EBM COMMENTARY

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SHOULD STATINS BE STARTED IN ALL TYPE 2 DIABETICS IRRESPECTIVE OF LDL-CHOLESTEROL LEVEL?

SS Vasanthakumar, Medical Student at IMU Clinical School
CL Teng MMed(FamMed), FAFPM, FRACGP, AM

Address for correspondence: Dr CL Teng, Associate Professor, International Medical University, Jalan Rasah, 70300 Seremban, Malaysia. Tel: 06-76777798, Fax: 06-7677709, Email: tengcl@gmail.com
Conflict of interest: none

Vasanthakumar SS, Teng CL. EBM Commentary: Should statins be started in all type 2 diabetics irrespective of LDL-cholesterol level? Malaysian Family Physician. 2007;2(2):74-75

Case Scenario
Mr S is a 38 year old Indian man who has type 2 diabetes mellitus for 3 years. He is currently on metformin 500mg BD. His BMI is 24.9 kg/m² (weight 72 kg, height 170 cm). His blood glucose is well controlled (HbA1c 6%). His fasting lipid levels are as follow: Total cholesterol 5.0 mmol/L, HDL-C 1.60 mmol/L, LDL-C 2.6 mmol/L and triglyceride 0.9 mmol/L. He has no family history of acute myocardial infarction. He is a smoker (14 sticks/day, 12 years) but non-hypertensive. He asks if he should take atorvastatin, a lipid-lowering drug that his father is taking.

Question
Should statins be started in type 2 diabetic patients without pre-existing coronary artery disease whose lipid level is not elevated?

Commentary
The use of statins in patients with type 2 diabetes mellitus and pre-existing coronary artery disease (CAD) is now generally accepted, for which guideline suggested the target LDL-cholesterol (LDL-C) should be <2.6 mmol/L.¹ Since diabetes mellitus is a CAD risk equivalent, it has been suggested that all patients with diabetes should receive statins even if they do not have CAD or raised LDL-C.² Three randomised controlled trials (RCTs) designed specifically to evaluate the benefit of statins in diabetic patients without overt CAD have so far been published;^3-5 followed soon after by two meta-analyses^6,7 (Table 1).

In the primary prevention component of the meta-analysis by Vijan et al,⁶ five RCTs were included; they concluded that statins showed a 22% relative risk reduction (RRR). The meta-analysis by Thavendiranathan et al⁷ included seven trials (n=42,848, 90% of them did not have history of cardiovascular disease), statins showed a RRR of major coronary events and major cerebrovascular events by 29.2% (95%CI, 16.7-39.8%, p<0.001) and 14.4% (2.8-24.6%, p=0.02), respectively. However, statins did not show significant reduction in the CAD mortality and overall mortality. Interestingly, there is yet another RCT published last year; in the ASPEN study⁵ there was no statistical difference in the major cardiovascular events after 4 years of follow up despite 29% reduction of LDL-cholesterol in the atorvastatin group.

Looking at the published RCTs and meta-analyses, what would be the appropriate response to Mr S? It appears that the evidence for statins in older diabetic patients without overt CAD is compelling enough. However, the RRR and NNT may change somewhat if CARDS and ASPEN studies were to be included in the meta-analysis. Moreover, published RCTs included diabetic patients >40 years of age and have multiple CAD risk factors (including LDL-C >2.6 mmol/L). For diabetic patients like Mr S who are <40 years and LDL-C <2.6 mmol/L, there is still insufficient evidence to recommend routine statins.

Reference

1. American Diabetic Association. Standard of medical care in diabetes. Diabetes Care. 2007;30(Suppl 1):S4-S41 [PubMed] [Full text]
2. Grundy SM. Diabetes mellitus and coronary risk equivalent. What does it mean? Diabetes Care. 2006;29(2):457-60 [PubMed] [Full text]
3. Collins R, Armitage J, Parish S, et al. MRC/BHF Heart Protection Study of cholesterol-lowering with simvastatin in 5963 people with diabetes: a randomised placebo-controlled trial. Lancet. 2003;361:2005-16 [PubMed]
4. 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 randomized placebo-controlled trial. Lancet. 2004;364:685-96 [PubMed]
5. Knopp RH, D’Emden M, Smilde JG, Pocock SJ, on behalf of the ASPEN Study Group. Efficacy and safety of atorvastatin in the prevention of cardiovascular end points in subjects with type 2 diabetes. The Atorvastatin Study for Prevention of Coronary Heart Disease Endpoints in Non-Insulin-Dependent Diabetes Mellitus (ASPEN). Diabetes Care. 2006;29:1478-85 [PubMed] [Full text]
6. Vijan S, Hayward RA. Pharmacologic lipid-lowering therapy in type 2 diabetes mellitus: background paper for the American College of Physicians. Ann Intern Med. 2004;140:650-8 [PubMed] [Full text]
7. Thavendiranathan P, Bagai A, Brookhart MA, Choudhry NK. Primary prevention of cardiovascular diseases with statin therapy: a meta-analysis of randomized controlled trials. Arch Intern Med. 2006;166:2307-13 [PubMed]