Combination of niacin extended-release and simvastatin results in a less atherogenic lipid profile than atorvastatin monotherapy

Figures & data

Figure 1 Study design.

Abbreviation: NER/S, niacin extended-release/simvastatin.

Table 1 Demographics and baseline characteristics

Parameter	Statistic	NER/S (n = 74)	Atorvastatin (n = 63)
Age (years)	Mean (SD)	55.0 (12.5)	51.9 (10.8)
Male	n (%)	27 (37)	32 (51)
Caucasian	n (%)	66 (89)	59 (94)
Weight (kg)	Mean (SD)	90.4 (24.2)	88.3 (23.7)
Women	Mean (SD)	86.6 (24.0)	82.0 (23.4)
Men	Mean (SD)	97.1 (23.3)	94.4 (22.7)
BMI (kg/m^2)a
<18.5 (underweight)	n (%)	1 (1)	0 (0)
18.5–24.9 (normal)	n (%)	8 (11)	9 (14)
≥25 (overweight)	n (%)	18 (24)	27 (43)
>30	n (%)	47 (64)	27 (43)
Current smoker	n (%)	13 (18)	12 (19)
Diabetes mellitus	n (%)	14 (19)	7 (11)
Hypertension	n (%)	39 (53)	24 (38)
CHD risk categoryb
0–1 risk factors	n (%)	25 (34)	25 (40)
≥2 risk factors	n (%)	27 (37)	26 (41)
CHD or CHD risk equivalent	n (%)	22 (30)	12 (19)
CHD disease	n (%)	6 (8)	2 (3)
Concomitant cardiac medications
ACE inhibitors/ARBs	n (%)	23 (31)	14 (22)
Beta-blockers	n (%)	11 (15)	8 (13)
Aspirin	n (%)	22 (30)	16 (25)
Lipids at baseline (mg/dL)
Total-C:HDL-C ratio	Mean (SD)	6.1 (1.1)	6.7 (1.4)
Non-HDL-C	Mean (SD)	199.0 (28.0)	205.8 (31.1)
LDL-C	Mean (SD)	162.4 (23.5)	168.0 (29.6)
HDL-C	Mean (SD)	39.9 (6.1)	37.6 (6.4)
TG	Median [Q1, Q3]	174.3 [135.5, 222.5]	175.5 [139.5, 235.5]
Lp(a)	Median [Q1, Q3]	15.3 [6.5, 30.5]	14.5 [8.0, 41.5]
Apo A-I	Median [Q1, Q3]	123.9 [115.9, 134.5]	121.7 [114.3, 131.2]
Apo B	Median [Q1, Q3]	130.3 [118.3, 146.9]	133.8 [124.1, 147.2]
Apo B:A-I ratio	Median [Q1, Q3]	1.0 [0.95, 1.2]	1.1 [0.98, 1.3]

Notes:

a Based on NIH BMI index guidelines;

b Based on the NCEP ATP III (2004) definition of risk factors.

Abbreviations: NER/S, niacin extended-release/simvastatin; CHD, coronary heart disease; ACE, angiotensin converting enzyme; ARB, angiotensin receptor blocker; SD, standard deviation; [Q1, Q3], [25th percentile, 75th percentile]; NIH, National Institutes of Health; BMI, body mass index; NCEP ATP, National Cholesterol Education Program Adult Treatment Panel; total-C, Total cholesterol; HDL-C, high-density lipoprotein cholesterol; Non-HDL-C, non-high-density lipoprotein cholesterol; LDL-C, low-density lipoprotein cholesterol; TG, triglycerides; Lp(a), lipoprotein(a); Apo, apolipoprotein.

Figure 2 Lipid efficacy from baseline to week 12. For total-C:HDL, non-HDL-C, LDL-C and HDL-C: Bars represent least square means, error bars are standard errors; For TG and Lp(a): Bars represent medians, error bars are [Q1, Q3].

Notes: *P = 0.05; **P < 0.001; repeated measures of covariance (ANCOVA) for total HDL-C, non-HDL-C, LDL-C, and HDL-C; Wilcoxon rank-sum test for TG and Lp(a).
Abbreviations: Total-C, total cholesterol; HDL-C, high-density lipoprotein cholesterol; Non-HDL-C, non-high-density lipoprotein cholesterol; LDL-C, low-density lipoprotein cholesterol; TG, triglycerides; Lp(a), lipoprotein(a); NER/S, niacin extended-release/simvastatin; [Q1, Q3], [25th percentile, 75th percentile].

Figure 3 Percent of patients who attained Apo B < 80 mg/dL at week 12.

Note: *P = 0.003 versus atorvastatin, Fisher’s exact test.
Abbreviations: NER/S, niacin extended-release/simvastatin; Apo, apolipoprotein.

Figure 4 Median percent change in Apo A-1, Apo B, and the Apo B:A-I ratio at final visit. Error bars are [Q1, Q3].

Notes: *P < 0.01, **P < 0.001 versus atorvastatin, Wilcoxon rank-sum test.
Abbreviations: NER/S, niacin extended-release/simvastatin; Apo, apolipoprotein.

Figure 5 Median percent change in LDL and VLDL particle size from baseline to week 12. Error bars are [Q1, Q3].

Notes: *P < 0.01; **P < 0.001, Wilcoxon rank-sum test.
Abbreviations: LDL, low-density lipoprotein; VLDL, very low-density lipoprotein; NER/S, niacin extended-release/simvastatin; [Q1, Q3], [25th percentile, 75th percentile].

Figure 6A Median percent change in LDL particle numbers from baseline to week 12. Error bars are [Q1, Q3].

Note: *P < 0.05, Wilcoxon rank-sum test.
Abbreviations: LDL, low-density lipoprotein; IDL, intermediate-density lipoprotein; NER/S, niacin extended-release/simvastatin; [Q1, Q3], [25th percentile, 75th percentile].

Figure 6B Median percent change in VLDL particle numbers from baseline to week 12. Error bars are [Q1, Q3].

Notes: *P < 0.05; **P < 0.001, Wilcoxon rank-sum test.
Abbreviations: VLDL, very low-density lipoprotein; NER/S, niacin extended-release/simvastatin; [Q1, Q3], [25th percentile, 75th percentile].

Figure 7 Shift in LDL particle size from baseline to week 12. Error bars are 95% confidence intervals.

Notes: *P = 0.005 versus atorvastatin based on Cochran-Mantel-Haenszel test. ^asubclass pattern B: predominance of small, dense LDL particles, triglycerides, and depressed HDL-cholesterol concentrations; ^bsubclass pattern A: increased large LDL and HDL particles, and decreased small LDL particles and triglycerides.
Abbreviations: LDL, low-density lipoprotein; HDL, high-density lipoprotein; NER/S, niacin extended-release/simvastatin.

Table 2 Summary of adverse events

	NER/S n = 74	Atorvastatin n = 63	P valuea
Patients, n (%)
Any TEAEb	61 (82.4)	26 (41.3)	<0.001
Any AE possibly drug-relatedc	52 (70.3)	9 (14.3)	<0.001
Any serious AEd	2 (2.7)	1 (1.6)	1.000
TEAEs in order of frequency occurring in ≥5% of patients in either treatment group, n (%)
Flushing	49 (66.2)	7 (11.1)	<0.001
Nausea	7 (9.5)	0 (0.0)	0.015
Vomiting	6 (8.1)	0 (0.0)	0.031
Diarrhea	5 (6.8)	1 (1.6)	0.218
Headache	5 (6.8)	1 (1.6)	0.218
Constipation	5 (6.8)	0 (0.0)	0.062

Notes:

a P values are based on Fisher’s exact test;

b including flushing;

c possible, probable, or definite relationship to treatment based on investigator assessment;

d a serious adverse event is defined as any untoward medical occurrence that at any dose results in death, is life-threatening, requires inpatient or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, is a medically important event or reaction that may not be immediately life-threatening or results in death or hospitalization, but may jeopardize the patient or require intervention to prevent any of the other outcomes listed above.

Abbreviations: NER/S, niacin extended-release/simvastatin; TEAE, treatment-emergent adverse event; AE, adverse event.