Benefits of intensive lipid-lowering therapies in patients with acute coronary syndrome: a systematic review and meta-analysis

Figures & data

Table 1. Characteristics of included studies.

Study	Population	Intervention treatment	Comparative treatment	Sample size (women)	Age, y	Study duration	Baseline LDL-C, mg/dL	LDL-C difference between groups after treatment, mg/dL	LDL-C after treatment (intervention, mg/dL)	LDL-C after treatment (control, mg/dL)
Cannon, 2015 [27]	ACS patients with LDL-C levels ≥ 50 mg/dL	Ezetimibe 10 mg, plus simvastatin 40 mg	Simvastatin 40 mg	18144 (25.4%)	63.6	7 y	94	17 (18.1%)	53.2	69.9
Japaridze, 2017 [29]	ACS patients with LDL-C levels ≥ 70 mg/dL	Ezetimibe 10 mg, plus atorvastatin 20 mg	Atorvastatin 40 mg	292 (46.2%)	62.4	12 w	108	12 (11.1%)	61.9	73.9
Liu, 2017 [31]	ACS patients	Ezetimibe 10 mg, plus atorvastatin 10 mg	Atorvastatin 20 mg	230 (48.3%)	84	1 y	87	8 (9.2%)	46.4	54.1
Ran, 2017 [33]	Non-ST segment elevation ACS patients underwent urgent PCI	Ezetimibe 10 mg, plus rosuvastatin 10 mg	Rosuvastatin 10 mg or 20 mg	125 (25.6%)	60.5	12 w	141	25 (17.7%)	46..0	64.0
Schwartz, 2018 [34]	ACS patients with LDL-C levels ≥ 70 mg/dL, non–HDL-C ≥ 100 mg/dL, or apolipoprotein B ≥ 80 mg/dL	Alirocumab 75 mg, plus atorvastatin 40 or 80 mg or rosuvastatin 20 or 40 mg	Atorvastatin 40 or 80 mg or rosuvastatin 20 or 40 mg	18924 (25.2%)	58.6	2.8 y	92	37 (40.2%)	66.0	101.0
Koskinas, 2019 [30]	ACS patients with LDL-C levels ≥ 70 mg/dL (high-intensity statin); ≥90 mg/dL (low or moderate intensity statin); or ≥ 125 mg/dL (without stable statin)	Evolocumab 420 mg, plus atorvastatin 40 mg	Atorvastatin 40 mg	308 (18.5%)	60.7	8 w	135	55 (40.7%)	36.7	80.0
Tan, 2021 [35]	ACS patients	Ezetimibe 10 mg, plus, atorvastatin 10 mg	Atorvastatin 40 mg	183 (44.8%)	49.0	24 m	128	35 (27.3%)	58.0	106.3
Räber, 2022 [32]	Patients underwent urgent PCI with LDL-C levels ≥ 70 mg/dL (receiving stable statin) or ≥ 125 mg/dL (without stable statin treatment)	Alirocumab 150 mg, plus rosuvastatin 20 mg	Rosuvastatin 20 mg	298 (18.8%)	58.5	52 w	153	55 (35.9%)	23.6	74.4
Yan, 2022 [28]	Patients underwent urgent PCI with LDL-C levels ≥ 116 mg/dL	Evolocumab 140 mg, plus atorvastatin 40 mg and ezetimibe 10 mg	Atorvastatin 40 mg and ezetimibe 10 mg	136 (31.6%)	62.2	3 m	137	27 (19.7%)	22.4	49.1

Abbreviations: ACS, acute coronary syndrome; LDL-C, low-density lipoprotein cholesterol; HDL-C, high-density lipoprotein cholesterol; PCI, percutaneous coronary intervention.

Figure 1. Risk of three-point MACE.

Figure 2. Risk of recurrent ACS.

Table 2. Association of aggressive lipid-lowering vs background statin therapy with primary and secondary outcomes among patients with ACS.

Endpoint	LDL-lowering, No./Total. (%)		RR (95%CI)	NNT
	Aggressive lipid-lowering	Background statin therapy
All eligible trials
Three-point MACE	1652/19280 (8.6)	1874/19335 (9.7)	0.88 (0.83, 0.9)	89
Recurrent ACS	1777/18876 (9.4)	2054/18921 (10.9)	0.82 (0.71, 0.96)	69
All-cause mortality	1553/18831 (8.2)	1624/18825 (8.6)	0.94 (0.82, 1.07)	263
Cardiovascular disease-related mortality	794/19244 (4.1)	823/19253 (4.3)	0.96 (0.88, 1.06)	673
Nonfatal MI	1592/19222 (8.3)	1836/19275 (9.5)	0.87 (0.81, 0.93)	80
Stroke	422/19153 (2.2)	513/19161 (2.7)	0.83 (0.73, 0.94)	211
Coronary revascularization	2480/19172 (12.9)	2704/19192 (14.1)	0.89 (0.79, 1.00)	64
Unstable angina-related hospitalization	199/18940 (1.1)	235/18982 (1.3)	0.57 (0.33, 0.99)	534
Analysis restricted to patients with atorvastatin
Three-point MACE	922/10027 (9.2)	1063/10024 (10.6)	0.87 (0.80, 0.94)	71
Recurrent ACS	676/9767 (6.9)	817/9761 (8.4)	0.49 (0.25, 0.99)	69
All-cause mortality	336/9617 (3.5)	392/9597 (4.1)	1.04 (0.35, 3.13)	169
Cardiovascular disease-related mortality	255/10030 (2.5)	285/10025 (2.8)	0.89 (0.75, 1.05)	333
Nonfatal MI	645/9966 (6.5)	749/9964 (7.5)	0.86 (0.78, 0.95)	96
Stroke	126/9939 (1.3)	167/9933 (1.7)	0.76 (0.61, 0.96)	242
Coronary revascularization	778/9958 (7.8)	883/9964 (8.9)	0.88 (0.77, 1.02)	95
Unstable angina-related hospitalization	43/9831 (0.4)	82/9822 (0.8)	0.53 (0.37, 0.77)	252
Analysis restricted to patients with high-intense statins
Three-point MACE	904/10111 (8.9)	1046/10147 (10.3)	0.87 (0.80, 0.94)	73
Recurrent ACS	676/9809 (6.9)	823/9844 (8.4)	0.50 (0.27, 0.93)	68
All-cause mortality	338/9764 (3.5)	393/9748 (4.0)	0.86 (0.74, 0.99)	175
Cardiovascular disease-related mortality	252/10069 (2.5)	282/10065 (2.8)	0.89 (0.75, 1.05)	334
Nonfatal MI	637/10047 (6.3)	742/10087 (7.4)	0.86 (0.78, 0.95)	98
Stroke	113/9978 (1.1)	157/9973 (1.6)	0.72 (0.57, 0.92)	226
Coronary revascularization	780/9997 (7.8)	905/10004 (9.0)	0.75 (0.56, 1.01)	80
Unstable angina-related hospitalization	43/9873 (0.4)	87/9905 (0.9)	0.52 (0.36, 0.75)	226

Abbreviations: ACS, acute coronary syndrome; LDL-C, low-density lipoprotein cholesterol; MACE, major adverse cardiovascular event; MI, myocardial infarction; RR, risk ratio; NNT, number needed to treat.

Figure 3. Subgroup analysis of the primary outcome.

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Availability of data and materials

All data generated or analysed during this study are included in this published article and its supplementary information files. Raw data (in excel sheet) used in the statistical analysis will be made available on request through the corresponding author (Jing-Chao Sun).