Evaluation of efficacy and safety of fixed dose lovastatin and niacinER combination in Asian Indian dyslipidemic patients: a multicentric study

Manoj Sharma1, Deepika R Sharma1, Vikram Singh1, RB Panwar2, HS Hira3, Bishav Mohan4, Naveen Kumar4, SK Sharma5, Rajeev Gupta61Clinical Research Division, Panacea-Biotec Ltd, New Delhi; 2SP Medical College, Bikaner; 3Maulana Azad Medical College, New Delhi; 4Dayanand Medical College, Ludhiana; 5SMS Medical College, Jaipur; 6Monilek Hospital and Research Center, Jaipur, India.Abstract: Asian Indian dyslipidemia is characterized by: borderline high low-density lipoprotein (LDL) cholesterol and apolipoprotein (apo) B; high triglycerides, low high-density lipoprotein (HDL) cholesterol and apoA1; and high lipoprotein(a) (lp[a]). We performed a controlled multicentric trial in India to evaluate the efficacy and safety of a fixed dose combination of lovastatin and niacin extended release (niacinER) formulation in patients with moderate to severe dyslipidemia. Consecutive subjects that satisfied the selection criteria, agreed to an informed consent, and with no baseline presence of liver/renal disease or heart failure were enrolled in the study. After a 4-week run-in period there were 142 patients with LDL levels ≥ 130 mg/dL. Eleven patients were excluded because of uncontrolled hyperglycemia and 131 patients were recruited. After baseline evaluation of clinical and biochemical parameters all subjects were administered lovastatin (20 mg) and niacinER (500 mg) combination once daily. Dose escalation was done on basis of lipid parameters at 8 weeks and in 11 patients increased to lovastatin (20 mg) and niacinER (1000 mg). An intention-to-treat analysis was performed and data was analyzed using nonparametric Wilcoxon signed rank test. Thirteen patients (10%) were lost to follow-up and 4 (3%) withdrew because of dermatological adverse effects: flushing, pruritus, and rash. The mean values of various lipid parameters (mg/dL) at baseline, and at weeks 4, 12, and 24 respectively were: total cholesterol 233.9 ± 27, 206.3 ± 27, 189.8 ± 31, and 174.9 ± 27 mg/dL; LDL cholesterol 153.4 ± 22, 127.3 ± 21, 109.2 ± 27, and 95.1 ± 23 mg/dL; triglycerides 171.1 ± 72, 159.5 ± 75, 149.2 ± 45, and 135.2 ± 40 mg/dL; HDL cholesterol 45.6 ± 7, 48.9 ± 7, 51.6 ± 9, and 53.9 ± 10 mg/dL; lp(a) 48.5 ± 26, 40.1 ± 21, 35.4 ± 21, and 26.9 ± 19 mg/dL; and apoA1/apoB ratio 0.96 ± 0.7, 1.04 ± 0.4, 1.17 ± 0.5, and 1.45 ± 0.5 (p < 0.01). The percentage of decline in various lipids at 4, 12, and 24 weeks was: total cholesterol 11.8%, 18.8%, and 25.2%; LDL cholesterol 17.0%, 28.8%, and 38.0%; triglyceride 6.8%, 12.8%, and 21.0%; lp(a) 17.5%, 26.9%, and 44.5% respectively (p < 0.01). HDL cholesterol and apoA1/apoB increased by 7.2%, 13.1%, and 18.2%; and 7.9%, 21.9%, and 51.6% respectively (p < 0.01). Target LDL levels (< 100 mg/dL in subjects with manifest coronary heart disease or diabetes; < 130 mg/dL in subjects with > 2 risk factors) were achieved in 92 (80.7%) patients. No significant changes were observed in systolic or diastolic blood pressure, blood creatinine, transaminases, or creatine kinase. A fixed dose combination of lovastatin and niacinER significantly improved cholesterol lipoprotein lipids as well as lp(a) and apoA1/apoB levels in Asian Indian dyslipidemic patients. Satisfactory safety and tolerability profile in this population was also demonstrated.Keywords: Hypercholesterolemia, South Asians, coronary heart disease, lipid abnormalities, low HDL, lipoprotein(a