Lipid modifying action of atorvastatin in escalating doses in patients of coronary artery disease

Suhrita Paul, Shirsendu Mondal, Hindol Mondal, Sajjad Hossain

Abstract


Background: A prospective, randomized controlled study with parallel treatment groups carried out to assess efficacy and tolerability of atorvastatin in escalating doses (10 mg, 20 mg, 40 mg and 80 mg) in modulating the lipid profile in patients of coronary artery disease in eastern Indian population and whether “Rule of six” commonly referred to in context of low-density lipoprotein (LDL) reduction by statins stands true in our population.

Methods: Patients randomly allocated into four groups (n=632) as per selection criteria. Groups A, B, C, D received atorvastatin 10 mg, 20 mg, 40 mg and 80 mg, respectively once daily at bedtime, for 24 weeks after which evaluation of efficacy and tolerability was done. Comparison between groups performed with one-way ANOVA; p<0.05 considered to be statistically significant.

Results: There was a significant reduction in cholesterol, LDL and triglycerides in all the groups, but between group comparisons did not reveal any significant reduction in lipid parameters between Groups C and D. “Rule of six” was not observed at higher doses of atorvastatin (40, 80 mg). Further, there was significant reduction of high-density lipoprotein (HDL) in Groups C and D, which is not accepted especially in Indian context where it is already low at baseline.

Conclusion: In Indian perspective, where HDL is low, and the LDL values are not very high, escalating dose of atorvastatin does not give additional clinical benefit. On the contrary, reduction of HDL itself predicts an adverse cardiovascular outcome. Increased adverse events and burden of cost must be taken into account, while prescribing atorvastatin.


Keywords


Atorvastatin, Low-density lipoprotein, Rule of six

Full Text:

PDF

References


Risk factors for cardiovascular disease in the developing world. A multicentre collaborative study in the International Clinical Epidemiology Network (INCLEN). INCLEN Multicentre Collaborative Group. J Clin Epidemiol. 1992;45(8):841.

Jha P, Enas E, Yusuf S. Coronary Artery Disease in Asian Indians: prevalence and Risk Factors. Asian Am Pac Isl J Health. 1993;1(2):163-75.

Kastelein JJP. The realities of dyslipidaemia: what do the studies tell us? Eur Heart J Suppl. 2005;7:F27-33.

Castelli WP. Cholesterol and lipids in the risk of coronary artery disease – the Framingham Heart Study. Can J Cardiol. 1988;4 Suppl A:5A-10.

Mahley RW, Bersot TP. Drug therapy for hypercholesterolemia and dyslipidaemia. Goodman and Gillmans: the Pharmacological Basis of Therapeutics. 11th Edition. New York: McGraw-Hill; 2006: 933.

Knopp RH. Drug treatment of lipid disorders. N Engl J Med. 1999;341(7):498-511.

Dominguez LJ, Galioto A, Ferlisi A, Pineo A, Putignano E, Belvedere M, et al. Ageing, lifestyle modifications, and cardiovascular disease in developing countries. J Nutr Health Aging. 2006;10(2):143-9.

Raymond SU, Leeder S, Greenberg HM. Obesity and cardiovascular disease in developing countries: a growing problem and an economic threat. Curr Opin Clin Nutr Metab Care. 2006;9(2):111-6.

Niskanen L, Turpeinen A, Penttilä I, Uusitupa MI. Hyperglycemia and compositional lipoprotein abnormalities as predictors of cardiovascular mortality in type 2 diabetes: a 15-year follow-up from the time of diagnosis. Diabetes Care. 1998;21(11):1861-9.

Goldberg IJ. Clinical review 124: diabetic dyslipidemia: causes and consequences. J Clin Endocrinol Metab. 2001;86(3):965-71.

Hansel B, Giral P, Nobecourt E, Chantepie S, Bruckert E, Chapman MJ, et al. Metabolic syndrome is associated with elevated oxidative stress and dysfunctional dense high-density lipoprotein particles displaying impaired antioxidative activity. J Clin Endocrinol Metab. 2004;89(10):4963-71.

Grundy SM, Cleeman JI, Merz CN, Brewer HB Jr, Clark LT, Hunninghake DB, et al. Implications of recent clinical trials for the National Cholesterol Education Program Adult Treatment Panel III Guidelines. J Am Coll Cardiol. 2004;44(3):720-32.

Herfindal ET, Gourley DR. Textbook of Therapeutics. Drug and Disease Management. 7th Edition. Philadelphia: Lippincott Williams & Wilkins; 2000: 407-27.

National Cholesterol Education program. ATP III guidelines at-a-glance quick desk reference. Available at http://www.nhlbi.nih.gov/guidelines/cholesterol/atglance.pdf. [Accessed on 2014 Mar 15].

Barter PJ, Brandrup-Wognsen G, Palmer MK, Nicholls SJ. Effect of statins on HDL-C: a complex process unrelated to changes in LDL-C: analysis of the VOYAGER Database. J Lipid Res. 2010;51(6):1546-53.

Gordon T, Castelli WP, Hjortland MC, Kannel WB, Dawber TR. High density lipoprotein as a protective factor against coronary heart disease. The Framingham Study. Am J Med. 1977;62(5):707-14.

Jones P, Kafonek S, Laurora I, Hunninghake D. Comparative dose efficacy study of atorvastatin versus simvastatin, pravastatin, lovastatin, and fluvastatin in patients with hypercholesterolemia (the CURVES study) Am J Cardiol. 1998;81(5):582-7.

Crouse JR 3rd, Frohlich J, Ose L, Mercuri M, Tobert JA. Effects of high doses of simvastatin and atorvastatin on high-density lipoprotein cholesterol and apolipoprotein A-I. Am J Cardiol. 1999;83(10):1476-7, A7.

Valera HR, Ganguly B. Study of plasma level of atorvastatin and its effect on lipid profile. Indian J Physiol Pharmacol. 2009;53(1):73-82.

Pedersen TR, Faergeman O, Kastelein JJ, Olsson AG, Tikkanen MJ, Holme I, et al. High-dose atorvastatin vs. usual-dose simvastatin for secondary prevention after myocardial infarction: the IDEAL study: a randomized controlled trial. JAMA. 2005;294(19):2437-45.