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

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Original Research

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

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

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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.

FIGURE 2
Patients who achieved an LDL-C level of <100 mg/dL
after receiving 12 weeks of atorvastatin

TABLE 1
Demographic profiles of patients with diabetes or metabolic syndrome
(This is an expanded version of the table that appeared in print.)

DIABETES	STATIN-FREE (N=744)	STATIN-TREATED (N=280)	ALL (N=1024)
Men, n (%)	410 (55.1)	161 (57.5)	571 (55.8)
Age, years	60.9±10.9	62.2±10.1	61.3±10.7
Weight, kg	85.0±18.0	83.3±16.0	84.6±17.5
Waist circumference, cm	103.3±13.8	102.3±13.0	103.0±13.6
Smokers, %	16.5	12.5	15.4
Type 2 diabetes, % (% treated with insulin)	96.8 (16.3)	96.8 (16.6)	96.8 (16.3)
Blood pressure, mm Hg	137.1±15.7/79.6±9.6	136.3±16.4/77.5±10.5	136.9±15.9/79.0±9.9
CHD, %	24.2	56.4	33.0
PVD, %	5.5	7.9	6.2
CVD, %	6.9	9.3	7.5
METABOLIC SYNDROME	STATIN-FREE (N=839)	STATIN-TREATED (N=412)	ALL (N=1251)
Men, n (%)	483 (57.6)	248 (60.2)	731 (58.4)
Age, years	62.0±10.2	62.7±10.1	62.2±10.2
Weight, kg	87.4±17.2	85.7±15.1	86.9±16.6
Waist circumference, cm	106.2±12.3	104.8±12.6	105.7±12.4
Smokers, %	23.0	19.7	21.9
Diabetes, % (% type 2 diabetes) (% treated with insulin)	60.4 (98.6) (15.6)	46.1 (98.9) (17.6)	55.7 (98.7) (16.1)
Blood pressure, mm Hg	140.1±14.8/81.4±9.3	139.7±14.6/79.4±10.0	140.0±14.7/80.7±9.6
CHD, %	41.8	75.5	52.9
PVD, %	6.4	9.0	7.3
CVD, %	9.8	10.0	9.8
Mean±standard deviation for continuous variables.
CHD, coronary heart disease; PVD, peripheral vascular disease; CVD, cerebrovascular disease.

TABLE 2
Mean percent change (95% CI) in lipid levels from baseline when patients with diabetes or metabolic syndrome took atorvastatin
(This is an expanded version of the table that appeared in print.)

DIABETES	STATIN-FREE				STATIN-TREATED
DIABETES	10 MG (N=395)	20 MG (N=98)	40 MG (N=90)	80 MG (N=161)	20 MG (N=216)	40 MG (N=28)	80 MG (N=36)
Total cholesterol*	-23.0 (-24.3 to -21.7)	-31.6 (-33.8 to -29.3)	-38.1 (-40.5 to -35.7)	-41.2 (-43.3 to -39.1)	-16.9 (-18.6 to -15.2)	-30.4 (-36.0 to -24.9)	-34.2 (-39.4 to -30.0)
LDL-C*	-33.9 (-35.6 to -32.2)	-43.4 (-46.0 to -40.7)	-51.0 (-54.1 to -48.0)	-53.0 (-55.6 to -50.4)	-23.9 (-26.3 to -21.6)	-40.3 (-47.2 to -33.5)	-42.1 (-50.2 to -33.9)
HDL-C	2.9^† (1.4 to 4.3)	0.4 (-2.1 to 2.9)	-0.7 (-3.9 to 2.6)	-2.8^† (-4.9 to -0.6)	-0.8 (-2.6 to 1.0)	0.5 (-4.8 to 5.8)	-0.8 (-3.8 to 2.2)
TC/HDL-C*	-24.2 (-25.7 to -22.7)	-31.2 (-34.1 to -28.4)	-36.7 (-39.5 to -33.9)	-39.1 (-41.0 to -37.3)	-15.1 (-17.3 to -12.9)	-30.2 (-35.6 to -24.7)	-33.3 (-37.8 to -28.8)
Triglycerides*	-14.4 (-17.3 to -11.4)	-19.1 (-24.5 to -13.6)	-23.6 (-29.5 to -17.7)	-23.6 (-28.3 to -18.9)	-7.3 (-13.2 to -1.4)	-24.9 (-35.7 to -14.1)	-20.7 (-29.5 to -11.9)
Non-HDL-C*	-30.8 (-32.4 to -29.3)	-40.6 (-43.5 to -37.7)	-47.9 (-50.7 to -45.1)	-50.0 (-52.3 to -47.6)	-21.8 (-24.0 to -19.6)	-38.3 (-44.9 to -31.7)	-42.3 (-47.2 to -37.4)
Apo B*	-30.6 (-32.0 to -29.1)	-39.1 (-41.6 to -36.6)	-46.2 (-48.7 to -43.6)	-47.8 (-50.0 to -45.6)	-22.3 (-24.2 to -20.4)	-34.7 (-40.3 to -29.0)	-39.1 (-43.6 to -34.6)
METABOLIC SYNDROME	STATIN-FREE				STATIN-TREATED
METABOLIC SYNDROME	10 MG (N=418)	20 MG (N=103)	40 MG (N=104)	80 MG (N=214)	20 MG (N=290)	40 MG (N=47)	80 MG (N=75)
Total cholesterol*	-24.6 (-25.8 to -23.3)	-31.6 (-33.6 to -29.5)	-37.6 (-39.7 to -35.5)	-39.5 (-41.4 to -37.6)	-16.2 (-17.7 to -14.7)	-30.3 (-33.5 to -27.2)	-33.0 (-36.0 to -30.1)
LDL-C*	-34.6 (-36.1 to -33.0)	-43.4 (-46.1 to -40.6)	-49.3 (-51.9 to -46.7)	-50.3 (-52.7 to -47.9)	-21.8 (-23.7 to -19.9)	-40.4 (-44.1 to -36.7)	-41.3 (-45.9 to -36.8)
HDL-C	4.4^† (2.9 to 5.8)	2.9^† (0.3 to 5.5)	2.3 (-0.6 to 5.3)	2.0 (-0.1 to 4.2)	1.3 (-0.3 to 2.9)	4.1^† (0.3 to 7.8)	-1.6 (-3.7 to 0.6)
TC/HDL-C*	-26.6 (-28.1 to -25.1)	-32.6 (-35.4 to -29.8)	-38.2 (-40.6 to -35.9)	-39.5 (-41.9 to -37.0)	-16.2 (-18.0 to -14.4)	-32.3 (-35.6 to -29.1)	-31.4 (-34.8 to -28.1)
Triglycerides*	-18.8 (-21.7 to -15.8)	-22.8 (-27.9 to -17.8)	-28.8 (-33.7 to -23.9)	-29.5 (-33.0 to -26.0)	-12.6 (-16.7 to -8.6)	-32.4 (-39.1 to -25.6)	-21.7 (-28.1 to -15.3)
Non-HDL-C*	-32.2 (-33.7 to -30.7)	-39.9 (-42.6 to -37.2)	-46.7 (-49.1 to -44.3)	-47.9 (-50.0 to -45.8)	-20.9 (-22.8 to -19.1)	-38.9 (-42.5 to -35.2)	-39.8 (-43.3 to -36.3)
Apo B*	-31.9 (-33.2, to -30.5)	-39.4 (-41.9 to -37.0)	-45.4 (-47.6 to -43.2)	-45.4 (-47.4 to -43.4)	-21.4 (-23.0 to -19.7)	-36.2 (-39.5 to -32.8)	-38.3 (-41.6 to -35.1)
CI, confidence interval; LDL-C, low-density lipoprotein cholesterol; HDL-C, high-density lipoprotein cholesterol; TC/HDL-C, total cholesterol/HDL-C ratio; Apo B, apolipoprotein B.
*P<.05 from baseline for all doses.
^†P<.05 from baseline for a specific dose.

Metabolic syndrome

The ITT population included 1251 patients with MetSyn, of whom 56% also had diabetes and 67% were statin-free ( TABLE 1 ). Baseline laboratory parameters are in TABLE W1 .

FAST TRACK

After 12 weeks of treatment, 78% of patients with metabolic syndrome who were statin free at baseline achieved their LDL-C target

After 12 weeks of treatment, 78% (95% CI, 74.9%-80.5%) of statin-free and 57% (95% CI, 52.5%-62.1%) of statin-treated patients achieved LDL-C target of <100 mg/dL ( FIGURE 2 ). Among patients without MetSyn (n=1454), 79% (95% CI, 76.2%-81.7%) of statin-free and 61% (95% CI, 56.8%-64.6%) of statin-treated patients achieved target. (Because of missing data, the presence or absence of MetSyn could not be confirmed in 12 patients.)

Mean percent reductions for MetSyn patients in total cholesterol, TC/HDL-C, LDL-C, triglycerides, non-HDL-C, and apo B were significant vs baseline for all doses in both statin-free and statin-treated patients ( TABLE 2 ). HDL-C increased significantly in the 10- and 20-mg statin-free groups and in the 40-mg statin-treated group.

Treatment was well tolerated

FAST TRACK

No safety issues arose when initiating atorvastatin at higher doses in patients with diabetes or metabolic syndrome

The incidences of treatment-related adverse events were similar in all patient groups, at around 10%. Most events were mild to moderate, with severe events reported in only 0.5% and 0.8% of patients with diabetes and MetSyn, respectively. Incidences of treatment-related musculoskeletal adverse events were 1.9% and 2%, respectively, in patients with and without diabetes; and were 1.7% and 2.3% in patients with and without MetSyn.