Individualized initiation of statin therapy determined by baseline LDL-C: Are you more likely to achieve goal LDL-C?

Figures & data

Table 1 Clinical trials: study design and patient demographics^16–21

	ATGOAL^Citation16	ACTFAST-1^Citation17	ACTFAST-2^Citation18	Ducobu et al^Citation19	Atorvastatin Study Group in Korea^Citation20	Ferrer-Garcia et al^Citation21
Study design	Multicenter, open-label, single-step titration	Multicenter prospective, open-label, single dose titration	Multicenter, prospective, open-label, single dose titration	Multicenter, prospective, open-label, single dose titration	Multicenter, prospective, open-label, single dose titration in type 2 diabetes	Prospective, no dose titration, type 2 diabetes
Study duration	8 weeks	12 weeks	12 weeks	12 weeks	8 weeks	24 weeks
Inclusion criteria	Men or non-pregnant women between of 18–80 years, baseline LDL-C 5.6 mmol/L (≤220 mg/dL), TG ≤ 600 mg/dL, and capable of maintaining lifestyle and dietary modifications	Men or women at least 18 years of age with diagnosed hyperlipidemia and a LDL-C > 2.6 mmo/L (100 mg/dL) along with a screening LDL-C ≤ 5.7 mmol/L (220 mg/dL), TG level of ≤6.8 mmol/L (600 mg/dL) and were considered high risk based on history CHD, CHD equivalent, or estimated 10-year CHD risk >20%	Men or women at least 18 years of age with diagnosed hyperlipidemia and a LDL-C > 2.6 mmo/L (100 mg/dL) along with a screening LDL-C ≤ 5.7 mmol/L (220 mg/dL), TG level of ≤6.8 mmol/L (600 mg/dL) and were considered high risk based on history CHD, CHD equivalent, or estimated 10-year CHD risk >20%	LDL-C of 3.0–6.1 mmol/L (115–235 mg/dL) after 3 months of lipid-lowering diet, TG level <400 mg/dL, ages 30–80 years, and were high CHD risk	Men or women of 18–80 years with hyperlipidemic type 2 diabetes, LDL-C ≥ 130 mg/dL or glycated hemoglobin ≤10% and TG ≤ 400 mg/dL at baseline	Patients were at least 18 years old, had a glycated hemoglobin of ≤10%, TG ≤ 6.8 mmol/L (600 mg/dL) and had a baseline LDL-C of >2.6 mmol/L (100 mg/dL) despite 6 to 12 weeks of dietary treatment
Mean age (years)	55.1 low-risk 58.8 medium-risk 61.6 high-risk	63	61.2	62.1	58.4	61.1
Gender (%)
Male	58	68	61	70.2	28.9	59.9
Female	42	32	39	29.8	71.1	40.1
Smokers	NR	21%	22.7%	23.3%	NR	29.7%
Diabetes	44% in the high-risk group only	39%	32.7%	34.4%	100%	100%
History of CHD	54% in the high-risk group only	61%	67%	61.9%	NR	NR
Mean baseline LDL-C mmol/L (mg/dL)	4.8 (187) low-risk 4.6 (176) medium-risk 4.1 (160) high-risk	3.9 (151) in statin-free group 3.5 (135) in the statin-treated group	4.1 (159) in statin-free group 3.8 (147) in statin-treated group	4.1 (158)	160.3 ± 22.4	4.10 ± 0.75

Abbreviations: NR, not reported; LDL-C, low-density lipoprotein cholesterol; TG, triglycerides; CHD, coronary heart disease.

Table 2 Clinical trials: initial dosing protocols of atorvastatin^16–21

Baseline LDL-C mmol/L (mg/dL)	ATGOAL study^Citation16
	Low-risk category		Medium-risk category	High-risk category
	≤1 CHD risk factor	≥2 risk factors with 10-year CHD risk <10%	≥2 risk factors with 10-year CHD risk 10%–20%	CHD, CHD equivalent, ≥2 risk factors with 10-year CHD risk >20%
2.6–3.3 (100–129)	NA	NA	NA	10 mg
3.4–3.6 (130–139)	NA	NA	10 mg	10 mg
3.6–3.9 (140–149)	NA	NA	10 mg	10 mg
3.9–4.1 (150–159)	NA	NA	10 mg	20 mg
4.1–4.4 (160–169)	10 mg	10 mg	10 mg	40 mg
4.4–4.6 (170–179)	10 mg	10 mg	10 mg	80 mg
4.7–4.9 (180–189)	10 mg	10 mg	20 mg	80 mg
4.9–5.7 (190–220)	10 mg	20 mg	20 mg	80 mg
Target LDL-C	<4.1 mmol/L (<160 mg/dL)	<3.4 mmol/L (<130 mg/dL)	<3.4 mmol/L (<130 mg/dL)	<2.6 mmol/L (<100 mg/dL)
	ACTFAST 1 and 2 studies^Citation17,Citation18
Baseline LDL-C mmol/L (mg/dL)	Statin-free group		Statin-treated group
2.6–3.8 (100–149)	10 mg		20 mg
3.9–4.1 (150–159)	20 mg		40 mg
4.2–4.4 (160–169)	40 mg		80 mg
4.5–5.7 (170–220)	80 mg		80 mg
	Ducobu et al^Citation19
Baseline LDL-C mmol/L (mg/dL)	Statin-naïve patients		Statin-treated patients
3.0–4.2 (115–164)	10 mg		20 mg
4.3–4.5 (165–174)	20 mg		40 mg
4.5–6.1 (175–235)	40 mg		40 mg
	Atorvastatin study group in Korea^Citation20
Baseline LDL-C mmol/L (mg/dL)
130–149	10 mg
150–159	20 mg
≥160	40 mg
	Ferrer-Garcia et al^Citation21
Baseline LDL-C mmol/L (mg/dL)	Dose		Target reduction in LDL-C level (%)
2.6–3.8 (100–147)	10 mg		38
3.9–4.1 (151–159)	20 mg		46
4.2–4.39 (162–170)	40 mg		51
≥4.40 (170)	80 mg		54

Abbreviations: CHD, coronary heart disease; NA, not-applicable; LDL-C, low-density lipoprotein cholesterol.

Table 3 Primary study outcomes^16–21

Clinical trial	Treatment groups	Proportion of subjects meeting goal (%) (95% CI)
		LDL-C
		6 weeks	8 weeks	12 weeks	24 weeks
ATGOAL^Citation16	Low risk (n = 322)	NR	92.9	NR	NR
	Medium risk (n = 237)	NR	84.0	NR	NR
	High risk (n = 657)	NR	81.1	NR	NR
ACTFAST-1^Citation17	Statin-free (n = 1345)
	Atorvastatin 10 mg	84.3 (81.5–87.0)	NR	83.1 (80.3–86.0)	NR
	Atorvastatin 20 mg	83.4 (78.0–88.8)	NR	80.7 (74.9–86.5)	NR
	Atorvastatin 40 mg	88.9 (83.9–93.9)	NR	82.2 (76.2–88.2)	NR
	Atorvastatin 80 mg	79.9 (75.3–84.4)	NR	72.1 (67.0–77.2)	NR
	Statin-treated (n = 772)
	Atorvastatin 20 mg	55.1 (51.0–59.2)	NR	60.3 (56.3–64.3)	NR
	Atorvastatin 40 mg	55.4 (44.1–66.7)	NR	60.3 (49.1–71.5)	NR
	Atorvastatin 80 mg	58.1 (48.7–67.5)	NR	50.9 (41.5–60.4)	NR
ACTFAST-2^Citation18	Statin free (n = 341 at wk 6; n = 345 at week 12)
	Atorvastatin 10 mg	77.8 (71.0–84.6)	NR	75.0 (67.9–82.1)	NR
	Atorvastatin 20 mg	82.0 (71.4–92.7)	NR	78.0 (66.5–89.5)	NR
	Atorvastatin 40 mg	86.5 (71.2–95.5)	NR	79.5 (66.8–92.2)	NR
	Atorvastatin 80 mg	69.1 (60.5–77.7)	NR	68.2 (59.4–77.1)	NR
	Statin-treated (n = 249 at week 6; n = 253 at week 12)
	Atorvastatin 20 mg	52.4 (44.3–60.5)	NR	67.8 (60.2–75.4)	NR
	Atorvastatin 40 mg	60.7 (42.6–78.8)	NR	62.1 (44.4–79.7)	NR
	Atorvastatin 80 mg	48.1 (36.9–58.2)	NR	46.8 (35.6–57.9)	NR
Ducobu et al^Citation19	Statin-naïve (n = 215)
	Atorvastatin 10 mg	NR	NR	NR	NR
	Atorvastatin 20 mg	NR	NR	95.7	NR
	Atorvastatin 40 mg	NR	NR	95.6	NR
Korea study^Citation20	(n = 149)
	Atorvastatin 10 mg	NR	87.5	NR	NR
	Atorvastatin 20 mg	NR	86.4	NR	NR
	Atorvastatin 40 mg	NR	93.9	NR	NR
	Atorvastatin 80 mg	NR	66.7	NR	NR
Ferrer-Garcia et al^Citation21	(n = 202)
	Atorvastatin 10 mg	NR	NR	NR	75
	Atorvastatin 20 mg	NR	NR	NR	67
	Atorvastatin 40 mg	NR	NR	NR	51
	Atorvastatin 80 mg	NR	NR	NR	59

Abbreviations: LDL-C, low-density lipoprotein cholesterol; NR, not reported.

Table 4 Secondary study outcomes^16–21

Clinical trial	Treatment groups	Percentage mean reduction of lipid parameters from baseline							Proportion of subjects
		LDL-C	TC	TG	HDL-C	TC/HDL-C	Apo-B	Non-HDL-C	TC/HDL-C ratio target <4
ATGOAL^Citation16 8-week results	Low-risk group (n = 335)	−39.1	−29.0	−18.6	−2.2	NR	NR	−31.2	NR
	Medium-risk group (n = 249)	−36.8	−28.7	−20.9	1.7	NR	NR	−31.4	NR
	High-risk group (n = 699)	−44.6	−35.0	−23.5	−2.4	NR	NR	−34.4	NR
ACTFAST-1^Citation17 12-week results	Statin-free (n = 1345)
	Atorvastatin 10 mg	−34.8	−23.9	−13.7	3.1	−25.4	−31.5	−32.1	83.1
	Atorvastatin 20 mg	−43.8	−31.6	−22.7	1.4	−32.0	−39.4	−41.0	85.9
	Atorvastatin 40 mg	−49.8	−37.2	−26.5	1.6	−37.4	−44.8	−47.1	86.9
	Atorvastatin 80 mg	−52.7	−39.7	−5.2	0.6	−39.1	−46.8	−48.7	79.1
	Statin-treated (n = 772)
	Atorvastatin 20 mg	−21.4	−15.3	−8.2	1.0	−15.4	−21.2	−20.4	79.3
	Atorvastatin 40 mg	−37.0	−27.5	−22.8	0.6	−27.3	−34.2	−35.2	78.4
	Atorvastatin 80 mg	−41.0	−32.0	−18.9	−2.7	−29.5	−38.0	−39.1	70.6
ACTFAST-2^Citation18 12-week results	Statin-free (n = 347)
	Atorvastatin 10 mg	−33.6	−23.6	−9.9	4.2	−24.6	−31.6	−31.2	77.8
	Atorvastatin 20 mg	−40.5	−28.4	−12.3	2.3	−29.3	−36.0	−36.8	80.8
	Atorvastatin 40 mg	−49.1	−36.4	−15.0	−3.7	−32.9	−44.3	−45.1	84.6
	Atorvastatin 80 mg	−49.4	−39.2	−21.9	−3.2	−36.3	−44.5	−47.1	75.0
	Statin-treated (n = 253)
	Atorvastatin 20 mg	−24.7	−17.4	−3.8	−2.7	−13.3	−22.5	−21.9	71.2
	Atorvastatin 40 mg	−36.6	−27.0	−19.9	4.1	−28.3	−33.1	−34.8	82.8
	Atorvastatin 80 mg	−40.2	−30.8	−19.5	−1.4	−29.1	−36.3	−37.7	66.7
Ducobu et al 12-week results^Citation19	Statin-naïve (n = 215) (Data NR based on dose)	−45.9	−32.4	NR	0.04	NR	NR	NR	NR
Korea study 8-week results^Citation20	Atorvastatin 10 mg (n = 56)	−42.5	−30.3	−19.3	2.8	NR	NR	−38.9	NR
	Atorvastatin 20 mg (n = 22)	−52.9	−37.5	−32.6	4.0	NR	NR	−49.4	NR
	Atorvastatin 40 mg (n = 65)	−58.7	−45.0	−20.9	−5.2	NR	NR	−53.0	NR
	Atorvastatin 80 mg (n = 6)	NR	NR	NR	NR	NR	NR	NR	NR
Ferrer-Garcia et al^Citation21 24-week results	Atorvastatin 10 mg (n = 75)	−16.5	−21.6	−12.3	−3.0	NR	NR	−27.1	NR
	Atorvastatin 20 mg (n = 61)	−35.6	−28.5	−18.0	−1.8	NR	NR	−36.7	NR
	Atorvastatin 40 mg (n = 35)	−35.5	−29.8	−26	−0.2	NR	NR	−38.2	NR
	Atorvastatin 80 mg (n = 17)	−55.7	−49.0	−32.5	−7.2	NR	NR	−56.7	NR

Abbreviations: NR, not reported; LDL-C, low-density lipoprotein cholesterol; TC, total cholesterol; TG, triglycerides; HDL-C, high-density lipoprotein cholesterol; TC/HDL-C, total cholesterol/low-density lipoprotein-cholesterol; Apo-B, apolipoprotein B; non-HDL-C, non-high-density lipoprotein cholesterol.

McKenneyJMDavidsonMHSaponaroJUse of a treatment algorithm to achieve NCEP ATP III goals with atorvastatinJ Cardiovasc Pharmacol20054659459916220065

 PubMed Web of Science ®Google Scholar

Ferrer-GarciaJCSnachez-BallesterEAlbalat-GaleraREfficacy of atorvastatin for achieving cholesterol targets after LDL-cholesterol based dose selection in patients with type 2 diabetesJ Cardiovasc Pharmacol Ther20081318318818635754

 PubMed Web of Science ®Google Scholar

MartineauPGawAde TeresaEEffect of individualizing starting doses of a statin according to baseline LDL-cholesterol levels on achieving cholesterol targets: The Achieve Cholesterol Targets Fast with Atorvastatin Stratified Titration (ACTFAST-1) studyAtherosclerosis200719113514616643923

 PubMed Web of Science ®Google Scholar

FarsangCAthyrosVGawAA multicentre, open study to assess the effect of individualizing starting doses of atorvastatin according to baseline LDL-C levels on achieving cholesterol targets: the Achieve Cholesterol Targets Fast with Atorvastatin Stratified Titration (ACTFAST-2) studyCurr Med Res Opin2007231945195617626713

 PubMed Web of Science ®Google Scholar

DucobuJClaeysMCommersKEfficacy of atorvastatin after LDL-cholesterol-based dose selection in high risk dyslipidaemic patients: results of the target dose studyCurr Med Res Opin2007231821182717609019

 PubMed Web of Science ®Google Scholar

Atorvastatin Study Group in KoreaFlexible initial dosing of atorvastatin based upon initial lo-density lipoprotein cholesterol levels in type 2 diabetic patientsKorean J Intern Med200823222918363276

 PubMedGoogle Scholar