Saturday, September 28, 2013


The European Society of Cardiology had their annual congress in early 2013, at Amsterdam. At that meeting, Dr Deepak Bhatt of Bringham and Women, Boston, presented the results of the SAVOR TIMI 53 trial. This interesting trial comparing the use of Saxagliptin Vs placebo, had heart failure as a prespecified endpoint. They found that after 2.1 year of followup, saxagliptn was non - inferior to placebo, but had a 27% increase incidence of heart failure. Now this is not nice. Saxagliptin, as predicted, did lower the HbA1c levels and improve glycemic control ( the numbers were better ).
Actually, I miss this paper.
However, yesterday at the European Association for the Study of Diabetes Congress in Barcelona, Dr John Murray of U of Glasgow, took up this point and presented the leading paper on why heart failure had been excluded as an endpoint in all the previous diabetic trials. He lament that it would appear that many diabetologist and cardiologist feel that heart failure is not important ( as opposed to heart attacks ), when in fact heart failure kills more diabetics than heart attacks, especially in diabetics who have nephropathy. Dr Murray's call ( and he re-examined all the previous large diabetic trials including VALUE, LIFE, RENAL, HOPE, ACCORD, ADVANCE, and note that heart failure was excluded when in  fact in his opinion, kills more diabetics. And even worse. He said that regulators have never asked pharmas carrying out trials to include heart failure as an endpoint.
I suppose to summarise, heart failure is common in diabetics especially those with nephropathy, and is often the cause for mortality. Some drugs can make it worse, like saxagliptin.
We have to keep an eye on heart in our diabetics and control the heart failure well as it may cause many to die.
In Dr Murray's presentation, he also made mention of cardiac friendly and cardiac harmful drugs which I also find interesting. Most of us agree, that the most cardiac friendly oral hypoglycemic agent is probably metformin. I wish they had another biguanide for us to choose from. The most cardiac harmful one is probably the glitazones, especially rosiglitazones. There is some data to show that the sulphonylureas may also harm the heart. As for the newer OHAs  like DDP4s and Gliptins, we really need more data. Saxagliptin may be cardiac adversed, looking at SAVOR TIMI 53.

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