Management of complex lipid abnormalities with a fixed dose combination of simvastatin and extended release niacin

Figures & data

Table 1 ER niacin–simvastatin trials

	Study population	Treatment duration	Treatment	N	Adherence
				N randomized (N end of study)
SEACOAST I^Citation13	LDL-C ≤ target + Non-HDL-C above goal on simva 20 mg	24 weeks	Simvastatin 20 mg + IR niacin 50 mg	121 (90)	99%
	Median age 58		Simvastatin 20 mg + ER niacin 1000 mg	108 (78)	96%
	Men 49 (−58%		Simvastatin 20 mg + ER niacin 2000 mg	56 (40)	97%
SEACOAST II^Citation12	Non-HDL-C above goal on simva 40 mg	24 weeks	Simvastatin 80 mg + IR niacin 50 mg	123 (90)	98%
	Median age 60 Men 51%–61%		Simvastatin 40 mg + ER niacin 1000 mg	118 (82)	98%
			Simvastatin 40 mg + ER niacin 2000 mg	102 (80)	98%
				N randomized (N wk 24; end of study)
OCEANS^Citation14	Non-HDL-C above goal on simva 40 mg	52 weeks	8 week titration to ER niacin 2000 mg	231 (142; 87)	82%
	Mean age 59–60 Men 55%–58%		12 week titration to ER niacin 2000 mg	232 (126; 74)	82%
				N end of study
ARBITER 2^Citation68	CHD 7 HDL-C < 45 mg/dL	12 months	Simvastatin ≥ 20 mg^Table Footnote§ + placebo	80	90%–95%
	Mean age 67		Simvastatin ≥ 20 mg^Table Footnote§ + ER niacin 1000 mg	87	90%–95%
	Men 91%

Non-HDL-C	LDL-C	HDL-C	Triglyceride	Lp(a)	Apo B	Apo A-I/ B ratio	Total/ HDL-C ratio
Baseline after 4 week simvastatin 20 mg lead-in in mg/dL (Median change from simvastatin 20 mg lead-in – ITT)
157 (−7%)	115 (−7%)	43 (7%)	209 (−15%)	15 (−8%)	101 (−4%)	1.2 (11%)	5 (−10%)
165 (−14%)	118 (−13%)	41 (18%)	210 (−27%)	12 (−17%)	103 (−14%)	1.3 (27%)	5 (−21%)
160 (−23%)	112 (−14%)	41 (25%)	214 (−38%)	9 (−25%)	96 (−18%)	1.3 (41%)	5 (31%)
Baseline after 4-week simvastatin 40 mg lead-in in mg/dL (Median change from simvastatin 40 mg lead-in)
131 (−10%)	99 (−13%)	47 (−1%)	141 0%	19 0%	89 (−9%)	1.5 (12%)	3.8 (−5%)
136 (−11%)	105 (−9%)	44 (15%)	147 (−23%)	20 (−17%)	90 (−10%)	1.5 (16%)	4.1 (−16%)
143 (−17%)	109 (−12%)	46 (22%)	156 (−32%)	23 (−21%)	92 (−14%)	1.4 (22%)	4.2 (−25%)
Baseline after 4 week simvastatin 40 mg lead-in in mg/dL (Median change from simvastatin 40 mg lead-in – ITT at 24 weeks [only subjects completing 52 weeks])
141 (−23%)	111 (−22%)	45 (22%)	145 (−33%)	24 (−25%)	94 (−22%)	1.4 (36%)	4.2 (−28%)
[–25%]	[–20%]	[27%]	[–40%]	[−29%]	[−25%]	[43%]	[−30%]
141 (−21%)	110 (−20%)	45 (20%)	152 (−27%)	21 (−21%)	94 (−17%)	1.4 (36%)	4.2 (−27%)
[−28%]	[−24%]	[25%]	[−34%]	[−25%]	[–26%]	[43%]	[−33%]
Baseline in mg/dL (Change from baseline in mg/dL)
121 (−5%)	91 (−6%)	40 (0%)	172 (−5%)				4.0 (−3%)
115 (−7%)	87 (−2%)	39 (21%)	154 (−13%)				3.95 (−17%)

^§ 93.4% received simvastatin.

Non-HDL-C = total cholesterol − HDL-C.

Abbreviations: CHD, coronary heart disease; ER, extended release; IQR, interquartile range; IR, immediate release; ITT, intent to treat; LDL-C, low-density lipoprotein cholesterol; Lp(a), lipoprotein (a); Non-HDL-C, non-high-density lipoprotein cholesterol; SR, slow release.

Table 2 Percent of patients experiencing treatment-related adverse events (AE)

Event	Simvastatin 20 mg/IR niacin 50 mg* (n = 114)	Simvastatin 80 mg/IR niacin 50 mg** (n = 119)	Simvastatin 20 mg/ER niacin 1000 mg* (n = 123)	Simvastatin 20 mg/ER niacin 2000 mg* (n = 64)	Simvastatin 40 mg/ER niacin 1000 mg** (n = 116)	Simvastatin 40 mg/ER niacin 2000 mg**† n = 100**/n = 509†
Any AE	17.5%	29.4%	25.2%	35.9%	29.3%	34%/48.7%
Any serious AE	0%	0.8%	0.8%	0%	0%	0%/0.6%
Gastric ulcer hemorrhage						/0.2%
Drug toxicity						/0.2%
Vasovagal syncope						/0.2%
Discontinuation due to AE	5.3%	4.2%	12.2%	15.6%	11.2%	12.0%/0.0%
Any flushing	45%	49.6%	54%	60%	57.0%	67%/71%
Flushing – serious or leading to	0%	2.5%	7.3%	10.9%	4.3%	6.0%/7.1%
discontinuation
Discontinuation due to flushing	0%	0.8%	6.5%	9.4%	4.3%	5.0%/7.1%
Pruritis		0%			4.3%	5.0%
Rash		0.8%			0.9%	3.0%/2.4%
Headache	0.9%	1.7%	2.4%	4.7%	3.4%	0%/2.6%
Dizziness	1.8%	1.7%	0%	0%	0.9%	2.0%
Hyperglycemia (increased HbA1c)	0%		1.6%	3.1%		0%/3.1% (4.1%)
Vomiting	0.9%		0%	3.1%		/ 2.6%
Gastritis	1.8%	0.8%	0%	3.1%	0.9%	2.0%
Abdominal pain	2.6%	0.8%	0.8%	0%	0.9%	2.0%
Nausea	0.9%	5.0%	2.4%	1.6%	1.7%	3.0%/4.1%
Myalgia (arthralgia)		0%			0.9%	2.0%/1.6% (1.8%)
Myopathy/rhabdomyolysis	0%	0%	0%	0%	0%	0%/0%
Gout	0%	0%	0%	0%	0%	1.0%/0% (0%)
ALT > 3 times ULN	0%	0%	0%	0%	0%	0%
CK > 3 times and <10 times		2.5%			0.9%	3.0%/2.2%
ULN
CK > 10 times ULN	0%	0%	0%	0%	0%	0%/0%

^* SEACOAST I

^** SEACOAST II

^† OCEANS

Abbreviations: ALT, alanine amino transferase; CK, creatine kinase; HbA1c, hemoglobin A1c; ULN, upper limit of normal.

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