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James Gamble's avatar

Dear Adam,

I think this is a really interesting article and thank you. I agree with the principle. As a heart failure physician I am going to comment on your points around the Emperor preserved study. I was all ready to refute you by saying that most of the patients in both groups were already on a loop diuretic, but somewhat amazingly the investigators do not report this data anywhere in the paper or supplementary appendix (unless I have missed it).

However the previous DELIVER trial of dapagliflozin in the same patient population did report this (UK authors win here!) ; 75% of both groups were on a loop diuretic. So it does appear that the benefit of dapagliflozin was in addition to the loop. https://www.nejm.org/doi/full/10.1056/NEJMoa2206286

I suspect there is a data torturing paper showing the benefit of SGLT2 inhibitors was the same with and without loop diuretics in the preserved ejection fraction population, but I have not found it yet. There is one showing that the presence or absence of diuretics did not seem to impact the efficiency of dapagliflozin in reduced ejection fraction population https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.120.047077

So I think here it looks like SGLT2 probably do work additionally to the loop diuretics. I agree however that particularly in the preserved EF group a trial of higher dose of loop versus SGLT2 would have been interesting - if less likely to get funded.

Finally, as someone who is handing out a lot of these medications (cost is much lower here in the UK, and funded by NHS), the clinical effect appears to be pretty clear and my patients do seem to feel better even when they have already been on a loop diuretic.

Best wishes,

James Gamble, cardiologist with an interest in heart failure

Oxford

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Roland Büchter's avatar

Agree: Many principles can be learned without being a genius. I guess the challenge with appraisal is that people are either content or methodology “experts” and to some extent you need both. As someone trained in methodology and working in health technology assessment for 15 years, dissecting the clinical aspects is generally the bigger challenge for me, while the clinicians often lack training in the methods. Unfortunately the discourses between these groups are not always constructive, but sometimes too much influenced by power struggles, vested interests, preconceptions, different perspectives (say population vs individual) or not distinguishing between data and what they might mean for practice. Science and its application is tricky and there should always be humility. I think of appraisal as a skill that is best honed lifelong. That’s why I enjoy following Sensible Medicine.

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