Nihar R. Desai, MD, MPH

Lipid Management in ASCVD: Current Guidelines and Key Clinical Updates

The panelists open the discussion by addressing the persistent cardiovascular risk seen in patients with established ASCVD, even with widespread statin use. The experts note that recurrent events remain common due to a combination of factors, including residual inflammatory, thrombotic, and cardiometabolic risk, along with insufficient LDL-C lowering. 

Data show that many secondary prevention patients still have LDL-C levels above 70 mg/dL, and therapy intensification is infrequent over time. The panelists emphasize that cumulative LDL-C exposure is a critical determinant of ongoing atherosclerotic progression—patients who experience a cardiac event often carry a lifelong burden of atherogenic exposure and are at highest risk shortly after their initial event. Many discontinue lipid-lowering therapy once they feel better, losing long-term benefit. 

The discussion concludes that sustained, aggressive LDL-C reduction beyond the acute phase is essential to alter the trajectory of recurrent cardiovascular risk in ASCVD management.

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This program brings together leading experts to discuss evolving strategies for reducing recurrent cardiovascular risk in patients with ASCVD, emphasizing the importance of cumulative LDL-C exposure and the need for earlier, more intensive lipid lowering. The panel explores current guidelines, emerging data from recent trials, and practical approaches to integrating PCSK9-targeting therapies to improve long-term adherence, access, and outcomes in secondary prevention

Cumulative LDL-C Exposure and the Persistent Challenge of Recurrent ASCVD

Bumetanide Nasal Spray and the Future of Edema With Josephine Harrington, MD, and Nihar Desai, MD

 approved bumetanide nasal spray for the treatment of edema associated with congestive 

, liver disease, and kidney disease. Under the name ENBUMYST, the spray is the first and only intranasal loop diuretic approved in the US offering a self-administered alternative between oral and intravenous diuretics.

Loop diuretics are the standard first-line treatment for congestion, and are used to control patients’ volume status in HF. Most patients admitted to the hospital are given intravenous loop diuretics, regardless of perfusion status or other factors. However, blunted use of loop diuretics leads to blunted diuretic response in acute decompensated HF, which is related to functional and structural tubular remodeling. Bumetanide nasal spray was developed in part to circumvent the gastrointestinal absorption issues.

In addition to revitalizing diuretic therapy for patients with HF, bumetanide has the capacity to overhaul key factors of the HF treatment landscape and open the way to address the unmet need of edema. 

 spoke with Josephine Harrington, MD, an advanced heart failure and transplant fellow at Duke University, and Nihar Desai, MD, MPH, an associate professor of medicine and vice chief of the section of cardiovascular medicine at Yale University, to discuss the implications of this groundbreaking approval.

“Too many of our patients become resistant, or traditional oral diuretics are ineffective, and so we need other ways to optimize their volume status,” Desai told 

. “I was quite excited to see the data for the intranasal bumetanide, and I think that it does have a very important role to play for some of our patients.”

Harrington expressed her curiosity on how bumetanide will fit into the overall HF treatment cascade. She highlighted the lack of intranasal medications in cardiology prior to this approval, leaving many clinicians with limited experience prescribing similar drugs. She noted this as a potential gap in knowledge, possibly limiting the clinical uptake of bumetanide nasal spray.

“I think there are some opportunities to understand how this could fit into a patient’s armamentarium for symptom relief,” Harrington said. “But candidly, I think a lot of us need a lot more experience with this. Most of us don’t prescribe intranasal drugs as cardiologists regularly.”

Edema and fluid overload are still the leading causes of hospitalization for patients with congestive HF – recent estimates suggest 6.7 million Americans live with heart failure, and fluid overload directly causes >1 million hospitalizations annually. The bumetanide nasal spray is a step towards alleviating this unmet need and could potentially provide a path towards approval for future diuretic drugs to follow.

“Getting back to the very fundamental aspects of heart failure management, diuretics have and always will play a very important role in that,” Desai told

. “Having some of these novel mechanisms and routes of administration offers a really important adjunctive part of our medical intervention for our patients.”

“Edema is a condition that bothers patients quite a great deal, and they’re always interested in ways to manage it that don’t affect their quality of life,” Harrington said. “I think having another arrow in your quiver to do that is always going to be a good thing. And exactly what the role is going to be compared to oral diuretics, I think still remains to be seen.”

Corstasis Therapeutics, Inc. Corstasis Therapeutics Announces FDA Approval of ENBUMYST (bumetanide nasal spray) for the Treatment of Edema Associated with Congestive Heart Failure, Liver Disease, and Kidney Disease. Business Wire. September 15, 2025. Accessed September 17, 2025. 

https://www.businesswire.com/news/home/20250915243998/en/Corstasis-Therapeutics-Announces-FDA-Approval-of-ENBUMYST-bumetanide-nasal-spray-for-the-Treatment-of-Edema-Associated-with-Congestive-Heart-Failure-Liver-Disease-and-Kidney-Disease

Biegus J, Ponikowska B, Canonico ME, Damman K, Palazzuoli A, Ambrosy AP. Bumetanide nasal spray: a novel approach to enhancing diuretic response and advancing ambulatory heart failure care?. Heart Fail Rev. 2025;30(5):1123-1126. 

Harrington and Desai weigh in with their thoughts on the bumetanide approval and how we can continue to battle edema in heart failure.

A Look Into the Future of LDL-C Management Post ACS

As the discussion turns to the future of lipid management, the importance of outcomes data, such as the anticipated results of the ORION-4 trial, is highlighted. While lipid-lowering therapies, particularly PCSK9 inhibitors, have demonstrated their ability to reduce cardiovascular events, health systems are waiting for long-term evidence to understand how these treatments will impact patient outcomes. This data will be crucial in securing broader acceptance and integration of these therapies into routine care, particularly as health care systems demand both clinical and economic validation before making widespread changes.

Looking 5 years ahead, the panel envisions 2 main areas of progress: more targeted primary prevention and improved adherence in secondary prevention. There is a growing emphasis on personalized approaches, using advanced tools like coronary calcium scoring to identify individuals with subclinical atherosclerosis. In addition, broader population-based prevention is a key focus, with hopes for more effective trial designs that will demonstrate the long-term benefits of early intervention. A shift toward treating higher-risk individuals more aggressively is also expected, especially among those with a history of cardiovascular events.

The conversation concludes with optimism for the future. With advancements in therapy, more robust clinical evidence, and evolving health care models, there is potential to make significant strides in lipid management. A focus on prevention, along with better risk stratification and health system alignment, could lead to a health care environment where proactive care is prioritized, ensuring that patients receive the best possible outcomes while reducing the long-term costs associated with cardiovascular disease.

Panelists discuss how the future of low-density lipoprotein cholesterol (LDL-C) management in patients with post-acute coronary syndrome (ACS) will involve more aggressive LDL-C target levels, expanded use of PCSK9 inhibitors (PCSK9i), emerging lipid-lowering therapies, personalized medicine, and the integration of lifestyle modifications and digital health tools to improve patient outcomes.

Nihar R. Desai, MD, MPH

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