Meta-analysis of outcomes from drug-eluting stent implantation in infrapopliteal arteries

Table 1 Main characteristics and baselines of the included studies

Ref.	Design	Coutry/Registry	Enrollment period	Drug on DES	Control	Optimal stentinga	Num of patients	Mean age (yr)	Male (%)	Num of limbs	Num of arteries	Num of lesions	Median RC	Mean LRD (mm)	Mean LL (mm)	CTO (%)	Follow up period (yr)b
Siablis et al[42], 2009	PCS	Greece	NA	S	PTA+BMSI	N vs N	62 vs 41	69 vs 72	71 vs 90	75 vs 47	NA	153 vs 77	5 vs 5	NA	55 vs 45	25 vs 35	1
Karnabatidis et al[44], 2011	ACS	Greece	2006-2009	S	PTA+BMSI	Y vs N	47 vs 34	71 vs 71	74 vs 82	51 vs 36	75 vs 57	102 vs 72	4 vs 5	NA	76 vs 77	17 vs 35	1
Scheinert et al[45], 2012	RCT	ACHILLES	2008-2010	S	PTA±BMSI	Y vs N	99 vs 101	72 vs 74	68 vs 75	NA	NA	113 vs 115	4 vs 4	2.6 vs 2.6	27 vs 27	81 vs 75	1
Rastan et al[26], 2012	RCT	Germany	2006-2008	S	PTA+BMSI	Y vs Y	82 vs 79	73 vs 72	68 vs 65	NA	NA	82 vs 79	4 vs 3	3.0 vs 3.0	30 vs 31	23 vs 22	3
Bosiers et al[43], 2012	RCT	DESTINY	2008-2009	E	PTA+BMSI	Y vs Y	74 vs 66	75 vs 76	61 vs 58	78 vs 76	78 vs 76	78 vs 76	4.5 vs 5	3.0 vs 2.9	16 vs 19	15 vs 17	1
Spreen et al[24], 2017	RCT	PADI	2007-2013	P	PTA±BMSI	Y vs N	73 vs 64	74 vs 73	67 vs 73	74 vs 66	NA	121 vs 91	5 vs 5	2.9 vs 2.9	21 vs 23	NA	3
Konijn et al[25], 2020	RCT	PADI	2007-2013	P	PTA±BMSI	Y vs N	73 vs 64	74 vs 73	67 vs 73	74 vs 66	NA	121 vs 91	5 vs 5	2.9 vs 2.9	21 vs 23	NA	10
Zuzek et al[27], 2022	RCS	USA	2016-2017	NA	PTA+BMSI	NA	1056 vs 761	72 vs 72	59 vs 64	NA	NA	NA	5 vs 5	NA	NA	NA	0.5

^aDES implantation was performed regardless of whether predilatation was performed or the outcome of predilatation.

^bApproximate mean. The data variables of double arms are presented in the form of "DES vs control".

PCS: Prospective cohort study; ACS: Ambispective cohort study; RCT: Randomized controlled trial; RCS: Retrospective cohort study; NA: Not available; DES: Drug-eluting stent; S: Sirolimus; E: Everolimus; P: Paclitaxel; PTA: Percutaneous transluminal angioplasty; BMSI: Bare metal stent implantation; N: No; Y: Yes; Num: Number; RC: Rutherford classification; LRD: Lesion reference diameter; LL: Lesion length; CTO: Chronic total occlusion.

Table 2 Definitions of the outcomes during follow-up extracted from the included studies

Ref.	ACD	MA	TLR	AE	PP
Siablis et al[42], 2009	All-cause death	Amputation above the ankle	Repeated revascularization on the target lesion prompted by deterioration of limb ischemia	NA	Absence of repeated intervention and occlusion detected by angiography in the target lesion
Karnabatidis et al[44], 2011	Same as the topa	NIa	Same as the top	ACD, or MA, or TLR	Same as the top
Scheinert et al[45], 2012	NA	NA	NA	ACD, or MA, or TLR, or RC ≥ 4a	NA
Rastan et al[26], 2012	NA	NA	NA	ACD, or MA, or target vessel revascularization, or myocardial infarction	NA
Bosiers et al[43], 2012	Same as the topa	NA	NI*	NA	Absence of ≥ 50% binary ISR detected by angiographya
Spreen et al[24], 2017	NA	Amputation above the ankle	NA	MA, or target limb revascularization	NA
Konijn et al[25], 2020	Same as the top	NA	NA	NA	NA
Zuzek et al[27], 2022	Same as the top	Amputation above the transmetatarsal	Same as the top	NA	NA

^aData extracted from survival curve presented in the article and thus transformed. ACD: All-cause death; NA: Not available; MA: Major amputation; NI: No information; TLR: Target lesion revascularization; AE: Adverse event; RC: Rutherford classification; PP: Primary patency; ISR: In-stent restenosis.

Table 3 Risk bias assessment results of included studies

The domains in RoB 2.0a for RCTs	Scheinert et al[45], 2012	Rastan et al[26], 2012	Bosiers et al[43], 2012	Spreen et al[24], 2017	Konijn et al[25], 2020
1 Randomisation process	Low	Low	Low	Low	Low
2 Deviations from the intended interventions	Low	Low	Low	Low	Low
3 Missing outcome data	Some concerns	Some concerns	High	High	High
4 Measurement of the outcome	Low	Low	Low	Low	Low
5 Selection of the reported result	Low	Low	Low	Low	Low
6 Overall	Some concerns	Some concerns	High	High	High
The domains in ROBINS-Ib for cohort studies	Siablis et al[42], 2009	Karnabatidis et al[44], 2011	Zuzek et al[27], 2022
1 Confounding	Low	Moderate	Moderate
2 Selection of participants	Low	Low	Low
3 Classification of interventions	Low	Low	Low
4 Deviations from intended interventions	Low	Low	Moderate
5 Missing outcome data	Moderate	Moderate	Moderate
6 Measurement of outcomes	Moderate	Moderate	Moderate
7 Selection of the reported result	Low	Low	Low
8 Overall	Moderate	Moderate	Moderate

^aThe risk is graded into 3 levels: low: some concerns: and high.

^bThe risk is graded into 5 levels: low: moderate: serious: critical: and no information. RoB: Risk of bias tool; RCT: Randomized controlled trial; ROBINS-I: Risk of bias in non-randomised studies-of interventions.

Table 4 Evidence quality grade assessment of pooled outcomes of interest

Outcome	Source of data	Num of participants	Pooled HR (DES vs control)	Certainty of the evidence (GRADE)a	Alteration to initial rating
ACD-free survival	2 RCTs	277	0.91 (95%CI: 0.38-2.18)	Moderate	-1b
ACD-free survival	3 cohort studies	2001	1.15 (95%CI: 0.68-1.95)	Low	+1c
MA-free survival	3 cohort studies	2001	1.20 (95%CI: 0.84-1.71)	Low	+1c
TLR-free survival	2 cohort studies	184	2.65 (95%CI: 1.56-4.50)	High	+3d
AE-free survival	3 RCTs	498	1.57 (95%CI: 1.23-2.01)	Moderate	-1b
PP survival	2 cohort studies	184	5.67 (95%CI: 3.56-9.03)	High	+3d

^aHigh certainty: We are very confident that the true effect lies close to that of the estimate of the effect; moderate certainty: We are moderately confident in the effect estimate; low certainty: Our confidence in the effect estimate is limited; very low certainty: We have very little confidence in the effect estimate.

^bThe reason for lowering rating was a suspect of overall bias.

^cThe reason for raising rating was a consideration of plausible confounding.

^dThe reason for raising rating was a consideration of large magnitude of effect, dose-response gradient, and plausible confounding. ACD: All-cause death; MA: major amputation; TLR: Target lesion revascularization; AE: Adverse event; PP: Primary patency; RCT: Randomized controlled trial; Num: number; HR: Hazard ratio; CI: Confidence interval; GRADE: Grading of recommendations assessment: Development and evaluation.