Perspectives in Circulation Today
Where are we with infrainguinal angioplasty?
Gruntzin and Schneider reported in 1971 that, following their experience with percutaneous transluminal angioplasty of peripheral arteries in 225 patients who had a 2 year patency rate of 70-80%, they investigated the suitability of the technique in dilating coronary lesions in dogs and postmortem humans. Subsequently, cardiologists who were well practiced in placing catheters in the coronary ostia for angiograms rapidly took up the practice of coronary angioplasty. It was commonly said that they would soon turn the catheter distally and practice infrainguinal angioplasties also. By 1981 Veith et al reported on the 679 (90%) of 755 patients who had attempted limb salvage procedures among 1196 patients who had presented with significant infrainguinal arteriosclerosis; 128 had transluminal angioplasty procedures while bypass procedures included 318 femoropopliteal, 204 small vessel and 29 axillopopliteal bypasses.
Fourteen years later, Tunis et al examined the effects of angioplasty and bypass on Medicare data in the state of Maryland (N Engl J Med. 325(8):556-62, 1991): "We estimated that from 1979 to 1989 the annual rate of percutaneous transluminal angioplasty for peripheral vascular disease of the lower extremities, adjusted for age and sex, rose from 1 to 24 per 100,000 Maryland residents (P less than 0.0001 by linear regression). Despite this increase in the use of angioplasty, the adjusted annual rate of peripheral bypass surgery also rose substantially, from 32 to 65 per 100,000 (P less than 0.001), whereas the adjusted annual rate of lower-extremity amputation remained stable at about 30 per 100,000."
In 1993, Sayers et al reviewed 17 years of data in the UK on the treatment of lower limb ischaemia (BR J Surg 80: 1269-1273, 1993): "Over the 17 year period, 2930 vascular procedures were performed for chronic lower limb occlusive disease. The major lower limb amputation rate did not change but there was a decrease in the AK to BKA ratio. In addition there was an increase in the percentage of patients over age 75 and in the attempted proportion of attempted bypass procedures before amputation. The mortality rates for amputation, bypass and angioplasty did not change. The duration of hospitalization for amputations increased while that for reconstruction decreased."
In 1991 Rutherford reviewed the problem of interpreting the results of invasive vascular procedures and made recommendations in standardizing patient categories (Angioplasty library). Leng et al in their 2000 Cochrane Database Review noted that bypass surgery for lower limb ischemia has become widespread in the absence of appropriate studies and recommended new large clinical trials (Angioplasty library).
This year (2007), Eskelinen and Lepantalo compared the roles of bypass surgery and infrainguinal angioplasty in the treatment of critical limb ischaemia by MEDLINE (1966-2005) and Cochrane library searchs. They found reports on infrainguinal angioplasty showing excellent limb salvage rates regardless of the patency rates. The Cochrane Database of systematic reviews had accepted two prospective randomised trials comparing bypass operations and angioplasty that showed no overall significant difference in amputation rates between the surgery and PTA groups. A multicentre, randomised controlled trial, the BASIL (Bypass versus Angioplasty in Severe Ischaemia of the Leg) trial likewise showed that after six months, the outcomes after angioplasty or surgery among CLI patients did not differ significantly with respect to amputation-free survival, all-cause mortality and quality of life. They pointed out, however, BASIL trial is not applicable for the majority of CLI patients as only 15% (70/456) of the patients with severe limb ischaemia were considered candidates for the trial. Essentially, angioplasty was equivalent to another unproved therapy, bypass surgery.
In spite of the lack of hard data justifying angioplasty, one in the patient care business can readily appreciate its growth. An arteriogram is commonly done in the evaluation of symptomatic PVD. Almost inevitably if the radiologist sees a lesion that can be dilated, he/she will either do it or call the referring physician and suggest that "while I am there, I can easily dilate the lesion for you." Physicians have a natural desire to practice their trade. Vogel et al have reviewed the usage of lower extremity angioplasty for claudication in Washington State hospital discharge database (J Vasc Surg 45: 762-7, 2007). They concluded: "The use of PTA for claudication dramatically increased during the 8-year study period. Claudication was more often the diagnosis for PTA in patients who were younger, healthier, and privately insured. PTA for claudication had a higher-than-expected morbidity, 30-day readmission, and rate of reintervention. Future studies should focus on the factors motivating the use of PTA, its associated outcomes, and global impact on patients and the health care system."
Neither the design or accomplishment of a clinical trial for peripheral arteriosclerosis are readily completed. One does well to consider the experience of the EXACT Trial (Hobbs SD, Bradbury AW: LETTERS TO THE EDITOR: The EXercise versus Angioplasty in Claudication Trial (EXACT): Reasons for recruitment failure and the implications for research into and treatment of intermittent claudication. J Vasc Surg 44:432-433, 2006). "The options for subjects with infrainguinal peripheral arterial disease (PAD) who remain unacceptably symptomatic despite best medical therapy are specific pharmacotherapy, balloon angioplasty, supervised exercise therapy, or surgery. Unfortunately, there is little or no evidence base regarding the absolute or relative clinical and cost-effectiveness of these adjuvant treatments. (1-3)
"The EXercise versus Angioplasty in Claudication Trial (EXACT) was a UK Health Technology Assessment (HTA) Programme multicenter, randomized-controlled trial designed to compare the adjuvant benefits over best medical therapy of supervised exercise and balloon angioplasty in patients with mild-to-moderate intermittent claudication due to infrainguinal disease.
"After persistent difficulties in recruitment at all four centers, the trial was closed early in late 2004 at a point where only 10% of the required patients had been entered. This report outlines the details of the recruitment problems in one center and discusses their implication for future trials.
"Reasons for nonrecruitment at the initial screening assessment are detailed in" their figure (not shown here). Thus of 372 screened patients at the close of the trial in September 2004, only 23 (6%) had been randomized.
The following specific issues are worthy of discussion:
1. Almost one quarter of the patients referred to the vascular surgical service by their general practitioner had no evidence of PAD, which casts doubt on whether a positive initial diagnosis of PAD can be made in primary care.
2. Many patients presented with bilateral symptoms of (near) equal severity. Such patients are more suitable for systemic therapy such as exercise or pharmacotherapy and not for a lesion-focused therapy such as balloon angioplasty or surgery.
3. Many patients had clear ideas about what treatment they did and did not want. In particular, several patients did not want to accept the small but nevertheless real risks of balloon angioplasty, and for others, the requirement to commit to a hospital-based supervised exercise program was a major disincentive.
4. Many patients who gave a clear history of exercise-limiting intermittent claudication were unable for a variety of reasons to reproduce their symptoms and estimated maximal walking distance on a standard treadmill test.
5. Many clinically eligible patients did not have a pattern of disease that is suitable for balloon angioplasty. It would have been possible to increase the numbers of patients in the trial by accepting more TASC category D lesions. However, the investigators and participating radiologists believed this would almost certainly have led to a much higher rate of balloon angioplasty failure and complications.
6. Last but not least, many of the relatively few eligible patients simply did not want to enter the trial after 3-6 months on best medical treatment. This is perhaps not surprising, given that intermittent claudication tends to affect an elderly population, who are often socioeconomically disadvantaged and have other comorbidity.
Unfortunately, the premature closure of EXACT means that for the foreseeable future, clinicians will continue to have little or no evidence regarding the adjuvant treatment of infrainguinal intermittent claudication. The question is whether a randomized-controlled trial to compare supervised exercise and balloon angioplasty in this condition is feasible and, if so, affordable."
Clinical surgical research continues, of course. Old procedures like open endarterectomy, new procedures using the transluminal endarterectomy catheter and a subintimal infrainguinal angioplasty approach are all accumulating data and are not covered in this Newsletter. As with the studies with vascular endothelial growth factor, patients enlisted in such studies are commonly advised they have limited other therapeutic options and the commercial availability of the Circulator Boot is not mentioned. Our patients have questioned if the institutional research review committees are doing their job.
Studies on Efficacy of Bypass and/or Angioplasty
Comparisons, Controls, Risk Criteria and Results
| Authors: | Journal | Kind of Study | Size | Controls | Indications for Revascularization | Success Criteria | Results |
| *Borozan et al | J Vasc Surg 2:785-93, 1985 | Angioplasty followup | 28 patients | None | ? | Rise of 0.15 in ABI | Infrainguinal 18.2% long term success |
| *Blair et al | J Vasc Surg 9:698-703, 1989 | Retrospective comparison infrainguinal bypass vs PTA | 54 PTA vs 56 bypass pts | None | ? | Patency & Limb Salvage | PTA: P18% %LS 78% @2 yrs; Bypass P for Fempop 68% & Fem-distal 47% and LS 74% |
| **Jensen et al | Eur J Vasc Endovasc Surg 12:282-6, 1996 | Results of Vascular Registry vs results of monitored trial | 102 pts followed in both databases | - | ? | Primary & Secondary Patency, Limb Salvage & Mortality | Registry vs Trial: PP 68% vs 52%; SP 90% vs 63%; LS 97% vs 71%; & M 5% vs 15% |
| *Söder et al | J Vasc Interv Radiol 11(8):1021-31, 2000. | Prospective trial of infrapopliteal PTA with follow-up 12-24 mos | 60 pts and 72 limbs | None | Rutherford categories 4 (7pts), 5 (58pts) & 6 (7pts) (See Rutherford in our Angioplasty library) |
For Stenoses & Occlusions: Primary Success (initial patency), Primary Clinical Success, Restenosis Rate |
PSS 84%, PSO 61% PCS 63% RRS 32% (10 mos) RRO 52% (10 mos) |
| *Lofberg et al | J Vasc Surg 34: 114-21, 2001 | Followup of femoropopliteal PTA | 92 pts: PTA's of SFA(68), pop(13) or SFA+pop(40) | None | "Subcritical" or "critical" leg ischemical | Technical Success (initial patency), Primary Success, Limb Salvage, Overall Survival | TS 88%, PS 12 mos 40% and 60 mos 27%, LS for bypass and PTA at 5yrs 86&, OS at 5 yrs 51%. Concl: bypass better than PTA. |
| *Jämsén T et al | J Vasc and Interventional Radiol 13:455-463, 2002 | Outcomes of all pts able to have and having infrainguinal PTA | 100 consecutive pts | None | rest pain 20%, ulcers 43% & gangrene 37% | Limb Salvage & Alive | A and LS: 3yrs 29%, 5yrs 18% and 8yrs 6% |
| *Kudo et al | J Vasc Surg 41: 423-35, 2005 | Followup PTA alone and PTA with stents IGp:Iliac PTA's 33%, (20 stents in 14 iliacs) > FPGp:Fem-pop30% > BKGp:Tibials 37% |
111 pts & 138 limbs | None | Rest pain 45%, ulcers/gangrene 55% | Standards Soc Vasc Surg & Internat Soc Cardiovasc Surg for initial success,& late follow-up by Kaplan-Meier method. | Primary Success IGp 51,6%@5 yrs FPGp 49.4@5yrs BKGp 23.5%@5yrs Leg Salvage IGp 95%@5yrs FPGp 92.7%@5yrs BK Gp 77.3%@5 yrs |
| *Faglia et al | Eur J Vasc Endovasc Surg 29:620-27, 2005 | "Prospective" follow-up of all diabetics able to have PTA | 1191 patients 993 get PTA 195 pts PTA not feasible |
None | 1 pedal pulse reduced or absent TcPO2<50 mm Hg Stenoses >50% artery diameter |
TASC Kaplan-Meier approach Follow-up by clinic or colleagues elsewhere |
17 major amputations Primary 5 yr patency 88% 5 yr survival 74% Concl PTA safe 1st choice procedure |
| *Haider et al | J Vasc Surg 43:504-12, 2006 | Two-year Outcomes Retrospective Infrainguinal procedures |
333 patients 180 pts get 198 PTA's (166 Fempop & 32 Infrapop) 153 get bypass (80 Fempop and 82 Infrapop) |
None PTA 1st choice |
Rest pain 39%, tissue loss 61% for PTA gp | ABI rise >0.15 Primary Patency Limb Salvage Survival |
PTA Fp: PP75%, LS90%, S88% PTA IP: PP60%, LS76%, S82% Bypass: Fp: PP69%,LS87%, S76% IP: PP53%, LS57%, S64% Limbs amp 16 PTA & 31 bypass 30PTA sent to bypass |