SYMPLICITY-3 was Medtronic's play to get into the hypertension business. They have a device that allows physicians to apply burn the sympathetic nerves of the renal arteries and lower the blood pressure. In a previous randomized trial it worked and SYMPLICITY-3 was what they were going to take to the FDA to get approval.
I started the day with our local hypertension guru explaining the inclusion criteria for Symplicity-4. An hour later this hit the wire:
|Full press release|
First CORAL, now SYMPLICITY 3. It’s been a bad couple of months for the renal arteries. They should get a better PR person.
— Joel Topf (@kidney_boy) January 9, 2014
Some thoughts on simplicity 3. The trial was on patients with severe resistant hypertension: office blood pressure over 160 on three blood pressure medications. These are hardcore hypertensives. This may not be an appropriate crucible to test the hypothesis of weather this works.
Thought two is that sympathetic discharge is thought to drive a lot of the hypertension in CKD and ESRD. (See this, this, and most importantly this editorial review) So maybe when SYMPLICITY-3 excluded patients with GFR's less than 45 they were excluding the very patients where the treatment would be most effective.
Thought three is that maybe in an effort to increase enrollment there were more inexperienced doctors doing the ablation. Unlike renal artery and coronary artery stenting there is no convenient sympathetic nerve ablation analog to TIMI-3 flow. At the end of the procedure the team has no idea if they successfully and adequately ablated the nerves. This could be a confounder.
It will be interesting in subgroup analysis pif they find a signal pointing to efficacy being related to operator experience or a signal to better efficacy with worse GFR.