Cardiovascular

Grand Rounds January 9, 2026: Pragmatic Care Embedded Randomization: Insights From the KP-VACCINATE Megatrial (Ankeet S. Bhatt, MD, MBA, ScM)

Posted on by Sophia Ramirez

Speaker

Ankeet S. Bhatt, MD, MBA, ScM
Cardiologist, Kaiser Permanente San Francisco Medical Center
Research Scientist, Kaiser Permanente Northern California Division of Research
Assistant Professor, Kaiser Permanente Bernard J. Tyson School of Medicine
Adjunct Professor, Stanford University School of Medicine

Keywords

Vaccination; Learning Health System; Implementation Science; Nudges; Influenza; Cardiovascular

Key Points

  • Every year, influenza leads to over 500,000 deaths and 3-5 million severe cases globally. It increases the risk of cardiovascular (CV) events like myocardial infarction and heart failure. Though health guidelines strongly recommend annual influenza vaccination, rates remain suboptimal globally and persistent inequities exist. There’s an urgent need for novel, effective, and scalable strategies to improve influenza vaccination rates.
  • The KP-VACCINATE trial is one of the largest ever conducted, randomizing over 3.6 million patients in under 30 days. It included several pragmatic elements, such as coordination with existing vaccine promotion efforts; randomization performed by operational health system teams; and endpoint capture fully embedded in the electronic health record.
  • The study team assessed the effect of a cardiovascular-focused nudge communication on influenza vaccination rates and found that there was no effect. Despite the negative results, the trial establishes that pragmatic and rapid randomization of communication strategies is operationally feasible at scale with routine healthcare workflows in the US.

Discussion Themes

The study team targeted a larger-than-usual population in order to 1) demonstrate the feasibility of randomization within a large-scale health system, and 2) be well-powered for subgroup analyses that could help tailor future interventions.

Dr. Bhatt viewed the negative result as an illustration of the importance of design and context for interventions based in behavioral science, rather than an indication that nudges are ineffective.

Future directions may include involvement of the broader care team, with primary care providers and specialty providers playing a potentially critical role in nudging patients towards vaccine uptake.

Grand Rounds October 3, 2025: Multi-Domain Rehabilitation for Older Patients With Myocardial Infarction: The PIpELINe Trial (Elisabetta Tonet, MD)

Posted on by Sophia Ramirez

Speaker

Elisabetta Tonet, MD
Cardiology Consultant
Cardiology Unit
Azienda Ospedaliero–Universitaria di Ferrara, Italy

Keywords

Cardiovascular; Myocardial Infarction; Rehabilitation

Key Points

  • The standard of care in myocardial infarction (MI) management has evolved dramatically in the 20th century, shifting from absolute bed rest to early ambulation to the modern cardiac rehabilitation concept focused on physical activity. This typically includes inpatient mobilization, a 6 – 12 week outpatient program, and a maintenance phase.
  • Traditional cardiac rehabilitation programs have several limitations, including standardized activities, early withdrawal, high costs, and low enrollment of older adults. The latter factor is increasingly significant, as the contemporary MI patient has also changed; 2/3 of MI patients are over 65 years old.
  • Despite advancements in acute care, older patients presenting with MI are the highest risk population with the worst prognosis. Older adults also represent the least physically active group, often experiencing functional decline, frailty and disability after MI.
  • The research team sought to assess a physical activity model with both remote and supervised, in-person, monthly sessions. In the HULK pilot study, this intervention was seen to improve short physical performance battery values 6 months after acute coronary syndrome.
  • The Physical Activity Intervention in Elderly Patients with Myocardial Infarction (PIpELINe) trial evaluated whether an early, tailored, multi-domain rehabilitation intervention improved outcomes in older patients (65+ years old) admitted to the hospital for MI and with impaired physical performance.
  • PIpELINe was an investigator-initiated, multicenter, prospective, superiority randomized trial conducted across 7 centers in Italy. The intervention included metabolic risk factors management; diet counseling; and exercise training. The primary outcome was cardiovascular (CV) death or CV-related, unplanned hospitalization.
  • The research team found that the multi-domain cardiac rehabilitation program reduced CV death or CV-related, unplanned hospitalization in their target population by 8% compared to usual care.

Discussion Themes

One difficulty cited by similar projects is older adults’ reluctance to participate in clinical trials. In this case, the research team found that a monthly, sustained program that provided guidance following an MI was attractive to this population. The main barrier to enrollment was the pandemic.

The impact of the intervention on heart failure and unplanned hospitalization may be more pertinent to this population than CV death, as they pertain to functional decline and quality of life.

The monthly pace renders this intervention low-cost with high availability.

The multidimensionality of the trial makes it difficult to identify which factors drove the effectiveness of the intervention and to what extent. Dr. Tonet suspects that the physical activity component was the most impactful.

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.