Insights From the INTERASPIRE Study | JACC Deep Dive

Dr. Harlan Krumholz reviews the STEP trial, which studied over 8,500 older adults in China to compare intensive versus standard blood pressure control. The trial found that lowering systolic blood pressure to 110–130 mm Hg significantly reduced major cardiovascular events by 26% without added safety risks, confirming benefits previously shown in the SPRINT trial. A six-year follow-up revealed a lasting "legacy effect," showing that starting intensive treatment earlier produced enduring cardiovascular protection even after pressures equalized. The key takeaway: early, sustained, and carefully monitored intensive control is safe, effective, and time-sensitive—each year of delay means missed opportunities to prevent heart attacks and strokes.

In this episode of JACC Deep Dive, Editor-in-Chief Dr. Harlan Krumholz explores groundbreaking findings from the CLEAR-IE registry—the largest study to date on percutaneous mechanical aspiration (PMA) for right-sided infective endocarditis. He discusses the procedure's feasibility, outcomes, and its role alongside surgery, offering insights into how PMA may reshape treatment options for high-risk patients.

In this JACC Deep Dive, Dr. Harlan Krumholz highlights a study by Ikemura et al. that used data from the ISCHEMIA trial to model how angina symptoms evolve over three years in patients with stable coronary disease treated either invasively or conservatively. The study identified six distinct symptom trajectories, showing that while most patients improved over time, those undergoing revascularization were more likely to experience rapid and complete symptom relief. However, the benefit was not uniform—patients with frequent baseline angina saw the greatest improvement, and some had persistent symptoms regardless of treatment. These findings underscore the importance of personalized, shared decision-making based on a patient's likely symptom trajectory rather than a binary treatment choice.

In this JACC Deep Dive, Dr. Harlan Krumholz discusses a pre-specified analysis from the SUMMIT trial, which evaluated the effects of tirzepatide in patients with heart failure with preserved ejection fraction (HFpEF) and obesity, both with and without type 2 diabetes. The study found that tirzepatide significantly improved symptoms, function, and reduced heart failure events, with similar benefits regardless of diabetes status, though weight loss was slightly less in those with diabetes. Importantly, cardiac structural improvements (LV mass and pericardial fat regression) were also similar across both groups, suggesting benefits beyond weight loss alone. The trial's strengths included its integrated design and imaging substudy, though limitations such as modest imaging power and baseline group differences were noted. Clinically, the results support using tirzepatide in HFpEF patients with obesity, regardless of diabetes status, as the benefits remain robust.

In this Deep Dive, Editor-in-Chief Dr. Harlan Krumholz explores a pragmatic, randomized crossover trial testing whether in-home HEPA filtration can reduce blood pressure in adults living near high-traffic roadways. The findings offer early insights into how targeted environmental interventions may influence cardiovascular risk—especially among individuals with elevated baseline systolic blood pressure.

In this episode of JACC Deep Dive, Dr. Harlan Krumholz explores new insights from a post hoc analysis of the MASTER DAPT trial, highlighting the real-world burden of ischemic and bleeding events in high bleeding risk patients after PCI. By examining recurrent—not just first—events, the study sheds light on how abbreviated dual antiplatelet therapy (DAPT) impacts total clinical outcomes. Key findings include reduced bleeding without increased ischemic risk and a notable clustering of ischemic events following bleeding. This analysis advances the conversation around patient-centered endpoints and the evolving science of recurrent event modeling in cardiology.

In this episode of JACC Deep Dive, KACC Editor-in-Chief Harlan M. Krumholz, MD, SM, FACC,  explores a post hoc analysis of the HELIOS-B trial, which examined whether echocardiographic parameters can track treatment response in transthyretin amyloid cardiomyopathy (ATTR-CM) patients treated with vutrisiran. The study found that changes in cardiac function correlated with clinical outcomes, suggesting a role for serial imaging in personalized care. Behind the scenes, reviewers were particularly intrigued by the potential of echocardiographic markers—especially global longitudinal strain—as surrogate endpoints, while also noting the exploratory nature of the findings and the need for further validation.

JACC focuses in again on Lipids in our June 3 issue, bringing critical insights into emerging targeted therapies. In the June 3 Deep Dive, editor-in-chief Harlan M. Krumholz, MD, SM, FACC, reviews the INTERASPIRE study by Ray et al, reviewing implications, key findings, and a thoughtful summary and analysis of the reviewer findings.

Go behind the scenes with JACC as editor-in-chief Harlan M. Krumholz, MD, SM, FACC, talks about what 's caught his attention in the latest JACC issue on amyloid. In this paper by Sheikh et al, the authors did a pre-specified exploratory analysis from the HELIOS-B trial, evaluating vutrisiran in patients with transthyretin amyloid cardiomyopathy (ATTR-CM). The study showed that vutrisiran helped preserve or improve functional capacity and quality of life over 30 months, with consistent benefits across both monotherapy and tefamidis-treated patients. Waterfall plots illustrated the full spectrum of individual patient responses, revealing meaningful improvements in many while underscoring variability in outcomes. The analysis emphasized this heterogeneity, supporting a move toward precision care in amyloidosis.

Join JACC Editor in Chief Harlan Krumholz, MD, SM, as he speaks about this ACC.25 presentation published in JACC. This fascinating study by Rohan Khera et al independently analyzed patient-level data from the SURMOUNT trials of tirzepatide for obesity. The study revealed striking individual variability in weight loss and metabolic response, even to a highly effective therapy—an insight powerfully illustrated through waterfall plots. Reviewers praised the transparent, sponsor-independent approach and the study's contribution to precision medicine, though they noted it was descriptive rather than predictive, underscoring the need for future research to identify what drives differential treatment response.