~ a rd i~V'asc u hi r ~llltl h]tt'rx eiltiona] Radiolo~.v Springer-Verlag New York, Inc. 1998 Cardiovasc Intervent Radiol (1998) 21:470-474 Percutaneous Transluminal Angioplasty and Enclosed Thrombolysis Versus Percutaneous Transluminal Angioplasty in the Treatment of Femoropopliteal Occlusions: Results of a Prospective Randomized Trial Tony Nicholson Department of Vascular and lnterventional Radiology, Royal Hull Hospitals Trust, Anlaby Road, Hull HU3 2JZ, United Kingdom Abstract Purpose: To determine whether percutaneous transluminal angioplasty (PTA) and enclosed thrombolysis (ET) is supe- rior to PTA alone in the treatment of femoropopliteal occlu- sions. Methods: Twenty-five patients with 5-15-cm-long occlu- sions in the femoropopliteal segments, with otherwise nor- mal run-in arteries and at least one normal tibioperoneal artery to the foot, were randomized to ET/PTA or PTA alone. Ankle brachial systolic index (ABI) was measured before the procedure and at 24 hr and 12 months after the procedure, when a duplex scan was also carried out. End points in the study were patency at, or repeat intervention before, 12 months. Results: Procedures were successful in 23 of 25 patients. There was one immediate occlusion of tibioperoneal arteries, and one early reocclusion of a reopened segment in the ET/PTA group. There was one early reocclusion in the PTA group. At 12 months patency was 70% and 69.2% in the ET/PTA and PTA groups respectively. Covariant analysis showed no significant difference in ABI between the two groups at any of the three measurement times. Conclusion: This trial demonstrated no difference between ET/PTA and PTA alone in femoropopliteal occlusions asso- ciated with normal proximal arteries and at least one normal tibioperoneal artery. Key words: Enclosed thrombolysis--Femoropopliteal oc- clusion--Percutaneous transluminal angioplasty Correspondence to: T. Nicholson, M.D., I"RCR In 1991 TCnncsen et al. [1, 21 used enclosed thrombolysis (ET) and percutaneous transluminal angioplasty (PTA) in 33 patients with 5-15-cm femoropopliteai occlusions and at least one patent tibioperoneal artery, and compared the same technique in 20 patients with similar femoropopliteal occlu- sive disease and no patent tibioperoneal arteries. They con- cluded that ET/PTA prevented early rethrombosis in the former group and was superior to PTA alone. The purpose of this study was to determine by randomization whether ET/ PTA prevents carly rethrombosis and confers any advantage over PTA alone in patients with femoropopliteal occlusions who have normal proximal and good distal arteries. Materials and Methods Twenty-five patients with 5-15-cm femoropopliteal occlusions were prospectively randomized to ET/PTA or PTA alone. Two patients were excluded from the study after randomization because of failure to cross the occluded segment from an antegrade ap- proach using conventional guidewire and catheter techniques. De- tails of the 23 patients included are shown in Table 1. Inclusion criteria required no angiographic abnormality of aortoiliac seg- ments and at least one tibioperoneal artery patent to the ankle. All patients had clinical disease category 2/3 (joint council of the Society for Vascular Surgery and the North American chapter of the International Society for Cardiovascular Surgery [3]). Informed consent was obtained and ethics approval granted by the Hull and East Yorkshire medical ethics committec. All patients were pre- scribed aspirin 300 rag/day before and after the procedure. The ankle brachial systolic index (ABI) was recorded immediately prior to the procedure. The occlusions were crossed from an antegrade approach using a hydrophilic wire (Terumo, Tokyo, Japan) and 7 Fr Van Andel catheter. The double-balloon catheter (Boston Scientific, Watertown, MA, USA) used in the study is well described elsewhere [1, 4].
Transcript
~ a rd i~V'asc u hi r ~llltl h]tt'rx eiltiona] Radiolo~.v
�9 Springer-Verlag New York, Inc. 1998 Cardiovasc Intervent Radiol (1998) 21:470-474
Percutaneous Transluminal Angioplasty and Enclosed Thrombolysis Versus Percutaneous Transluminal Angioplasty in the Treatment of Femoropopliteal Occlusions: Results of a Prospective Randomized Trial Tony Nicholson
Department of Vascular and lnterventional Radiology, Royal Hull Hospitals Trust, Anlaby Road, Hull HU3 2JZ, United Kingdom
Abstract Purpose: To determine whether percutaneous transluminal angioplasty (PTA) and enclosed thrombolysis (ET) is supe- rior to PTA alone in the treatment of femoropopliteal occlu- sions. Methods: Twenty-five patients with 5-15-cm-long occlu- sions in the femoropopliteal segments, with otherwise nor- mal run-in arteries and at least one normal tibioperoneal artery to the foot, were randomized to ET/PTA or PTA alone. Ankle brachial systolic index (ABI) was measured before the procedure and at 24 hr and 12 months after the procedure, when a duplex scan was also carried out. End points in the study were patency at, or repeat intervention before, 12 months. Results: Procedures were successful in 23 of 25 patients. There was one immediate occlusion of tibioperoneal arteries, and one early reocclusion of a reopened segment in the ET/PTA group. There was one early reocclusion in the PTA group. At 12 months patency was 70% and 69.2% in the ET/PTA and PTA groups respectively. Covariant analysis showed no significant difference in ABI between the two
groups at any of the three measurement times.
Conclusion: This trial demonstrated no difference between ET/PTA and PTA alone in femoropopliteal occlusions asso- ciated with normal proximal arteries and at least one normal tibioperoneal artery.
In 1991 TCnncsen et al. [1, 21 used enclosed thrombolysis (ET) and percutaneous transluminal angioplasty (PTA) in 33 patients with 5-15-cm femoropopliteai occlusions and at least one patent tibioperoneal artery, and compared the same technique in 20 patients with similar femoropopliteal occlu- sive disease and no patent tibioperoneal arteries. They con- cluded that ET/PTA prevented early rethrombosis in the former group and was superior to PTA alone. The purpose of this study was to determine by randomization whether ET/ PTA prevents carly rethrombosis and confers any advantage over PTA alone in patients with femoropopliteal occlusions who have normal proximal and good distal arteries.
Materials and Methods Twenty-five patients with 5-15-cm femoropopliteal occlusions were prospectively randomized to ET/PTA or PTA alone. Two patients were excluded from the study after randomization because of failure to cross the occluded segment from an antegrade ap- proach using conventional guidewire and catheter techniques. De- tails of the 23 patients included are shown in Table 1. Inclusion criteria required no angiographic abnormality of aortoiliac seg- ments and at least one tibioperoneal artery patent to the ankle. All patients had clinical disease category 2/3 (joint council of the Society for Vascular Surgery and the North American chapter of the International Society for Cardiovascular Surgery [3]). Informed consent was obtained and ethics approval granted by the Hull and East Yorkshire medical ethics committec. All patients were pre- scribed aspirin 300 rag/day before and after the procedure. The ankle brachial systolic index (ABI) was recorded immediately prior to the procedure. The occlusions were crossed from an antegrade approach using a hydrophilic wire (Terumo, Tokyo, Japan) and 7 Fr Van Andel catheter.
The double-balloon catheter (Boston Scientific, Watertown, MA, USA) used in the study is well described elsewhere [1, 4].
T. Nicholson: PTA and Enclosed Thrombolysis vs PTA for Femoropopliteal Occlusions 471
Table 1. Patient details
ET/PTA PTA
No. of patients l0 13 Sex (M/F) 6/4 8/5 Age (years): range (mean) 45-65 (58) 51-73 (62) Smokers 5 5 Ex-smokers (within 1 year) 5 7 Diabetics 1 2 Occlusion length (cm)
5 2 3 5-10 4 7 10-15 4 3
Tibioperoneal arteries 2 8 10 3 2 3
Claudication category 2/3 2/3
ET = enclosed thrombolysis; PTA = percutaneous transluminal angio- plasty.
Basically it is a 7 Fr, four-lumen catheter with a 5/6-mm • 4-cm distal balloon used for angioplasty and distal occlusion and a 7-mm x 2-cm proximal balloon 20 cm from the distal balloon used for proximal occlusion. With a wire in place, 3000 IU of heparin was given and the distal balloon inflated to between 7 and 10 arm for 1 min at as many levels as it took to reopen the occluded segment. It was then advanced beyond the occlusion and both balloons inflated to systolic pressure. The reopened segment was thus isolated (Fig. 1). The volume of the occluded segment was then replaced with a solution of saline containing 5 mg of recom- binant tissue plasminogen activator (rtPA, Actilyse, Boehringer, Ingelheim, Germany) and 1000 IU of heparin. This was injected via a third lumen with a side port between the two balloons. The balloons were kept inflated for 30 min. During this time the central lumen was infused with 300 ml of saline containing 1000 IU of heparin to prevent distal arterial thrombosis. After this time the balloon was deflated and a check angiogram performed.
Patients randomized to angioplasty underwent the same proce- dure in terms of balloon size, inflation time, and heparin dose (5000 IU). However, after dilatation no ET was performed, the procedure being completed with a check angiogram.
ABIs were rechecked at 24 hr and again at 12 months, when a duplex scan was also performed. Patients were also seen at 3 and 6 months for clinical assessment. Evidence of occlusion or restenosis at any of these times was an indication for reintervention.
Results The results are presented in Table 2. Covariant analysis
showed no significant difference in ABI between the ET/
PTA group and the PTA-only group prior to intervention
( p = 0.659). In the ET/PTA group, seven of 10 patients had
sustained improvement in ABI with category 0/1 claudica-
tion and an average improvement in ABI of 0.44 at 1 year.
Duplex scanning revealed only one patient with significant
segmental velocity increase at 12 months; however, he was
asymptomatic and a femoral angiogram suggested no more than a 20% restenosis at the site of previous angioplasty. However, there was one immediate failure, one early failure, and one late failure in this group. The immediate failure
Fig. 1. Enclosed thrombolysis catheter isolating an oc- cluded segment of superficial femoral artery following angio- plasty. The large arrows point to the proximal and distal balloons and the small arrow to the rtPA/heparin mixture, in this case mixed with contrast to demonstrate the infusion port.
occurred following ET/PTA of a 12-cm femoropopliteal segment. After complet ing the procedure check angiography revealed a patent femoropopliteal artery but occluded run off (Fig. 2A). Thrombolysis with 5 mg of rtPA and suction embolectomy retrieved the situation (Fig. 2B) and the an-
gioplasty site was patent at 24 hr. However, reintervention was necessary at 7 months because of reocclusion of the
femoropopliteal segment. A second patient reoccluded a
10-cm segment within 24 hr (Fig. 3A, B). This was throm-
bolysed with r tPA over 6 hr and an underlying dissection
flap, not seen on previous completion angiography, diag-
nosed (Fig. 3C). Despite no further treatment the ABI im-
proved and the artery was patent at 1 year with normal ABI
and no velocity increase seen on duplex scan. A third patient
had a good immediate result from ET/PTA of a 10-cm occlusion, with a 0.3 improvement in ABI at 24 hr. How- ever, the segment reoccluded at 6 months and reintervention was necessary.
472 T. Nicholson: PTA and Enclosed Thrombolysis vs PTA for Femoropopliteal Occlusions
2 0,5 0.8 0.9 3 0.4 0.7 0.9 4 0.6 0.7 1.0 6 0.4 1.0 D i e d a t 3 m o n t h s 8 0.5 1.0 1.0
l0 0.6 0.8 0.8 11 0.5 0.9 0.9 14 0.6 0.9 0,9
15 0.5 0.8 O.9
16 0.5 0.5 1.0
19 0.5 0.5 Occluded ~ 0.5 thrombolysis/PTA failed
20 0.6 0.9 Repeat PTA 8 months
22 0.5 0.8 Repeat PTA 3/6/ 11 months
12 months: p = 0.629
ABI = ankle brachial index.
Thirteen patients underwent PTA alone. One patient died at 3 months after a myocardial infarction. His ABI at 24 hr is included in the study. Nine of 13 patients had sustained improvement in ABI, with improved claudication category and an average improvement in ABI of 0.4. Again only one significant velocity increase was seen at duplex examination. This patient was asymptomatic and refused intervention. She reoccluded the femoropopliteal segment at 18 months. There was one early reocclusion of an 8-cm segment which failed thrombolysis and subsequent endovascular procedures. Two further patients reoccluded at 3 and 8 months. The former failed angioplasty on three subsequent occasions.
Covariant analysis of the ABIs at 24 hr and 1 year revealed no significant difference between the ET/PTA and PTA groups (p = 0.104 and 0.629 respectively).
Discussion Between 49% and 57% of atherosclerosis causing intermit- tent claudication is located in the femoropopliteal segment [5]. The technical success of short-segment angioplasty im- proved from 70% in 1980 to 9I% in I989 I6-8]. Similarly reports of 1-year patency in long-segment (> 10 cm) angio- plasty in the femoropopliteal segment have improved from 48% in 1982 [9] to 69% in 1995 [10]. There are many factors associated with reocclusion. These include segment length, operator experience, patency of run-in and run-off arteries, flow-altering dissections, and post-angioplasty recoil. There
are also a variety of social and medical factors. The rationale behind ET is that up to 40% of angioplasties of long-segment femoropopliteal PTA may reocclude in the first 24 hr [11, 12]. It was proposed by T0nnesen et al. [12] that this was due to residual thrombus precipitating rethrombosis. However, the published data take little account of different etiologic factors and in large series there may be multiple factors involved in early reocclusion. In addition, though early re- thrombosis rates of up to 41% were described [8, 13] for long-segment femoropopliteal angioplasty, this has not been a problem in more recent studies, where 18-month patency rates of 69% have been described [10]. This improvement may be due to improvement in equipment design, better patient selection, changes in patients' social habits, and increasing operator experience. In our own practice late restenosis and occlusion is a far greater problem than early rethrombosis in long-segment femoropopliteal angioplasty. Immediate and early rethrombosis in this series did occur in both groups due to a technical complication in one patient in the ET/PTA group (20 rain occlusion of the popliteal artery below the collateral insertion) and flow-limiting dissections in the other two patients.
In T0nnesen's study it was suggested that ET/PTA was superior to PTA alone in a group of claudicants with good run off (1-year patency 90%) but not in those with no infrapopliteal artery (1-year patency 62%). In this random- ized study of the former group we have found no difference
T. Nicholson: PTA and Enclosed Thrombolysis vs PTA for Femoropopliteal Occlusions 473
Fig. 2. A Immediate occlusion of the distal popliteal artery following enclosed thrombolysis. B Result of thrombolysis and suction embolectomy following distal occlusion after enclosed thrombolysis. Areas of spasm responded to vasodilators.
Fig. 3. A Patent superficial femoral artery (SFA) following enclosed thrombolysis. B The patent PTA site occluded within 3 hr. C Following thrombolysis the SFA is patent though there is a dissection flap.
C
474 T. Nicholson: PTA and Enclosed Thrombolysis vs PTA for Femoropopliteal Occlusions
between ET/PTA and PTA alone at either 24 hr or 1 year. In addition the rate of early rethrombosis was much lower in the
PTA-only group than in T0nnesen 's early series (7,7% com-
pared with a reported 41%), suggesting that patient selection
(in this case patients with isolated disease) plays an impor- tant role in early patency. Covariant analysis suggests that there is no difference between the two groups at 24 hr or 1
year. Given the lack of demonstrable statistical difference
between the two groups and the immediate run-off occlusion
in one patient, it was decided not to enter any more patients
into the study. However, this randomized study is small and
the possibil i ty of a type II error exists, i.e., there may be a
statistically significant difference if more patients were en-
tered. In conclusion, no difference was demonstrated between
ET/PTA and PTA alone. Procedure time for the double procedure is prolonged and there is the potential for outflow
occlusion. In the author 's opinion the technique cannot be
recommended in patients with isolated long-segment femo- ropopliteal disease. However, the remarkable 62% 1-year
patency following PTA and ET in patients with long-seg-
ment femoropopli teal occlusion and no infrapopliteal arter-
ies reported by Tcnnesen [1] is worthy of a further
randomized study.
Acknowledgment. The author would like to thank Mr. Robert West for his help in organizing this trial, Drs. J.F. Dyet, Eric Gardner and K.H. Tcnnesen for advice, and Mr. A. Wilkinson for referring patients.
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