SMAC AF: BP-Lowering Alone Won't Improve Ablation Success

John M. Mandrola, MD; Jonathan P. Piccini, MD, MHS


December 05, 2016

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John M. Mandrola, MD: Hi, everyone. This is John Mandrola from on Medscape, and I am here in New Orleans at the 2016 American Heart Association sessions. I am happy to have Jonathan Piccini, an Associate Professor at Duke, here with me to discuss an important Canadian trial called SMAC AF.[1] This was a randomized controlled trial looking at the effect of aggressive blood pressure lowering on ablation outcomes in patients with atrial fibrillation (AF). Welcome, John.

Jonathan P. Piccini, MD, MHS: Thank you for having me.

Dr Mandrola: Can you tell us about the background of this trial?

Dr Piccini: Sure. Dr Parkash and colleagues[1] randomly assigned about 180 patients who were undergoing catheter ablation for AF that was paroxysmal and persistent but not longstanding. What they did was randomly assign patients 1:1 to either aggressive blood pressure reduction with a goal blood pressure of 120/80 mm Hg with a stepped program or standard treatment. They then followed patients out to 1 year and beyond to look at recurrent AF as a function of aggressive blood pressure monitoring.

Dr Mandrola: They were doing blood pressure lowering before the patients even had ablation. What were they thinking?

Dr Piccini: The goal was to decrease substrate progression and hopefully lead to improved outcomes. I think it is well known that catheter ablation is highly effective for the treatment of drug-refractory AF. We also know that recurrences are very common in long-term follow-up. Because hypertension has been a risk marker for recurrent AF after ablation, and because important clinical trials like ARREST-AF have shown that risk factor modification can reduce recurrences of AF after ablation, they wanted to test the hypothesis that if you could control blood pressure even better and aggressively reduce it to 120/80 mm Hg, you would see less AF recurrence after ablation.

Dr Mandrola: How did they go about this? This was an investigator-driven trial.

Dr Piccini: That is right, a multicenter trial using a stepped program of medications, including an angiotensin-converting enzyme inhibitor, a thiazide diuretic, a calcium channel blocker, a beta blocker, and an alpha blocker.

Dr Mandrola: That strategy was pretty good at reducing blood pressure.

Dr Piccini: Absolutely. They not only reduced blood pressure, but they were able to keep it reduced throughout the 12 months of follow-up.

Dr Mandrola: What were the results?

Dr Piccini: There were no significant difference in recurrent atrial arrhythmias defined as 30 seconds or more at 12 months.

Dr Mandrola: What about the secondary outcomes?

Dr Piccini: Of note, there actually was an increase in AF-related hospitalizations in the aggressive arm, probably driven by hypotensive episodes because the patients were on larger amounts of medical therapy.

Dr Mandrola: I am going to ask you why you think the trial was negative, but what were their conclusions?

Dr Piccini: Their conclusions were that aggressive treatment of blood pressure in the settings of the clinical trial did not appear to improve outcomes and that, in the future, we are going to have to look at things like the duration of therapy and additional interventions to be able to tell if it is a cogent strategy.

Dr Mandrola: This is a little bit provocative because Dr Sander's group from Adelaide has shown in the ARREST-AF trial[2] that risk factor modification can yield about fivefold better outcomes after AF ablation. Here is a trial that shows clearcut blood pressure lowering but no change. What is up with that?

Dr Piccini: When you have differences between two very important trials, I think it is a huge learning opportunity for all of us in the field. When you look at SMAC AF, the only thing they did was improve blood pressure control. To be honest, the patients who started in the study were very close to the JNC-8 blood pressure targets to begin with. They were not that hypertensive. When you look at ARREST-AF, they not only improved blood pressure control, but there was significant weight loss, probably less obstructive breathing in the patients who had sleep apnea, and improved glycemic control, so I think one of the take-home messages is that improved blood pressure control in isolation is probably not enough to improve outcomes after AF ablation. You probably have to target multiple risk factors.

Dr Mandrola: Was it not true in ARREST-AF that there was more blood pressure lowering than there was in SMAC AF, or was it about the same?

Dr Piccini: It was about the same. If a patient loses a significant amount of weight, we know that it is going to improve their blood pressure. Perhaps that type of blood pressure lowering may be more physiologically important than iatrogenic blood pressure lowering with medical therapy.

Dr Mandrola: Wait, I want to emphasize that. Blood pressure lowering with weight loss and risk factor modification may be better than drug-induced blood pressure lowering.

Dr Piccini: Absolutely. Weight loss-associated blood pressure reduction probably has a lot of pleiotropic effects. It is not just one single physiologic target.

Dr Mandrola: To change the atrial substrate may take more than just a short-term lowering of blood pressure.

Dr Piccini: Absolutely. While the study did not have measures of atrial substrate such as MRI with delayed enhancement or changes in echo parameters, most of us in the clinic have seen those patients who lose a lot of weight—their sleep apnea goes away, their blood pressure improves, and their AF burden shrinks a great deal. I suspect the same exact thing is true with our catheter ablation patients.

Dr Mandrola: Great. Thank you for being here. I really appreciate our conversation.

Dr Piccini: It is a pleasure to be here. Thank you for having me.

Dr Mandrola: Thank you for watching. That is it from this session at the American Heart Association sessions here in New Orleans. This is John Mandrola from from Medscape.


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