Critical limb ischemia treatment shows no improvement at three months

March 12, 2018, American College of Cardiology

Patients with foot ulcers or gangrene who received the experimental drug JVS-100 did not show evidence of faster wound healing, compared with those receiving a placebo, in a study presented at the American College of Cardiology's 67th Annual Scientific Session.

The study focused on with a condition known as critical limb ischemia, which occurs when the arteries that supply blood to the limbs (typically the legs) become stiffened or blocked. A lack of adequate blood to the extremities can lead to painful skin lesions or gangrene sores that persist for months or years.

The only available treatment for the condition is , a procedure to restore blood flow by either inflating a balloon to open a blocked artery or by grafting a new blood vessel to bypass the blocked one. While revascularization can help blood flow through the major arteries in the legs, it does not necessarily restore adequate blood flow to the smaller blood vessels closer to the skin surface, where lesions can fester. JVS-100 is an designed to improve blood flow in those smaller blood vessels.

JVS-100 is a biologic therapy that delivers DNA that encodes proteins involved in the production of blood vessels. Its developers had hoped it would stimulate the growth of vessels to provide more routes for blood to reach blood-starved tissue.

The study, which enrolled 109 patients at 25 centers in the U.S., assessed whether JVS-100 helped wounds heal when used in concert with revascularization. In the trial, only about a quarter of patients' wounds had healed completely three months after undergoing revascularization. That proportion was the same for patients who received the experimental drug and those who received a placebo.

"These results clearly highlight the need for identifying additional therapies, or perhaps combinations of therapies, that could help these patients," said Mehdi Shishehbor, DO, PhD, MPH, director of the cardiovascular interventional center at University Hospitals Harrington Heart and Vascular Institute and the study's lead author. "The fact that only about 25 percent of these patients had healed at three months, despite being in a very rigorous, highly monitored environment both from the standpoint of wound healing and revascularization, makes us even more motivated to continue to seek additional therapies."

Patients were randomly assigned to receive either JVS-100 or a placebo in a series of two injections, one within 12 days of their revascularization procedure and one three months later. Half of those receiving JVS-100 were given a higher dose of the experimental drug and half were given a lower dose. Neither the patients nor those administering the injections knew which patients received the drug and which received the placebo.

All patients had undergone revascularization for critical limb ischemia but showed poor blood flow to the toe (scoring 0.51 or less with a measurement called toe brachial index, or TBI) after the procedure. Most of the patients suffered from multiple illnesses; 90 percent had diabetes and 7 percent were on dialysis. Diabetes can speed up the accumulation of deposits in arteries, including smaller ones, which in turn increases the risk of and amputation.

The researchers tracked wound healing as well as rates of death, amputation and major adverse limb events (MALE), a combined endpoint that includes major amputation, bypass or balloon revascularization in the affected limb. In addition to low rates of , the researchers found high rates of adverse events in both groups. Three months after the initial injection, 15 percent of patients in the and 20 percent of patients in the treatment group had undergone amputation. The overall MALE rate was 9 percent in the placebo group and 14 percent in the treatment group. Additionally, 21 percent of those in the placebo group and 30 percent of those in the treatment group saw their wounds grow by 25 percent or more during the three-month follow-up. Differences in the rates of these outcomes were not statistically significant between groups.

A unique aspect of the study, according to Shishehbor, was its close assessment of flow in the smaller arteries at baseline and during follow-up using TBI. Despite undergoing extensive revascularization to improve , none of the patients achieved a normal TBI (greater than 0.71) after revascularization or at three months. There was no significant difference in TBI at three months between the treatment and groups.

The researchers will continue to track patient outcomes for at least 12 months.

"We are very much looking forward to the six-month data," Shishehbor said. "Based on those results, we will determine whether we will investigate this biologic therapy in a longer study, or perhaps consider studying a combination therapy that involves more than one biologic therapy."

Explore further: Dabigatran reduces major CV complications in patients with myocardial injury after noncardiac surgery

Related Stories

Dabigatran reduces major CV complications in patients with myocardial injury after noncardiac surgery

March 12, 2018
Treatment with the blood-thinning drug dabigatran significantly reduced the risk of death, heart attack, stroke and other heart or blood-vessel complications among patients who were at elevated risk for these events because ...

Statins may bring benefits at time of treatment for heart attack, angina

March 12, 2018
Getting a large dose of a statin did not have an impact on major adverse cardiac events among a broad population of patients slated to undergo percutaneous coronary intervention (PCI), a procedure to clear blocked arteries, ...

Alirocumab reduces cardiovascular events after acute coronary syndrome

March 12, 2018
Among patients with persistently high cholesterol despite high-intensity statin therapy, the proprotein convertase subtilisin-kexin 9 (PCSK9) inhibitor alirocumab reduced rates of major adverse cardiovascular events (MACE) ...

Heart attack risk increases with six-month dual antiplatelet therapy

March 12, 2018
The combined rate of death from any cause, heart attack or stroke within 18 months was not significantly different in patients with acute coronary syndrome (ACS) who were randomly assigned to receive dual antiplatelet therapy ...

Restoring leg blood flow is better option than exercise for PAD patients

May 6, 2016
Restoring blood flow to the legs of patients with peripheral artery disease (PAD) may stop the progression of scarring in their leg muscles, according to preliminary research presented at the American Heart Association's ...

New angioplasty procedure improves blood flow in blocked arteries to extremities

July 24, 2012
Patients with blocked arteries to their extremities, known as peripheral artery disease (PAD) or critical limb ischemia (CLI), may now find relief from lower leg pain and wounds caused by impaired leg artery circulation with ...

Recommended for you

Prosthetic valve mismatches common in transcatheter valve replacement, ups risk of death

September 24, 2018
In the largest multi-institutional study to date, led by researchers from Penn Medicine, the team found that among patients who underwent a transcatheter aortic valve replacement (TAVR), a high number experienced severe and ...

Study reveals a promising alternative to corticosteroids in acute renal failure treatment

September 21, 2018
A protein produced by the human body appears to be a promising new drug candidate to treat conditions that lead to acute renal failure. This is shown by a study conducted at São Paulo State University (UNESP) in São José ...

Can a common heart condition cause sudden death?

September 20, 2018
About one person out of 500 has a heart condition known as hypertrophic cardiomyopathy (HCM). This condition causes thickening of the heart muscle and results in defects in the heart's electrical system. Under conditions ...

New drugs could reduce risk of heart disease when added to statins

September 20, 2018
New drugs that lower levels of triglycerides (a type of fat) in blood could further reduce the risk of heart attack when added to statins. These new drugs, which are in various stages of development, could also reduce blood ...

Mediterranean-style diet may lower women's stroke risk

September 20, 2018
Following a Mediterranean-style diet may reduce stroke risk in women over 40 but not in men—according to new research led by the University of East Anglia.

Inflammation critical for preventing heart attacks and strokes, study reveals

September 19, 2018
Inflammation, long considered a dangerous contributor to atherosclerosis, actually plays an important role in preventing heart attacks and strokes, new research from the University of Virginia School of Medicine reveals.

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.