Summary of findings 3. Alirocumab compared with ezetimibe and statins.

Alirocumab compared with ezetimibe and statins
Patient or population: people at high risk of CVD (history of CVD or high LDL‐C despite treatment) Setting: outpatient care settings Intervention: alirocumab PCSK9 monoclonal antibodies Comparison: ezetimibe and statins
Outcomes	Illustrative comparative risk (95% CI)		Relative effect (95% CI)	RD (95% CI)	Number of participants (studies)	Certainty of the evidence (GRADE)	Comments
	Assumed risk	Corresponding risk with PCSK9 inhibition
CVD Follow‐up: 6–12 months	CVD risk was 28 per 1000 participants	CVD risk in the intervention group was 37 (20 to 50 higher) per 1000 participants	OR 1.37 (0.65 to 2.87)	0.01 (–0.01 to 0.03)	1379 (3 RCTs)	⊕⊕⊝⊝ Lowa	< 1 is beneficial
All‐cause mortality Follow‐up: 6–12 months	All‐cause mortality risk was 9 per 1000 participants	All‐cause mortality risk in the intervention group was 3  (0 to 12) per 1000 participants	OR 0.51 (0.18 to 1.40)	–0.01 (–0.02 to 0.00)	1733 (5 RCTs)	⊕⊕⊝⊝ Lowa	< 1 is beneficial
Myocardial infarction Follow‐up: 6–12 months	Myocardial infarction risk was 28 per 1000 participants	Myocardial infarction risk in the intervention group was 35 (22 to 48) per 1000 participants	OR 1.45 (0.64 to 3.28)	0.01 (–0.01 to 0.02)	1734 (5 RCTs)	⊕⊕⊝⊝ Lowa	< 1 is beneficial
Any stroke Follow‐up: 6–12 months	Stroke risk was 27 per 1000 participants	Stroke risk in the intervention group was 23 (20 to 26) per 1000 participants	OR 0.85 (0.13 to 5.61)	0.00 (–0.01 to 0.01)	1734 (5 RCTs)	⊕⊕⊝⊝ Lowa	< 1 is beneficial
CI: confidence interval; CVD: cardiovascular disease; LDL‐C: low‐density lipoprotein cholesterol; OR: odds ratio; RCT: randomised controlled trial; RD: risk difference.
GRADE Working Group grades of evidence High certainty: we are very confident that the true effect lies close to the estimate of effect. Moderate certainty: we are moderately confident in the effect estimate: the true effect is likely to be close to the estimate of effect but may be substantially different. Low certainty: our confidence in the effect estimate is limited: the true effect may be substantially different from the estimate of 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.

^aLow event rates and confidence intervals crossed null effect included both appreciable harm and benefit. Downgraded two levels for imprecision.