Stephen Greene, MD

The debate around low sodium diets and its effects on clinical outcomes is one that has raged for decades, but for the first time it appears cardiologists have tangible evidence related to sodium reduction in multiple patient populations.

At ESC 2021, the Salt Substitute and Stroke Study (SSaSS) took centerstage and demonstrated use of a sodium/potassium salt substitute results in a significant reduction in stroke and MACE among patients in the trial. However, limitations within the study limit the applicability of findings.

At ACC.22, SODIUM-HF was among the most anticipated trials from the conference’s late-breaking clinical data. In the trial, sodium reduction failed to reduce risk of a composite endpoint of all-cause mortality, CV-related hospitalizations, and CV-related emergency department visits, but was associated with improvements in quality of life as measured by KCCQ and in NYHA class.

Now, with multiple randomized clinical trials providing insight on the topic, cardiologists, advanced practice providers, and care providers in other disciplines have begun to compare the design and results from both trials to further understand the interaction between sodium reduction and event risk for specific populations.

In a recent episode of Don't Miss a Beat, advisory board member Stephen Greene, MD, associate professor of medicine at Duke University School of Medicine, highlighted SODIUM-HF as one of the trials to watch from ACC.22's late-breakers. Additionally, in the 2021 year in review edition of Don't Miss a Beat, Greene chose SSaSS as the most impactful trial of the year.

With an interest in learning more about how heart failure specialists can apply data from SODIUM-HF and how to interpret the differences in results seen in both sodium reduction trials, Practical Cardiology caught up with Greene on the floor at ACC.22 for his perspective. A transcript of that conversation can be found below.

Q&A on Sodium Restriction in Heart Failure

Practical Cardiology: What was your reaction to SODIUM-HF?

Stephen Greene, MD: SODIUM-HF was a really interesting trial and I was really excited for this. We know from the results there was no difference in the primary endpoint of cardiovascular events and all-cause mortality with a low sodium diet versus the regular diet, but, interestingly, there was in secondary endpoints benefit on patient-reported quality of life as measured by the KCCQ and it was more than 3 points.

So, on one hand, you now have your neutral outcome benefits for heart clinical events, but you do have this patient-reported outcome benefit that seemed apparent with a low sodium diet. It just makes the conversation that much more nuanced and evidence based. Now, when you counsel your patients, you can talk about how there's no evidence that it'll reduce your risk to go into the hospital or help you live longer, but if you are able to reduce on your diet it can make you feel better.

So, I think this gives me more information to really effectively counsel patients, because, right now, the evidence has been disproportionately low compared to the emphasis we place on this. Now, we at least have more data to really inform an educated conversation with patients.

PC: From the heart failure perspective, what was the most immediately impactful trial to come from ACC.22?

SG: I think, from the heart failure perspective, SODIUM-HF is probably going to be remembered very well. Again, for over 100 years, we've been preaching about low salt diet and it essentially have a class 1c recommendation in the older guidelines. It's such a thing that's inherently talked about all the time with patients. We even have fliers in clinics that talk about low sodium diet that patients are seeing all the time and, now, we have actually data to inform that discussion and not have it be a mandate, but really now an informed decision about the pros and cons of trying it, what you might get from sodium restriction, and what you might not get from sodium restriction. To me, given how much emphasis we placed in salt restriction, SODIUM-HF is probably going to be a big takeaway.

PC: In SSaSS we saw a significant reduction in events with sodium restriction that was not observed in SODIUM-HF, how do you interpret this data?

SG: I think this really goes to show how a lot of things that we talk about in our non-heart failure patient populations, such as things that are important that reduce risk or associated risk, are different when you actually have heart failure. For example, with BMI, higher BMI is associated with higher risk of developing heart failure, but once you have heart failure, higher BMI is actually associated with better outcomes. Same thing with like lipids—there's like a paradox where higher LDL is associated with increased risk of developing heart failure, but, once you have heart failure, we have some evidence that actually lower LDL might be associated with harm.

So, this might be another interesting feature here too.SSaSS was clearly positive, in a non-heart failure population. Lowering sodium decreased the risk of stroke and other really meaningful endpoints, but, once patients have established heart failure and we look in terms of heart failure outcomes and cardiovascular outcomes, that benefit is not there anymore with salt restriction. That could be one way to piece together SSaSS and juxtapose it with what you see in SODIUM-HF. It's interesting how potentially having heart failure or not having heart failure kind of changes the effect of some of these widespread interventions.