Changes in LDL-C levels and goal attainment associated with addition of ezetimibe to simvastatin, atorvastatin, or rosuvastatin compared with titrating statin monotherapy

Figures & data

Table 1 Estimated low-density lipoprotein cholesterol (LDL-C) lowering efficacy levels for statin and ezetimibe added onto statin therapiesa

LDL-C-lowering potency level*	Estimated % LDL-C reduction range**	Mg (estimated % LDL-C reduction)
		Rosuvastatin(b)	Atorvastatin(c)	Simvastatin(d)	Ezetimibe + rosuvastatin	Ezetimibe + atorvastatin(e)	Ezetimibe + simvastatin
Low	20–32			5 (26)
				10 (32)†
Medium	36–50		10 (38)	20 (36)†
		5 (45)	20 (44)	40 (41)†
		10 (49)‡	40 (50)				10 (47)§
High	52–70	20 (54)‡	80 (55)			10 (53)	20 (52)§
		40 (60)‡			5 (59)¶	20 (54)	40 (56)§
					10 (61)††	40 (56)	80 (60)║
					20 (66)¶	80 (61)
					40 (70)‡‡

Notes:

a Reprinted with modification from Toth PP, Ballantyne CM, Davidson MH et al. Changes in prescription patterns before and after reporting of the Ezetimibe and Simvastatin in Hypercholesterolemia Enhances Atherosclerosis Regression trial (ENHANCE) results and expected effects on low-density lipoprotein-cholesterol reduction. J Clin Lipidol. 2012;6(2):180–191. Copyright 2012, with permission from Elsevier.¹¹

* Potency levels low, medium, and high based on LDL-C-lowering as described in prescribing information for each drug and in previously reported randomized clinical trials as indicated

** data are not placebo-adjusted. % LDL-C reductions from:

b Crestor prescribing information;¹²

c average of data in Lipitor prescribing information¹³ and clinical studies;^17–19

d Zocor prescribing information;¹⁴

e Liptruzet prescribing information;¹⁵

† average of data in Zocor prescribing information¹⁴ and Bays et al;²⁰

‡ average of data in Crestor prescribing information¹² and Catapano et al;²¹

§ average of data in Vytorin prescribing information¹⁶ and Ballantyne et al;^17,18

¶ calculated using 26% LDL-C reduction in Pearson, et al;²²

║ average of data in Vytorin prescribing information,¹⁶ Ballantyne, et al.^17,18 and Catapano et al;²¹

†† data from Kosoglou et al;²³

‡‡ data from Ballantyne et al.²⁴

Figure 1 Patient flow.

Abbreviations: BL, baseline; EZE, ezetimibe; FW, follow-up; LLT, lipid-lowering therapy; CHD, coronary heart disease; LDL-C, low-density lipoprotein cholesterol.

Table 2 Baseline patient characteristics

Characteristic	Simvastatin		Atorvastatin		Rosuvastatin
	Add-on (n = 540)	Titrate (n = 4,170)	Add-on (n = 1,504)	Titrate (n = 7,653)	Add-on (n = 268)	Titrate (n = 1,230)
Age, years, mean (SD)	57.1 (7.9)	56.2 (8.1)	57.2 (7.4)	56.3 (8.2)	56.5 (8.3)	56.2 (8.1)
Sex, males, %	67.8	58.7	71.3	62.1	68.3	61.7
Time to index date,* mean days (SD)	525.0 (399.8)	460.7 (417.2)	617.0 (484.8)	541.2 (464.3)	355.7 (278.7)	322.4 (255.5)
Days to baseline LDL-C (from initial start), mean (SD)	495.7 (396.4)	421.0 (413.3)	583.0 (485.2)	496.9 (461.2)	324.1 (274.9)	280.2 (249.5)
Days to follow-up LDL-C (from index date), mean (SD)	170.8 (94.9)	191.4 (96.1)	192.7 (97.1)	198.7 (96.1)	176.6 (94.3)	184.0 (94.4)
Year of index date %
2002	3.0	0	1.1	0	0	0
2003	32.2	11.8	17.6	10.1	0	0
2004	34.4	16.5	22.5	17.7	12.7	6.7
2005	11.1	12.7	25.6	22.7	23.1	11.4
2006	7.4	14.0	19.4	20.3	20.9	17.6
2007	4.4	12.0	8.6	12.0	20.1	17.6
2008	5.0	20.7	3.3	11.4	12.7	30.2
2009	2.4	12.3	1.9	5.7	10.4	16.7
Baseline comorbidities %
Acute myocardial infarction	6.5	4.4	6.9	4.6	6.7	4.4
Previous myocardial infarction	7.4	5.1	10.4	4.7	9.0	4.1
Ischemic stroke	2.2	1.9	2.5	2.2	0.7	2.1
Peripheral vascular disease	2.6	2.0	2.8	2.0	2.2	1.3
Diabetes	53.9	69	49.3	66.9	44	67.5
Angina pectoris	17.8	9.2	14.2	9.8	15.3	10.9
Acute ischemic heart disease	10.0	7.0	12.5	6.9	10.1	6.1
Revascularization	8.0	4.7	7.9	5.2	8.6	6.3
Acute carotid artery procedures	0.6	0.3	0.5	0.2	0	0.4
Chronic ischemic heart disease	58.9	32.6	63.1	37.7	60.1	32.5
Atherosclerosis	22.8	15.9	23.3	17.0	25.0	18.7
CHD/CHD risk-equivalent	100	100	100	100	100	100
Baseline dose (immediately before LDL-C) %
5 mg	0.7	1.5	0	0	3.4	19.9
10 mg	2.0	15.0	9.4	51.3	43.7	62.2
20 mg	19.6	54.3	25.1	35.6	34	17.5
40 mg	43.9	28.6	39.4	12.7	19	0.4
80 mg	33.7	0.6	26.1	0.4	0	0
Follow-up dose (immediately before LDL-C) %
5 mg	0.4	0.1	0	0	3.4	0.9
10 mg	3.3	1.9	7.8	2.7	32.8	21.1
20 mg	16.1	14.9	22.3	44.2	38.8	56.8
40 mg	45.4	53.8	39.4	38.4	25	21.2
80 mg	34.8	29.3	30.4	14.8	0	0

Note:

* Time to index date (non-add-on and non-titrate episodes were applied an index date based on distribution of add-on/titrate).

Abbreviations: CHD, coronary heart disease; LDL-C, low-density lipoprotein cholesterol; SD, standard deviation.

Figure 2 Percent change from baseline in LDL-C.

Note: *Significant at 5% level for add-on versus titrate therapy.
Abbreviation: LDL-C, low-density lipoprotein cholesterol.

Table 3 Baseline and follow-up lipid values

	Simvastatin		Atorvastatin		Rosuvastatin
	Add-on (n = 540)	Titrate (n = 4,170)	Add-on (n = 1,504)	Titrate (n = 7,653)	Add-on (n = 268)	Titrate (n = 1,230)
BL LDL-C*
mmol/L (SD)	3.1 (0.8)	2.8 (0.7)	2.9 (0.8)	2.7 (0.7)	2.9 (0.8)	2.6 (0.8)
mg/dL (SD)	118.2 (29.5)	108.2 (27.8)	112.9 (30.5)	103.8 (28.5)	112.7 (30.4)	101.7 (32.6)
FW LDL-C*
mmol/L (SD)	2.2 (0.7)	2.5 (0.7)	2.1 (0.7)	2.3 (0.7)	2.1 (0.7)	2.3 (0.7)
mg/dL (SD)	84.8 (28.0)	94.9 (25.8)	80.3 (25.6)	90.5 (25.2)	80.3 (27.9)	88.6 (28.7)
Difference in LDL-C
FW versus	−33.4	−13.3	−32.6	−13.3	−32.3	−19.3
BL* (95% CI)	(−35.8, −31.0)	(−14.1, −12.6)	(−34.0, −31.2)	(−13.9, −12.7)	(−35.8, −28.9)	(−14.8, −11.3)

Note:

* Significant at 5% level for add-on versus titrate.

Abbreviations: BL, baseline; FW, follow-up; LDL-C, low-density lipoprotein cholesterol; SD, standard deviation; CI, confidence interval.

Figure 3 Percent attainment of LDL-C < 2.6 and 1.8 mmol/L (100 and 70 mg/dL).

Note: *Significant at 5% level for statin titration versus add-on baseline therapy and for add-on versus titrate follow-up therapy.
Abbreviations: BL, baseline; FW, follow-up; LDL-C, low-density lipoprotein cholesterol.

Table 4 Multivariate models of percent change from baseline in LDL-C and the odds of goal attainment

Parameter	Add ezetimibe versus titrate simvastatin	Add ezetimibe versus titrate atorvastatin	Add ezetimibe versus titrate rosuvastatin
Difference (95% CI)†	−13.1	−14.8	−14.4
% change from baseline	(−15.4, −10.8)	(−16.3, −13.4)	(−18.0, −10.7)
Odds (95% CI)‡ attainment FW	2.8	3.2	2.6
LDL-C <2.6 mmol/L (100 mg/dL)	(2.1–3.6)	(2.7–3.9)	(1.8–3.8)
Odds (95% CI)‡ attainment FW	2.9	3.1	2.5
LDL-C <1.8 mmol/L (70 mg/dL)	(2.2–3.8)	(2.7–3.7)	(1.8–3.4)

Notes:

† Percent change from baseline in LDL-C was assessed by an analysis of covariance model adjusted for age, sex, baseline LDL-C, and baseline statin potency

‡ odds of attainment of LDL-C goals were assessed by logistic regression adjusted for age, sex, baseline goal attainment, and statin potency.

Abbreviations: CI, confidence interval; FW, follow-up; LDL-C, low-density lipoprotein cholesterol.

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