, R. Preston, Peter Libby, and Deepak L. Bhatt. 2020. “Emerging Mechanisms of Cardiovascular Protection for the Omega-3 Fatty Acid Eicosapentaenoic Acid.” Arteriosclerosis, Thrombosis, and Vascular Biology. https://doi.org/10.1161/ATVBAHA.119.313286.

Mozaffarian, Dariush, and Jason H.Y. Wu. 2011. “Omega-3 Fatty Acids and Cardiovascular Disease: Effects on Risk Factors, Molecular Pathways, and Clinical Events.” Journal of the American College of Cardiology. https://doi.org/10.1016/j.jacc.2011.06.063.

Nicholls, Stephen J, A Michael Lincoff, Michelle Garcia, Dianna Bash, Christie M Ballantyne, Philip J Barter, Michael H Davidson, et al. 2020. “Effect of High-Dose Omega-3 Fatty Acids vs Corn Oil on Major Adverse Cardiovascular Events in Patients at High Cardiovascular Risk: The STRENGTH Randomized Clinical Trial.” JAMA, November. https://doi.org/10.1001/jama.2020.22258.

Reiffel, James A., and Arline McDonald. 2006. “Antiarrhythmic Effects of Omega-3 Fatty Acids.” American Journal of Cardiology. https://doi.org/10.1016/j.amjcard.2005.12.027.

 

“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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Bending the Curve for CV Disease- Precision or PolyPill?

Mary Branch, MD, MS

Source: https://www.phri.ca/

Drs. Yusuf and Pais from the Population Health Research Institute in Ontario, Canada presented data from the International Polycap Study (TIPS)-3 study[1] as part of the Late-Breaking Science Session: Bending the Curve for CV Disease-Precision or PolyPill? at the AHA20 Scientific Sessions. The aim of this study was to try to simplify primary prevention via a ‘polypill’ (Polycap) for not only cardiovascular disease (CVD) but also conditions with similar risk profiles, such as breast cancer and osteoporosis. The polypill contains 3 blood pressure medications (hydrochlorothiazide (25mg), atenolol (100 mg), ramipril (10mg)) and a statin (simvastatin (40 mg). They are searching for a ‘magic bullet’ if you will, to reduce these chronic diseases with a high burden in the U.S and around the world. Precision medicine can be effective but is costly. The use of a polypill can help to reduce the curve of disease burden or at least shift it towards reducing the number of high cardiovascular risk people worldwide.

Source: Joseph et al. The International Polycap Study-3 (TIPS-3): Design, baseline characteristics and challenges in conduct. Am Heart J. 2018 206:72-79

This study enrolled 5,713 middle aged participants from 10 different countries (Including India, Tanzania, and Tunisia). With a 2x2x2 factorial design, randomized controlled trial investigators aimed to assess the effectiveness of PolyCap the ‘Polypill’.  Participants were eligible for the study if they did not have prior heart disease or stroke. Participants were excluded if they had any contraindications to the study medications, low and symptomatic  hypotension, history of malignancy, and inability to attend follow-up. There were three treatment arms. The participants were randomized to the polypill vs placebo. In addition, participants were also randomized to receive aspirin (75 mg) and vitamin D (60,000 IU monthly) each vs. placebo. The primary outcome was major cardiovascular disease (CVD) (CV death, non-fatal stroke, non-fatal MI), plus heart failure, resuscitated and cardiac arrest, or revascularization with evidence of ischemia in participants taking Polycap versus placebo. For the aspirin arm, the primary outcome was composite CV events ( CV death, MI or stroke) and cancer. For vitamin D arm, the primary outcome was risk of fractures in participants taking Vitamin D. The data presented at AHA2020 Scientific Sessions was for the Polypill with and without aspirin alone vs. placebo. This was an intention to treat analysis. Investigators also conducted a sensitivity analysis for those who were not able to adhere to medications and identified outcomes at 30 days in the active and placebo groups.

Source: Joseph et al. The International Polycap Study-3 (TIPS-3): Design, baseline characteristics and challenges in conduct. Am Heart J. 2018 206:72-79

After a follow-up time up to 5 years, the investigators enrolled a cohort of 53% women with intermediate CVD risk based on the IH (INTERHEART) risk score (1.5 % per year risk of CVD). For participants taking the Polypill vs. placebo, there was a significant mean reduction in systolic blood pressure by approximately 5 mm Hg and LDL-C by approximately 19 mg/dL. There was a 21% reduction in the primary outcome; however, overall mortality was not significantly different. The greatest reduction was seen with revascularization with a 60% reduction compared to the placebo. There was a reduction in cancer outcomes as well, but not significantly; this is likely related to low events. The bleeding risk profile was low. With the combination of aspirin and the Polypill, there was a 31 % risk reduction compared to placebo, aspirin alone, and the Polypill alone ( compared to 14% with aspirin vs. placebo alone)  in the composite primary outcome but no overall mortality benefit. This was mainly driven by a reduction in stroke. CVD death and cancer were significantly reduced by 30% compared to placebo. There was also a reduction with systolic blood pressure and LDL-C as seen with the Polypill alone. Aspirin alone did not show any difference with major/minor bleeding or GI bleeding likely related to having a run-in period and a lower dose of asa (75 mg). In both cases, the heart failure rate was higher in both groups but this was not significant with a wide confidence interval with low event. It is important to note that lifestyle modification teaching was also instituted and the reduction in outcomes is therefore contributed to both the medication and education.  One main issue was adherence to the medications (just two pills) up to 43%! This was in part due to COVID19 by the end of the study.  Per the sensitivity analysis, the outcomes of those with some adherence (<30 days) were still significantly lower than the placebo. Taking something for even a short period of time is better than nothing.

The authors highlight the significant limitation of non-adherence which can create a selection bias in the data. However,  if only half eligible people adhere to this regimen, 3-5 million CVD events can be avoided each year globally. They note that the challenge of adherence lies in social determinants of health, which have a great impact on CVD outcomes. More needs to be done to understand cost-effective ways to ‘bend the CVD curve’ by identifying effective implementation programs (including telehealth) to distribute this combination of medications.

References:

Joseph et al. The International Polycap Study-3 (TIPS-3): Design, baseline characteristics and challenges in conduct. Am Heart J. 2018 206:72-79

 
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Late Breaking Trials: Scientific Sessions – Chicago 2018

Fawaz Alenezi, MD, MSc


Cardiovascular risk assessment is a process, not just a calculation! This year, I was very pleased to attend the 2018 guidelines for cholesterol management at the American Heart Association (AHA) Scientific Sessions – Chicago 2018. I highly recommend that you check the guidelines as there are many changes that may impact your daily practice. Here, I’m summarizing the late breaking trials that were presented at the last AHA and encouraging you to join us at the next AHA Scientific Sessions meeting – Philadelphia 2019.

 

Critical Questions in Cardiovascular Prevention:

The VITamin D and OmegA-3 TriaL (VITAL): Principal Results for Vitamin D and Omega-3 Fatty Acid Supplementation in the Primary Prevention of Cardiovascular Disease and Cancer.

  • RESULTS: Major CVD events and total invasive cancer not significantly reduced by Omega-3 or vitamin D3. Omega-3 significantly reduced total MI, especially in African Americans and those with lower baseline fish intake.

The Primary Results of the REDUCE-IT Trial.

  • RESULTS: High-dose icosapent ethyl vs. placebo in at-risk patients significantly reduced the composite CVD endpoint: risk of CV death, MI, stroke, coronary revascularization, and unstable angina.

Ezetimibe in Prevention of Cerebro- and Cardiovascular Events in Middle- to High-Risk, Elderly (75 Years Old or Over) Patients with Elevated LDL-Cholesterol: A Multicenter, Randomized, Controlled, Open-Label Trial.

  • RESULTS: Ezetimibe monotherapy + diet counselling vs diet counselling alone for primary prevention (elevated LDL-C; no history of CAD) in an over-75 y/o Japanese population significantly prevented cerebral and cardiovascular events.

Cost-Effectiveness of Alirocumab Based on Evidence from a Large Multinational Outcome Trial: The ODYSSEY OUTCOMES Economics Study.

  • RESULTS: For the patients in the ODYSSEY OUTCOMES trial (post-ACS and LDL-C ≥100 mg/dL), alirocumab was found to be cost effective.

 

Novel Approaches to CV Prevention:

The Dapagliflozin Effect on Cardiovascular Events (DECLARE)-TIMI 58 Trial.

  • RESULTS: Dapagliflozin compared to placebo in patients with T2DM was safe, reduced the composite of CV death or hospitalization for heart failure, but did not impact MACE.

The Cardiovascular Inflammation Reduction Trial (CIRT): Low Dose Methotrexate for the Prevention of Atherosclerotic Events.

  • RESULTS: Low dose methotrexate compared to placebo in patients with prior MI or multivessel CVD and either type 2 diabetes or metabolic syndrome, did not reduce inflammatory markers, and CV events weren’t lower than placebo.

Safety and Efficacy of AKCEA-APO(a)-LRx to Lower Lipoprotein(a) Levels in Patients with Established Cardiovascular Disease: A Phase 2 Dose-Ranging Trial.

  • RESULTS: Dose-dependent lowering of Lp(a) levels by AKCEA-APO(a)-LRx were seen in patients with pre-existing CV disease or PAD in this phase 2 trial

 

Harnessing Technology and Improving Systems for Global Health:

Effects of a Multifaceted Intervention to Narrow the Evidence-Based Gap in the Treatment of High Cardiovascular Risk Patients: The BRIDGE CV Prevention Cluster Randomized Trial.

  • RESULTS: Adherence to evidence-based therapies (antiplatelets, statins and ACE inhibitors) for high CV risk Brazilian patients was improved with use of a multifaceted quality improvement educational intervention vs routine practice.

Alert-Based Computerized Decision Support to Increase Anticoagulation Prescription Prevents Stroke and Myocardial Infarction in High-Risk Hospitalized Patients with Atrial Fibrillation: A Randomized, Controlled Trial.

  • RESULTS: Alert-based computerized decision support in high-risk hospitalized AF patients increased prescribing of anticoagulation for stroke prevention and reduced major adverse cardiovascular events, MI and stroke.

Efficacy of Electronic Clinical Decision Support in Atrial Fibrillation: Results of the Integrated Management Program Advancing Community Treatment of Atrial Fibrillation (IMPACT-AF).

  • RESULTS: An online, evidence-based computer decision support system did not significantly affect the number of patients experiencing the unplanned cardiovascular hospitalization and/or AF-related emergency room visit at 12 months.

 

Preserving Brain & Heart in Acute Care Cardiology:

Pre-Hospital Resuscitation Intra-Arrest Cooling Effectiveness Survival Study – The Princess Trial.

  • RESULTS: Survival with good neurologic outcome 90 days after cardiac arrest was not statistically different for pre-hospital trans-nasal evaporative intra-arrest cooling compared to standard care.

Early Goal-Directed Hemodynamic Optimization in Comatose Survivors After Out-of-Hospital Cardiac Arrest: The Neuroprotect Trial.

  • RESULTS: A higher mean arterial pressure (MAP) in the ICU during the first 36 hours after cardiac arrest improved cerebral perfusion and oxygenation but did not decrease anoxic brain damage or improve functional outcome compared to the lower MAP target of 65mmHg.

A Randomized, Double Blind, Placebo-Controlled, Parallel Group, Multicenter Clinical Trial of Low-Dose Adjunctive Alteplase During Primary PCI (T-TIME).

  • RESULTS: Compared to placebo, microvascular obstruction was not different for low-dose alteplase during primary PCI for acute STEMI.

Optimal Timing of Intervention in Non St-Elevation Acute Coronary Syndromes Without Pretreatment.

  • RESULTS: In not pre-treated intermediate and high-risk NSTEACS patients, a very early (<2 hours) invasive intervention strategy compared to a delayed one (≥12-72 hours) was highly significant for reduction in CV death or recurrent ischemic events @ 30 days.

Mechanically Unloading the Left Ventricular and Delaying Reperfusion in Patients with Anterior ST-Segment Elevation Myocardial Infarction: The Door to Unload Pilot Trial.

  • RESULTS: In patients with anterior STEMI, mechanical unloading of the left ventricle followed by either immediate vs delayed reperfusion found no difference in MACCE between the two groups and no increase in 30-day infarct size in the delayed group.

 

Hot News in HF:

Angiotensin Receptor-Neprilysin Inhibition in Patients Hospitalized with Acute Decompensated Heart Failure: Primary Results of the PIONEER-HF Randomized Controlled Trial.

  • RESULTS: This comparison of sacubitril/valsartan to enalapril in patients hospitalized with HFrEF found that sacubitril/valsartan resulted in significantly more reduction in NT-proBNP levels.

Withdrawal of Pharmacological Heart Failure Therapy in Recovered Dilated Cardiomyopathy – A Randomised Controlled Trial (TRED-HF).

  • RESULTS: Withdrawal of therapy in ‘recovered’ dilated cardiomyopathy patients resulted in relapse for 40% compared to 0% relapse for those who remained on therapy. “Recovered’ patents are in remission.

Effects of Rivaroxaban on Thrombotic Events in Heart Failure Patients with Coronary Disease and Sinus Rhythm.

  • RESULTS: Low-dose rivaroxaban use in HF significantly reduced the risk for thromboembolic events in the COMMANDER HF trial population.

EMPA-HEART Cardiolink-6 Trial: A Randomized Trial Evaluating the Effect of Empagliflozin on Left Ventricular Structure, Function and Biomarkers in People with Type 2 Diabetes (T2D) and Coronary Heart Disease.

  • RESULTS: In patients with T2DM and stable CAD, LV mass was significantly reduced by empagliflozin compared to placebo.

 

Coronary Revascularization:

Endoscopic Vein Harvest for Coronary Bypass Surgery in a Randomized Multicenter Trial with Long-Term Follow-Up.

  • RESULTS: Late findings for endoscopic vs open SVG harvesting for CABG found MACE rates were similar @ 2.7 years’ follow-up.

Long-Term Survival Following Multivessel Revascularization in Patients with Diabetes: The FREEDOM Follow-On Study.

  • RESULTS: At the 8-year FREEDOM trial follow-up, CABG showed lower rate of all-cause mortality over 8-year follow-up compared to PCI in patients with diabetes and multivessel coronary artery disease.

TiCAB: A Randomized, Double-Blind Study of Ticagrelor versus Aspirin in Patients Undergoing Coronary Bypass Surgery.

  • RESULTS: In patients having CABG, major CV events and bleeding rates were not significantly reduced with ticagrelor monotherapy compared to aspirin.

Ten-Year Clinical Outcomes After Coronary Drug-Eluting Stents with Biodegradable or Permanent Polymer Coating: Results from the Randomized ISAR-TEST 4 Trial.

  • RESULTS: 10-year CV outcomes were superior for three limus-eluting stents with different polymer coatings compared to early-generation stents.

Intramyocardial Injection of Mesenchymal Precursor Cells in Left Ventricular Assist Device Recipients: Impact on Myocardial Recovery and Morbidity.

  • RESULTS: Successful temporary LVAD weans over 6 months and 1-year mortality were similar for intramyocardial mesenchymal precursor cell injection vs sham injection.

 
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Beyond Embargoes: A Vision for Future Scientific Sessions

Nosheen Reza, MD

At my first two AHA Scientific Sessions, I sat in the Main Event Hall, shoulder-to-shoulder with my co-fellows, eagerly awaiting the results of the Late Breaking Clinical Trials and guideline updates. I remember whispers cascading across the room after the presentation of NEAT-HFpEF in 2015 and the hundreds of cellphones in the air snapping pictures of the hypertension guideline release in 2017. This year as an AHA Early Career Blogger, I learned the results of the Late Breaking Clinical Trials with other news writers at embargoed media briefings. These intimate press conferences are routinely offered to health care journalists at major medical meetings and by top medical journals. Members of the media receive early access to manuscripts and data and discuss trial findings with investigators and outside experts with the understanding that nothing should be published until after trial results are publicly released. Generally, media pieces are published very soon after the embargo is lifted. At my first embargoed briefing, I heard one reporter’s question that has spurred me to imagine a new, more inclusive future for scientific meetings.

On Sunday of Sessions, I joined other health care reporters for the VITAL and REDUCE-IT presentations. In VITAL, 1 gram/day of omega-3 fatty acid supplementation (containing 460 mg of eicosapentaenoic acid [EPA] and 380 mg of docosahexaenoic acid [DHA]) was not effective for primary prevention of cardiovascular events in healthy middle-aged adults. In REDUCE-IT, icosapent ethyl (a purified EPA) at a dose of 2 grams twice daily reduced cardiovascular events among patients at risk for or with known cardiovascular disease and with high triglycerides already on statin therapy with good LDL-C control. After both trials were presented, one news writer probed the primary investigators’ thoughts on communicating these results to patients. The reporter wondered if the trials could be interpreted as sending mixed messages about the cardiovascular benefits of omega-3 fatty acids to the general public. Both trials’ primary investigators acknowledged this concern and systematically reviewed the differences in drug composition, patient populations, and study goals that, in their estimation, led to the outcomes. Multiple panelists implored the journalists to integrate these differences into their stories with hopes that consumers and potential patients would be able to understand the distinctions on their own.

After the briefing, I walked to the Main Event Hall to re-experience the Late Breaking Clinical Trials and thought about how we translate these breakthroughs, frequently announced at scientific meetings, to the public and our patients. Recent data suggest that the use of social media at cardiovascular conferences, a key approach to broadcasting late-breaking scientific developments, is rapidly growing. At these meetings, physicians comprise the largest group of Tweeters and compose nearly half of all tweets.1 Identifying the full scope of our social media audience, though, is more elusive. Ensuring veracity in scientific communication has become progressively challenging as the attitudes and tools to perpetuate misinformation have spread. We know that across multiple information domains, false news spreads faster, farther, and deeper than the truth.2 Just this week, Dictionary.com chose “misinformation” as the 2018 word of the year.3 Clinicians and scientists are now especially vulnerable to this insidious erosion of public trust.

How do we combat the propagation of falsehood while encouraging this new democratization of science? I have thought about how the importance of trust was so admirably exemplified in a recent study of blood pressure reduction in black barbershops.4 What if we could leverage our meetings to spread science to where our patients are and with trusted people delivering the message? The AHA has recognized this opportunity and does have programs in place, like “Students at Sessions”, to share Scientific Sessions with non-medical communities.5 Can we imagine a future state of Scientific Sessions where internationally recognized clinicians and scientists deliver a talk at a barbershop or civic center in the host city, where community leaders are invited to participate in panels and plenaries, where large scale cardiovascular risk screenings happen just outside our conference center doors?

The 2019 Scientific Sessions will be held in my current home base of Philadelphia, Pennsylvania. I am looking forward to learning the results of the next round of Late Breaking Clinical Trials and guideline updates in the Main Event Hall, but next year, I hope to sit shoulder-to-shoulder not only with my cardiology colleagues, but with my fellow citizens, community leaders, and patients.

 

References:

  1. Tanoue MT, Chatterjee D, Nguyen HL, et al. Tweeting the Meeting: Rapid Growth in the Use of Social Media at Major Cardiovascular Scientific Sessions From 2014-2016. Circ Cardiovasc Qual Outcomes. 2018;11:e005018.
  2. Vosoughi S, Roy D, Aral S. The spread of true and false news online. Science. 2018;359:1146–1151. doi: 10.1126/science.aap9559.
  3. Italie, Leanne. “Dictionary.com Chooses ‘Misinformation’ as Word of the Year.” Associated Press, 26 Nov. 2018, https://www.apnews.com/e4b3b7b395644d019d1a0a0ed5868b10.
  4. Victor RG, Lynch K, Li N, et al. A Cluster-Randomized Trial of Blood-Pressure Reduction in Black Barbershops. N Engl J Med. 2018;378(14):1291-1301.
  5. “High schoolers enjoy peek into world of cardiovascular science.” American Heart Association News. 21 Nov. 2017. https://newsarchive.heart.org/high-schoolers-enjoy-peek-into-world-of-cardiovascular-science/.

 
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Yoga CaRe: When Evidence-Based Science Meets Ancient Wisdom

Abhishek Sharma, MD

Yoga can be vaguely defined as group of ‘mind-body’ exercises. Though exact timing remains debatable, origin of yoga can be traced back to more than 3,000 years ago when it was first mentioned in ancient Indian text ‘Rigveda’. Yoga is among one of six fundamental ‘Darshanas’ of Hindu philosophy. Various yoga practices were integral part of Indian sages’ routine, who taught and propagate various yogic practices across ancient India.

In western society, yogic practices involving ‘Asanas’ (stretching/body posture), ‘Pranayama’ (breathing exercise), and Meditation have become popular as mean of reducing stress and improving physical well-being.  Several small studies have reported beneficial effects of yoga in primary and secondary prevention of cardiovascular disease (CVD) [1-3]. Yoga based cardiac rehabilitation program post coronary artery bypass graft surgery has been reported to be associated with improvement in left ventricle function, lipid profile, stress reduction and quality of life [1, 2]. However, studies reported beneficial effects of yoga have been limited by small sample size, lack of adequate control, and non-uniform methodologies. Thus, utility of yoga based rehabilitation program in patients with pre-existing CVD remains uncertain.

Against this background, group of Indian physicians conducted a multi-center randomized controlled trial, to evaluate effectiveness of yoga-based cardiac rehab (yoga-CaRe) in patients with acute myocardial infarction. Dr. Dorairaj Prabhakaran from Center for Chronic Disease Control (New Delhi, India) presented the results of this study in a late-breaking science session at the American Heart Association 2018 Scientific Sessions. Study randomized 3,959 patients with acute MI patients from 24 Indian centers to 14 weeks of either Yoga-CaRe or enhanced standard care (ESC). Patients in Yoga-CaRe group underwent 13 sessions of yoga (3 health rejuvenating exercises, 15 postures, 5 breathing techniques & 5 meditative techniques) under trained yoga instructor guidance. ‘Asanas’ (body posture) in Yoga-CaRe group were carefully selected to avoid significant tachycardia.  ESC was comprised of 3 educational sessions (before discharge from the hospital and subsequently at weeks 5 and 12) and printed leaflet delivered by nurse or another member of cardiac care team either individually or in groups to avoid contamination. At 42-month follow up, compared to ESC, patients in Yoga-CaRe had numerically fewer composite endpoint events (death, nonfatal MI, nonfatal stroke, or emergency cardiovascular hospitalization) in the intention-to-treat analysis; however this difference was not statistically significant. The secondary endpoint of self-rated quality of life, and rate of patient return to pre-infarct daily activities were better in Yoga-CaRe group at three months. As per Dr. Prabhakaran ‘.. it (yoga) improve quality of life and made patient return to pre-infarct activities as quickly as possible….wherever people adhere to yoga i.e they attend more than 10 sessions there was reduction in composite end point particularly in death..’

Despite been a class I recommendation cardiac rehabilitation remains highly underutilized in post MI patients.  Situation is even worse in underdeveloped countries where structured cardiac rehabilitation post MI is almost nonexistent due to limited resources. In this context, results of this study are very relevant as yoga is relatively inexpensive and can be delivered by trained instructor to group of patients without further straining already overburden health care system. As pointed out by Dr. Prabhakaran ‘Yoga is feasible, and it can be ambitiously scaled up in term of cardiac rehabilitation..’. This could have far reaching benefits in low- and middle-income countries with limited health staff and resources, and high CVD burden.

However, due to lack of standardized physical exercise component in control arm of Yoga-CaRe trial, it remains unclear if yoga offers any additional benefits over traditional exercise performed for equal duration. Further, Yoga-CaRe enrolled relatively younger patients (mean age ~53yr) and predominately males (>85%). Thus, potential role of yoga in post MI elderly and females patients remains unexplored. Future, large-scale studies addressing these limitations and evaluating yoga based cardiac rehab in other CVD like heart failure would be useful in testing utility of these age old ‘mind-body’ exercises in modern world.

 

References:

  1. Raghuram N, Parachuri VR, Swarnagowri MV et al. Yoga based cardiac rehabilitation after coronary artery bypass surgery: one-year results on LVEF, lipid profile and psychological states–a randomized controlled study. Indian Heart J. 2014 Sep-Oct;66(5):490-502.
  2. Amaravathi E, Ramarao NH, Raghuram N et al. Yoga-Based Postoperative Cardiac Rehabilitation Program for Improving Quality of Life and Stress Levels: Fifth-Year Follow-up through a Randomized Controlled Trial. Int J Yoga. 2018 Jan-Apr;11(1):44-52.
  3. Yeung A, Kiat H, Denniss AR, Cheema BS et al. Randomised controlled trial of a 12 week yoga intervention on negative effective states, cardiovascular and cognitive function in post-cardiac rehabilitation patients. BMC Complement Altern Med. 2014 Oct 24;14:411.
  4. Prabhakaran D, et al “Effectiveness of a yoga-based cardiac rehabilitation (Yoga-CaRe) program: a multi-centre randomised controlled trial of patients with acute myocardial infarction from India” AHA 2018.