Cardiology

Grand Rounds March 13, 2026: Behavioral Economics and Medication Adherence for Hypertension: A Randomized Clinical Trial (John A. Dodson, MD, MPH)

Posted on by Sophia Ramirez

Speaker

John A. Dodson, MD, MPH
Associate Professor of Medicine and Population Health
Director, Geriatric Cardiology Program
Director, Cardiovascular Digital Health Laboratory
NYU Langone Health
NYU Grossman School of Medicine

Keywords

Behavioral Economics; Cardiovascular Disease; Hypertension; Medication Adherence

Key Points

  • Roughly half of patients with cardiovascular disease (CVD) are nonadherent with their medications. This occurs across conditions and for multiple reasons, including cost, side effects, lack of symptoms, and inconvenience. BETTER-BP, a phase 2, multisite trial, sought to test the effect of a lottery on antihypertensive adherence. The lottery intervention was based in behavioral economics, a field that represents a novel and potentially scalable approach to improving medication adherence.
  • In a safety-net population, the lottery doubled adequate antihypertensive medication adherence from baseline to 6 months. This did not translate to a significant reduction in office-measured systolic blood pressure (BP) and increased adherence was not sustained after the lottery was removed. Other strategies will likely be required for long-term behavior change.
  • BETTER-BP had pragmatic components and non-pragmatic components. It was pragmatic in that it utilized minimal exclusion criteria; took place in a real-world setting; used existing medications; paired study visits with regular ambulatory visits; and used the electronic health record to ascertain some measures. It was not pragmatic in that it utilized traditional informed consent; the intervention and monitoring strategies were not usual practice; and the primary outcome was measured via an in-person BP assessment.

Discussion Themes

Dr. Dodson noted that many trials of behavioral economics in CVD medication adherence have not had durable effects on either adherence or clinical outcomes. Even with trials that are positive, no intervention has been a “home run.”

The lottery payouts (ranging from $5 to $50) were based on an estimated daily value intended to influence behavior without being coercive or exceeding study budgets.

Recruitment for the trial was a challenge; the team made approximately 9,000 phone calls to reach their final sample of 400 participants.

Behavioral incentives might be better suited for time-limited interventions, such as smoking cessation, rather than the lifelong management required for conditions like hypertension.

Grand Rounds February 27, 2026: Optimal Transfusion Strategy in High Cardiac Risk Patients After Major Surgery: Results of the TOP Trial (Panos Kougias, MD, MSc; Sherene Sharath, PhD, MPH)

Posted on by Sophia Ramirez

Speakers

Panos Kougias, MD, MSc
Professor and Chair
Department of Surgery, SUNY Downstate Health Sciences University

Sherene Sharath, PhD, MPH
Assistant Professor
Department of Surgery, SUNY Downstate Health Sciences University

Keywords

Blood Transfusion; Surgery; Cardiology; Cardiac Outcomes

Key Points

  • Postoperative anemia is common after major operations. While the current guidelines recommend transfusion for hemoglobin (Hb) below 7 g/dL, the safety of this restrictive strategy is unclear – particularly after major operations and in high cardiac risk patients.
  • The study team sought to evaluate whether a more liberal transfusion strategy reduces the risk of mortality or major ischemic events in high cardiac risk patients undergoing major operations. They randomized eligible veterans from 16 VA medical centers to receive transfusion at either Hb<10 g/dL (the “liberal” arm) or Hb<7 g/dL (the “restrictive” arm).
  • They found that the rates of mortality and major ischemic events were similar between the groups. While the rates of most secondary outcomes were also similar, a composite outcome of heart failure and arrhythmias was more frequent in the restrictive arm.
  • The study team noted that a one-size-fits-all approach may not be applicable for transfusion strategies. Potential cardiac-outcome related benefits should be explored in future trials.

Discussion Themes

In the weighting of composite outcomes, the analysis treated all events (e.g., death vs. minor complications) as having equal clinical severity. This may have reduced the trial’s statistical power.

The actual event rate (10%) was much lower than the anticipated 30%. The study team attributed this to improved perioperative care and better cardiovascular outcomes over the last decade compared to the historical data used for initial calculations.

Communicating nuanced findings may require some extra legwork; clinicians often struggle to interpret results that are not clear-cut “wins” or “losses.”

Grand Rounds May 2, 2025: Fluid REStriction in Heart failure versus liberal fluid UPtake: The FRESH-UP Study (Roland RJ van Kimmenade, MD, PhD)

Posted on by Sophia Ramirez

Speaker

Roland RJ van Kimmenade, MD, PhD
Cardiologist, Radboud University Medical Center
Nijmegen, the Netherlands

Keywords

Heart Failure; Fluids; Cardiology

Key Points

  • We are facing a pandemic of heart failure (HF), with an incidence of 1 – 20 cases of heart failure per 1,000 people. The incidence of HF is stable – if not declining – but mortality remains high, at about 15 – 30% after one year. Attributable health care costs are up, and the prevalence of HF in the general population is increasing.
  • Orthopnea and edema are symptoms of heart failure caused by congestion, or “fluid retention.” This has led to an intuitive assumption that patients should monitor their fluid intake to 1.5 – 2L per day (including beverages, ice cream, soup, and some fruit). Patients are advised to do things like chew gum or suck on frozen grapes to relieve dry mouth and thirst.
  • The literature supporting fluid restriction is limited; as of 2018, the studies supporting it had small sample sizes and heterogeneous populations. They found no differences in mortality and hospitalization. Sets of clinical practice guidelines from 2021 and 2022 also noted that more evidence was needed for fluid restriction, and that existing evidence was low quality.
  • To address this gap in the evidence, the research team used crowdfunding to conduct the Fluid REStriction in Heart failure versus liberal fluid Uptake (FRESH-UP) Study. The randomized, open-label, multicenter clinical trial study took place between May 17, 2021 and June 13, 2024.
  • The primary outcome was health status at 3 months, as assessed by the Kansas City Cardiomyopathy Questionnaire – Overall Summary Score (KCCQ-OSS). The key secondary outcome was thirst distress at 3 months, as assessed by the Thirst Distress Scale for patients with HF (TDS-HF).
  • Participants were randomized to one of two arms: liberal fluid intake (no restriction) or fluid restriction, with a maximum of 1500 mL of fluid per day.
  • After three months, the research team found that the difference in KCCQ-OSS (adjusted for baseline scores) was 2.17, with a p value of 0.06. These findings favor liberal fluid intake, but the primary outcome was not met.
  • Thirst distress was higher in the fluid restriction group. No differences were observed for safety events between groups.
  • The FRESH-UP study questions the benefit of fluid restriction in chronic HF.

Discussion Themes

Patient-centered research is key in pragmatic trials; this trial came about because a patient voiced their discomfort and questioned the validity of fluid restriction. The researchers took this as a cue to question a key assumption in their field.

The Dutch Heart Foundation facilitated the crowdfunding, from the legal requirements to the website. The money raised from crowdfunding got them far enough to apply for a second grant.

As in clinical practice, the pragmatic nature of the trial made it difficult to guarantee participant fidelity throughout the entire experiment (though they did monitor intake at week six). The research team conducted a survey of participants afterwards to assess adherence. 93% of the patients reported that they adhered well to their regimes.

“Gaps in Evidence” in clinical guidelines is not a summary of failure, but a source of inspiration!

Grand Rounds April 18, 2025: Colchicine and Spironolactone Post-MI — A Review of the Late-Breaking Results of the CLEAR OASIS 9 Trial (Sanjit S. Jolly, MD, MSc, FRCPC)

Posted on by Sophia Ramirez

Speaker

Sanjit S. Jolly, MD, MSc, FRCPC
Interventional Cardiologist, Hamilton Health Sciences
Stuart Connolly Chair in Cardiology
Professor of Medicine, McMaster University

Keywords

Myocardial Infarction; Cardiology; Heart Failure; Colchicine; Spironolactone

Key Points

  • 20 years ago, an article published in Nature hypothesized that if we could find a cardioprotective drug to lower cardio-reactive protein (CRP), we could eliminate heart disease.
  • Over the last 2 decades, there have been successes and failures on that front. The Cardiovascular Inflammation Reduction Trial (CIRT) found that methotrexate did not reduce the rate of major adverse cardiovascular events. The Canakinimab Anti-inflammatory Thrombosis Outcomes Study (CANTOS) found that higher doses of canakinumab reduced cardiovascular (CV) death, myocardial infarction (MI), or stroke by over 15% during follow-up.
  • The CoLchicine and spironolactonE in patients with myocardial infARction/SYNERGY Stent Registry – Organization to Assess Strategies of Ischemic Syndromes 9 (CLEAR SYNERGY OASIS 9) Trial was a large, simple, randomized trial of 7,000 patients with ST-elevation myocardial infarction or large non-ST-elevation myocardial infarction. Participants were randomized in a 2×2 factorial; first to either colchicine or placebo, then to either spironolactone or placebo.
  • The primary outcome in the first factorial was the effect was treatment with colchicine vs placebo on a composite of CV death, MI, stroke, or IDR. The co-primary outcomes in the subsequent factorial were the effects of spironolactone vs a placebo on 1) a composite of CV death or heart failure (HF) and 2) a composite of CV death, HF, stroke, or MI.
  • There have been 2 large trials looking at colchicine in cardiovascular disease: COLCOT and LODOC02. The CLEAR trial started before the results of the COLCOT trial, as the research team believed a larger confirmatory trial with more power was needed and replication of power results were important for Class 1 indications in guidelines. CLEAR is the largest trial of colchicine in acute MI, with substantially more events than prior trials.
  • In the first factorial, they found that while CRP was reduced with colchicine, acute and long-term colchicine did not reduce the composite of CV death, MI, stroke, or ischemia-driven revascularization. Colchicine was also associated with an increase in diarrhea, a known side effect of the drug. The research team believes the role of colchicine post-MI remains uncertain.
  • There have been 2 trials looking at Mineralocorticoid Receptor Antagonists (MRA) post-MI in patients without HF: REMINDER and ALBATROSS. Their results left some questions unanswered.
  • In the second factorial, they found that routine spironolactone post-MI did not reduce either co-primary outcome. There was a reduction in new or worsening heart failure, and on-treatment analysis suggests a potential benefit.

Discussion Themes

Outcomes have improved remarkably over the last 20 years, such that HF event rates in a population with predominantly ST-elevation MI are around 3%; a significant drop from the roughly 20% HF event rate in that population 20 years ago. That makes it more difficult to show treatment effects in this population.

The study team developed their inclusion criteria to select for a study population that would be applicable in standard clinical practice. The trial became more pragmatic as the study went on as a result of pivots they made in response to the COVID-19 pandemic.

Key challenges were driven by the COVID-19 pandemic. These included shipping expenses, which spiked significantly; shifting logistics, regarding who would receive the materials; and a pause in recruitment. The study team also came up against varying drug approvals in different locations; this was a global trial, taking place over roughly 70 sites in 11 countries.