Randomized clinical trials

Terlouw LG, van Dijk LJD, van Noord D, Bakker OJ, Bijdevaate DC, Erler NS et al, on behalf of the Dutch Mesenteric Ischemia Study Group.

Lancet Gastrohepatol 2024; 9: 299-309.

Ninety-four patients with chronic mesenteric ischaemia were included. Only one patient died. After 24 months, the patency of covered stents was better than bare metal stents: 81 versus 49 per cent, P<0.0001. Access site adverse events were more common in covered stent procedures.

Comment: This study does not address whether symptoms were improved alongside patency.

Turner B, Machin M, Salih M, Lawton R, Siracusa F, Gwozdz AM et al.

Ann Surg 2024; 279: 29-36.

Evidence from head to head meta-analysis and pooled trial arms shows no benefit from adding stockings to pharmacological thromboprophylaxis: risk ratio 0.85 per cent, 95 per cent confidence interval 0.54 to 1.36.

Comment: Additional stockings not needed if low molecular weight heparin used.

Burgess L, Babber A, Shalhoub J, Smith S, de la Rosa CN, Fiorentino F et al, for the NESIC Trial Investigators.

Br J Surg 2023; 110: 1785-1792. 

The addition of neuromuscular electrical stimulation did not improve walking distance over standard care (medical therapy and supervised exercise therapy) after three months in this study that included 160 patients with claudication. It did have a beneficial effect on mild claudication. 

Comment: Exercise therapy remains the best treatment for claudication.  

Varcoe RL, DeRubertis BG, Kolluri R, Krishnan P, Metzger DC, Bonaca MP et al, for the LIFE-BTK Investigators.

N Engl J Med 2024;390: 9-19. 

Some 261 patients with critical ischaemia and tibial artery disease were included. The chance of avoiding amputation, vessel occlusion or further revascularisation was higher with the scaffold: 74 vs. 44 per cent, absolute difference 30 per cent, P<0.001. Serious adverse event rates were similar. 

Comment: Important study justifying the use of the drug eluting scaffold in the tibial arteries.

Norgren L, Weiss N, Nikol S, Lantis JC, Patel MR, Hinchliffe RJ et al.

Br J Surg 2024; 111:  znad437.

This study included 143 patients with limb-threatening ischaemia, unsuitable for standard treatment. Intramuscular injections of placental-derived mesenchymal cells, 60 days apart did not affect amputation-free survival: 28.6 per cent, versus 33 per cent with placebo. The effect was more positive in non-diabetics.

Comment: Interesting subgroup analysis that may be the basis for further study.

Mihara M, Hara H, Kawasaki Y, Mitsuhashi T, Orikasa H, Ando H et al.

Br J Surg 2024; 111: znad372.

A total of 336 patients were included from two studies. Lymphovenous anastomosis did not reduce limb circumference or pain, but it did reduce the frequency of lymphoedema-associated cellulitis over six months, by 35 per cent in the large dataset, and by 60 per cent (95 per cent confidence interval -0.94 to -0.27 per cent) in the per protocol analysis.

Comment: The role of lymphovenous anastomosis still not clear, with only few studies outside Japan.

Mack MJ, Leon MB, Thourani VH, Pibarot P, Hahn RT, Genereux P et al, for the PARTNER 3 Investigators.

N Engl J Med 2023; 389:1949-1960.

This study included 1000 patients followed for five years. The composite endpoint included death, stroke, and rehospitalization for valve complications. The primary endpoint occurred in 2.8 per cent of patients after TAVI and 27.2 per cent after open surgery, P=0.07.

Comment: Minor differences in outcome, but major advantages of TAVI for patients

Gao Y, Chen W, Pan Y, Jing J, Wang C, Johnston SC et al, for the INSPIRES investigators

N Engl J Med 2023; 389:2413-2424.

Some 6100 patients were included; most were randomized over 24h after the new event. A new stroke within 90 days occurred in 7.3 percent of the dual antiplatelet group compared with 9.2 per cent of those given aspirin alone (hazard ratio 0.79, 95 per cent confidence interval 0.66 to 0.94; P=0.008).

Comment: Although small increase in risk of bleeding, a conclusive result due to the large number of participants, and contemporary data.

Kirkham AM, Candeliere J, McIsaac DI, Stelfox HT, Dubois L, Gill HL et al.

Ann Surg 2023; 278: e447-e456.

There were 26 RCTs including 4752 patients. Twelve strategies were evaluated but only two showed definite benefits: pre-incision antibiotics (four studies) relative risk 0.25, 95 per cent confidence interval 0.11 to 0.57; and negative pressure wound therapy (five studies) – 0.54, 0.38 to 0.78.

Comment: Interesting that negative pressure wound dressing has found a place in vascular surgery, when it has not for many other procedures. Perhaps particularly effective in groin incisions?

Shirasu T, Takagi H, Yasuhara J, Kuno T, Kent KC, Farivar BS et al.  

Ann Surg 2023; 278: 172-178.

The analysis included nine RCTs with 1477 patients. After a mean of 3.6 years of follow-up, the rate of development of critical ischaemia was similar: rate ratio 0.77, 95 per cent confidence interval 0.36 to 1.69, P=0.51. Rates of amputation and death were also similar.

Comment: No advantage to life or limb from revascularisation, but may of course benefit symptoms in the shorter term.

Ma Y, Wang T, Wang H, Amin-Hanjani S, Tong X, Wang J et al, for the CMOSS Investigators.

JAMA 2023; 330: 704-714.

Some 330 patients with transient ischaemic attack or non-disabling stroke were included. The endpoint was a composite of death within 30 days or ipsilateral stroke up to two years. The outcomes were similar after surgery and medical treatment: 8.6 versus 12.3 per cent respectively, P=0.39.

Comment: Still no definitive role for this procedure.

AbuRahma Z, Williams E, Lee A, Jordan MD, Veith C, Dargy N et al.

J Vasc Surg 2023; 77: 1694-1699.

Two hundred procedures were included in this study. After a median follow-up of 80 months, there was no difference in the rate of freedom from stroke: ACUSEAL 93 per cent, pericardial patch 92 per cent. Whilst rates of freedom from > 80 per cent recurrent stenosis were similar, more patients with the ACUSEAL developed stenosis > 50 per cent,  P=0.49.

Comment: Whilst no clinical differences were reported, this may be enough to dissuade vascular surgeons from using the PTFE patch.

Enzmann FK, Nierlich P, Hölzenbein T, Aspalter M, Kluckner M, Hitzl W et al.

Ann Surg 2023; 277: e1208-e1214.

The study included 218 legs in 209 patients. After four years, there was no difference in patency, limb survival or complications, but patients who had a surgical bypass reported greater clinical improvement.

Comment: More fuel for the debate started by the and BESTCLI and BASIL trials.

Gasior SA, O’Donnell JPM, Davey M, Clarke J, Jalali A, Ryan E et al.

Eur J Vasc Endovasc Surg 2023; 65: 690-699.

Over 14000 people were included  in this analysis. It concluded modern best medical therapy had similar reductions in stroke and death rates to carotid endarterectomy. It was not possible to define any subgroups that might benefit from vascular intervention.

Comment: complex and detailed study undermining the previously agreed role of vascular intervention.

Bekken JA, Vroegindeweij D, Vos JA, de Vries J-PPM, Lardenoije JWHP, Petri B-J et al.

Eur J Vasc Endovasc Surg 2023; 65: 359-368.

Freedom from restenosis after two years was 84.7 per cent after bare stents versus 89.1 per cent with covered stents (P=0.4) in this study that included 174 limbs. Technical success and complication rates were similar.

Comment: no advantage for the covered stent.

Gunnarson T, Bergman S, Parsson H, Gottsater A, Lindgren H.

Eur J Vasc Endovasc Surg 2023; 65: 513-519.

In this study that included 100 patients, after 30 months, insertion of a stent improved role physical quality of life (QoL) scores, but not overall QoL, compared to best medical therapy. By 60 months QoL was similar in the two groups.

Comment: endovascular intervention for SFA disease is not a good long term solution.

Bradbury AW, Moakes CA, Popplewell M, Meecham L, Bate GR, Kelly L et al, on behalf of the BASIL-2 Investigators.

Lancet 2023; 401: 1798-1809.

Some 345 patients with critical leg ischaemia were treated and followed for two years. The outcome of major amputation or death occurred in  63 per cent of the surgery first group compared to 53 per cent after endovascular treatment first, P=0 .037. This outcome was mainly due to the high rate of death in the two years after surgery (53 versus 45 per cent).

Comment: This was an unexpected result after the converse outcome in the recent BestCLI trial. It requires further explanation. Were the patients with critical leg ischaemia different in the UK and USA?

Lim AJM, Abduraheem HM, Hitchman LH, Lathan R, Bharadhwaj R, Sidapra MM et al.

Br J Surg 2023; 110: 562-567.  

Four randomized trials including 654 patients were analyzed. The rate of occlusions was lower after mechanical ablation: risk ratio of 0.85, 95 per cent confidence interval 0.78 to 0.91, P<0.000. There was no difference in pain during the procedure or clinical outcomes.

Comment: The role of mechanical ablation remains unproven. It doesn’t seem as effective as endothermal ablation, although the occlusion rate as an endpoint may not be ideal.

Scheerders ERY, van der Velden SK, Goossens LMA, Hamann SAS, de Maeseneer MGR, Malskat WSJ et al, for the members of the SAPTAP group.

Br J Surg 2023: 110: 333–342.

Some 464 patients had ambulatory phlebectomies first; 227 were randomized to subsequent saphenous trunk ablation. Only 57 (25 per cent) of patients who had phlebectomies alone required later truncal ablation on symptomatic grounds. Overall disease-specific quality of life was similar in both groups at one year.

Comment: This revolutionary study reverses the standard treatment of truncal ablation first. Longer term outcomes are needed to test the hypothesis fully.

Farber A, Menard MT, Conte MS, Kaufman JA, Powell RJ, Choudhry NK et al, for the BEST-CLI Investigators.

N Engl J Med 2022; 387: 2305-2316.

This international trial enrolled 1830 patients, and the endpoint was a composite of amputation, major reintervention or death. In the group with adequate saphenous vein, after a median of 2.7 years of follow-up, the endpoint was reached by 42.6 per cent of the surgery group compared to 57.4 per cent of the endovascular first group P<0.001). Outcomes were equivalent in those without an adequate vein.

Comment: Great study that confirms what many vascular surgeons have thought for a long time: endovascular treatment is great, but if you are fit enough and have vein for a bypass it will probably last you longer.

Dewulf M, Muysoms F, Vierendeels T, Huyghe M, Miserez M, Ruppert M et al.

Ann Surg 2022; 276: e217-e222.

After five years, 67 patients were available for analysis by clinical examination. The rate of incisional hernias was 49.2% in the no mesh group versus none in the mesh group. Some 5/23 in the no mesh group required reoperation.

Comment: Prophylactic mesh remains controversial, but the evidence of benefit is increasing, and incisional hernia can be very debilitating in this patient group who tend to be elderly.

Stubenrouch FE, Peters LJ, de Mik SML, Klemm PL, Peppelenbosch AG, Schreurs SC et al, on behalf of the OVIDIUS study group.

Eur J Vasc Endovasc Surg 2022; 64: 73-81.

The study included 342 patients with various vascular conditions. Those seen by clinicians trained in how to apply shared decision making (SDM) had improved OPTION-5 scores (an objective tool to assess the level of SDM): 28.7 to 37.8 per cent, P=0.025.

Comment: More support for shared decision making.

Eid MA, Barry MJ, Tang GL, Henke PK, Johanning JM, Tzeng E et al, for the Preferences for Open Versus Endovascular Repair of Abdominal Aortic Aneurysm (PROVE-AAA) Study Team.

JAMA Surg 2022; 157: e222935.

The study included 235 patients with a large AAA suitable for both open and endovascular repair. Patients seen in clinics where a decision aid was used were more likely to receive their preferred type of repair: 95 versus 86 per cent, P=0.03.

Comment: More support for the use of a decision aid.

McDermott M, Bazzano L, Peterson CA, Sufit R, Ferrucci L, Domanchuk K et al.

JAMA 2022; 328: 1315-1325.

After six months, Telmisartan, an angiotensin receptor blocker, did not improve six-minute walking distance compared with placebo in this study that included 114 patients (P=0.08).

Comment: Still no good medicines for claudication.

Lindholt JS, Sogaard R, Rasmussen LM, Mejldal A, Lambrechtsen J, Steffensen FH et al.

N Engl J Med 2022; 387: 1385-1394.

Some 46,611 men were randomized. After five years, intention to treat analyses showed no difference in overall mortality rate compared to controls: hazard ratio 0.95, 95 per cent confidence interval 0.9 to 1.0, P=0.06. There was no significant reduction in the rates of stroke, myocardial infarction or aortic aneurysm rupture.

Comment; This is a very disappointing result after the same authors’ previous study showed a significant mortality reduction. It’s back to the drawing board for cardiovascular screening.

Goeteyn J, Pesser N, Houterman S, van Sambeek MR, van Nuenen BFL, Teijink JAW.

Eur J Vasc Endovasc Surg 2022; 64: 119-127.

This study included 50 patients. After three months mean Disability of the Arm, Shoulder and Hand (DASH) score was significantly better in the surgery group: 45.1 versus 64.9, P<0.001. All patients in the conservative group applied for surgery after three months.

Comment: Although small, this is the first study to justify TOS surgery in this group.

Pham T-T, Gariani K, Richard J-C, Kressmann B, Jornayvaz FR, Philippe J et al.

Ann Surg 2022; 276: 233-238.

In this pilot trial, clinical remission at two months occurred after 27/35 patients who had 10 days of antibiotics versus 22/31 who had them for 20 days, P=0.32.

Comment: Is the full trial justified?

Haile ST, Joelsson-Alm E, Johansson B, Loof H, Palmer-Kazen U, Gillgren P et al.

Br J Surg 2022; 109: 846-856.

Nurse led follow-up did not increase compliance with best medical therapy after one year in this study that included 214 patients: 79 versus 82 per cent.

Comment: Disappointing, but useful for planning ongoing care. The focus must be on comprehensive patient information at the point of treatment.

Mohamed AH, Thadani S, Mohamed SH, Sidapra M, Smith G, Chetter I, et al.

Br J Surg 2022; 109: 679-685.

There were 18 studies including 2584 legs. Use of compression for 1 to 2 weeks after intervention was associated with improved comfort and quality of life. Use of compression after 1-2 weeks was not beneficial.

Comment: This is helpful, but not novel. Focus should turn to which is the best form of compression.

Koelemay M, van Reijen NS, van Dieren S, Frans FA, Vermeulen EJG, Buscher HCJL, et al for the SUPER Study Collaborators.

Eur J Vasc Endovasc Surg 2022; 63: 421-429.

The trial was terminated after 240 patients were included and analysed. Compliance with supervised exercise was 50 per cent at six months. After one year, mean maximum walking distance improved similarly in both groups (P=0.69).

Comment: The authors conclude that supervised exercise should be the initial treatment, followed by revascularisation if that is not successful.

Ashrafi M, Ahmad SA, Antoniou SA, Khan T, Antoniou GA.

Eur J Vasc Endovasc Surg 2022; 63: 323-334.

Seven RCTs were examined. Active clot removal strategies resulted in higher patency than anticoagulation alone for proximal (iliofemoral) DVTs. Complication rates were similar. Active treatments have not been shown to reduce post thrombotic syndrome.

Comment: Lots more work to be done here before active clot removal can be recommended routinely.

Belramman A, Bootun R, Tang TY, Lane TRA, Davies AH.

JAMA Surg 2022; 157: 395-404.

Pain scores were similar after both of these non tumescent venous ablation methods in this study that included 167 procedures. Both methods improved disease-specific quality of life.

Comment: Late clinical outcomes will be important.

Hu H, Wang J, Wu Z, Liu Y, Ma Y, Zhao J et al.

Eur J Vasc Endovasc Surg 2022; 63: 103-111.

There were seven RCTs including 1146 procedures. Wearing a compression stocking reduced early postoperative pain (P<0.001), but had no effect on complications, quality of life, vein occlusion rates, or time to return to work.

Comment: Post intervention compression is not necessary.

Katsanos K, Spiliopoulos S, Teichgraber U, Kitrou P, Del Giudice C, Bjorkman P et al.

Eur J Vasc Endovasc Surg 2022; 63: 60-71.

This analysis included 21 RCTs with 3760 treated legs. Amputation was increased in the paclitaxel group: 4 versus 2.7%, hazard ratio 1.66, 95 per cent confidence interval 1.14 to 2.42, P=0.008.

Comment: a previous review suggested an increased death rate; this study suggests amputations are increased too with paclitaxel balloons.

Bearne M, Volkmer B, Sekhon M, Fisher G, Galea Homes MN, Douiri A, et al for the MOSAIC Trial Collaboration.

JAMA 2022; 327: 1344-1355.

The study included 190 participants randomly allocated to a walking exercise behaviour change intervention by physiotherapists. After three months, those who had received the intervention had an improved 6-minute walking test by around 30m (P=0.009).

Comment: The questions remain whether this improvement is meaningful and durable.

Souroullas P, Barnes R, Carradice D, Smith G, Huang C, Chetter I.

Br J Surg 2022; 109: 426-432.

In this study that included 152 procedures, the five day course reduced the rate of surgical site infection (11.8 versus 39.5 per cent, P<0.001) and revisional surgery (6.6 versus 21 per cent, P=0.01).

Comment: Is this now the standard of care?