. 2016 Oct 14;70(11):886–897. doi: 10.1111/ijcp.12881

Table 1.

Overview of key trials with efficacy data from patients with very low LDL‐C levels

Study name	N	Patient population and study duration	Treatment regimen	Baseline LDL‐C level, mmol/L (mg/dL)	Achieved LDL‐C level, mmol/L (mg/dL)	Rate of CV end‐point, % (n)^a	HR^b (95% CI)
Statin monotherapy studies
TNT13, 20	10 001	Coronary heart diseaseLDL‐C <3.4 mmol/L (130 mg/dL)Median follow‐up: 4.9 years	Atorvastatin 80 mg	2.5 (97)^c	2.0 (77)^c	8.7 (434)	0.78 (0.69–0.89), P < .001
TNT13, 20	10 001		Atorvastatin 10 mg	2.5 (98)^c	2.6 (101)^c	10.9 (548)	0.78 (0.69–0.89), P < .001
PROVE IT‐TIMI 2221, 46	4162	Post‐ACSTotal cholesterol <6.2 mmol/L (240 mg/dL)Mean follow‐up: 2 years	Atorvastatin 80 mg	2.7 (106)^d	1.6 (62)^d	22.4 (470)	0.84 (0.74–0.95), P=.005
PROVE IT‐TIMI 2221, 46	4162		Pravastatin 40 mg	2.7 (106)^d	2.5 (95)^d	26.3 (543)	0.84 (0.74–0.95), P=.005
JUPITER22, 47	17 802	Healthy individualshs‐CRP ≥2.0 mg/LMedian follow‐up: 1.9 years	Rosuvastatin 20 mg	2.8 (108)^d	1.4 (55)^d	1.6 (142)	0.56 (0.46–0.69), P <.00001
JUPITER22, 47	17 802		Placebo	2.8 (108)^d	2.8 (110)^d	2.8 (251)	0.56 (0.46–0.69), P <.00001
Statin + ezetimibe combination study
IMPROVE‐IT23, 38	18 144	Post‐ACSLDL‐C 1.3–2.6 mmol/L (50–100 mg/dL) with LLT or 1.3–3.2 mmol/L (50–125 mg/dL) with no LLTMedian follow‐up: 6 years	Simvastatin 40 mg + ezetimibe 10 mg	2.43 (94)^c	1.4 (53)^c	32.7 (2965)	0.94 (0.89–0.99), P = .016
IMPROVE‐IT23, 38	18 144		Simvastatin 40 mg + placebo	2.43 (94)^c	1.8 (70)^c	34.7 (3150)	0.94 (0.89–0.99), P = .016
Statin + PCSK9 inhibitor combination studies
ODYSSEY LONG TERM24	2341	High CV riskLDL‐C ≥1.8 mmol/L (70 mg/dL)Receiving statin treatment at maximum tolerated doseMean follow‐up: 1.5 years	Alirocumab 150 mg Q2W	3.2 (123)^c	1.2 (48)^c	1.7 (27)	0.52 (0.31–0.90), P=.02
ODYSSEY LONG TERM24	2341		Placebo	3.2 (122)^c	3.1 (119)^c	3.3 (26)	0.52 (0.31–0.90), P=.02
OSLER‐1 and OLSER‐225	4465	Varying Median follow‐up: 0.9 years	Evolocumab 140 mg Q2W or 420 mg QM + ST	3.1 (120)^d	1.2 (48)^d	1.0 (28)	0.47 (0.28–0.78), P=.003
OSLER‐1 and OLSER‐225	4465	Varying Median follow‐up: 0.9 years	Placebo + ST	3.1 (121)^d	NR	2.2 (32)	0.47 (0.28–0.78), P=.003

ACS, acute coronary syndrome; CI, confidence interval; CV, cardiovascular; HR, hazard ratio; hs‐CRP, high‐sensitivity C‐reactive protein; LDL‐C, low‐density lipoprotein cholesterol; LLT, lipid‐lowering therapy; MI, myocardial infarction; NR, not reported; PCSK9, proprotein convertin subtilisin/kexin type 9; Q2W, every 2 weeks; QM, every month; ST, standard therapy; UA, unstable angina. ^aIn the TNT study, the primary end‐point was defined as death from coronary heart disease, non‐fatal non‐procedure‐related MI, resuscitation after cardiac arrest or stroke; in the PROVE IT‐TIMI 22 study, the primary end‐point was defined as a composite of death, MI, stroke, revascularisation and UA requiring hospitalisation; in the JUPITER study, the primary end‐point was defined as a composite of MI, stroke arterial revascularisation, UA or death from CV causes; in the IMPROVE‐IT study, the primary end‐point was defined as a composite of CV death, MI, UA, coronary revascularisation after 30 days and stroke; in the OSLER studies, the CV end‐point was defined as the incidence of CV events including death, coronary events (MI, UA requiring hospitalisation or coronary revascularisation), cerebrovascular events (stroke or transient ischaemic attack) and heart failure requiring hospitalisation; in the OSYSSEY LONG TERM study, the CV end‐point was defined as a composite of death from coronary heart disease, non‐fatal MI, fatal or non‐fatal ischaemic stroke or UA requiring hospitalisation. ^bHR associated with CV end‐point. ^cMean. ^dMedian.