Rise in Endovascular Therapy for PAD Parallels Improved Outcomes

Key Points:
Endovascular treatment for PAD has waxed as surgery has waned
Contemporary PAD patients tend to be sicker
Nonetheless, decreases seen in major amputations, mortality

From: TCTMD - The Source for Interventional Cardiovascular News and Education
By Kim Dalton
Wednesday, January 13, 2010


Over the past decade, as angioplasty increasingly displaced surgery for revascularization of peripheral arterial disease (PAD), rates of major amputation as well as mortality and other complications declined. The shift occurred despite patients presenting with more comorbidities, according to a study published online January 4, 2010, ahead of print in the Journal of Vascular Surgery.
To evaluate the shift in treatment of lower-extremity PAD and the impact of this trend on different patient groups, investigators led by Roman Nowygrod, MD, of Columbia University Medical Center (New York, NY), analyzed data from the National Inpatient Sample as well as New York State inpatient and outpatient databases on patients at least 40 years old who underwent either surgical or endovascular lower leg procedures or major amputations from 1998 to 2007.
Comparing 2007 with 1998, hospitalizations for invasive treatment of lower-extremity PAD decreased slightly, from 192 to 183 per 100,000 people aged ≥ 40 years. However, the proportion of open vs. endovascular revascularizations changed substantially, with the former declining 67% while the latter almost doubled. Meanwhile, the per capita volume of major amputations decreased by 38%.
Although most procedures were performed for critical limb ischemia, the overall rate of lower-extremity revascularizations in this group declined by 20%, from 93 per 100,000 in 1998 to 75 per 100,000 in 2007. Likewise, the incidence of interventions (endovascular or open surgical) for other PAD diagnoses decreased slightly, from 78 to 70 per 100,000. On the other hand, after a stable period from 1998 to 2002, interventions for claudication increased by almost 50% from 2003 to 2007.
The rate of procedures for critical limb ischemia declined steeply for octogenarians (from 317 to 240 per 100,000) and more moderately for patients aged 65 to 79 years (199 to 160 per 100,000), while interventions for claudication increased for all age groups (≥ 40 years). Meanwhile, outpatient interventions increased for all PAD diagnoses in all age groups.
Differing Fortunes of Open vs. Endovascular Intervention

While the proportion of open procedures decreased, use of endovascular revascularization increased substantially, quadrupling for critical limb ischemia and doubling for claudication.

Over the same period, rates of major amputations declined from 42% to 30% for critical limb ischemia, from 0.9% to 0.3% for claudication, and from 18% to 14% for other PAD diagnoses. Importantly, the improvement in patients with critical limb ischemia occurred despite the fact that they were twice as likely to have diabetes and 3 times more likely to have renal disease as those with claudication. In fact, comparable reductions in major amputations were seen in both diabetics (27%) and nondiabetics (32%).
Complications Decline for Both Revascularization Strategies
Over the study period, even as the prevalence of comorbidities such as CAD, COPD, renal disease, and (among claudicants) diabetes increased, operative mortality rates decreased for both revascularization procedures, as did postoperative cardiac complications, bleeding, and stroke. In addition, the incidence of infection declined with endovascular revascularization.

The mean length of hospital stay also declined over the decade, from 9.5 days in 1998 to 7.6 days in 2007. In addition, 35% of patients were discharged within 1 to 2 days in 2007, compared to only about 16% in 1998.
“Our analysis of national inpatient and outpatient state data supports the trend toward increasing treatment of PAD by endovascular intervention,” the authors write, predicting that given the safety of the minimally invasive approach, the percentage of outpatient procedures is likely to continue to grow.
The investigators caution that “although the decline in amputation rates seems likely due in large part to the increased use of endovascular interventions, other variables are clearly operative, including improved endovascular technology, better diabetes management and foot care, and improving and more ubiquitous application of medical therapies.”
In addition, the study findings are based on administrative data and thus subject to certain limitations, the authors note. For example, the absence of anatomic characteristics and condition variables precluded a careful analysis of treatment groups. Also, the inability to track patients over time meant they could not distinguish primary from secondary interventions, readmission, or complications.
Endovascular Trend Justified
“This is a very important paper,” William A. Gray, MD, of Columbia University Medical Center (New York, NY), told TCTMD in a telephone interview. “It both validates trends that we have perceived in the [vascular] community and justifies the increased use [of the endovascular approach] that it documents.”
“It’s not surprising that an easier, more accessible procedure is increasing,” Dr. Gray observed. “But that is nicely balanced by the fact that outcomes appear to be improving too—fewer mortalities, morbidities, shorter length of hospital stay. There are also fewer admissions for critical limb ischemia—likely because claudicants are being treated earlier. And treatment of claudicants may be leading to fewer patients with end-stage PAD.”
Though the study only reports hospitalization trends, “it speaks to the improvement in surveillance and care that these patients have been getting over the past decade, which is quite striking. This translates into a lot of saved limbs and lives,” Dr. Gray said, adding that it also reflects changes in the training of vascular surgeons, who are increasingly receiving instruction in endovascular techniques from fellow surgeons, as documented in a recent study in the Journal of Vascular Surgery.

Source:
Egorova NN, Guillerme S, Gelijns A, et al. An analysis of the outcomes of a decade of experience with lower extremity revascularization including limb salvage, lengths of stay, and safety. J Vasc Surg. 2010;Epub ahead of print.

Disclosures:
Drs. Nowygrod and Gray report no relevant conflicts of interest.

Pathway Medical Technologies Receives FDA 510(k) Clearance For JETSTREAM G3™ Atherectomy System

From: Medical News Today

Pathway Medical Technologies, Inc., an innovator of endovascular treatments for peripheral vascular disease (PVD), announced that the U.S. Food & Drug Administration (FDA) has granted the company 510(k) clearance to market JETSTREAM G3™, its newest peripheral revascularization catheter for the treatment of PVD. With a new distal cutter and enhanced aspiration efficiency, JETSTREAM G3 offers a significant improvement in cutting and removing disease as compared to previous versions. JETSTREAM G3 is used for treating the entire spectrum of disease found in the PVD patient, including hard and soft plaque, calcium, thrombus and fibrotic lesions.

"JETSTREAM G3 is the next step in atherectomy treatment for peripheral vascular disease. These enhancements incorporate a new state-of-the-art cutter that will enable physicians to treat PVD more quickly, safely and effectively than any of the existing technologies," said Pathway Medical Technologies President and CEO Paul Buckman. "Over the past twelve months Pathway has made significant advances to our atherectomy system. We believe that JETSTREAM G3 now represents the definitive treatment for all lesion morphologies, including calcium and total occlusions. We are fully committed to the continued development of innovative medical devices for the treatment of vascular disease."

"The JETSTREAM device is a highly effective technology for the treatment of occlusive and thrombotic peripheral arterial disease," stated Tom Shimshak MD, an interventional cardiologist and Director of the Cardiovascular Laboratory and Medical Director of the Cardiovascular Institute, Wheaton Franciscan Healthcare, All Saints, Racine, Wisconsin. "The advances in the cutting tip and increased power in the JETSTREAM G3 device will be particularly desirable for long, diffusely diseased segments, including calcification, chronic total occlusions and traditional 'no-stent' zones."

JETSTREAM is a peripheral revascularization catheter designed to remove all kinds of artery-clogging plaque in the lower limbs of patients. This innovative and minimally invasive solution clears blockages in the peripheral vasculature, restores blood flow and effectively treats PVD. JETSTREAM consists of a sterile, single-use catheter and control pod and a reusable, compact console that mounts to a standard I.V. stand. The catheter has an expandable cutting tip that safely debulks and preemptively removes both hard and soft plaque, as well as calcium, thrombus and fibrotic lesions. Excised tissue and thrombus are continually aspirated from the peripheral treatment site through ports in the catheter tip to a collection bag located on the console. The distal portion of the catheter also possesses infusion ports that provide continuous infusion of sterile saline during the atherectomy procedure. Active aspiration is a safety feature that minimizes the risk of distal embolization.

With simple set up and an ergonomic design for easy operation by trained clinicians, JETSTREAM maximizes treatment effectiveness and offers renewed hope for non-surgical candidates and the benefits of a minimally invasive treatment option, including faster recovery and decreased systemic complications.

Peripheral Arterial Disease (PAD)

Peripheral Arterial Disease (PAD) is also known as atherosclerosis, poor circulation, or hardening of the arteries. PAD progresses over time at variable rates in each individual depending on the area of circulation effected and one's health and family history. The signs and symptoms of PAD may not arise until later in life. For many, the outward indications will not appear until the artery has narrowed by 60 percent or more.

One method the body uses to adapt to the narrowed arteries is the development of smaller peripheral arteries that allow blood flow around the narrowed area. This process is known as collateral circulation and may help explain why many can have PAD without feeling any symptoms.

When a piece of cholesterol, calcium or blood clot abruptly breaks from the lining of the artery or a narrowed artery blocks off completely, blood flow will be totally obstructed and the organ supplied by that artery will suffer damage. The organs in PAD most commonly affected and researched are the legs.

What happens if the disease worsens?

The severity of PAD depends on when it is detected and any pre-existing health factors; especially smoking, high cholesterol, heart disease or diabetes. In the later stages, leg circulation may be so poor that pain occurs in the toes and feet during periods of inactivity or rest. This is especially true at night. This is known as rest pain, which usually worsens when the legs are elevated and is often relieved by lowering the legs (due to the effects of gravity on the blood flow).

Critical Limb Ischemia

The most advanced stages of PAD can lead to Critical Limb Ischemia (CLI) . Here the legs and feet have such severe blockage that they do not receive the oxygen rich blood required for growth and repair of painful sores and even gangrene (dead tissue). This condition, if left untreated, may require amputation.

Saving limbs with drug-eluting stents

July 16, 2009
Saving limbs with drug-eluting stents
Filed under: Uncategorized — reducedapmiami @ 1:55 pm

Attempts to explore deprecatory limb ischemia in peripheral arterial disorder (PAD) patients with unworthy of-the-knee angioplasty are still thwarted by restenosis (the re-narrowing of the artery at the situate of angioplasty or stenting), the extremity due to the fact that replay treatments and the continued progression of atherosclerotic complaint, leading to tissue death (gangrene) and amputation.

Interventional radiologists have been studying a potential solution - the use of drug-eluting stents - and have found that these types of stents lessened the rate of repeat procedures to open these small arteries, according to results presented at the Society of Interventional Radiology’s 34th Annual Scientific Meeting.

“This is encouraging news for PAD patients with critical limb ischemia. The smaller blood vessels below the knee are more difficult to treat due to their size (3 millimeters) and are more prone to reclog than larger vessels. The use of drug-eluting stents in the tiny infrapopliteal arteries of the leg may significantly impact their care,” said Dimitris Karnabatidis, M.D., assistant professor of interventional radiology at Patras University Hospital in Rion, Greece. “Drug-eluting (or drug-coated) stents have emerged as a potential solution to the limitations of endovascular treatment of PAD patients with critical limb ischemia,” he added. An interventional radiologist performs a balloon angioplasty to open a clogged blood vessel and then places a drug-eluting stent in that artery. The stent acts as scaffolding to hold the narrowed artery open. Drug-eluting stents slowly release a drug for several weeks to block cell proliferation or regrowth, thus inhibiting restenosis.

Researchers from a single center studied 103 patients in a double-arm prospective registry who had critical limb ischemia and who underwent infrapopliteal revascularization with angioplasty and placement of either a drug-eluting stent (with sirolimus, an immunosuppressant drug) or a bare-metal stent (without a drug coating). The patients had regular follow-ups up to three years, and researchers studied how they did by stent type. In the first group, 41 patients (75.6 percent diabetics) were treated with bare-metal stents, and in the second group 62 patients (87.1 percent diabetics) were treated with drug-eluting stents.

At three years, those patients with drug-eluting stents had “significantly higher patency” (length of time the blood vessels stayed open and moved blood flow efficiently); reduced restenosis of the vessels; and consequently less clinical recurrence requiring repeat angioplasty, said Karnabatidis. “In the drug-eluting stent group, an estimated 60 percent of the treated arteries remained open at three years. This is significantly longer than the bare-metal stent group, where the arteries remained open only approximately 10 percent at 3 years,” said Karnabatidis. “This corresponds to a more than 5 times increased risk of vessel reclogging when bare metal stents were used,” he added. “Because of the reduced vessel restenosis, repeat angioplasties were necessary in only 15 percent of the patients in the drug-eluting stent group versus almost 35 percent in the bare-metal stent group up to 3 years - this being the equivalent to an almost 2.5-fold risk of repeat procedures in the case of bare metal stents,” noted Karnabatidis. “These statistical results are based on three-year adjusted survival analysis after application of a Cox model for multivariable analysis,” he explained.

If a person has critical limb ischemia, it means he or she is at great risk for tissue death due to lack of blood flow, which carries oxygen and nutrients to the cells. The severely restricted blood flow results in severe pain in the feet or toes, even while resting, and sores and wounds that will not heal. Tissue death (gangrene) and amputation are imminent at this advanced stage of PAD, which is caused by atherosclerosis, the hardening and narrowing of the arteries over time due to the buildup of fatty deposits called plaque.

“Multicenter randomized trials are necessary to support these promising results and build on the level of clinical evidence supporting the integral value of infrapopliteal drug-eluting stents in critical limb ischemia treatment,” he added. In the United States, drug-eluting stents are FDA-approved for the coronary arteries but not for infrapopliteal arteries. In Europe, drug-eluting stents have CE Mark approval for below-the-knee use.

http://www.sirweb.org/

Critical Limb Ischemia

From Woundresearch.com

Critical Limb Ischemia
PUBLICATION DATE: Aug 01 2008
Issue:
8

author:
Laura Bolton, PhD, FAPWCA

Dear Readers:
Critical limb ischemia (CLI), the most severe stage of peripheral arterial disease, affects 250,000 new patients annually in the United States with an estimated 40% requiring amputation within 12 months of a CLI episode, in addition to an annual mortality rate of more than 20%.1,2 Distal bypass surgery prompts healing of lower extremity ulcers associated with CLI if resulting arterial patency supports skin perfusion pressure of at least 35 mmHg.3 Surgical bypass of the occluded arterial segment improves3,4 and extends primary arterial patency, though there is insufficient evidence to support improved amputation rates or mortality compared to most other modalities.4 What options are available to the individual for whom bypass surgery is no longer feasible? This month’s Evidence Corner reviews two studies evaluating efficacy of modalities for treating CLI in patients without further vascular surgery options, as the search for an effective treatment of CLI continues.
Critical Limb Ischemia
Reference: Kavros SJ, Delis KT, Turner NS, et al. Improving limb salvage in critical ischemia with intermittent pneumatic compression: a controlled study with 18-month follow-up. J Vasc Surg. 2008;47(3):543–549.
Rationale: Intermittent pneumatic compression (IPC) is a noninvasive method of increasing arterial circulation and ameliorating intermittent claudication in patients with peripheral arterial disease (PAD).
Objective: Evaluate clinical efficacy of IPC in patients with chronic CLI, nonhealing foot ulcers, and minor toe or transmetatarsal amputation after further options for arterial revascularization had been exhausted.
Methods: This retrospective cohort study compared two similar groups, each consisting of 24 consecutive patients, for whom further surgical bypass was not an option, and were cared for in a multidisciplinary community clinic from 1998–2004. Resting ankle-to-brachial ratios of systolic blood pressure (ABI), sitting transcutaneous oximetry (TcPO2) duplex graft surveillance, and foot radiography confirmed vascular status. Both groups received weekly debridement and biologic dressings for tissue loss and nonhealing amputation wounds of the foot due to CLI. Intermittent pneumatic compression allocation was based solely on a patient’s willingness to use it. The IPC inflation pressure was 85 mmHg to 95 mmHg and was applied for 2 seconds with a 0.2-second rise, 3 cycles per minute, for three 2-hour daily sessions. Adherence was monitored closely. Healing outcomes were “favorable” if complete healing with limb salvage occurred during 18 months. Outcomes were considered “adverse” if nonhealing caused below-knee amputation during that time.
Results: Groups were comparable at baseline on all arterial and wound parameters; prior amputation and comorbid factors were assessed. Four patients (17%) in the control group and 14 IPC (58%) patients healed (P < 0.01). The likelihood of limb loss in the control group was 7 times that of IPC subjects who also increased in TcPO2 (P = 0.0038).
Authors’ Conclusions: When used within a protocol of standard wound care, IPC significantly improves clinical healing and below-knee amputation outcomes of patients with inoperable CLI. This research sets the stage for rigorous prospective, multicenter, randomized, controlled trials (RCTs) of IPC to establish its role in healing while clarifying its indications for use.
FGF-1 Gene Therapy Decreases Amputation Rates in Patients With CLI
Reference: Nikol S, Baumgartner I, Van Belle E, et al. Therapeutic angiogenesis with intramuscular NV1FGF improves amputation-free survival in patients with critical limb ischemia. Mol Ther. 2008;16(5):972–978.
Rationale: Although controversial, with its long-term effects under scrutiny, angiogenic growth factor therapy has been proposed for treatment of critical limb ischemia in end-stage PAD. Acidic fibroblast growth factor (FGF-1) is a potent mitogen for vascular endothelial cells, inducing blood vessel formation in vitro and in vivo. A plasmid-based gene transfer delivery system for FGF-1, NV1FGF with “Conditional Origin of Replication” (pCOR), reduces the potential for propagation in the host environment while sustaining local FGF-1 production permitting less frequent treatment.
Objective: A Phase 2b, double blind, randomized, placebo-controlled clinical trial investigated the efficacy and safety of intramuscular NV1FGF versus placebo in subjects with CLI at high risk of amputation.
Methods: A European multicenter trial screened 125 patients with CLI ineligible for revascularization as confirmed by a vascular surgeon. Each patient had at least 1 nonhealing ulcer, a TcPO2 £ 20 mmHg, ankle pressure
£ 70 mmHg, and toe pressure £ 50 mmHg. Patients were randomly assigned to receive 8 intramuscular injections of 2.5 mL NV1FGF in a 0.2 mg/mL solution (n = 59) or similar placebo injections (n = 56) on study days 1, 15, 30, and 45. Percent of patients with at least 1 ulcer completely healed at week 26 was the primary outcome. Secondary outcomes TcPO2, ABI, amputation, and death were evaluated at week 52.
Results: Among 107 subjects evaluated for healing, 19.4% of NV1FGF-treated and 14.3% of control patients healed during 26 weeks (P = 0.514; not significant). Likelihood of amputation or of major amputation was reduced in the NV1FGF group (P = 0.011), which also experienced improvement in time to death or major amputation. No other secondary outcomes were statistically significant. Adverse events were comparable in both groups, supporting the safety of NV1FGF.
Authors’ Conclusions: This was the first double blind, prospective RCT in patients ineligible for bypass surgery. Despite the fact that no improvement in wound healing was seen it showed the potential for NV1FGF to significantly reduce amputation risk, potentially lowering mortality rates in these high-risk patients.

Clinical Perspective
Both publications aim to improve the lot of patients with serious vascular impairment, using either biochemical or physical modalities. Plasmid gene transfer of NV1FGF administered once every 2–3 weeks for the first 7.5 weeks of care appears to save limbs, though its effect on ischemic ulcer healing remains uncertain. Other plasmid growth factors either lack healing and amputation effects5 or heal wounds without reducing amputation.6 The capacity to save limbs in high-risk patients for whom surgery is no longer an option is equally compelling for NV1FGF and IPC. Limb salvage plus the healing benefits of properly applied IPC are unprecedented, although it was a small retrospective study and was potentially biased by selection of IPC-willing patients. Larger prospective RCTs on patients with CLI, perhaps comparing IPC with and without NV1FGF, would seem necessary. As a physical modality, IPC may be compatible with gene or biochemical therapy. These studies open potential care options for patients with CLI who are faced with possible amputation.

References:
1. Dormandy J, Heeck L, Vig S. The fate of patients with critical leg ischemia. Semin Vasc Surg. 1999;12(2):142–147.
2. Dormandy J, Mahir M, Ascady G, et al. Fate of the patient with chronic leg ischaemia: A review article. J Cardiovasc Surg. 1989;30(1):50–57.
3. Tsuji Y, Hiroto T, Kitano I, Tahara S, Sugiyama D. Importance of skin perfusion pressure in treatment of critical limb ischemia. WOUNDS. 2008;20(4):95–100.
4. Fowkes F, Leng GC. Bypass surgery for chronic lower limb ischaemia. Cochrane Database Syst Rev. 2008 Apr 16;(2):CD002000.
5. Powell RJ, Simons M, Mendelsohn FO, et al. Results of a double-blind, placebo-controlled study to assess the safety of intramuscular injection of hepatocyte growth factor plasmid to improve limb perfusion in patients with critical limb ischemia. Circulation. 2008;118(1):58–65.
6. Kusumanto YH, van Weel V, Mulder NH, et al. Treatment with intramuscular vascular endothelial growth factor gene compared with placebo for patients with diabetes mellitus and critical limb ischemia: a double-blind randomized trial. Hum Gene Ther. 2006;17(6):683–691.