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Drug-eluting stent favourable for treatment of patients with peripheral vascular disease

Thursday, 10 Jan 2013 10:41

Sumaria Macdonald, Freeman Hospital, Newcastle, UK, in a presentation at the British Society of Interventional Radiology’s (BSIR) Annual Meeting (14–16 November, Bournemouth, UK) told delegates that drug-eluting stents ease severe pain when walking in patients with peripheral vascular disease.

 The speaker said that balloon angioplasty was the most common treatment and was safe and effective. However, balloons, according to the speaker, were not a durable, long-term solution to intermittent claudication and patients suffered restenosis within one year after treatment.

MacDonald presented the data from five randomised trials and said that future trials for drug-eluting stent systems should have clinically meaningful end points such as restenosis, patency, and lesion revascularisation

Macdonald summarised the findings of a trial that compared the everolimus-eluting stent (Xience V, Abbott) against a bare-metal stent, and the data came out in favour of the everolimus-eluting stent. The trial data showed promising restenosis rate for the drug-eluting devices and were presented in comparison with balloon angioplasty at six months and with favourable one year patency.

She also said that the trials were conducted on long lesions and therefore they more accurately reflected real world practice.
As an alternative to balloon angioplasty, the speaker said, drug-eluting stents are an option as there is evidence to suggest that drug-eluting stents are more favourable to bare-metal stents and balloon angioplasty.

“There is a growing body of evidence to show that there are clear benefits of drug elution, in that they provide a more durable response to the treatment of intermittent claudication compared with standard therapies and may offer an improved quality of life to thousands of patients adversely affected in the UK,” MacDonald said.

“While drug-eluting technology does currently carry a higher initial cost per patient, commissioners should understand that by reducing the risk of a recurrent re-narrowing of the arteries, there is a strong cost effectiveness argument, with patients less likely to need further treatment freeing up an already stretched NHS hospital capacity,” she concluded.

Drug-eluting balloons significantly reduce late lumen loss in femoropopliteal artery disease compared with uncoated balloons

Friday, 14 Dec 2012 12:05

According to results from the PACIFIER (Paclitaxel-coated balloons in femoral indication to defeat restenosis) trial, led by Michael Werk, Martin Luther Hospital, Berlin, Germany, and published in Circulation: Cardiovascular Interventions, percutaneous transluminal angioplasty (PTA) with drug-eluting balloons (DEBs) is associated with significant reductions in late lumen loss and restenosis compared with angioplasty with uncoated balloons in patients with femoropopliteal artery disease.
In the study, 85 patients with femoropopliteal artery disease were randomised to receive percutaneous transluminal angioplasty with a paclitaxel-eluting balloon (41; IN.PACT Pacific, Medtronic) or angioplasty with an uncoated balloon (44; Pacific Xtreme, Medtronic). Six of these patients were re-randomised to receive additional treatment—five had a new femoropopliteal stenosis of the contralateral leg and one had a restenosis of the target lesion six months after the initial procedure. The patient with the restenosis was included twice because the restenosis developed after the primary endpoint was reached (late lumen loss at six months) and the restenosis was considered to be an identical target lesion. Therefore, there were a total of 91 randomised cases.

The primary endpoint of the study was late lumen loss at six months (assessed by quantitative angiography) and secondary endpoints were binary restenosis and Rutherford class change at six months, and target lesion revascularisation (TLR) plus major adverse clinical events (eg, death) at six and 12 months.

At six months, Werk et al observed from the quantitative angiography analysis, that drug-eluting balloons were associated with a significantly lower rate of late lumen loss compared with uncoated balloons: 0.01mm vs. 0.65mm, respectively (p=0.001). Also, there were fewer binary restonoses in the DEB group (8.6% for the DEB group vs. 32.4% for the uncoated balloon group; p=0.01). The authors reported that at the six month follow-up point, there were three cases of revascularisation in the drug-eluting balloon group compared with 10 cases of TLR (in nine patients) in the uncoated balloon group. They added that no additional cases of target lesion revascularisation for the drug-eluting balloon group were reported at the 12-month follow-up point compared with five additional cases in the uncoated balloon group.

Werk et al wrote that one of the implications of their study was that angioplasty with the IN.PACT Pacific DEB was “feasible and safe without extensive predilation” in femoropopliteal artery disease. They added the intervention also “significantly reduces restenosis entity and rates (ie, angiographic late lumen loss and binary restenosis) in comparison with state-of-the-art uncoated balloons. Such angiographic superiority translates into significant clinical benefits.”

The authors commented that angioplasty with stents (bare metal or drug-eluting stents) have been proposed as an alternative approach to standard angioplasty (with uncoated balloons) and have been shown to have “superior results”. However, Werk et al wrote that angioplasty plus stenting permanently changes the structure of the vessel and that “in-stent restensosis is more difficult to treat in non-stented segments”. They added: “Drug-coated balloons combine the advantages of local drug delivery (with ensuring inhibition of restenotic processes), but lacking any permanent implant typical of balloons.”

The PACIFIER trial, according to Werk et al, provides further evidence favouring the use of dug eluting balloons for femoropopliteal percutanous transluminal angioplasty.

They concluded: “This randomised clinical study of paciltaxel-coated balloon catheter in the femoropopliteal arteries confirms that potent inhibition of restenosis and reduction in target lesion revascularisation at one year. In agreement with previous studies, no coating-related adverse events were observed.”

One-year results from the Symplicity HTN-2 show sustained reduction in blood pressure with the Symplicity renal denervation system

Wednesday, 19 Dec 2012 12:42
Symplicity renal denervation system
Symplicity renal denervation system

Results from the Symplicity HTN-2, the first randomised clinical trial investigating renal denervation, were published online before print in Circulation, the Journal of the American Heart Association. These data showed patients, who initially received treatment with the Symplicity renal denervation system (n=47), sustained a significant drop in blood pressure (-28/-10 mm Hg [p<0.001]) compared to baseline at 12 months. The 12 month results demonstrated preservation of the benefit at six month follow-up (-32/-12 mm Hg). No device related serious adverse events, no late vascular complications, and no significant decline in kidney function were reported at 12 months.

The Symplicity renal denervation system is not approved by the US Food and Drug Administration (FDA) for commercial distribution in the United States. Also reported in the manuscript were six month results of 35 patients in the control group who received renal denervation after the primary endpoint was assessed at six months post randomisation (referred to as the crossover group). The crossover group also showed a significant drop in blood pressure six months after the renal denervation procedure (-24/-8 mm Hg [p<0.001]). This decrease in blood pressure is similar to the blood pressure reduction in the initial treatment arm at six months.

“We continue to see positive results from the Symplicity HTN-2 clinical trial, demonstrating consistent, long-term blood pressure reduction with the Symplicity system in patients with treatment-resistant hypertension, who have a three-fold increase in risk of cardiovascular events,” said Murray Esler, principal investigator of the Symplicity HTN-2 trial and senior director of the Baker IDI Heart and Diabetes Institute of Melbourne, Australia. “These data further substantiate the clinical benefits of renal denervation with Symplicity over longer periods of time in this difficult-to-treat patient group.”

Symplicity HTN-2 trial

The Symplicity HTN-2 trial is an international, multi-centre, prospective, randomised, controlled study of renal denervation in patients with treatment-resistant hypertension. One hundred and six patients were randomly allocated in a one-to-one ratio to undergo renal denervation with previous anti-hypertensive medication treatment or to maintain previous anti-hypertensive medication treatment alone (control group) at 24 participating centers. Patients in the control arm of the study were offered renal denervation following assessment of the trial’s primary endpoint at six months following randomisation.

Symplicity renal denervation system

The Symplicity system’s catheter and proprietary generator and algorithms were specifically developed for the renal denervation procedure. The Symplicityrenal denervation system was launched commercially in April 2010 and is currently available in parts of Europe, Asia, Africa, Australia and the Americas and has been used to treat patients with treatment resistant hypertension worldwide.

The Symplicity renal denervation system consists of a flexible catheter and proprietary generator. In an endovascular procedure, similar to an angioplasty, the physician inserts the small, flexible Symplicitycatheter into the femoral artery in the upper thigh and threads it into both renal arteries in turn. Once the catheter tip is in place within the renal artery, the Symplicitygenerator is activated to deliver a controlled, low-power radio-frequency energy routine according to a proprietary algorithm, or pattern, aiming to deactivate the surrounding renal nerves. This, in turn, reduces hyper-activation of the sympathetic nervous system, which is an established contributor to chronic hypertension. The procedure does not involve a permanent implant.

The FDA has granted Medtronic approval for the protocol for SYMPLICITY HTN-3, the company’s US clinical trial of the Symplicity renal denervation system for treatment.

EVAR as an ambulatory procedure is safe and can be performed in up to 40% of patients

Monday, 04 Feb 2013 10:30

Treating abdominal aortic aneurysm patients in an outpatient setting is feasible, with 0% mortality in a series conducted in Switzerland, according to data presented at the Controversies & Updates in Vascular Surgery symposium (17–19 January 2013) in Paris, France. Mario Lachat, University Hospital Zurich, Switzerland, told delegates that this type of procedure saves hospital costs and can be used in up to 40% of EVAR patients.
“Ambulatory surgery, also called same day home, day surgery, outpatient surgery, or surgery in outclinic patient, has shown significant clinical and economical advantages, but there is few information on these for EVAR or TEVAR cases,” Lachat said.
The first experience with EVAR in outpatients was reported by Jacques Bleyn, Antwerp Blood-vessel Center, Belgium, at the CX Symposium in 2003. In that experience, 23 patients treated underwent percutaneous EVAR with local anaesthesia between 1998 and 2002. All patients were discharged, with no deaths in the group. “Bleyn told me he had to stop this programme because of reimbursement issues,” Lachat stated.
Last year, Lachat added, a paper (Selection, 30-day outcome and costs for short stay endovascular aortic aneurysm repair, SEVAR) was published in the European Journal of Vascular and Endovascular Surgery by N Al-Zuhir et al. Out of 100 patients, the authors selected 33 patients to undergo short stay EVAR. They had a turndown rate of 19%, mainly due to logistics, challenging procedure and urologic complications.
Lachat noted that, accompanying the paper there was a commentary by HH Dosluoglu and ML Dryjski, which said: “There is a strong trend in the USA to discharge patients on the first postoperative day. [...] Nevertheless, the majority of uncomplicated percutaneous EVAR patients, particularly those who undergo procedure under local anaesthesia, do remarkably well and can be safely discharged home the same day.” The problem, Lachat stated, is that only 6% of patients in the USA undergo EVAR under local anaesthesia. He added there are no data on this topic, and Jacques Bleyn did not publish the results of his series in a journal.
“So we decided to start outpatient EVAR at the University Hospital Zurich because we had good EVAR experience over 15 years (>1,000 patients) with local anaesthesia, and two years with percutaneous access. We identified that most of the relevant complications happened during or immediately after EVAR, less than three hours after the procedure, and started our series in 2011,” Lachat explained.
The inclusion criteria were straightforward anatomy for EVAR, transfer time to hospital for eventual re-admission shorter than 60 minutes, adult observer assistance for the first 24 hours, informed consent and technically successful procedure. Patients who had any serious intra-operative complication, procedural time over four hours or incomplete sealing of access vessels were excluded.
All the outpatient procedures were performed with local anaesthesia, femoral cutdown and percutaneous access with Proglide and the procedures were performed with urinary condoms instead of catheters. Lachat added that the EVAR procedures are being performed in a hybrid operating room, with reduced amount of contrast. Also, in contrast with an inpatient setting, patients are taken to a recovery room after the procedure.
In order to compare outcomes of outpatient and inpatient procedures, Lachat and colleagues decided create a cohort of outpatients including patients from Zurich (29) and the cohort treated by Bleyn in Antwerp (23) (n=52 patients). These were compared to 52 EVAR in-patients. The results, Lachat said, showed that in-patient cases were clearly more complex, with one conversion and one case of bleeding, but overall there were no significant difference in outcomes between the two groups. Lachat commented that, so far, 100 cases have been treated, and still there was no difference in outcomes.
The group also performed a cost-benefit analysis, comparing 21 outpatients with 21 in-patients treated with a simple modular stent graft, with main body and contralateral limb module. “In our hospital, there was a benefit for outpatients in terms of ward/care costs, medical-technical costs, administration costs and total costs,” Lachat said.
Summarising his findings, Lachat told delegates that ambulatory EVAR is feasible in up to 40% of abdominal aortic aneurysm patients, with 0% mortality in 100 cases, and is reproducible, with two centres assessed at two different periods of time. The major advantages, he continued, are that there were no nosocomial or wound infections, no delirium, excellent patient acceptance (97%) and significant cost reduction.
“The feasibility, reproducibility and safety of ambulatory EVAR have been proven in selected patients, percutaneously, with local anaesthesia and with safety rules for the patient. There are major clinical and economic advantages, but probably a randomised controlled trial would be useful,” he said. “Patients fulfilling outpatient criteria should be treated or at least considered as outpatients and medical care should be minimised to allow spontaneous recovery.”
Finally, Lachat stated that in approximately 40% of the EVAR cases, there is no need for routine use of general anaesthesia, intensive care, intermediate care or bed rest. In addition, there is no need for routine urinary catheter and no need for basic analgesia, often nephrotoxic.”


Supera peripheral stent shows zero device fracture at 12 months

Thursday, 07 Feb 2013 13:51

On 5 February 2013, IDEV Technologies announced the publication of positive clinical outcomes for the Supera peripheral stent system in the Journal of American College of Cardiology (JACC) Cardiovascular Interventions. The publication, “Treatment of Complex Atherosclerotic Popliteal Artery Disease with a New Self-Expanding Interwoven Nitinol Stent: 12-Month Results of the Leipzig Supera Popliteal Registry,” was authored by Dierk Scheinert and colleagues from Park Krankenhaus Hospital in Leipzig, Germany.
In the Leipzig experience, 101 consecutive patients were implanted with 125 Supera stents and studied. Total occlusions were present in 47.5% of the patients, and 49.5% of the patients were diabetic. The mean length of implanted stents was 84.3mm with a range of 40mm to 240mm. The primary patency rate at 12 months was 87.7%. Zero stent fractures were reported.
“To achieve superficial femoral artery-like patency results at 12 months in stenting of these significantly diseased popliteal arteries validates Supera as a treatment option for patients that would not have been offered a standard nitinol stent for their disease,” noted Scheinert. “The finding of zero stent fractures in the popliteal artery, a vessel subject to high forces of compression, torque, rotation and flexion, validates the unique Supera design and the associated benefits of this vascular mimetic stent.”
To derive information that was both scientifically and clinically meaningful, the registry intentionally allowed enrollment of patients with a wide range of obstructions, including long lesions, total occlusions, and calcified vessels, without pre-specified inclusion and exclusion criteria. As a result, the patient cohort represents a real-world population recognisable by physicians.
IDEV president and chief executive officer, Chris Owens, commented, “We are excited to see such encouraging results from this targeted popliteal application of the Supera stent. Physicians continue to report consistently strong results in using Supera to treat femoropoliteal disease.”
IDEV is currently working with the FDA on a randomized IDE trial for the study of popliteal stenting in the United States.
The Supera stent is engineered with proprietary interwoven wire technology that mimics vascular anatomy. The Supera stent is currently cleared in the USA for the palliative treatment of biliary strictures produced by malignant neoplasms. In multiple other countries, the Supera stent is indicated for the treatment of biliary strictures produced by malignant neoplasms and for peripheral vascular use following failed percutaneous transluminal angioplasty.


What is the impact of drug-eluting balloons in Europe?

Friday, 04 Jan 2013 17:30

By Nicolas Diehm

Endovascular therapy has matured to be the primary revascularisation strategy for about 90% of patients with peripheral arterial disease (EVEM panel data Q2/2012).
Ever since the first percutaneous transluminal angioplasty carried out in Switzerland in 1977, restenosis remains a major drawback of endovascular therapy. Numerous attempts to improve patency after balloon angioplasty including drug treatment approaches, endovascular brachytherapy, bare metal nitinol stents and paclitaxel-coated nitniol stents have been investigated.
To date, despite technical refinements in nitinol stent technology, restenosis occurs in approximately every third patient undergoing femoropopliteal stenting with bare metal nitinol stents. The Zilver PTX randomised study has yielded promising results with the use of a polymer-free paclitaxel-coated stent. However, as for other studies investigating bare metal nitinol stents, no data exist on long-term outcomes. Moreover, the presence of a metal implant remains a cause of concern in a biomechanically challenging environment such as the femoropopliteal and below-the-knee arteries.
Subsequent to the publication of the THUNDER and FEMPAC trials, drug-eluting balloon technology has attracted many interventionalists in Europe. The concept of drug-eluting balloons seems particularly appealing since it allows for the use of anti-restenosis technology without having to leave a foreign body behind in the arterial segment to be treated.
While the class of drug-eluting balloon can meanwhile be considered established for the prevention of restenosis in the femoropopliteal arterial tract, data on the clinical utility in infrapopliteal arteries are scarce. Six randomised trials have shown a reduction of restenosis and need for target lesion revascularisation for the femoropopliteal arteries, three of which have been published in peer-reviewed journals. Moreover, two studies (one randomised and one non-randomised, the latter being published in written) have shown that the use of a drug-eluting balloon reduces restenosis and target lesion revascularisation in patients undergoing endovascular below-the-knee revascularisation.
The widespread clinical adoption of drug-eluting balloons for peripheral arterial revascularisation, however, clearly depends on scientific evidence and local reimbursement policies in different countries. According to current market research reports, drug-eluting balloons are used in about 10% of lower limb procedures in Europe, with a projected increase to 15–20% by the year 2015. It does not take specific behavioural economic models to describe the clear correlation of reimbursement by healthcare providers with sales numbers of various endovascular devices. In Germany, for example, drug-eluting balloons were reimbursed in the year 2011, but not in 2012, which has led to a substantial drop in drug-eluting balloon sales. Based on current negotiations, reimbursement for drug-eluting balloons will be available for 2013, however.
Considering that the price for a drug-eluting balloon makes up only a fraction of the entire budget of a patient undergoing endovascular therapy and the need for re-do interventions as compared to plain balloon angioplasty of the femoropopliteal arteries was shown to be reduced within at least six randomised trials, it is very likely that cost efficacy of drug-eluting balloon is favourable in many healthcare scenarios. However, medical device companies offering drug-eluting balloons should take the hurdles of calculating cost efficacy for individual markets before a widespread distribution of these devices can be recommended for specific countries.
In summary, based on currently available published evidence, drug-eluting balloons are an established strategy for prevention of restenosis in femoropopliteal arteries while randomised data for below-knee arteries are pending. If considered cost-effective in individual countries, drug-eluting balloons may be an interesting anti-restenosis technology for femoropopliteal revascularisation for patients not requiring a stent due to insufficient angioplasty results.
Nicolas Diehm, is a senior consultant and director of Clinical Research, Clinical and Interventional Angiology, Inselspital, University Hospital Bern, Switzerland

Pregnancy following uterine artery embolization is a viable option for women under 40 years old

Friday, 08 Feb 2013 10:54

A study by Bruce McLucas, University of California Los Angeles, David Geffen School of Medicine, Los Angeles, California, USA, and published ahead-of-print in Minimally Invasive Therapy has said that women who desire future fertility could be considered for uterine artery embolization. He reported the outcomes of his patient cohort who became pregnant after the procedure.
McLucas said that premature menopause, hysterectomy and radiation exposures have been identified as barriers to fertility when treating women with uterine artery embolization. However, he added that uterine fibroids themselves are not thought to cause infertility but could be a causative factor of pregnancy loss.
The author advised the participants of the study to wait six months or more after uterine artery embolization before attempting to conceive of which the reported time range before attempting to conceive was 13 months to 108 months (average time of 41 months).

In a retrospective chart review of patients under the age of 40 (44 patients) who wished to spare their fertility that underwent uterine artery embolization from 1996 to 2010, 22 patients reported 28 pregnancies of which three were miscarriages. Three more pregnancies were complicated by premature labour.

McLucas reported that 22 of the 28 pregnancies were normal full-term pregnancies, 16 women had become pregnant once, four had become pregnant twice, and one woman had become pregnant three times. The remaining patients did not conceive.
In the study there was no reported intrauterine growth retardation in the prenatal period, foetal distress during labour, and no problems related to uterine integrity. Two patients reported problems during pregnancy which were borderline oligohydramnios and low lying placenta.

As a fertility-sparing procedure, the authors noted that in their cohort of women who did conceive, overall, 21 out of 24 births proceeded normally without any complications (86.3%).

“Our group of 28 pregnancies is small, but does confirm successful pregnancy after uterine artery embolization,” said McLucas. “Our 47.7% pregnancy rate in women less than 40 years old who achieved a term pregnancy compares favourably with women who underwent myomectomy via a number of techniques.”

According to the author, in his cohort, of the women who did conceive, subsequent birth proceeded normally (86.3%). McLucas compared this to abdominal myomectomy where the term pregnancy rate was in the range of 10–46%, laproscopic myomectomy (16 to 33%), and hysteroscopic mymomectomy (8–35%), which means the implications for uterine artery embolization as a primary treatment for uterine fibroids as a fertility sparing technique is favourable.

“Our preliminary data suggest that fertility is further enhanced in women who underwent uterine fibroid embolization as a first procedure to control myomata,” he added.

Interventional treatment with radioactive beads could help colon cancer patients live longer

Monday, 28 Jan 2013 10:37

Patients who received minimally invasive treatment with yttrium-90 (Y-90) radioactive beads to treat colorectal cancer that had spread to the liver lived almost a year longer compared to those who received the standard of care therapy, data presented at the 5th annual Symposium on Clinical Interventional Oncology, in collaboration with the International Symposium on Endovascular Therapy (ISET) has suggested.
Researchers also determined that the Y-90 treatment was more successful in patients who had not been treated with bevacizumab (standard of care biologic therapy) for at least three months prior to radioembolization therapy.

“Patients with liver-dominant metastases from colorectal cancer should be offered radioembolization in addition to chemotherapy because it may offer a survival benefit compared with chemotherapy alone,” said Dmitry Goldin, a radiology resident at Beaumont Hospital, Royal Oak, Michigan, USA, and lead author of the study.
 In the study, 39 patients underwent Y-90 radioembolization, 30 of whom had also received treatment with bevacizumab. Radioembolization patients who received treatment with bevacizumab within the previous three months had a median survival of 30.5 months after diagnosis with metastatic colorectal cancer but those who had either not received bevacizumab or had been treated more than three months previously had a median survival of 37.9 months, although the difference was not statistically significant. Taking into account all the study subjects, survival averaged about 11 to 12 months longer than historical survival estimates among patients who receive standard of care treatment with modern chemotherapy and biologics alone.
Bevacizumab reduces arterial capacity. Patients who had received bevacizumab within three months of radioembolization were more likely to have therapy stopped early due to slow blood flow. This resulted in delivering less of the prescribed radiation to the tumours.
[Image: "A hepatic arteriogram from the presentation in a patient about to undergo radioembolization for metastatic liver-dominant colorectal cancer. This is a patient that never received bevacizumab and demonstrates a normal-sized proper hepatic artery and normal hepatic arterial distribution and caliber distally. This is unlike patients who received resent treatment with bevacizumab which demonstrate small and pruned hepatic arteries," said Goldin.]

The PRESERVE study: Randomised controlled trials may not be required for the evaluation of safety and efficacy for inferior vena cava filters

Friday, 08 Feb 2013 10:51

In a presentation at the International Symposium on Endovascular Therapy (ISET; 19–23 January 2013, Miami, USA) Matthew Johnson, Indiana University, Indiana, USA spoke to delegates about the trends in using inferior vena cava filters in the USA.
Johnson said that inferior vena cava filters “have been used in the treatment of patients with venous thromoembolism for decades.” He added that the trend, since the early 2000s, was to use retrievable inferior vena cava filters that have cleared by the the Food and Drug Administration (FDA) 510(k) approval process. According to the speaker, in 2010, over 200,000 retrievable inferior vena cava filters were placed. He said that currently “Many, perhaps the majority of retrievable inferior vena cava filters, are being placed in people without venous thromboembolism."

Johnson added that, recently, a joint foundation has been founded—the Society of Radiology and the Society for Vascular Surgery called the IVC Filter Study Group Foundation—which will choose the company research organisation (CRO) to run the study within the coming weeks.

According to Johnson, the FDA issued an initial communication on 9 August 2012, suggesting that retrieval inferior vena cava filters should be removed when they are no longer required—which was issued after a perceived increased in filter-related complications, according to the MAUDE (Manufacturer and user facility device experience) database. The complications outlined by MAUDE were: caval perforation, filter fracture, migration and embolization.

In his presentation the speaker said that discussions have been ongoing between the Society of Interventional Radiology, the Society for Vascular Surgery and the FDA since November 2010 where the FDA created a series of defined questions in order to assess the safety and efficacy of filters. The best way to answer these questions was said to be conducting a randomised controlled trials (however scope, participants and logistics were also taken into account).

The FDA, from the discussions, also said that filters should have 522 mandatory post-market evaluations such as randomised controlled trial vs. another clearance test. However, Johnson postulated that randomised controlled trials were inadequate to address the “complicated landscape” of using filters and that registries (such as MAUDE) have “no denominator.” He suggested that a prospective study with definitions such as study population, devices, goals, terms, methodology and outcomes would be favourable to randomised controlled trials.

Johnson then went on to present an alternative to the post market evaluations; the PRESERVE (Predicting the safety and effectiveness of inferior vena cava filters) study, which has been lead by the Society of Radiology, the Society for Vascular Surgery, the FDA and manufacturers of inferior vena cava filters who have received clearance of their devices. The aim of PRESERVE, according to the speaker, was to evaluate the safety and effectiveness of inferior vena cava filters as well as answering the defined questions set by the FDA (the data of which was presented to the FDA on 10 August 2012).

The PRESERVE study is a prospective, multicentre, single-arm clinical trial of adults in whom inferior vena cava filters are clinically indicated. The primary endpoints are safety (freedom from major complications) and effectiveness (freedom from pulmonary embolism). Johnson told delegates that it is expected that 2,500 to 3,000 subjects will be enrolled in the study with a predicted 300 subjects per filter type. The patients whose filters are removed will be followed up three months after removal, and then for two years with imaging.

“The PRESERVE trial represents a paradigmatic shift, in which each group has agreed to work together to address an important healthcare concern,” said Johnson. “The PRESERVE trial also represents a shift toward recognition that demonstration of safety and efficacy may not necessarily require a randomised controlled trial.”

Predicting the removal of optionally retrievable caval filters

Thursday, 24 Jan 2013 12:20

By Bertrand Janne d’Othée
The introduction of new optionally retrievable filters approximately a decade ago generated lots of initial excitement. Hopes were rising high that many of these filters could be easily removed once they were no longer necessary. Much of the early literature focused on success rates of attempted filter retrieval, or stressed that these devices can be removed after increasingly longer dwelling times—often well beyond manufacturers’ instructions. Most filter removals are indeed uneventful, with a high degree of success, and this may have encouraged even further the adoption of these devices in practice.

About five years later, however, new reports started voicing concerns that too few optionally retrievable filters ended up being actually removed (1, 2). Real life experience had shown that removal rates were quite, in fact, low and most likely removed in less than half of patients (the actual rate is unknown). This is unfortunate as technical success of attempted removal is high (3). Low removal rates are expected to increase the risks of long-term filter implantation.

Causes for non-removal of implanted optional filters are multiple and may include technical, clinical, patient management or follow-up reasons. The major causes seem to be other than technical and several studies have attempted to better understand the reasons behind the problem (4, 5), but the overall picture from the existing literature, taken as a whole, is confusing.

Many factors of undetermined importance have been identified among these studies and with incompletely overlapping findings among studies it becomes very difficult to know which factors are the most important predictors that lead to the eventual removal of the filter. For example, some predictors have been found in more than one published series, including age, malignancy, filter tilting or malpositioning, caval thrombosis or presence of large clots trapped in filters, prolonged indwelling time after implantation, patient non-compliance, loss to follow-up, the absence of patient follow-up by the procedural service performing filter implantation, and the absence of a longitudinal follow-up programme after filter implantation supported by dedicated personnel.

However, other significant predictors have been mentioned only once in a single study; this does not necessarily imply that they might be less valid or important. They include, for example, the onset of a new clinical need for permanent interior vena cava filtration, cases of prolonged filtration extending beyond the filters’ time window for retrievability, patients not being discharged on anticoagulants, insufficient patient education, deep vein thrombosis, and the involvement of a large number of healthcare providers in a given patient. Still, other predictors have been found that may not always have an obvious explanation but might still be important clinically (eg. female gender, or various settings in which the discharge from the hospital or intensive care unit happened.)

Hence, all these publications have shown so much between-study variability and incompletely overlapping conclusions that one might wonder: what predictors are really the important ones, and which one(s) should we go after primarily? None of these predictors seem to be the best single explanation to the problem of low removal rates, and it appears there is likely no single miracle solution. An unknown combination of some predictors probably accounts better for the overall picture (not to mention other possible predictors that have yet to be identified). Finding the correct combination (the “best model”) is crucial to better direct efforts and resource utilisation to solve the problem of low filter removal rates.

If we had to pick one best predictor, most studies would agree that the first choice is the absence of a dedicated longitudinal follow-up programme. Such programmes lead to higher removal rates, more retrieval attempts, and decreased loss to follow-up. Although the benefits of these programmes are undeniable and should not be underestimated, these initiatives alone have not been able to fully solve the problem yet—that factor alone cannot explain everything. Further efforts are needed to find additional complementary solutions that can be implemented in parallel to these longitudinal follow-up programmes. For example, other ideas have also been launched that seem reasonable too, including (a) sensitisation of referring physicians to the clinical advantages of filter removal, (b) sensitisation of interventionalists to the cost advantage of filter removal (2), and (c) better identification of patients at risk of no future filter removal. The latter is where the role of predictive models comes into play.

The problem with the existing models is that many of the published studies reported their observations in a single patient cohort, built a model based on it, and then stopped short of validating their model. Therefore the question arises—how well does the model describe reality when used in a set of patients that is comparable but different from the study cohort? In the absence of validation, the models’ equation could simply describe what was observed in a given study sample, and not be generalisable to other similar patient groups (6).

This validation step is often forgotten in the medical literature, even in so-called clinical prediction rules. The time is ripe for future, second-generation studies to attempt to verify whether the aforementioned candidate predictors are indeed significant predictors and what their relative importance is. Model validation can be done by splitting upfront any new patient cohort into a training set and a testing set prior to data analysis, or by using bootstrapping (a specific statistical technique). The quality of these second-generation studies might also benefit from being integrated in new research reporting standards for studies focusing on optionally retrievable filters.

These questions are gaining interest as filter placement is increasingly performed nationwide in the USA, in part due to the perceived harmlessness of retrievable filters. A few well-designed studies (even small retrospective ones) are needed to elucidate convincingly the causes of low removal rates and translate their findings into improvements in patient care.

Bertrand Janne d’Othée is associate professor of Radiology, University of Maryland Medical Center, USA, and chair of the Evidence-Based Interventional Radiology (EBIR) Committee of the SIR Foundation.

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