Impact of endovascular revascularization, pharmacotherapy, and supervised exercise therapy on long-term cardiovascular, cerebrovascular, mortality, and limb outcomes in patients with peripheral artery disease: a systematic review and network meta-analysis

Objective This systematic review and network meta-analysis compared the long-term effects of endovascular reconstruction/revascularization (ER), supervised exercise therapy (SET), medical therapy (MT), and their combined regimens on cardiovascular and cerebrovascular events, all-cause mortality, and limb outcomes in patients with peripheral artery disease (PAD). Methods Chinese and English databases were searched from inception to April 8, 2026 for randomized controlled trials (RCTs) comparing ER, SET, MT, or their combinations in adults with PAD. The protocol was registered prospectively in PROSPERO (CRD420261362458). Risk of bias was assessed using the Cochrane RoB 2.0 tool. A frequentist network meta-analysis was performed in Stata 19.0. Odds ratios (ORs) were used for binary outcomes and mean differences (MDs) for continuous outcomes. Treatment ranking was summarized using the surface under the cumulative ranking curve (SUCRA), network consistency was evaluated by node-splitting, and certainty of evidence was assessed using the CINeMA framework. Results Fifteen RCTs including 1,461 participants were eligible. For all-cause mortality, ER + SET + MT had the highest SUCRA value (99.4%), suggesting the greatest probability of benefit within the available evidence network. For cardiovascular events and cerebral infarction, ER + MT ranked highest, with SUCRA values of 76.7 and 85.3%, respectively. For amputation, SET + MT showed the highest SUCRA value (77.7%), indicating a greater probability of limb-salvage benefit. For ABI improvement, ER + SET + MT ranked highest (85.2%). Subgroup analyses suggested that the apparent amputation-protective effect of ER combined with ordinary medical therapy (ER + OMT) was larger than that of ER combined with best medical therapy (ER + BMT), although the direction of effect was consistent. Sensitivity analyses did not materially change the main rankings. Overall certainty of evidence was mainly moderate to low, largely because of clinical heterogeneity, sparse direct comparisons, limited reporting quality in some trials, and possible publication bias. Conclusion In patients with PAD, ER + SET + MT may offer a favorable ranking profile for all-cause mortality and limb perfusion, ER + MT appears to rank favorably for cardiovascular and cerebrovascular events, and SET + MT may be particularly relevant for amputation prevention. These rankings should be interpreted cautiously because SUCRA values indicate relative ranking probability rather than definitive clinical superiority, and several comparisons were supported by limited direct evidence, heterogeneous populations, and moderate-to-low certainty. Further large, long-term, head-to-head RCTs are needed to confirm the optimal integrated treatment strategy for different PAD phenotypes.