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Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Primary safety outcome: death or any stroke between randomisation and 30 days after treatment Show forest plot	10	5396	Odds Ratio (M‐H, Random, 95% CI)	1.70 [1.31, 2.19]

1.1 Symptomatic carotid stenosis	8	5184	Odds Ratio (M‐H, Random, 95% CI)	1.74 [1.30, 2.33]
1.2 Asymptomatic and symptomatic carotid stenosis combined	2	212	Odds Ratio (M‐H, Random, 95% CI)	1.00 [0.23, 4.34]
2 Death or any stroke between randomisation and 30 days after treatment according to age Show forest plot	6	4861	Odds Ratio (M‐H, Random, 95% CI)	1.67 [1.22, 2.28]

2.1 Aged < 70 years	6	2453	Odds Ratio (M‐H, Random, 95% CI)	1.11 [0.74, 1.64]
2.2 Aged ≥ 70 years	6	2408	Odds Ratio (M‐H, Random, 95% CI)	2.23 [1.61, 3.08]
3 Death or any stroke between randomisation and 30 days after treatment according to sex Show forest plot	6	4861	Odds Ratio (M‐H, Random, 95% CI)	1.69 [1.21, 2.35]

3.1 Men	6	3395	Odds Ratio (M‐H, Random, 95% CI)	1.82 [1.10, 3.02]
3.2 Women	6	1466	Odds Ratio (M‐H, Random, 95% CI)	1.52 [0.96, 2.41]
4 Death or any stroke between randomisation and 30 days after treatment according to minimum pretrial experience in endovascular treatment of carotid stenosis Show forest plot	7	5080	Odds Ratio (M‐H, Random, 95% CI)	1.76 [1.32, 2.36]

4.1 ≤ 10 procedures	3	2456	Odds Ratio (M‐H, Random, 95% CI)	2.21 [1.56, 3.13]
4.2 > 10 procedures	4	2624	Odds Ratio (M‐H, Random, 95% CI)	1.37 [0.98, 1.94]
5 Death or major or disabling stroke between randomisation and 30 days after treatment Show forest plot	7	4983	Odds Ratio (M‐H, Random, 95% CI)	1.36 [0.97, 1.91]

6 Death of any cause between randomisation and 30 days after treatment Show forest plot	10	5264	Odds Ratio (M‐H, Random, 95% CI)	1.35 [0.69, 2.61]

7 Any stroke between randomisation and 30 days after treatment Show forest plot	8	5113	Odds Ratio (M‐H, Random, 95% CI)	1.78 [1.38, 2.29]

8 Fatal, major, or disabling stroke between randomisation and 30 days after treatment Show forest plot	7	4983	Odds Ratio (M‐H, Random, 95% CI)	1.34 [0.93, 1.92]

9 Myocardial infarction between randomisation and 30 days after treatment Show forest plot	8	4994	Odds Ratio (M‐H, Random, 95% CI)	0.47 [0.24, 0.94]

10 Death or any stroke or myocardial infarction between randomisation and 30 days after treatment Show forest plot	6	4861	Odds Ratio (M‐H, Random, 95% CI)	1.43 [1.14, 1.80]

11 Primary combined safety and efficacy outcome: death or any stroke between randomisation and 30 days after treatment or ipsilateral stroke until the end of follow‐up Show forest plot	8	5080	Odds Ratio (M‐H, Random, 95% CI)	1.51 [1.24, 1.85]

12 Death or any stroke between randomisation and end of follow‐up Show forest plot	9	5292	Odds Ratio (M‐H, Random, 95% CI)	1.23 [1.03, 1.46]

12.1 6–24 months' follow‐up	4	1627	Odds Ratio (M‐H, Random, 95% CI)	1.33 [0.75, 2.37]
12.2 ≥ 4 years' follow‐up	5	3665	Odds Ratio (M‐H, Random, 95% CI)	1.24 [1.02, 1.51]
13 Any stroke during follow‐up (periprocedural events and people dying in the periprocedural period excluded) Show forest plot	6	4837	Odds Ratio (M‐H, Random, 95% CI)	1.15 [0.82, 1.62]

13.1 18–24 months' follow‐up	2	1204	Odds Ratio (M‐H, Random, 95% CI)	0.97 [0.52, 1.82]
13.2 ≥ 4 years' follow‐up	4	3633	Odds Ratio (M‐H, Random, 95% CI)	1.21 [0.79, 1.86]
14 Ipsilateral stroke during follow‐up (periprocedural events and people dying in the periprocedural period excluded) Show forest plot	6	4837	Odds Ratio (M‐H, Random, 95% CI)	1.05 [0.75, 1.47]

14.1 18–24 months' follow‐up	2	1204	Odds Ratio (M‐H, Random, 95% CI)	1.07 [0.45, 2.54]
14.2 ≥ 4 years' follow‐up	4	3633	Odds Ratio (M‐H, Random, 95% CI)	1.05 [0.73, 1.50]
15 Death or any stroke or myocardial infarction between randomisation and 30 days after treatment or ipsilateral stroke until end of follow‐up Show forest plot	7	4907	Odds Ratio (M‐H, Random, 95% CI)	1.39 [1.15, 1.69]

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Death or any stroke between randomisation and 30 days after treatment Show forest plot	7	3378	Odds Ratio (M‐H, Random, 95% CI)	1.72 [1.00, 2.97]

2 Death or major or disabling stroke between randomisation and 30 days after treatment Show forest plot	2	2601	Odds Ratio (M‐H, Random, 95% CI)	1.54 [0.39, 6.11]

3 Myocardial infarction between randomisation and 30 days after treatment Show forest plot	6	2945	Odds Ratio (M‐H, Random, 95% CI)	0.53 [0.24, 1.15]

4 Death or any stroke or myocardial infarction between randomisation and 30 days after treatment Show forest plot	6	2978	Odds Ratio (M‐H, Random, 95% CI)	1.16 [0.73, 1.85]

5 Death or any stroke between randomisation and 30 days after treatment or ipsilateral stroke until end of follow‐up Show forest plot	6	3315	Odds Ratio (M‐H, Random, 95% CI)	1.27 [0.87, 1.84]

6 Death or any stroke or myocardial infarction between randomisation and 30 days after treatment or ipsilateral stroke until end of follow‐up Show forest plot	5	2882	Odds Ratio (M‐H, Random, 95% CI)	1.10 [0.76, 1.59]

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Death or any stroke between randomisation and 30 days after treatment Show forest plot	2	397	Odds Ratio (M‐H, Random, 95% CI)	0.95 [0.39, 2.28]

2 Fatal, major, or disabling stroke between randomisation and 30 days after treatment Show forest plot	1	334	Odds Ratio (M‐H, Random, 95% CI)	0.66 [0.11, 4.02]

3 Death of any cause between randomisation and 30 days after treatment Show forest plot	2	397	Odds Ratio (M‐H, Random, 95% CI)	0.47 [0.10, 2.15]

4 Any stroke between randomisation and 30 days after treatment Show forest plot	2	397	Odds Ratio (M‐H, Random, 95% CI)	1.40 [0.48, 4.14]

5 Myocardial infarction between randomisation and 30 days after treatment Show forest plot	2	397	Odds Ratio (M‐H, Random, 95% CI)	0.39 [0.12, 1.25]

6 Death or any stroke or myocardial infarction between randomisation and 30 days after treatment Show forest plot	2	397	Odds Ratio (M‐H, Random, 95% CI)	0.66 [0.33, 1.34]

7 Death or any stroke between randomisation and 30 days after treatment or ipsilateral stroke until end of follow‐up Show forest plot	2	397	Odds Ratio (M‐H, Random, 95% CI)	1.09 [0.58, 2.06]

8 Death or any stroke or myocardial infarction between randomisation and 30 days after treatment or ipsilateral stroke until end of follow‐up Show forest plot	2	397	Odds Ratio (M‐H, Random, 95% CI)	0.84 [0.48, 1.47]

9 Any stroke during follow‐up (periprocedural events and people dying in the periprocedural period excluded) Show forest plot	2	397	Odds Ratio (M‐H, Random, 95% CI)	1.02 [0.49, 2.10]

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Severe (≥ 70%) restenosis during follow‐up Show forest plot	9	5744	Odds Ratio (M‐H, Random, 95% CI)	1.21 [0.76, 1.93]

2 Moderate (≥ 50%) or severe (≥ 70%) restenosis during follow‐up Show forest plot	4	2115	Odds Ratio (M‐H, Random, 95% CI)	2.00 [1.12, 3.60]

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Cranial nerve palsy within 30 days of procedure Show forest plot	13	8277	Odds Ratio (M‐H, Random, 95% CI)	0.10 [0.06, 0.16]

1.1 Symptomatic carotid stenosis	7	4965	Odds Ratio (M‐H, Random, 95% CI)	0.10 [0.05, 0.18]
1.2 Asymptomatic carotid stenosis	5	2915	Odds Ratio (M‐H, Random, 95% CI)	0.09 [0.03, 0.27]
1.3 Elevated surgical risk	2	397	Odds Ratio (M‐H, Random, 95% CI)	0.13 [0.02, 1.14]
2 Death or neurological complication up to 30 days after treatment Show forest plot	6	3642	Odds Ratio (M‐H, Random, 95% CI)	0.73 [0.55, 0.98]

2.1 Symptomatic carotid stenosis	5	3557	Odds Ratio (M‐H, Random, 95% CI)	0.74 [0.57, 0.98]
2.2 Asymptomatic carotid stenosis	1	85	Odds Ratio (M‐H, Random, 95% CI)	0.13 [0.01, 2.59]
3 Access site haematoma Show forest plot	10	7731	Odds Ratio (M‐H, Random, 95% CI)	0.32 [0.15, 0.68]

3.1 Symptomatic carotid stenosis	8	5012	Odds Ratio (M‐H, Random, 95% CI)	0.40 [0.17, 0.96]
3.2 Asymptomatic carotid stenosis	3	2719	Odds Ratio (M‐H, Random, 95% CI)	0.14 [0.02, 0.90]

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Death or any stroke between randomisation and end of follow‐up Show forest plot	2	61	Odds Ratio (M‐H, Random, 95% CI)	0.22 [0.01, 7.92]

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Death or any stroke between randomisation and 30 days after treatment Show forest plot	2	469	Odds Ratio (M‐H, Fixed, 95% CI)	1.76 [1.06, 2.92]

2 Any stroke during follow‐up (periprocedural events and people dying in the periprocedural period excluded) Show forest plot	1	443	Odds Ratio (M‐H, Random, 95% CI)	1.85 [1.06, 3.24]

3 Death or any stroke between randomisation and 30 days after treatment or ipsilateral stroke until the end of follow‐up Show forest plot	1	452	Odds Ratio (M‐H, Random, 95% CI)	1.47 [0.93, 2.33]

4 Ipsilateral stroke during follow‐up (periprocedural events and people dying in the periprocedural period excluded) Show forest plot	1	443	Odds Ratio (M‐H, Random, 95% CI)	1.33 [0.62, 2.83]

5 Severe (≥ 70%) restenosis during follow‐up Show forest plot	1	413	Odds Ratio (M‐H, Random, 95% CI)	3.48 [1.99, 6.07]

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Death or any stroke between randomisation and 30 days after treatment Show forest plot	1	52	Odds Ratio (M‐H, Random, 95% CI)	1.11 [0.17, 7.28]

2 Death or any stroke between randomisation and 30 days after treatment or ipsilateral stroke until the end of follow‐up Show forest plot	1	52	Odds Ratio (M‐H, Random, 95% CI)	1.11 [0.17, 7.28]

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Carotid artery stenting compared to endarterectomy for symptomatic carotid stenosis
Patient or population: people with symptomatic carotid stenosis Setting: hospital Intervention: carotid artery stenting Comparison: endarterectomy
Outcomes	*Anticipated absolute effects (95% CI)**		Relative effect (95% CI)	№ of participants (studies)	Certainty of the evidence (GRADE)	Comments
	Risk with endarterectomy	Risk with carotid artery stenting
Death or any stroke between randomisation and 30 days after treatment	Study population		OR 1.70 (1.31 to 2.19)	5396 (10 RCTs)	⊕⊕⊕⊕ High	—
	44 per 1000	72 per 1000 (56 to 91)
Death or any stroke between randomisation and 30 days after treatment or ipsilateral stroke until end of follow‐up	Study population		OR 1.51 (1.24 to 1.85)	5080 (8 RCTs)	⊕⊕⊕⊕ High	—
	70 per 1000	102 per 1000 (85 to 122)
Death or major or disabling stroke between randomisation and 30 days after treatment	Study population		OR 1.36 (0.97 to 1.91)	4983 (7 RCTs)	⊕⊕⊕⊕ High	—
	24 per 1000	33 per 1000 (23 to 45)
Death or any stroke or myocardial infarction between randomisation and 30 days after treatment	Study population		OR 1.43 (1.14 to 1.80)	4861 (6 RCTs)	⊕⊕⊕⊕ High	—
	56 per 1000	78 per 1000 (63 to 96)
* The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: confidence interval; OR: odds ratio; RCT: randomised controlled trial.
GRADE Working Group grades of evidence High 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: the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different. Low certainty: our confidence in the effect estimate is limited: the true effect may be substantially different from the estimate of the effect. Very low certainty: we have very little confidence in the effect estimate: the true effect is likely to be substantially different from the estimate of effect.

Carotid artery stenting compared to endarterectomy for asymptomatic carotid stenosis
Patient or population: people with asymptomatic carotid stenosis Setting: hospital Intervention: carotid artery stenting Comparison: endarterectomy
Outcomes	*Anticipated absolute effects (95% CI)**		Relative effect (95% CI)	№ of participants (studies)	Certainty of the evidence (GRADE)	Comments
	Risk with endarterectomy	Risk with carotid artery stenting
Death or any stroke between randomisation and 30 days after treatment	Study population		OR 1.72 (1.00 to 2.97)	3378 (7 RCTs)	⊕⊕⊕⊝ Moderate ^a	—
	14 per 1000	25 per 1000 (14 to 42)
Death or any stroke between randomisation and 30 days after treatment or ipsilateral stroke until end of follow‐up	Study population		OR 1.27 (0.87 to 1.84)	3315 (6 RCTs)	⊕⊕⊕⊝ Moderate ^a	—
	36 per 1000	45 per 1000 (31 to 63)
Death or major or disabling stroke between randomisation and 30 days after treatment	Study population		OR 1.54 (0.39 to 6.11)	2601 (2 RCTs)	⊕⊕⊕⊝ Moderate ^b	—
	3 per 1000	5 per 1000 (1 to 19)
Death or any stroke or myocardial infarction between randomisation and 30 days after treatment	Study population		OR 1.16 (0.73 to 1.85)	2978 (6 RCTs)	⊕⊕⊕⊝ Moderate ^a	—
	28 per 1000	32 per 1000 (20 to 50)
* The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: confidence interval; OR: odds ratio; RCT: randomised controlled trial.
GRADE Working Group grades of evidence High 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: the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different. Low certainty: our confidence in the effect estimate is limited: the true effect may be substantially different from the estimate of the effect. Very low certainty: we have very little confidence in the effect estimate: the true effect is likely to be substantially different from the estimate of effect.
^a Downgraded one level due to wide confidence intervals surrounding the effect measures for the primary short‐ and long‐term outcome in people with asymptomatic carotid stenosis. ^b Downgraded one level as evidence was only available from two randomised trials.

Carotid artery stenting compared to endarterectomy for prevention of severe restenosis in people with symptomatic or asymptomatic carotid stenosis
Patient or population: people with symptomatic or asymptomatic carotid stenosis Setting: hospital Intervention: carotid artery stenting Comparison: endarterectomy
Outcomes	*Anticipated absolute effects (95% CI)**		Relative effect (95% CI)	№ of participants (studies)	Certainty of the evidence (GRADE)	Comments
	Risk with endarterectomy	Risk with carotid artery stenting
Severe (≥ 70%) restenosis during follow‐up	Study population		OR 1.21 (0.76 to 1.93)	5744 (9 RCTs)	⊕⊕⊝⊝ Low ^a,b	—
	56 per 1000	67 per 1000 (43 to 103)
* The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: confidence interval; OR: odds ratio; RCT: randomised controlled trial.
GRADE Working Group grades of evidence High 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: the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different. Low certainty: our confidence in the effect estimate is limited: the true effect may be substantially different from the estimate of the effect. Very low certainty: we have very little confidence in the effect estimate: the true effect is likely to be substantially different from the estimate of effect.
^a Downgraded one level due to substantial heterogeneity in the assessment of severe restenosis between trials. ^b Downgraded one level due to wide confidence intervals of effect measures.

Carotid artery stenting compared to endarterectomy for symptomatic carotid stenosis
Patient or population: people with symptomatic carotid stenosis Setting: hospital Intervention: carotid artery stenting Comparison: endarterectomy
Outcomes	*Anticipated absolute effects (95% CI)**		Relative effect (95% CI)	№ of participants (studies)	Certainty of the evidence (GRADE)	Comments
	Risk with endarterectomy	Risk with carotid artery stenting
Death or any stroke between randomisation and 30 days after treatment	Study population		OR 1.70 (1.31 to 2.19)	5396 (10 RCTs)	⊕⊕⊕⊕ High	—
	44 per 1000	72 per 1000 (56 to 91)
Death or any stroke between randomisation and 30 days after treatment or ipsilateral stroke until end of follow‐up	Study population		OR 1.51 (1.24 to 1.85)	5080 (8 RCTs)	⊕⊕⊕⊕ High	—
	70 per 1000	102 per 1000 (85 to 122)
Death or major or disabling stroke between randomisation and 30 days after treatment	Study population		OR 1.36 (0.97 to 1.91)	4983 (7 RCTs)	⊕⊕⊕⊕ High	—
	24 per 1000	33 per 1000 (23 to 45)
Death or any stroke or myocardial infarction between randomisation and 30 days after treatment	Study population		OR 1.43 (1.14 to 1.80)	4861 (6 RCTs)	⊕⊕⊕⊕ High	—
	56 per 1000	78 per 1000 (63 to 96)
* The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: confidence interval; OR: odds ratio; RCT: randomised controlled trial.
GRADE Working Group grades of evidence High 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: the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different. Low certainty: our confidence in the effect estimate is limited: the true effect may be substantially different from the estimate of the effect. Very low certainty: we have very little confidence in the effect estimate: the true effect is likely to be substantially different from the estimate of effect.

Carotid artery stenting compared to endarterectomy for asymptomatic carotid stenosis
Patient or population: people with asymptomatic carotid stenosis Setting: hospital Intervention: carotid artery stenting Comparison: endarterectomy
Outcomes	*Anticipated absolute effects (95% CI)**		Relative effect (95% CI)	№ of participants (studies)	Certainty of the evidence (GRADE)	Comments
	Risk with endarterectomy	Risk with carotid artery stenting
Death or any stroke between randomisation and 30 days after treatment	Study population		OR 1.72 (1.00 to 2.97)	3378 (7 RCTs)	⊕⊕⊕⊝ Moderate ^a	—
	14 per 1000	25 per 1000 (14 to 42)
Death or any stroke between randomisation and 30 days after treatment or ipsilateral stroke until end of follow‐up	Study population		OR 1.27 (0.87 to 1.84)	3315 (6 RCTs)	⊕⊕⊕⊝ Moderate ^a	—
	36 per 1000	45 per 1000 (31 to 63)
Death or major or disabling stroke between randomisation and 30 days after treatment	Study population		OR 1.54 (0.39 to 6.11)	2601 (2 RCTs)	⊕⊕⊕⊝ Moderate ^b	—
	3 per 1000	5 per 1000 (1 to 19)
Death or any stroke or myocardial infarction between randomisation and 30 days after treatment	Study population		OR 1.16 (0.73 to 1.85)	2978 (6 RCTs)	⊕⊕⊕⊝ Moderate ^a	—
	28 per 1000	32 per 1000 (20 to 50)
* The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: confidence interval; OR: odds ratio; RCT: randomised controlled trial.
GRADE Working Group grades of evidence High 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: the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different. Low certainty: our confidence in the effect estimate is limited: the true effect may be substantially different from the estimate of the effect. Very low certainty: we have very little confidence in the effect estimate: the true effect is likely to be substantially different from the estimate of effect.
^a Downgraded one level due to wide confidence intervals surrounding the effect measures for the primary short‐ and long‐term outcome in people with asymptomatic carotid stenosis. ^b Downgraded one level as evidence was only available from two randomised trials.

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