Effects of simvastatin 20 mg/d on serum lipid profiles in Japanese hyperlipidemic patients: A prospective, open-label pilot study.
BACKGROUND
Hyperlipidemia is a major risk factor for ischemic heart disease. Hydroxymethylglutaryl coenzyme A reductase inhibitors ("statins") (eg, simvastatin) are considered first-line cholesterol-lowering therapy because they are effective and well tolerated, even at high doses. Based on a literature search, no studies have been published concerning the effects of simvastatin 20 mg/d in Japanese patients who had not previously received lipid-lowering treatment.


OBJECTIVE
The aim of this study was to assess the clinical tolerability and effectiveness of simvastatin 20 mg/d in achieving the target lipid concentrations recommended in the 2002 Japan Atherosclerosis Society (JAS) guidelines in Japanese patients with hyperlipidemia.


METHODS
This prospective, open-label pilot study was conducted at Kashiwa Hospital, Jikei University School of Medicine, Kashiwa, Japan. Male and postmenopausal female patients aged ≥18 to 70 years with hyperlipidemia (total cholesterol [TC], ≥220 mg/dL; triglycerides [TG], 150-400 mg/dL) who had not received lipid-lowering medications for at least 6 months before the study were enrolled. Patients received simvastatin 20 mg PO QD for 4 weeks. Effectiveness was assessed using serum concentrations of TC, low-density lipoprotein cholesterol (LDL-C), TG, and lipid peroxide, measured at 0 (baseline) and 4 weeks. Target serum TC and LDL-C concentrations as outlined by the JAS were as follows: category A, TC <240 mg/dL and LDL-C <160 mg/dL; category B1 and B2, TC <220 mg/dL and LDL-C <140 mg/dL; and category C, TC <200 mg/dL and LDL-C <120 mg/dL. A subanalysis of the correlation between baseline high-density lipoprotein cholesterol (HDL-C) and target achievement rates was conducted by baseline HDL-C concentration (<50 or ≥50 mg/dL). Tolerability was assessed using spontaneous reporting of adverse events and laboratory analysis, including liver function tests.


RESULTS
Twenty-two patients participated in the study (16 women, 6 men; mean [SD] age, 56.0 [8.0] years; mean [SD] body mass index, 23.6 [3.4] kg/m(2)). Mean serum TC, LDL-C, TG, and lipid peroxide concentrations significantly decreased from baseline (changes, -28.6%, -40.4%, -24.0%, and -14.5%, respectively; P < 0.001, <0.001, <0.001, and <0.01, respectively). The mean HDL-C concentration significantly increased from baseline (change, 7.2%; P < 0.001); the mean increase was significantly greater in patients with baseline HDL-C <50 mg/dL compared with those with baseline HDL-C ≥50 mg/dL (changes, 11.3% vs 4.4%; P < 0.05). Target TC and LDL-C concentrations were achieved in 90.9% of patients. No serious adverse events were observed, and liver enzyme and creatine kinase concentrations did not increase to above-normal values.


CONCLUSIONS
The results of this study suggest that simvastatin 20 mg/d might be useful in the clinical treatment of hyperlipidemia in Japanese patients. The study drug was well tolerated.
Division of General Medicine, Department of Internal Medicine, Kashiwa Hospital, Jikei University School of Medicine, Kashiwa, Japan ; Department of Laboratory Medicine, Kashiwa Hospital, Jikei University School of Medicine, Kashiwa, Japan.
Hiroshi
H
Yoshida
Division of General Medicine, Department of Internal Medicine, Kashiwa Hospital, Jikei University School of Medicine, Kashiwa, Japan.
Hidekatsu
H
Yanai
Department of Laboratory Medicine, Kashiwa Hospital, Jikei University School of Medicine, Kashiwa, Japan.
Toru
T
Shoda
Division of General Medicine, Department of Internal Medicine, Kashiwa Hospital, Jikei University School of Medicine, Kashiwa, Japan.
Nobuyuki
N
Furutani
Division of General Medicine, Department of Internal Medicine, Kashiwa Hospital, Jikei University School of Medicine, Kashiwa, Japan.
Noriko
N
Sato
Division of General Medicine, Department of Internal Medicine, Kashiwa Hospital, Jikei University School of Medicine, Kashiwa, Japan.
Norio
N
Tada
2002 Japanese Atherosclerosis Society guideline; Japanese hyperlipidemic patients; lipid goal; low high-density lipoprotein cholesterol; simvastatin 20 mg