January 22nd, 2015

New Device to Lower Resistant Hypertension Shows Early Promise

A novel implantable device appears to show early promise in the treatment of resistant hypertension. The “Coupler” device from ROX Medical is about the size of a paper clip and is delivered via a catheter to the upper thigh, where it creates an anastomosis between the distal external iliac vein and artery, thereby mechanically lowering blood pressure.

In a paper published in the Lancet, European investigators report the results of an open-label trial in in which 83 patients with persistent high blood pressure despite taking multiple antihypertensive drugs were randomized to implantation of the Coupler device or current treatment. After six months there were large and highly significant reductions in blood pressure in the treatment group but not in the control group: systolic BP measured in the office decreased by 26.9 mm Hg in the treatment group versus 3.7 mm Hg in the control group; systolic blood pressure measured by a 24-hour ambulatory monitor decreased 13.5 mm Hg in the treatment group versus 0.5 mm Hg in the control group. The same pattern was evident in the group of 17 who had previously undergone renal denervation.

Twenty-nine percent of patients who received the device developed edema in the leg caused by venous stenosis, which was treated with venoplasty or stenting. Three patients in the control group and none in the treatment group were admitted to the hospital for a hypertensive crisis.

In their discussion the investigators pointed out that, unlike renal denervation as it has been performed in the past, “technical success with the arteriovenous coupler is documented during the procedure and is associated with an immediate fall in blood pressure. This difference eliminates the placebo effect and isolates the sham effect to an interaction between a patient’s knowledge of treatment allocation with longer-term clinical behaviors.” In a press statement, Melvin Lobo, the study principal investigator, said:

This is an entirely new and highly promising concept in high blood pressure treatment. Existing drugs focus on hormonal or neurological regulation of blood pressure, and newer treatments such as renal denervation are uniquely centered on the renal nervous system. The Coupler effectively targets the mechanical aspects of how blood circulation works — so it’s a totally new approach to controlling blood pressure. The Coupler also highlights the importance of arterial stiffness as a major cause of resistant high blood pressure and it targets this issue both safely and successfully. Once the Coupler is placed, the results are also immediate, which again is unique to this treatment.”

Hypertension experts Franz Messerli and Sripal Bangalore offered the following comment:

This is an exceedingly provocative study identifying a novel mechanism to treat hypertension. By creating an arterio-venous anastomosis with an arterio-venous coupler, the investigators create an additional big branch in a stiff arterial tree, thereby improving  overall arterial compliance, restoring the Windkessel function and of course, lowering peripheral resistance and blood pressure. In contrast to renal denervation, this innovative technique is straightforward and easy to understand. However, as fascinating as such an approach  of “letting off steam” in a high pressure system seems at a first glance, a few items will have to be scrutinized. Most important will be the long-term sequelae to the local venous system that now will have to bear the brunt of a potentially destructive hemodynamic burden. Could several small shunts possibly be better tolerated than a single large one? Are we setting the stage for a high-output heart failure situation?  And of course after the sobering results of Symplicity HTN-3, we have become skeptical about interventional studies without a sham control. Finally, if this really were to work, shouldn’t there be little or no hypertension in our dialysis patients with arterio-venous fistula?”


3 Responses to “New Device to Lower Resistant Hypertension Shows Early Promise”

  1. I received a late comment from Deepak Bhatt, co-principal investigator of the Simplicity HTN-3 trial of renal denervation. Here is his response to the Lancet paper:

    “Lack of a sham control is a limitation, as the authors acknowledge. However, practically speaking, it would have been difficult to do a sham procedure here, as it involves creation of an AV shunt. I suppose the patients could have been randomized to a sham femoral puncture. However, the authors indicate that the blood pressure dropped right after the procedure. If substantial effect does manifest right away, that makes the need for a sham control much less. I think the bigger issues here have to do with the fact that a third of the patients developed symptomatic venous stenosis, which was easily treated in this small study, but in a larger population might lead to DVTs and PEs. The created shunt appears to be small enough not to cause high output heart failure, but that really would need to be confirmed in a much larger study before this device would be ready for actual clinical use.”

  2. The long term consequences of having an AV fistula in place really needs to be ironed out here.
    Not only have AV fistulae been implicated in high output heart failure, but also pulmonary vascular remodeling and pulmonary arterial hypertension. Thus, although the pressures are lower, long term follow up will be critical to ensure there are not significant sequelae.

  3. And here’s another late comment from David Kandzari, who was the other co-PI of the Symplicity HTN-3 trial:

    Overall, despite the commonality with renal denervation to treat hypertension, the method of study with this technology does not follow the same model as renal denervation. I do think the comments regarding need for sham controls represent unfamiliarity with this therapy and highlight differences from therapies such as renal denervation, for which there is an opportunity to blind patients to treatment. In this case, blood pressure reductions are immediately apparent, and the palpable thrill and audible bruit with creation of an arteriovenous fistula is unmistakable to both patient and practitioner. Moreover, lower extremity edema is also an indicator of successful treatment. Concerns regarding high output heart failure are reasonable, but keep in mind that hemodialysis results in creation of a much greater shunt and is considered an acceptable therapy. To be sure, a larger pivotal trial is needed before this therapy could be adopted in routine practice, but the differences between this technology and renal denervation highlight that one size does not fit all for (studying) and treating resistant hypertension.