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I wonder that if I walked the wards at Montefiore, would I find many more patients that have not been diagnosed accurately, and yet it is an area that is an important one for this meeting because we haven't had a very successful trial that can say oh yes, we have found the perfect solution, the perfect drug, or the perfect treatment for HFpEF. We have been waiting anxiously for the TOPCAT trial, which was presented today by Mark Pfeffer from Boston.[1]

TOPCAT randomly assigned over 3000 patients in both the United States and abroad, so even though this was a National Institutes of Health (NIH) trial, multiple centers were picked in many countries, including Russia and South America -- a big group of patients from Argentina, a country that has always participated in excellent clinical trials. The patients had to have been symptomatic.

Of note, the trial had over 50% women, which makes me feel that this may be the right population, because about 50% of the patients whom I see with HFpEF are women. The age group was in the high 60s, and that is a little younger than my patients. I have the 70-year-olds and the 80-year-olds, but certainly approaching the right population, I believe; the peak age was 74 years.

The patients were randomly assigned to receive either spironolactone or placebo, so this is a randomized, controlled, double-blind trial as we consider the gold standard, and the endpoint was a combined primary endpoint -- again, which we see very often -- of cardiovascular mortality, heart failure hospitalizations, and arrhythmias causing sudden death. Sudden death was an interesting question because in the RALES trial of spironolactone, there was actually an approximately 30% reduction in sudden death.[2] Because of that, we have wondered whether this is an intrinsic property of spironolactone, or is it because potassium levels tend to rise and maybe potassium levels are protected?

Of note, the TOPCAT trial did not show a significant reduction in the combined primary outcome. When we look at the individual components of the primary outcome (which we often do), the heart failure hospitalizations seem to have been reduced, with a P value of .04 -- so just reaching statistical significance. I am sure that we will see more subgroup analysis and more post hoc analysis from this important trial that has now gathered tons of data, data that we have really needed to track these patients.

As expected, there was more hyperkalemia in the spironolactone group, which caused some of the patients to be taken off the drug; however, the study was not stopped either for benefit or for worsening adverse events that would have been of concern. We will see within the next few days, maybe, a deeper teasing out of that hyperkalemia. We have in the guidelines that potassium levels must be followed closely.

We also have in the guidelines that renal function must be followed closely, and if you have a patient who will not come back for clinic or you are concerned about their follow-up, maybe that is not the right patient to put on spironolactone. At least 30% of the patients had diabetes, so again, typical of the comorbidities that really plague this group of patients, among whom mortality may not be severe, but there are certainly readmissions -- and very often these readmissions are not because of the heart failure symptoms, but because of all of the other comorbidities. So stay tuned for more; I will bring you more news about this trial.


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