Highlights from the first ever virtual American College of Cardiology World Congress of Cardiology 2020 (ACC.20/WCC)

I would like to begin with expressing my gratitude and appreciation for healthcare workers around the world caring for patients in need and all their efforts to overcome the COVID-19 pandemic.

As lives around the globe are moving online, cardiovascular professionals from more than 135 countries took advantage of the vital science and education that made up ACC.20/WCC Virtual. I want to congratulate Program Chair Dr Andrew M. Kates and the organizing committee for creating a virtual experience that delivered cutting edge science, emerging technologies, and novel educational formats directly to cardiovascular clinicians, scientists, and other key stakeholders worldwide. The virtual meeting was free of charge for all participants from 28 to 30 March, and unlimited online access for 90 days after the meeting is available.

While the ACC.20/WCC meeting went virtual, the original conference location in Chicago, McCormick Place, was converted into Illinois’ first field hospital to handle 3000 COVID-19 patients. ACC President Dr Richard J. Kovacs said in his opening remarks: ‘The ACC.20/WCC Virtual meeting is an opportunity for all of us to connect as a global community and emphasize the fact that none of us are in this crisis alone’.

The kick-off of ACC.20/WCC Virtual on Saturday was the first Late-Breaking Clinical Trial Session featuring the VICTORIA trial testing vericiguat an oral soluble guanylate cyclase (sGC) stimulator in patients with heart failure with reduced ejection fraction (HFrEF).1 The trial met its primary endpoint and showed that vericiguat vs. placebo was able to reduce cardiovascular death or hospitalization for HFrEF with a hazard ratio, 0.90 (0.82–0.98; P = 0.02). However, the benefit was really driven by reduction in hospitalization rather than cardiovascular (CV)- or all-cause mortality. CV mortality was numerically lower, but this did not reach statistically significance. The incidence for symptomatic hypotension and syncope were numerically but not statistically higher in the treatment group. Vericiguat emerges as yet another medicine to reduce heart failure hospitalization with a modest effect, and it remains to be seen how this will impact the treatment landscape of HFrEF in light of recent advances with sacubitril/valsartan, SGLT2 inhibitors, or GLP-1 receptor agonists. Manipulating the sGC pathway is a novel and potentially important pathway in HFrEF.2

The ACC.20/WCC meeting was the big virtual stage for several studies evaluating the efficacy of direct oral anticoagulants (DOAC) in different clinical scenarios, including the VOYAGER PAD,3 COMPASS,4 PRONOMOS,5 AUGUSTUS,6 and Caravaggio Study.7 I want to highlight three of these studies starting with the COMPASS and COMPASS Diabetes sub-analysis. COMPASS showed that rivaroxaban plus aspirin was associated with fewer adverse atherosclerotic cardiovascular disease (ASCVD) events, but more major bleeding events compared to aspirin alone in patients with stable ASCVD. The COMPASS diabetes sub-analysis provided further insight that the combination of aspirin 100 mg daily plus rivaroxaban 2.5 mg twice daily provided a similar relative degree of benefit on ASCVD endpoints compared to patients without diabetes. However, given the significantly higher baseline risk of diabetics, the absolute benefit appeared greater in those with diabetes, including a three-fold larger reduction in all-cause mortality. Similar to the parent study, overall bleeding risk was increased in the rivaroxaban/aspirin group, however, not in fatal- or intracranial-bleeding.

The second DOAC highlight was a secondary analysis from the previously reported, practice changing AUGUSTUS trial,6 which studied the risk of increased bleeding and benefit of reduction in ischaemic events with apixaban vs. warfarin and aspirin vs. placebo in patients with atrial fibrillation and a recent acute coronary syndrome (ACS) and/or percutaneous coronary intervention (PCI). This secondary analysis now suggested the use of aspirin for up to 30 days results in an equal balance between an increase in significant bleeding and reduction in severe ischaemic events. The take home message from this study was that in selected patients with a high risk for recurring ischaemic events and low-bleeding risk, triple therapy for 1 month followed by a P2Y12 inhibitor and apixaban was a reasonable and safe strategy.

The results from the Caravaggio study were widely anticipated in the vascular community.7 The Caravaggio study assessed whether oral apixaban was non-inferior to subcutaneous low molecular weight heparin (dalteparin) for the treatment of acute proximal deep vein thrombosis and/or pulmonary embolism in patients with active or previously treated cancer (excluding brain malignancies or metastasis). The results showed overall non-inferiority for the apixaban strategy and the P-value for superiority was marginal at 0.08. These results are clinically important and likely practice changing to simplify lives for cancer patients.

A second highlight of the ACC.20/WCC meeting was the results on dual anti-platelet (DAPT) therapy after PCI from the TICO8 and TWILIGHT-COMPLEX9 studies. First on stage the TICO trial provided evidence that ticagrelor monotherapy after 3 months of DAPT was superior at preventing ischaemia and bleeding after PCI for ACS. Followed by the TWILIGHT-COMPLEX results which indicated in patients requiring multiple drug-eluting stents for complex CAD and at high ischaemic or bleeding risk, that short-duration (3 months) DAPT followed by ticagrelor monotherapy for 1-year resulted in less bleeding events compared with a strategy of longer-duration DAPT (12 months). The comparison of ischaemic rates met criteria for non-inferiority. Both studies highlight that ticagrelor monotherapy is an emerging strategy, especially for patients with increased bleeding risk, after a short duration of DAPT. However, neither of these trials addressed if aspirin instead of ticagrelor monotherapy in the 3- to 12-month period would be equally effective.

Switching gears, the Spyral HTN-OFF MED PIVOTAL trial aimed to evaluate renal denervation via a transcatheter approach compared with sham among patients with uncontrolled hypertension not on antihypertensive therapy.10 Overall, this was a positive study with a significant reduction in ambulatory and office blood pressure readings in the renal denervation group. One important caveat to the findings was that in the sham group more patients were started on anti-hypertensive therapy during the follow-up period compared to the intervention group which may have underestimated the effect of the treatment. This was a nice validation of renal denervation being a safe procedure in the short trial follow-up period (3 months) and effective in lowering blood pressure. The follow-up study, SPYRAL HTN-ON MED, will shed more light on the clinical applicability of these findings.

Finally, the REDUCE-IT EPA,11 secondary analysis of the REDUCE-IT study, gave us more insight on the mechanism of eicosapentaenoic acid (EPA) reducing cardiovascular events among patients with high triglyceride levels and either known ASCVD or those at high risk for developing it. The results show that the higher the EPA serum levels, the lower the rates of the different cardiovascular events/deaths and even total mortality. The lead author, Dr Deepak L. Bhatt from Brigham and Women’s Hospital in Boston commented: ‘Changes in triglycerides levels and other cardiovascular risk markers, including LDL cholesterol, HDL cholesterol, apolipoprotein B, and C-reactive protein, appear to be responsible for a significantly lesser portion of the overall observed benefit’. The results of this secondary analysis suggest that we may be seeing the statin story written all over again for EPA.

Cardiovascular Research Onlife will be releasing expert clinical commentaries on many of the study results announced at this virtual meeting in the upcoming months, check our homepage regularly for updates: https://academic.oup.com/cardiovascres/pages/cvr_onlife_latest

Last but not least, I want to highlight the Distinguished Scientist (Basic Domain Award) which was awarded to Dr Andrew L. Wit for his significant contributions in the areas of cellular and clinical electrophysiology of arrhythmias. His work in the field provided important insight on the mechanisms of arrhythmias caused by cardiac ischaemia and infarction.12

In summary, during the first ever virtual ACC.20/WCC meeting, important results in all fields of cardiovascular medicine and research were presented on the virtual stage, while several randomized clinical trials reported breakthrough results with the potential of changing clinical guidelines regarding the management of heart failure, ASCVD, venous thromboembolism, and hypertension. The important clinical trial messages included the potential for vericiguat in HFrEF, that ticagrelor monotherapy is an emerging strategy after a short duration of DAPT post-PCI and the significance of higher EPA concentrations reducing ASCVD events.

Conflict of interest: none declared.

Funding

T.M.L. is supported by an American Heart Association Career Development Award (19CDA34760040) and a Pilot Project award from the NIH National Institute on Aging, Johns Hopkins Older Americans Independence Center (P30AG021334).

References

Armstrong

Pieske

Anstrom

Ezekowitz

Hernandez

Butler

Lam

CSP

Ponikowski

Voors

Jia

McNulty

Patel

Roessig

Koglin

O’Connor

Group

VS.

Vericiguat in patients with heart failure and reduced ejection fraction

N Engl J Med

2020

;doi: 10.1056/NEJMoa1915928.

Hausenloy

Garcia-Dorado

Botker

Davidson

Downey

Engel

Jennings

Lecour

Leor

Madonna

Ovize

Perrino

Prunier

Schulz

Sluijter

JPG

Van Laake

Vinten-Johansen

Yellon

Ytrehus

Heusch

Ferdinandy

Novel targets and future strategies for acute cardioprotection: Position Paper of the European Society of Cardiology Working Group on Cellular Biology of the Heart

Cardiovasc Res

2017

;

113

564

–

585

Bonaca

Bauersachs

Anand

Debus

Nehler

Patel

Fanelli

Capell

Diao

Jaeger

Hess

Pap

Kittelson

Gudz

Matyas

Krievins

Diaz

Brodmann

Muehlhofer

Haskell

Berkowitz

Hiatt

WR.

Rivaroxaban in peripheral artery disease after revascularization

N Engl J Med

2020

;doi: 10.1056/NEJMoa2000052.

Bhatt

Eikelboom

Connolly

Steg

Anand

Verma

Branch

KRH

Probstfield

Bosch

Shestakovska

Szarek

Maggioni

Widimsky

Avezum

Diaz

Lewis

Berkowitz

Fox

KAA

Ryden

Yusuf

; COMPASS Steering Committee and Investigators.

The role of combination antiplatelet and anticoagulation therapy in diabetes and cardiovascular disease: insights from the COMPASS trial

Circulation

2020

;doi: 10.1161/CIRCULATIONAHA.120.046448.

Samama

Laporte

Rosencher

Girard

Llau

Mouret

Fisher

Martinez-Martin

Duverger

Deygas

Presles

Cucherat

Mismetti

Investigators

Rivaroxaban or enoxaparin in nonmajor orthopedic surgery

N Engl J Med

2020

;doi: 10.1056/NEJMoa1913808.

Alexander

Wojdyla

Vora

Thomas

Granger

Goodman

Aronson

Windecker

Mehran

Lopes

RD.

The risk/benefit tradeoff of antithrombotic therapy in patients with atrial fibrillation early and late after an acute coronary syndrome or percutaneous coronary intervention: insights from AUGUSTUS

Circulation

2020

;doi: 10.1161/CIRCULATIONAHA.120.046534.

Agnelli

Becattini

Meyer

Munoz

Huisman

Connors

Cohen

Bauersachs

Brenner

Torbicki

Sueiro

Lambert

Gussoni

Campanini

Fontanella

Vescovo

Verso

Caravaggio

Apixaban for the treatment of venous thromboembolism associated with cancer

N Engl J Med

2020

;doi: 10.1056/NEJMoa1915103.

Kim

BK.

Ticagrelor with or without aspirin in acute coronary syndrome after PCI – TICO. American College of Cardiology Virtual Annual Scientific Session Together With World Congress of Cardiology (ACC 2020/WCC), 30 March

2020

. https://www.acc.org/latest-in-cardiology/clinical-trials/2020/03/27/ 22/47/tico.

Dangas

Baber

Sharma

Giustino

Mehta

Cohen

Angiolillo

Sartori

Chandiramani

Briguori

Dudek

Escaned

Huber

Collier

Kornowski

Kunadian

Kaul

Oldroyd

Sardella

Shlofmitz

Witzenbichler

Ya-Ling

Pocock

Gibson

Mehran

Ticagrelor with aspirin or alone after complex PCI: the TWILIGHT-COMPLEX analysis

J Am Coll Cardiol

2020

;

27172

Böhm

Kario

Kandzari

Mahfoud

Weber

Schmieder

Tsioufis

Pocock

Konstantinidis

Choi

East

Lee

Ewen

Cohen

Wilensky

Devireddy

Lea

Schmid

Weil

Agdirlioglu

Reedus

Jefferson

Reyes

D’Souza

Sharp

ASP

Sharif

Fahy

DeBruin

Cohen

Brar

Townsend

Akarca

Allaqaband

Andrikou

Aoki

Arnold

Aronow

Asami

Bachinsky

Barton

Bass

Batson

Bell

Bertolet

Bewarder

Bihlmaier

Binner

Bloom

Blossom

Brar

Brown

Burke

Butler

Calhoun

Campbell

Carroll

Chapman

Chasen

Cheng

S-C

Chia

Choksi

Cohen

Connolly

Contreras

Cusack

Dangas

David

Davies

Dederer

Denker

Desch

Didangelos

Dienemann

Dimitriadis

Dorval

J-F

Estess

Fan

Fengler

Ferguson

Fudim

Fuster

Garcia

Garton

Gessler

Ghali

Gummadi

Gupta

Gutierrez

Hardesty

Hartung

Haught

Haun

Hays

Helmreich

Hill

Hopper

Horiuchi

Hoshide

Howard

Ikeda

Jan

Jauhar

Jay

Johnson

Johnston

Jones

Jung

Kalos

Kanitkar

Kannenkeril

Kasiakogias

Kazziha

Keene

Khitha

Kikushima

Kobayashi

Komiyama

Komori

Kotter

Kouparanis

Krasnow

Kulenthiran

Kumar

L’Allier

Laney

Lauder

Lavoie

Lerche

Linesky

Little

Lomboy

Lucic

Lurz

Lynch

Mansukhani

McDuffie

McGrath

McLaurin

Meade

Meraj

Millenaar

Moore

Mori

Munch

Murphy

Murray

Nanjundappa

Ninomiya

Oba

O’Connor

Ogata

Ogoyama

Onsrud

Ott

Padaliya

Pagidipati

Patel

Petteinidou

Porr

Rao

Razi

Regan

Remetz

Rizik

Robison

Rommel

K-P

Rosseel

Rothstein

Rough

Saavedra

Saba

Schwartz

Selcer

Sen

Sennott

Shadman

Shah

Shemin

Shimizu

Shimpo

Shishehbor

Shun-Shin

Sierra

Singh

Sirajeldin

Skeik

Soliman

Statton

Stehli

Steigerwalt

Striepe

Stuck

Suppan

Svetkey

Takker

Tanabe

Tanaka

Tomii

Torre

Traverse

Tyson

Vasquez

Velasquez

Vemulapalli

Waki

Walton

Wang

Weber

Wells

Wilkins

Wright

Yahagi

Yeung

Zadegan

Zeller

Ziada

Ziakas

Zidar

Efficacy of catheter-based renal denervation in the absence of antihypertensive medications (SPYRAL HTN-OFF MED Pivotal): a multicentre, randomised, sham-controlled trial

Lancet

2020

. pii: S0140-6736(20)30554-7. doi: 10.1016/S0140-6736(20)30554-7.

Bhatt

DL.

Reduction of cardiovascular events with icosapent ethyl, REDUCE-IT EPA. American College of Cardiology Virtual Annual Scientific Session together with World Congress of Cardiology (ACC 2020/WCC). 30 March

2020

. https://www.acc.org/latest-in-cardiology/clinical- trials/2018/11/08/22/48/ reduce-it.

Cabo

Yao

Boyden

Chen

Hussain

Duffy

Ciaccio

Peters

Wit

AL.

Heterogeneous gap junction remodeling in reentrant circuits in the epicardial border zone of the healing canine infarct

Cardiovasc Res

2006

;

241

–

249

Author

Biography: Dr Thorsten M. Leucker is an Assistant Professor of Medicine in the Division of Cardiology at Johns Hopkins University. He presently serves as the Director of Basic and Translational Vascular Biology Research within the Ciccarone Center for the Prevention of Heart Disease. His clinical work focuses on cardiac critical care at Johns Hopkins Hospital. In addition, Dr Leucker is a core faculty member with the Ciccarone Center, attends in the Advanced Lipid Disorders Clinic and he is a Diplomate of the American Board of Clinical Lipidology. In addition, Dr Leucker is a physician–scientist and runs a basic vascular laboratory as well as several translational clinical trials to better understand the impact of vascular inflammation in patients with acute coronary syndrome. In his basic laboratory, he investigates the impact of pro-inflammatory mediators on basic endothelial cell function. To test endothelial cell function and assess vascular inflammation in patients, he uses imaging modalities such as positron emission tomography and magnetic resonance imaging. Dr Leucker is the principal investigator on several intra- and extra-mural research grants investigating underlying mechanisms of pro-inflammatory disease states, such as diabetes, HIV infection and aging, on vascular and myocardial dysfunction.

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