Conference report: the 67th American College of Cardiology conference

The 67th American College of Cardiology (ACC) conference (ACC.18) took place in the Orange County Convention Center in Orlando, Florida, USA on 10–12 March 2018 and was attended by more than 16,600 delegates. This report focuses on a selection of talks delivered at the conference. Given the huge plethora of interesting sessions, I was unable to visit all of them, as such, I describe here a personal selection of each day’s most notable talks.

Day 1

ACC.18 opening showcase featuring the 2018 Simon Dack keynote

Day one started with a warm welcome from the president of ACC Mary Norine Walsh (St. Vincent Heart Center of Indiana, Indianapolis, IN, USA). Her speech focused on the importance of advocacy in cardiovascular care and highlighted three different ways by which this can be carried out. The first was patient advocacy by having cardiovascular professionals be patient centred. Walsh stressed that there is also a need for collegial advocacy where professionals advocate for each other to avoid burnout, encourage diversity and improve team care. The final way is to advocate for quality by using the plethora of real-world data stemming from the huge number of randomized controlled trials (RCTs) in cardiology to strive for innovation.

After her address, Walsh welcomed this year’s Simon Dack keynote speaker, Nanette Kass Wenger (Emory University School of Medicine, Atlanta, GA, USA), a pioneer for her work in women’s cardiovascular health. Her talk focused on the journey that led to the understanding of the importance of cardiovascular disease (CVD) in women. She highlighted that medical research historically neglected health needs in women and that there are disparities in CVD burden amongst subgroups and minorities. Wenger closed the talk by stressing that more targeted research is needed to highlight these disparities, as well as challenging journal editors to encourage reporting clinical trials outcomes for men and women separately, given the current underrepresentation of the latter.

This set the scene for the rest of the congress, which had the recurring theme of disparities in CVD clinical trials.

Cardiovascular outcomes with alirocumab after acute coronary syndrome: results of the ODYSSEY outcomes trial

The first late-breaking clinical trial session started with the much awaited ODYSSEY outcomes trial, presented by Philippe Steg (Imperial College London, UK).

The results suggested that the use of the proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor alirocumab reduces ischaemic events and low-density lipoprotein-cholesterol in patients with acute coronary syndrome (ACS). In this study, the safety and efficacy of alirocumab was compared with placebo among patients with recent ACS already on intensive or maximum-tolerated statin therapy. The trial indicated that the use of alirocumab significantly reduced major adverse cardiac events (MACEs), ischaemic stroke and myocardial infarctions (MIs) as well as being associated with a lower rate of all-cause death in the treatment groups versus the placebo group. The treatment was safe and well tolerated. There was no difference in treatment-emergent adverse events between the groups, except for a minor difference in reactions at the injection site. Together with the FOURIER trial, this is the second PCSK9 inhibitor outcomes trial study reporting a reduction in cardiovascular events which, in Dr Steg’s words, “may change the equation for these drugs”.

Efficacy of a wearable cardioverter-defibrillator after MI: results of the VEST trial

An additional highlight of this late-clinical trial session was the VEST study, presented by Jeffrey E. Olgin (University of California, San Francisco, CA, USA).

VEST was a multicentre, randomized, open-label trial. The study included 108 enrolling sites in the USA and Europe between 2008 and 2017. The aim of the trial was to compare the efficacy of a wearable cardioverter-defibrillator (WCD) in reducing sudden cardiac death (SCD) among post- MI patients with a left ventricular ejection fraction of less than 35%. The results indicated that the WCD did not reduce SCD up to 90 days among patients with moderate to severe left ventricular dysfunction immediately post-MI compared with controls. However, there was a significant decrease in all-cause mortality.

Despite the reported negative outcomes and the open-label nature of the trial, WCDs may be beneficial for eligible patients given the reduction in all-cause mortality observed during the study.

Emerging therapies in heart failure: the crystal ball

This exciting session highlighted current emerging innovative therapies for heart failure. The talks spanned numerous different treatments such as pharmacotherapeutics, stem cells, devices, electrical therapies as well as nonsurgical treatments.

The number of emerging pharmacotherapeutics being developed for this condition was of particular interest during this session. John Teerlink (University of California San Francisco, San Francisco, CA, USA) talked about emerging therapies for acute heart failure (AHF). One of these treatments is nitroxyl (HNO), a reactive-nitrogen species that enhances contractility and relaxation. It is being trialled for AHF in a phase IIb study of the StandUP AHF trial. This trial’s aim is to evaluate the safety and efficacy of continuous 48-h intravenous infusions of nitroxyl in hospitalized patients with heart failure and impaired systolic function.

Another highlight was the update on current stem cell clinical therapies given by Joshua Hare (University of Miami, Miami, FL, USA). Studies with autologous and allogeneic stem cell therapies suggest that they have an excellent safety profile and their current delivery systems are both safe and effective. Stem cell research is generally receiving major interest from regulatory bodies. The progress of these therapies is supported by accelerated approval designations, such as the 21st Century Cures Act and the US Food and Drug Aministration’s Regenerative Medicine Advanced Therapy Designation in the USA as well as the Pharmaceuticals and Medical Devices Agency accelerated approval in Japan.

Day 2

Loading doses of atorvastatin versus placebo in patients with ACS and planned revascularization: the SECURE-PCI trial

The aim of the SECURE-PCI trial (Otavio Berwanger, Hospital Israelita Albert Einstein, Sao Paulo, Brazil) was to compare the safety and efficacy of two loading doses of atorvastatin given early among patients presenting with all types of ACS who were scheduled to undergo percutaneous coronary intervention (PCI). The study randomized 4197 patients with ACS in 58 centres in Brazil. Results revealed that a large loading dose of atorvastatin did not reduce the primary outcome of MACEs and was not superior to placebo at 30 days. However, both MACE and non-PCI-related MI were significantly reduced in the prespecified subset of patients who underwent PCI. ¹

This study could pave the way for the testing of new indications for lipid-lowering agents. The investigators are now planning further trials to focus on the potential benefits of statins in patients undergoing PCI.

Impact of patient co-payment reduction on P2Y12 inhibitor persistence and clinical outcomes after MI: the Affordability and Real-world Antiplatelet Treatment Effectiveness after Myocardial Infarction Study (ARTEMIS) randomized trial

The ARTEMIS trial results, presented by Tracy Wang (Duke University, Durham, NC, USA), outlined the outcomes of the first large, prospective multicentre trial to examine how co-payment vouchers affect patient adherence to recommended medical therapy. The study enrolled 11,001 patients who had been treated for MI at one of 301 participant hospitals in the USA.

In a cluster design, participating hospitals were randomly assigned to either the intervention arm, where patients received a voucher (131 hospitals), or the usual-care arm (136 hospitals). Patients were enrolled prior to hospital discharge and physicians used their clinical judgement to prescribe the P2Y12 inhibitors, clopidogrel or ticagrelor. The aim of the study was to compare the efficacy of co-payment intervention of antiplatelet agent use among patients with ACS and outcomes at 1 year. The co-primary endpoint for adherence was continued use of the prescribed antiplatelet drug at 1 year without a gap in use of 30 days or longer. The results suggested that whilst co-payment reduction significantly affected clinicians’ choice of P2Y12 inhibitor use post-ACS presentation and improved patient persistence with treatment, it did not impact clinical outcomes at 1 year. Further, even among patients in the intervention arm, 28% did not use their vouchers.

The negative clinical outcome result was attributed to the single drug being targeted, the modest co-payment differences, high baseline persistence as well as the incomplete use of co-payment vouchers during the study.

Wang hypothesized that broad-scale interventions are needed to improve further medication persistence and patient outcomes. Furthermore, co-payment reduction should be considered as part of a multipronged strategy to enhance medication persistence and outcomes in patients.

Further analysis of these data is planned.

International clinical trials in heart failure: beyond cultural barriers

The Joint Symposium of the Heart Failure Society and the ACC entitled ‘International Clinical Trials in Heart Failure: Beyond Cultural Barriers’ presentations highlighted the importance as well as the barriers surrounding diversity and minorities in clinical trials – a major theme during this year’s ACC conference.

Marc Pfeffer’s (Harvard Medical School, Boston, MA, USA) talk focused on the evolution of RCTs by comparing studies pre- and post-2000. Earlier RCTs were characterized by tight geography, relatively clear eligibility, an enrolment number of approximately 2000 and the endpoint of the study was usually death. The transition occurred post-2000 with larger studies, broader geographical spread and composite endpoints. One such study was the CHARM programme, which included patients from 26 different countries and had a composite primary outcome for each trial. ²

The session continued with John McMurray (University of Glasgow, Glasgow, UK) who focused on the underrepresentation of women and minorities and their impact on clinical trials. He debated whether women were really underrepresented, and whether that mattered given the differences in epidemiology, biology, response to treatment and differing treatment needs in men and women. The different traits have some implications during trials; different criteria, like endpoints and event rates, need to be taken into consideration. Similarly, McMurray noted that there is a huge lack of representation of black communities in clinical trials. There is a need to build clinical trial capacity in Africa if more black patients are to be enrolled globally, and special policies and incentives should be established in the USA to enrol a higher number of African-Americans in these studies.

Day 3

Anti-inflammatory therapy with canakinumab and incident type 2 diabetes: a prespecified key secondary endpoint of the CANTOS trial

According to the results of an analysis from the CANTOS study, presented by Brendan Everett (Harvard Medical School, Boston, MA, USA), interleukin-1β inhibition with the monoclonal antibody canakinumab reduces MACE rates among high-risk atherosclerosis patients with moderate to severe chronic kidney disease (CKD). Interleukin-1β inhibition with canakinumab had similar effects on MACEs among those with and without diabetes, although the treatment did not reduce incident diabetes. The data demonstrated that anti-inflammatory therapy with canakinumab has considerable cardiovascular efficacy in high-risk patients with moderate to severe CKD, although, the monoclonal antibody did not prevent the progression of diabetes. ³

The investigators recommended a future clinical trial in which canakinumab is given to patients with severe renal failure recently initiating haemodialysis, an area with considerable unmet need.

Blood-pressure reduction in black barbershops

Non-Hispanic black men have the highest rate of hypertension-related death in the USA and the lowest interaction with physicians, as well as being underrepresented in pharmacist intervention trials in traditional healthcare settings. As a result, uncontrolled hypertension (HTN) is a major problem among non-Hispanic black men.

The aim of the Blood-Pressure Reduction in Black Barbershops trial was to reach out to this community by developing an effective intervention linking health promotion by barbers to drug therapy by pharmacists and to evaluate efficacy in a cluster randomized clinical trial. ⁴

Black male patrons with uncontrolled HTN were randomized by barbershop into an interventional therapy group (n = 139) and a standard therapy group (n = 180). Interventional therapy consisted of barbers who promoted monthly follow up with specialty-trained pharmacists who prescribed antihypertensive medication and point-of-care electrolytes at the barbershop. In the standard therapy group, barbers promoted lifestyle modification and follow up with primary-care physicians.

The long-awaited results, presented by Ronald Victor (Cedars-Sinai, Los Angeles, CA, USA), revealed that interventional therapy was effective in reducing systolic blood pressure among black barbershop patrons with uncontrolled HTN at 6 months compared with standard therapy. Furthermore, there was 95% cohort retention and interventional therapy was associated with a high rate of optimal blood-pressure control without serious adverse events.

Blood-pressure reductions could aid reducing high HTN-related disability and death among black men with multiple CVD risk factors in the USA.

The trial was largely complimented by the panel and called it a potential ‘new model of chronic disease management’. Other questions centred on the complexity of integrating this model into health systems and the cost of this therapy. Victor stated that the investigators would carry out a 12-month follow up followed by a cost-effectiveness analysis.

ACC.19 will be taking place in New Orleans, LA, USA at the New Orleans Ernest N. Morial Convention Center on 16–18 March 2019.