I know that for you and the world, your primary focus is the CoVid pandemic and that is entirely right. #ACC2020 is currently ongoing and if you will forgive me, I will run a thread on the results of one of the late-breakers.
The trial I'm going to discuss is the SPYRAL PIVOTAL OFF MED trial of renal denervation, which has just been released as a late-breaker.
Renal Denervation? That doesn’t work does it?! Well, since 2014, that has been the mountain to climb. Symplicity HTN-3 was negative. Why was that?
Several reasons – imperfect circumferential denervation of the renal artery; extensive medication changes between treatment and the primary blood pressure assessment; severe HT with 5 meds amongst them
Perhaps the most important recent finding is that renal nerves start far away from the artery at the origin & converge on the renal arterial bifurcation distally, meaning the technique needed to adapt to ensure successful denervation with RF ablation 
The SPYRAL catheter was designed to make circumferential renal artery denervation more likely by denervating 4 points at once. The catheter used in Symplicity 1, 2 and 3 trials was a single-point catheter that may have been less reliable.
The results from the pivotal trial of RDN in mild-moderate hypertension, whereby we could safely test RDN against a sham procedure in patients who were not taking any medications were released today: the SPYRAL PIVOTAL OFF MED trial
The trial has been published today in The Lancet and is available on the website now. thelancet.com/journals/lance…
The design was very similar to that of SPYRAL OFF trial - published in the Lancet in 2017.
This design similarity allowed a relatively novel trial design in cardiology – a Bayesian design with an informative prior. The results from the pilot study were used to power the PIVOTAL study and folded into the sample size (The FDA supported the design)
Now the results…
Does Renal Denervation lower blood pressure in patients with hypertension over & above sham? *Yes*.
The primary endpoint was 24hr Systolic BP, which showed a 4.7mmHg fall, compared to 0.6mmHg with sham (diff 4.0mmHg; p<0.001 for sig). Similar results to pilot study.
The primary endpoint was 24hr Systolic BP, which showed a 4.7mmHg fall, compared to 0.6mmHg with sham (diff 4.0mmHg; p<0.001 for sig). Similar results to pilot study.
The 24-hour ABPM profiles were also encouraging. Note the separation during night-time and early morning, before the morning surge in BP comes.
Office BP was a secondary endpoint but it is what most doctors use to guide day-to-day BP management. It showed a 9.2mmHg drop with denervation versus 2.5mmHg fall with sham (p<0.001); again, similar to the results of the pilot study.
So does RDN lower blood pressure? Yes, it does. There have been several sham-controlled studies in the last three years, with different patients, different researchers & different technologies showing similar results – RDN does lower BP
OK, it works. But is that sort of BP fall *really* important? The RDN arm fell by 4-5 points on ABPM and 9-10 points on office BP across the three recent studies, including this one. Is that important?
Well, if we achieved a 10mmHg drop in office systolic BP with a drug, what would be the expected benefit?
Falls of 4-5mmHg in ABPM would be expected to produce similar benefits.
Do we know that RDN would produce something similar to drugs? No, though we do get similar effects from non-pharmacological measures of blood pressure reduction so it seems likely that we would with RDN.
Do we know that RDN would produce something similar to drugs? No, though we do get similar effects from non-pharmacological measures of blood pressure reduction so it seems likely that we would with RDN.
What next? SPYRAL HTN ON MED should report next year, a trial of RDN in >200 patients whose blood pressure is uncontrolled despite the use of 1,2, or 3 medicines. The SPYRAL DYSTAL trial is also about to start, looking at a leaner treatment technique to shorten the procedure.
Why do we need RDN? Because 30-50% of patients with hypertension continue to be uncontrolled after decades of more than enough drugs than we could possibly want.
Many patients do not like medications, do not take medications and/or do not tolerate medications. New treatments are required. RDN is not going to cure hypertension outright, but it lowers BP with an effect size similar to that of one anti-hypertensive drug.
We continue to refine our understanding of the procedure and the patient response, in an effort to better control blood pressure - the chronic disease that is responsible for half of all heart attacks and two thirds of all strokes.
Summary: RDN reduces blood pressure. The effect size is similar that seen with a single drug. The effect works day and night and we now have another tool in the fight against hypertension - the number one cause of death worldwide. Thanks.
