arznei-telegramm 2003; 34: 65

 
 
HEART PROTECTION STUDY: SIMVASTATIN (e.g. ZOCOR) FOR ALL DIABETICS?

One of the main objectives of diabetes therapy which has still not been achieved is to lower the increased risk of myocardial infarction and stroke in diabetic patients. The largest study to date on the preventative potential of statins in diabetes is the Heart Protection Study (HPS) (1). In this study, as a predefined subgroup, 5,963 diabetic patients between the ages of 40 and 80 (mean age of 62) with a total cholesterol over 135 mg/dl were included and treated over a period of five years with a daily dose of 40 mg simvastatin (e.g. ZOCOR) or placebo. Of these patients, 90% had type 2 diabetes, 40% had treated hypertension, 70% were male, 68% smokers or former smokers. In half of the patients, there were no known cardiovascular diseases.

Over the five year study period, under simvastatin, 20.2% of the patients had severe vascular events (cardiovascular death, myocardial infarction, stroke, or revascularisation procedures) compared with 25.1% under placebo (Number Needed to Treat [NNT] = 21). Coronary events were reduced from 12.6% to 9.4% (NNT = 32), strokes from 6.5% to 5.0% (NNT = 67) and necessary revascularisations from 10.4% to 8.7% (NNT = 59). Where there was a known vascular disease in addition to diabetes, the risk of a severe vascular event went down from 36% to 31% (NNT = 20), in patients without a known atherosclerotic disease the risk was reduced from 13.5% to 9.3% (NNT = 24).

As in the overall study (a-t 2002; 33: 83-4), diabetes patients also benefited from simvastatin regardless of age, sex, weight and levels of total cholesterol, LDL and HDL cholesterol or triglycerides. The duration of diabetes and the HbA1c value also had no impact on the benefit of the treatment. Simvastatin significantly slowed deterioration of kidney function as assessed by changes in serum creatinine: in the placebo group, the calculated glomerular filtration rate decreased by 1.34 ml/min per year, under simvastatin however only by 1.18 ml/min per year. This value almost equals the usual age-related reduction in kidney function in healthy individuals. The damage typical of statins to liver and muscle tissue occurred comparatively seldom, in the groups of diabetic and non-diabetic HPS participants alike.

In our opinion, the HPS cannot answer the question as to whether simvastatin therapy is beneficial to all diabetes patients over the age of 40. The study was designed as a primary and secondary prevention study. However, the conclusion that diabetic patients with a low cardiovascular risk also benefit from simvastatin cannot be drawn from HPS, because the included patients were not systematically examined for existing cardiovascular diseases. Even a meta-analysis of randomised studies concluded that it is uncertain whether statins have a primary prevention effect on vascular diseases in patients with diabetes (2). According to the current state of knowledge, a benefit is only proven for the undoubtedly large majority of diabetic patients who have manifest atherosclerotic diseases or are at high risk for such diseases, and has only been demonstrated for simvastatin.

It is possible that the positive effects are specific to simvastatin and are not a uniform group effect of statins. In the ASCOT-LLA* study with atorvastatin (SORTIS), there was no positive effect in the 2,532 diabetic patients (a-t 2003; 34: 38) (3). The ALLHAT-LLT* study with pravastatin (MEVALOTIN, PRAVASIN) failed to show a positive effect on mortality or cardiovascular events either in the total group or in the group of 3,638 diabetes patients (a-t 2003; 34: 14-5) (4).

A daily dose of 40 mg simvastatin (e.g ZOCOR) lowers the rate of severe cardiovascular events from 25% to 20% in patients over 40 with diabetes mellitus and a total cholesterol of over 135 mg/dl who have manifest atherosclerotic diseases or are at high risk of such diseases.
As is the case in non-diabetic patients, the benefit exists regardless of age, sex and cholesterol values. Therefore, therapy management according to monitored serum cholesterol is unnecessary.
From data at present available, including from the Heart Protection Study, it cannot be concluded that simvastatin is beneficial to diabetes patients with a low cardiovascular risk. For other statins, no benefit in diabetes has been established at all.

 

(R = randomised study, M = meta-analysis)

R

1

Heart Protection Study Collaborative Group: Lancet 2003; 361: 2005-16

M

2

GAMI, A.S. et al. : BMJ 2003; 326: 528-9

R

3

SEVER, P.S. et al.: Lancet 2003; 361: 1149-58

R

4

ALLHAT Officers: JAMA 2002; 288: 2998-3007


*


ALLHAT-LLT = The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial - Lipid Lowering Trial
ASCOT-LLA = Anglo-Scandinavian Cardiac Outcomes Trial - Lipid Lowering Arm



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