How to reach LDL targets quickly in patients with diabetes or metabolic syndrome

,

Original Research

How to reach LDL targets quickly in patients with diabetes or metabolic syndrome

J Fam Pract. 2008 October;57(10):661-668

By

Lawrence A. Leiter, MD, FRCPC, FACP

With a simple algorithm developed from the ACTFAST trials, most patients can reach goal safely in 6 to 12 weeks

PDF Download

References

1. NCEP. Executive Summary of The Third Report of The National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, And Treatment of High Blood Cholesterol In Adults (Adult Treatment Panel III). JAMA. 2001;285:2486-2497.

2. Olson K, Tsuyuki R. Patients' achievement of cholesterol targets: a cross-sectional evaluation. Am J Prev Med. 2003;25:339-342.

3. Pearson T, Laurora I, Chu H, et al. The lipid treatment assessment project (L-TAP): a multicenter survey to evaluate the percentages of dyslipidemic patients receiving lipid-lowering therapy and achieving low-density lipoprotein cholesterol goals. Arch Intern Med. 2000;160:459-467.

4. Leiter L, Betteridge D, Chacra A, et al. AUDIT study. Evidence of global undertreatment of dyslipidaemia in patients with type 2 diabetes mellitus. Br J Diabetes Vasc Dis. 2006;6:31-40.

5. Haffner S, Lehto S, Ronnemaa T, et al. Mortality from coronary heart disease in subjects with type 2 diabetes and in nondiabetic subjects with and without prior myocardial infarction. N Engl J Med. 1998;339:229-234.

6. Grundy S, Cleeman J, Merz C, et al. Implications of recent clinical trials for the National Cholesterol Education Program Adult Treatment Panel III guidelines. Circulation. 2004;110:227-239.

7. Grundy SM. Diabetes and coronary risk equivalency: what does it mean? Diabetes Care. 2006;29:457-460.

8. Miettinen H, Lehto S, Salomaa V, et al. Impact of diabetes on mortality after the first myocardial infarction. The FINMONICA Myocardial Infarction Register Study Group. Diabetes Care. 1998;21:69-75.

9. Hurst RT, Lee RW. Increased incidence of coronary atherosclerosis in type 2 diabetes mellitus: mechanisms and management. Ann Intern Med. 2003;139:824-834.

10. McNeill A, Rosamond W, Girman C, et al. The metabolic syndrome and 11-year risk of incident cardiovascular disease in the atherosclerosis risk in communities study. Diabetes Care. 2005;28:385-390.

11. Lakka H, Laaksonen D, Lakka T, et al. The metabolic syndrome and total and cardiovascular disease mortality in middle-aged men. JAMA. 2002;288:2709-2716.

12. Hu G, Qiao Q, Tuomilehto J, et al. Prevalence of the metabolic syndrome and its relation to all-cause and cardiovascular mortality in nondiabetic European men and women. Arch Intern Med. 2004;164:1066-1076.

13. Ford E. The metabolic syndrome and mortality from cardiovascular disease and all-causes: findings from the National Health and Nutrition Examination Survey II Mortality Study. Atherosclerosis. 2004;173:309-314.

14. Martineau P, Gaw A, de Teresa E, et al. Effect of individualizing starting doses of a statin according to baseline LDL-cholesterol levels on achieving cholesterol targets: The Achieve Cholesterol Targets Fast with Atorvastatin Stratified Titration (ACTFAST) study. Atherosclerosis. 2006;191:135-146.

15. Farsang C, Athyros V, Gaw A. A multicentre, open study to assess the effect of individualizing starting doses of atorvastatin according to baseline LDL-C levels on achieving cholesterol targets: the Achieve Cholesterol Targets Fast with Atorvastatin Stratified Titration (ACTFAST-2) study. Curr Med Res Opin. 2007;23:1945-1956.

16. Report of the expert committee on the diagnosis and classification of diabetes mellitus. Diabetes Care. 2002;25(suppl 1):S5-S20.

17. Saydah SH, Fradkin J, Cowie CC. Poor control of risk factors for vascular disease among adults with previously diagnosed diabetes. JAMA. 2004;291:335-342.

18. Haffner S, Alexander C, Cook T, et al. Reduced coronary events in simvastatin-treated patients with coronary heart disease and diabetes or impaired fasting glucose levels: subgroup analyses in the Scandinavian Simvastatin Survival Study. Arch Intern Med. 1999;159:2661-2667.

19. Goldberg RB, Mellies MJ, Sacks FM, et al. Cardiovascular events and their reduction with pravastatin in diabetic and glucose-intolerant myocardial infarction survivors with average cholesterol levels: subgroup analyses in the cholesterol and recurrent events (CARE) trial. The Care Investigators. Circulation. 1998;98:2513-2519.

20. American Diabetes Association: clinical practice recommendations 2002. Diabetes Care. 2002;25(suppl 1):S1-S147.

21. Sacks FM, Tonkin AM, Shepherd J, et al. Effect of pravastatin on coronary disease events in subgroups defined by coronary risk factors: the Prospective Pravastatin Pooling Project. Circulation. 2000;102:1893-1900.

22. Sever PS, Poulter NR, Dahlof B, et al. Reduction in cardiovascular events with atorvastatin in 2532 patients with type 2 diabetes: Anglo-Scandinavian Cardiac Outcomes Trial—lipid-lowering arm (ASCOT-LLA). Diabetes Care. 2005;28:1151-1157.

23. Colhoun HM, Betteridge DJ, Durrington PN, et al. Primary prevention of cardiovascular disease with atorvastatin in type 2 diabetes in the Collaborative Atorvastatin Diabetes Study (CARDS): multicentre randomised placebo-controlled trial. Lancet 2004;364:685-696.

24. Stender S, Schuster H, Barter P, et al. Comparison of rosuvastatin with atorvastatin, simvastatin and pravastatin in achieving cholesterol goals and improving plasma lipids in hypercholesterolaemic patients with or without the metabolic syndrome in the MERCURY I trial. Diabetes Obes Metab. 2005;7:430-438.

25. Hunninghake D, Ballantyne C, Maccubbin D, et al. Comparative effects of simvastatin and atorvastatin in hypercholesterolemic patients with characteristics of metabolic syndrome. Clin Ther. 2003;25:1670-1686.

26. Jones PH, McKenney JM, Karalis DG, et al. Comparison of the efficacy and safety of atorvastatin initiated at different starting doses in patients with dyslipidemia. Am Heart J. 2005;149(1):e1-e8.Available at: http://www.ahjonline.com/article/S0002-8703(04)00476-4/fulltext. Accessed September 10, 2008.

27. McKenney JM, Davidson MH, Saponaro J, et al. Use of a treatment algorithm to achieve NCEP ATP III goals with atorvastatin. J Cardiovasc Pharmacol. 2005;46:594-599.

28. Newman CB, Palmer G, Silbershatz H, et al. Safety of atorvastatin derived from analysis of 44 completed trials in 9416 patients. Am J Cardiol. 2003;92:670-676.

29. Newman C, Tsai J, Szarek M, et al. Comparative safety of atorvastatin 80 mg versus 10 mg derived from analysis of 49 completed trials in 14,236 patients. Am J Cardiol. 2006;97:61-67.

30. Athyros V, Papageorgiou A, Mercouris B, et al. Treatment with atorvastatin to the National Cholesterol Educational Program goal versus 'usual' care in secondary coronary heart disease prevention. The GREek Atorvastatin and Coronary-heart-disease Evaluation (GREACE) study. Curr Med Res Opin. 2002;18:220-228.

31. Koren MJ, Hunninghake DB. Clinical outcomes in managed-care patients with coronary heart disease treated aggressively in lipid-lowering disease management clinics: the alliance study. J Am Coll Cardiol. 2004;44:1772-1779.

32. Baigent C, Keech A, Kearney PM, et al. Efficacy and safety of cholesterol-lowering treatment: prospective meta-analysis of data from 90,056 participants in 14 randomised trials of statins. Lancet. 2005;366:1267-1278.

Practice recommendations

You can reduce elevated LDL-C levels in more patients with diabetes and metabolic syndrome using this study's algorithm.
Choose a starting dose of a statin according to the gap between baseline and target LDL-C values.
Using a tailored starting dose of atorvastatin, most patients with type 2 diabetes or metabolic syndrome can achieve LDL-C target levels safely within 6 to 12 weeks, without raising the initial dose or with a single titration step.

Abstract

Purpose To investigate whether using an algorithm to select the starting dose of a statin according to baseline and target LDL-cholesterol (LDL-C) values would facilitate achieving lipid targets in patients with diabetes or the metabolic syndrome.

Methods Two 12-week, prospective, open-label trials enrolled 2717 high-risk subjects, of whom 1024 had diabetes and 1251 had metabolic syndrome. Subjects with LDL-C between 100 and 220 mg/dL (2.6-5.7 mmol/L) were assigned a starting dose of atorvastatin (10, 20, 40, or 80 mg/d) based on LDL-C level and status of statin use at baseline (statin-free [SF] or statin-treated [ST]), with a single uptitration at 6 weeks, if required.

Results Among patients with diabetes, 81% of SF subjects (82%, 84%, 82%, and 76% with 10, 20, 40, and 80 mg, respectively) and 60% of ST subjects (61%, 68%, and 47% with 20, 40, and 80 mg, respectively) achieved LDL-C target. Among patients with metabolic syndrome, 78% of SF subjects (81%, 84%, 82%, and 66% with 10, 20, 40, and 80 mg, respectively) and 57% of ST subjects (58%, 70%, and 47% with 20, 40, and 80 mg, respectively) achieved LDL-C target. Among ST subjects, we observed reductions in LDL-C with atorvastatin beyond those achieved with other statins used at baseline in patients with diabetes and patients with metabolic syndrome. Atorvastatin was well tolerated.

Conclusions The ACTFAST studies confirm that a targeted starting dose of atorvastatin allows most patients with type 2 diabetes or the metabolic syndrome to achieve their LDL-C target safely with the initial dose or just a single titration. This therapeutic strategy may help overcome the treatment gap still observed in the treatment of lipids in diabetes.

How many of your patients with type 2 diabetes or metabolic syndrome have a low-density lipoprotein cholesterol (LDL-C) level below the target of 100 mg/dL? Your answer, undoubtedly, is not enough of them. The good news we report in this article is that you can safely achieve the target more often, within 6 to 12 weeks, using a simple algorithm that helps you determine the optimal starting dose of a statin.

Good reason for concern. Individuals with coronary heart disease (CHD) or CHD risk equivalents such as diabetes have the highest cardiovascular risk and, according to the National Cholesterol Education Program (NCEP) III and other guidelines, must aim for the lowest target levels of LDL-C.¹ As the number of cardiovascular risk factors increases in a population, the percentage of patients reaching targets decreases^2,3—to as low as 37% among those at highest risk.² The international Analysis and Understanding of Diabetes and Dyslipidaemia: Improving Treatment (AUDIT) survey found that out of all patients with type 2 diabetes being treated, only 54% achieved target.⁴

Type 2 diabetes purportedly imparts a cardiovascular risk comparable to that of a prior cardiovascular event.^1,5-7 Moreover, the outcome of such events in patients with diabetes is worse than in patients without diabetes, with approximately 7 out of 10 patients dying from the event or its complications.^7-9

FAST TRACK

The gap between LDL-C baseline and target values determined the optimal starting doses

The metabolic syndrome (MetSyn) also increases risk of cardiovascular events and mortality, even in individuals without diabetes or CHD.^10-13 In 1 study, the risks of all-cause and cardiovascular mortality in patients with MetSyn were 1.38 to 1.44 and 2.26 to 2.78, respectively, compared with those who did not have MetSyn.¹²

The algorithm we describe in this article was developed from results of the Achieve Cholesterol Targets Fast with Atorvastatin Stratified Titration (ACTFAST) trials. These trials were designed to assess whether, according to the degree of reduction required in LDL-C, an optimal starting dose of atorvastatin could be identified so that patients would achieve LDL-C targets quickly, with no change in the dose or with just one titration step, and regardless of statin use at baseline.

The main results of ACTFAST 1 and 2 have been published elsewhere.^14,15 We report specifically on a prespecified analysis of pooled results in the subset of patients with diabetes or MetSyn.