Wounds in peripheral arterial disease

• Primary outcome — no clear evidence of benefit: HR 1.08 (95% CI 0.88-1.32), p=0.47 (abstract p 1689; table 2 p 1694). Median time to healing 187 days (95% CI 169-226) with NPWT versus 195 days (158-213) with usual care — a difference of 8 days (p 1695).
• The confidence interval's upper bound is the trial's own target effect. The sample size was set "to detect a 25% reduction in median time to healing (from 86 days with usual care to 65 days with NPWT equating to a hazard ratio [HR] of 1·32 and a control group event proportion of 0·95), with 90% power" and 20% attrition, requiring 696 participants, 348 per group (p 1693). The paper says so itself: the HR of 1.08 "narrowly includes our target effect size" (p 1695). This is the strongest statement the result will bear: the trial did not exclude its own pre-specified clinically meaningful effect — it failed to demonstrate it. The authors put the same point in plain terms: the finding "is, however uncertain and NPWT might increase the time to healing by as much as 12% or decrease it by as much as 32%" (p 1695).
• Healing within 12 months occurred in 202 (57.9%) NPWT and 196 (58.2%) usual-care participants; 159 (23.2%) were censored for death, amputation, withdrawal or loss to follow-up (83 [23.8%] NPWT, 76 [22.6%] usual care) (p 1695).
• Masked photographic assessment agreed with the unmasked primary outcome: HR 1.13 (95% CI 0.87-1.47), p=0.36 (table 2 p 1694). Results were also consistent across all sensitivity analyses (competing risks by Fine and Gray, correction for stratification errors, adjustment for the baseline smoking and alcohol imbalance, a Complier Average Causal Effect instrumental-variable analysis) and the pre-specified subgroup analysis by previous SWHSI history (p 1695).
• No significant difference in any clinical secondary outcome (table 2 p 1694, denominators n=320 per arm): hospital admission 63 (19.7%) vs 58 (18.1%), OR 1.13 (0.76-1.69), p=0.54; reoperation 78 (24.4%) vs 69 (21.6%), OR 1.20 (0.82-1.74), p=0.35; amputation 35 (10.9%) vs 36 (11.2%), OR 0.98 (0.60-1.62), p=0.95; wound infection 102 (31.9%) vs 100 (31.2%), OR 1.05 (0.75-1.48), p=0.77; antibiotic use for the SWHSI 211 (65.9%) vs 210 (65.6%), OR 1.01 (0.70-1.45), p=0.96; death 40 (11.5%) vs 43 (12.8%), OR 0.89 (0.56-1.41), p=0.61.
• No significant difference in any patient-reported outcome at any timepoint — Bluebelle Wound Healing Questionnaire at 3, 6 and 12 months (p=0.66, 0.70, 0.22) and visual-analogue wound pain at 3, 6 and 12 months (p=0.85, 0.94, 0.80) (table 2 p 1694).
• Harms were similar. 448 adverse events, of which 14 were serious (nine participants in the NPWT group and five participants in the usual care group); 124 were deemed potentially related to treatment (abstract p 1689). At least one adverse event occurred in 150/349 (43.0%) NPWT and 139/337 (41.2%) usual care, risk difference -1.7% (95% CI -9.1 to 5.7); wound infection was the commonest event in both arms, and major wound infection the commonest serious event. Ten of the 14 serious events (71.4%) were judged unrelated or unlikely to be related to study treatment (table 3 p 1695; p 1696).
• NPWT was not cost-effective. Adjusted incremental QALYs +0.007 (95% CI -0.024 to 0.038) and adjusted incremental cost +£251.44 (95% CI -£2192.63 to £2695.52) over 12 months, neither significant. Incremental net monetary benefit -£93.22 at £20 000 and -£18.65 at £30 000 per QALY; probability of cost-effectiveness 47.2% at £20 000 and 49.7% at £30 000 (p 1696). Unadjusted mean per-participant cost was £5782.13 (95% CI £4151.32-£7412.95) for NPWT and £5801.99 (£3897.19-£7706.78) for usual care. Sensitivity analyses reduced the probability of cost-effectiveness further when participants who died were excluded and when cross-over was accounted for; a complete-case analysis suggested NPWT might be cost-effective but rests on 75.7% missing data and the authors call it likely biased (p 1696).
• The population is close to a South African vascular unit's. 549 of 686 (80.0%) were diabetic — 281 (85.4%) and 268 (84.5%) of those with the field recorded; peripheral vascular disease 181 (55.0%) and 168 (53.0%); wounds arose after vascular surgery in 619 (90.2%), with surgery type recorded as vascular in 314 (90.0%) and 305 (90.5%); wound location foot 279 (79.9%) and 272 (80.7%), leg 40 (11.5%) and 29 (8.6%), abdomen 11 (3.2%) and 13 (3.9%); 620 (90.4%) were on the foot or leg. Median wound area 18.30 cm² (IQR 8.10-35.00) and 18.00 cm² (7.26-33.75); the wound was classified dirty in 190 (54.4%) and 210 (62.3%) and the surgery was an emergency in 205 (58.7%) and 194 (57.6%). Median age 63 years (IQR 55-72), 74.8% male, 91.8% White (table 1 pp 1693-94; results p 1695).
• Funding and interests are clean. NIHR HTA Programme, project reference 17/42/94, and "The funder of the study had no role in study design, data collection, data analysis, data interpretation, or writing of the report" (p 1695). Declared interests are minimal: CA reports support for attendance to present the study at Vascular Society of Great Britain and Ireland annual meetings, LM reports independent Data Monitoring and Ethics Committee membership for two unrelated studies (REACH-ASD and ACORN II), and "All other authors declare no competing interests" (p 1698). This matters — the trial cannot be dismissed as an interested party's work, in either direction.
• For context the paper cites the contrary aggregate evidence and explains it: the Cochrane review on this question found only two small trials at risk of bias, and "A separate meta-analysis of 48 low-quality studies at high risk of bias suggested a benefit in healing for SWHSI treated with NPWT (OR 1·56 [95% CI 1·15-2·13]; p=0·008)" (p 1696).

CAT: OCEBM 2 · Start High (rct); no downgrade. RoB 2 overall Some concerns, from one domain only (unmasked primary outcome) — and that domain is mitigated by a pre-specified masked photographic assessment that pointed the same way (HR 1.13, 95% CI 0.87-1.47), while unmasking in an open-label trial biases towards the intervention and therefore cannot manufacture a null. Imprecision was considered and NOT taken: the 95% CI 0.88-1.32 narrowly includes the trial's own pre-specified target HR of 1.32, which is a real borderline, but with 686 randomised, 398 healing events, and concordance across every sensitivity, subgroup, competing-risks, CACE and masked analysis, the benefit-of-the-doubt tie-breaker (Dr Weir, 19 Jul 2026) holds this at High rather than Moderate. A null result from a well-conducted, publicly funded trial is not a weak result.

Figures: Figures checked

CAT: OCEBM 2 (randomised trial) / GRADE Low · Start HIGH (randomised, ethics-approved, independent, unfunded). −1 risk of bias: open-label, which the authors correctly describe as unavoidable since a pump on the leg cannot be masked; wound area and healing are assessed by unblinded staff, and pain, quality of life and physical activity are self-reported by unblinded patients. −1 imprecision, and it is decisive: 14 against 17 patients, below the calculated sample size, with the shortfall caused by dropouts and deaths. The authors state this as their first limitation and attribute the non-significant trends to it, which is the correct reading. Net low. Two points of design quality deserve recording because they are rare in this literature. First, both arms followed the dynamic time strategy for wound bed preparation, so the comparator is structured standard care rather than the undemanding 'conventional dressing' that inflates so many NPWT trials — this vault has repeatedly flagged weak comparators, and this one is not weak. Second, the exclusion criteria are strict and clinically sensible — malignancy, chemotherapy or corticosteroids, NPWT or hyperbaric oxygen in the preceding seven days, haematological abnormality, deep vein thrombosis, malnutrition, and exposure of muscle, tendon OR bone. That last exclusion matters for transfer: the trial studied wounds WITHOUT exposed deep structures, which is not the difficult end of the vascular caseload. Multiplicity is unaddressed: healing rate, healing time, area reduction, infection, adverse events, pain, quality of life and physical activity are all examined in 31 patients with no correction and no hierarchy, so any individual significant secondary finding must be read as exploratory.

Figures: Figures checked

• iNPWT did NOT change 30-day SSI: 16.7% vs 20.9% (p=0.53, RR 0.999).
• iNPWT did NOT change 30-day SSO: 37.9% vs 44.8% (p=0.42).
• It DID reduce early SSO: 19.7% vs 35.8% (p=0.044).
• It DID reduce seroma: 4.6% vs 19.4% (p=0.014).
• This trial is MIXED/NEGATIVE for its primary endpoint.

CAT: OCEBM 2 · The primary outcome is null and that part is sound: 30 day surgical site infection 11 of 66 (16.7%) with iNPWT against 14 of 67 (20.9%), and 30 day surgical site occurrence 25 of 66 (37.9%) against 30 of 67 (44.8%). None of the four printed relative risks reproduce from the paper's own event counts, in either direction. Recomputed here from Table 2: SSI relative risk 0.80 against a printed 0.999 in the abstract and 0.99 in the text; SSO 0.85 against a printed 1.29; early SSO 0.55 against a printed 1.45; seroma 0.23 against a printed 1.73. Inverting the direction gives 1.25, 1.18, 1.82 and 4.27 — still none of them. Each printed ratio does sit at the geometric centre of its own printed interval, so the intervals were derived from the ratios; but the ratios were not derived from the counts, the paper never says what they were derived from, and a ratio above 1.0 is presented throughout as a reduction. The two positive findings are printed with two different p-values in the same paper. The abstract gives early SSO p = .044 and seroma p = .014; the Results text and Table 2 give .037 and .008. Recomputation resolves it: the uncorrected chi-square on 13 of 66 against 24 of 67 gives p = .0380 and on 3 of 66 against 13 of 67 gives p = .0085, matching Table 2 exactly, while Fisher exact gives .0525 and .0143. So the abstract's seroma value is Fisher exact; Its early-sso value of .044 matches neither chi-square (.038), nor Fisher exact (.053), nor the continuity-corrected chi-square (.060). And that matters: the headline surgical-site-occurrence result is significant only on an uncorrected chi-square and fails on an exact test. The seroma result does survive Fisher exact at .014 and is the more robust of the two. GRADE for the null primary is LOW: start High, minus one for risk of bias (no blinding of assessment), minus one for imprecision (the interval on the recomputed relative risk of 0.80 is wide enough to admit both a halving and a substantial increase). GRADE for the seroma finding is VERY LOW: a secondary outcome, in a trial with 40 clustered incisions treated as independent, with abstract and table disagreeing and the printed effect estimate unreproducible.

Figures: Figures checked

The direction of the healthcare-cost column is the finding most readers will get wrong. NPWT did not cost the NHS more in care. It cost £2059 less in care — fewer GP visits, fewer nurse home visits, lower medication costs. It lost the analysis entirely on the price of the device and its consumables, where it cost £4852 more. Everything else in this paper is downstream of that one gap.

And the gap comes from a single ratio. NPWT cost £30.61 per day (s.e. 0.18); a standard dressing cost £4.17 per day (s.e. 0.11). NPWT is 7.3 times more expensive per day of treatment, and mean time on NPWT was 46.6 days (s.e. 4.12) against 164.3 days (s.e. 4.7) on standard dressings. Both daily costs are centre-specific costings from Hull and Cornwall, built from the actual mix of dressing and canister sizes used in the trial and the averaged price of advanced dressings — not list prices. That is the most transportable thing in the paper, because it means a reader elsewhere can substitute their own two numbers and see what happens.

The threshold the paper prints is the other half of the answer. For NPWT to become cost-effective at the NICE thresholds, it would have to increase the probability of wound healing by 16% relative to standard dressings. The pooled hazard ratio for healing was 1.07 (95% c.i. 0.82 to 1.71) and the SWHSI-2 trial itself gave 1.08 (0.88 to 1.32). Neither is anywhere near 16%, and neither excludes harm.

CAT: OCEBM 2 · START at OCEBM 2 — a decision model built on a Bayesian synthesis that includes patient-level data from the largest randomised trial ever run in this population. NO DOWNGRADE for the internal question: the model is transparent, the structure is clinically defensible, the NICE reference case is followed, the code is offered on request and the data are deposited at osf.io/echxv. −1 for the quality of the effectiveness input, which the authors themselves flag: Five of the six external trials were judged to be at moderate OR high risk of bias, the trials are small, and the pooled hazard ratio 1.07 (0.82 to 1.71) carries almost all the uncertainty in the result. NO further downgrade for imprecision at the level of the DECISION, because imprecision in this model does not rescue NPWT — the incremental net monetary benefit is negative across the entire range of thresholds from 1,000 to 20,000 pounds per QALY, and the probability of cost-effectiveness never exceeds about 30%. NET MODERATE for the UK conclusion. The mechanism of the result is the part worth carrying, and it is not what most readers will assume. NPWT did not lose on healthcare costs — It won on them: mean lifetime healthcare costs were 73,881 pounds with NPWT against 75,940 pounds with standard dressings, a saving of 2,059 pounds. It lost entirely on the cost of the device and its consumables, 18,554 pounds against 13,702 pounds, a gap of 4,852 pounds. The whole verdict therefore rests on ONE ratio: the daily cost of NPWT, 30.61 pounds, against the daily cost of a standard dressing, 4.17 pounds — 7.3 times more expensive per day. The threshold the paper prints is the other half of the answer: for NPWT to become cost-effective it would have to raise the probability of wound healing by 16% relative to standard dressings, and the trial and the synthesis both found no clear effect at all. GRADE is not applicable to the south african question. There is no South African estimate here, no South African cost input, and no South African willingness-to-pay threshold to compare against. What can be said is which inputs would have to move, and in which direction — set out in full on the page.

Figures: Figures checked

• Adjusted, NPWT patients were 2.63× more likely to achieve wound closure than non-NPWT patients (95% CI 1.87-3.70) (p.5).
• Healing benefit by ulcer type: diabetic HR 3.26 (2.21-4.83), arterial HR 2.27 (1.56-3.78), venous HR 6.31 (1.49-26.6); pressure ulcers not significant (HR 1.72, 0.43-6.95) (Table 4, p.5).
• Crude healing rates: 90.5 vs 43.0 wounds healed per 100 person-years (NPWT vs non-NPWT) across all ulcers (Table 3, p.5).
• Earlier NPWT improved healing: early users (≤3 months after ulcer onset) HR 3.38 (1.68-6.82, P<0.01) and intermediate users (4-12 months) HR 2.18 (0.94-5.07) versus late users (≥1 year) (Table 5, p.6).
• NPWT cohort was sicker (more diabetic and arterial ulcers, more CKD) yet still healed faster (p.4).

CAT: OCEBM 4 · What the matching achieved, and what it could not. Matching was on age, sex and surgical incision and drainage — three variables, none of which drives healing — and the abstract and Methods do not even agree on which three. It achieved balance on age (61.3 against 60.8 years) and sex (99 men in each arm), and nothing else. It did not balance the variables that decide whether a lower-limb ulcer heals. From Table 2: arterial ulcers 66.7% against 34.9%, P < 0.01; diabetic 81.8% against 69.4%, P < 0.05; chronic renal disease 49.7% against 28.1%, P < 0.01; inpatient ulcer care 94.7% against 66.7%, P < 0.01. And ulcer site, which matters most: toe ulcers 60/171 (35.2%) against 15/171 (8.8%); heel 19 (11.1%) against 36 (21.1%); leg 27 (15.7%) against 50 (29.2%). The NPWT arm had four times as many toe ulcers and half as many heel and leg ulcers. Table 2 prints P > 0.05 for the whole location block, which is not credible on those counts, and the Results text calls the locations nearly equal — contradicted by its own table. Ulcer site is not in the adjustment set. The effect itself is denominator, not numerator. Table 3 records 118 ulcers healed without NPWT and 119 with — 69.0% against 69.6%. The crude proportion healed is identical. What differs is person-time: 274.36 person-years against 131.47, a mean follow-up of 1.60 years against 0.77. The rates of 43.01 and 90.51 per 100 person-years reproduce exactly from those cells, and the pattern holds in every subgroup, the crude proportions healed differing by a few points at most. And the person-time is defined by clinic attendance: follow-up is right-censored at the last clinic note describing the index ulcer, so a healed ulcer stops accruing time while an unhealed one keeps accruing it. That is informative censoring running with the result. Adjusted hazard ratios: all ulcers 2.63 (1.87 to 3.70); diabetic 3.26 (2.21 to 4.83); arterial 2.27 (1.56 to 3.78) in the abstract and Table 4 but 2.26 in the Results text; venous 6.31 (1.49 to 26.6) on 26 events; PRESSURE ULCERS 1.72 (0.43 to 6.95), NOT SIGNIFICANT. Two estimates fail an internal check: the unadjusted all-ulcer HR 2.25 (1.73 to 3.96) is not symmetric on the log scale, which for a Cox ratio means a mistyped bound, and the adjusted arterial interval fails the same check. Timing: 3.38 (1.68 to 6.82) within 3 months and 2.18 (0.94 to 5.07), P = 0.07, NOT SIGNIFICANT, at 4 to 12 months. No conflict-of-interest and no funding statement appears anywhere.

Figures: Figures checked

• Four core mechanisms of action underpin every indication: (1) reduces tissue oedema; (2) increases granulation tissue formation; (3) increased perfusion as a secondary/later effect; (4) with instillation and dwell time can reduce wound contamination.
• Vascular surgery: high-level evidence supports NPWT for infected vessels and prosthetic vascular grafts — strong recommendation for high-risk surgical patients with a fully exposed, infected prosthetic vascular graft, together with debridement and appropriate antibiotics; continuous suction at lower levels (-50 to -100 mmHg) recommended to avoid bleeding.
• Traumatic/surgical wounds: NPWT is first-line for preoperative wound-bed preparation post-debridement, typically 7-10 days before definitive surgery; strong for open fractures that cannot be closed primarily (used between debridement and reconstruction); caution when tendon/bone exposed; do not use if underlying arterial impairment is not addressed (red).
• Diabetic foot ulcers: first-line post-surgical treatment for DFU once ischaemia is excluded (University of Texas Grade A2/A3); consider for chronic DFU not progressing after 4 weeks; contraindicated where ischaemia is due to concomitant peripheral arterial disease (red).
• Sternal dehiscence: NPWT is the method of choice for post-sternotomy mediastinitis (strong); caution in the haemodynamically unstable patient; the open sternum with exposed vulnerable structures is not an indication (red).
• Abdominal / dehisced abdominal wounds: strong for the open abdomen and for dehisced wounds with intact abdominal wall; NPWT with instillation (NPWTi-d) is effective in reducing infection in the infected open/dehisced abdomen (moderate); do not use if size/severity does not merit it.
• Skin grafts, burns, venous ulcers, pressure injuries, enterocutaneous fistulae: NPWT endorsed for wound-bed optimisation before grafting and intra-operative graft stabilisation; acute burn indications supported but not a substitute for grafting; venous ulcers only if <30% area reduction in 4 weeks and ABPI 0.8-1.2 (contraindicated if ABPI <0.6); NPIAP stage 3/4 pressure injuries until surgical closure (moderate); ECF in selected collapsible/low-output cases only, never in unexplored fistulae.
• Closed incisional NPWT (ciNPT): recommended to decrease wound complications, dehiscence, haematoma/seroma and surgical site infection (strong).
• Contraindications listed: clotting disorders, active non-capillary bleeding post-debridement, exposed organs/vasculature/anastomoses, eschar or dry necrosis, neoplastic tissue, untreated osteomyelitis, non-enteric and unexplored fistulae.

AGREE II: Recommended with modifications — Scope 67% · Stakeholders 56% · Rigour 23% · Clarity 67% · Applicability 46% · Independence 25%

Figures: Figures checked