Chronic limb-threatening ischaemia (CLTI) is a manifestation of peripheral arterial disease that occurs as chronic ischaemic rest pain or ischaemic skin lesions, ulcers, or gangrene with symptoms present for longer than two weeks. The symptoms are a result of impaired blood flow to the leg and the foot due to narrowing of the arteries by atherosclerosis. Atherosclerosis is a disease of the arteries caused by a buildup of plaque composed of fat, cholesterol, calcium, and other substances in the blood; over time, the plaque narrows the artery. Patients can have narrowing of the artery in the thigh or below the knee. This review focusses on a subgroup of patients with below-knee arterial disease (infrapopliteal arterial disease) who might benefit from an intervention that re-establishes blood flow by inserting and inflating a balloon to re-open the narrowed artery (percutaneous transluminal angioplasty). This can be performed with or without additional placement of a stent (a scaffold made of metal alloy or other material). The types of stents used in this procedure vary from a simple bare-metal stent to a stent coated with medication. However, it is not clear whether deploying stents after ballooning in narrowed below-knee arteries (infrapopliteal arteries) provides any additional benefit for the patient.
Study characteristics and key results
We identified seven trials with a combined total of 542 participants comparing percutaneous transluminal angioplasty (PTA) alone versus PTA with stent placement (current until June 2018). One trial randomised limbs to PTA alone or PTA with stent placement, and the remaining studies randomised participants. Full analysis of five trials shows that the technical success rate of re-opening the narrowed artery was higher in the stent group than in the PTA group. However, we noted no clear differences in patency (opened vessel remaining open) of the treated vessel at six months. The complication rate of the procedure, the number of major amputations at 12 months, and the number of deaths at 12 months also did not differ greatly between treatment groups.
Certainty of the evidence
The overall certainty of evidence provided by the trials included in this review was moderate. Trials differed in their methods. Two studies reported poorly on the methods used to generate random numbers and to allocate participants to different groups. All studies were unblinded. All included studies were rated as direct in their relevance to the review question. Overall, we downgraded the certainty of evidence for all outcomes by one level to moderate due to inconsistency of results across studies and the small numbers of studies and participants.
PTA with stent placement is better than PTA alone for restoring vessel patency immediately; however we found no clear difference in short-term patency at six months between the two groups. Trials show no clear differences between groups in complications at or around the time of the procedure, major amputation, and death. Currently available data suggest that high-certainty evidence is insufficient to show that PTA with stent placement is superior to PTA alone for treatment of infrapopliteal arterial lesions. Further studies should standardise the use of blood-thinning drugs (antiplatelets/anticoagulants) before and after both interventions to improve the comparability of the two treatments.
Trials show that the immediate technical success rate of restoring luminal patency is higher in the stent group but reveal no clear differences in short-term patency at six months between infrapopliteal arterial lesions treated with PTA with stenting versus those treated with PTA without stenting. We ascertained no clear differences between groups in periprocedural complications, major amputation, and mortality. However, use of different regimens for pretreatment and post-treatment antiplatelet/anticoagulant medication and the duration of its use within and between trials may have influenced the outcomes. Limited currently available data suggest that high-quality evidence is insufficient to show that PTA with stent insertion is superior to use of standard PTA alone without stenting for treatment of infrapopliteal arterial lesions. Further studies should standardise the use of antiplatelets/anticoagulants before and after the intervention to improve the comparability of the two treatments.
Chronic limb-threatening ischaemia (CLTI) is a manifestation of peripheral arterial disease (PAD) that includes chronic ischaemic rest pain or ischaemic skin lesions, ulcers, or gangrene for longer than two weeks. The severity of the disease depends on the extent of arterial stenosis and the availability of collateral circulation. Treatment for CLTI aims to relieve ischaemic pain, heal ischaemic ulcers, prevent limb loss, improve quality of life, and prolong survival. CLTI due to occlusive disease in the infrapopliteal arterial circulation (below-knee circulation) can be treated via an endovascular technique by a balloon opening the narrowed vessel, so called angioplasty, with or without the additional deployment of a scaffold made of metal alloy or other material, so called stenting. Endovascular interventions in the infrapopliteal vasculature may improve symptoms in patients with CLTI by re-establishing in-line blood flow to the foot. Controversy remains as to whether a balloon should be used alone to open the vessel, or whether a stent should also be deployed.
To determine the efficacy and safety of percutaneous transluminal angioplasty (PTA) alone versus PTA with stenting of infrapopliteal arterial lesions (anterior tibial artery, posterior tibial artery, fibular artery (formerly known as peroneal artery), and common tibioperoneal trunk) for patients with chronic limb-threatening ischaemia (CLTI).
The Cochrane Vascular Information Specialist searched the Cochrane Vascular Specialised Register, CENTRAL, MEDLINE, Embase, CINAHL, and AMED databases, as well as World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov trials registers to 25 June 2018. We applied no language restrictions.
We planned to include randomised or quasi-randomised controlled trials comparing PTA versus PTA with a stent and including patients aged 18 years or over with CLTI. We defined CLTI as Fontaine stage III (ischaemic rest pain) and IV (ischaemic ulcers or gangrene) or consistent with Rutherford category 4 (ischaemic rest pain), 5 (minor tissue loss), and 6 (major tissue loss), with stenotic (> 50% luminal loss) or occluded infrapopliteal artery, including tibiofibular trunk, anterior tibial artery, posterior tibial artery, and fibular artery. We included all types of stents irrespective of design (e.g. bare-metal, drug-eluting, bio-absorbable).
Two review authors (CC-TH and GNCK) independently selected suitable trials, assessed trial quality, and extracted data. An additional third review author (MLvD) assessed trial quality and, when necessary, acted as arbiter for study selection and data extraction. Outcomes included technical success of the procedure, procedural complications, patency, major amputation, and mortality. We assessed the quality of evidence using the GRADE approach.
We included in the review seven trials with 542 participants. One trial randomised limbs to undergo PTA alone or PTA with stent placement, and the remaining studies randomised participants. Five trials with 476 participants show that the technical success rate was greater in the stent group than in the angioplasty group (odds ratio (OR) 3.00, 95% confidence interval (CI) 1.14 to 7.93; 476 lesions; 5 studies; I² = 23%). Meta-analysis of three eligible trials with 456 participants did not show a clear difference in short-term (within six months) patency between infrapopliteal arterial lesions treated with PTA and those treated with PTA and stenting (OR 0.88, 95% CI 0.37 to 2.11; 456 lesions; 3 studies; I² = 77%). Results also did not show clear differences between treatment groups in procedure complication rate (OR 0.87, 95% CI 0.01 to 53.60; 360 participants; 5 studies; I² = 85%), rate of major amputations at 12 months (OR 1.34, 95% CI 0.56 to 3.22; 306 participants; 4 studies; I² = 0%), and rate of mortality at 12 months (OR 0.71, 95% CI 0.43 to 1.17; 497 participants; 6 studies; I² = 0%). Heterogeneity between studies was high for the outcomes procedure complications and primary patency. The overall methodological quality of the trials included in this review was moderate due to selection and performance bias. Studies used different regimens for pretreatment and post-treatment antiplatelet/anticoagulant medication. We downgraded the certainty of the overall evidence for all outcomes by one level to moderate due to inconsistency of results across studies and large confidence intervals (small numbers of trials and participants).