Defining the Role of Statins in Diabetes
Defining the Role of Statins in Diabetes
Diabetes increases cardiovascular risk, and is recognised as a cardiovascular disease equivalent. Effective reduction of cardiovascular risk factors in diabetes patients is therefore vital. Several landmark clinical trials, including the Heart Protection Study, showed that statins reduce cardiovascular risk, even in patients with pretreatment low-density lipoprotein cholesterol (LDL-C) below 3 mmol/L. The Collaborative Atorvastatin Diabetes Study demonstrated that statin therapy significantly reduces LDL-C and major coronary events in patients with type 2 diabetes. Several studies have assessed which statins are most effective at reducing LDL-C. In patients with diabetes, rosuvastatin 10 mg and atorvastatin 10 mg bring 94% and 79% of patients, respectively, to European LDL-C goals. The benefits of more effective lipid lowering using high-dose statin therapy are being investigated in trials such as Treating to New Targets. Furthermore, studies indicate that combining a fibrate or niacin with a statin may offer more comprehensive lipid control in diabetes patients.
The prevalence of type 2 diabetes continues to rise. More than 5% of adults (32 million people) in the International Diabetes Federation European Region are currently affected by the condition, and it is estimated that the prevalence of type 2 diabetes will increase by approximately 20% between 2000 and 2036 in the UK. In the US, between 30% and 40% of individuals born in 2000 are likely to develop the condition. The rising prevalence of type 2 diabetes stems from several interrelated factors: an ageing population, excessive dietary energy intake and a sedentary lifestyle. Obesity, often the result of such factors, is also increasing in prevalence and is a significant risk factor for diabetes.
Diabetes leads to a 2- to 8-fold increase in the risk of vascular disease. The underlying pathologies in patients with type 2 diabetes are often more diffuse and severe than in non-diabetic subjects, and mortality rates are higher. Overall, up to 80% of patients with type 2 diabetes die from cardiovascular complications and average life expectancy is reduced by approximately 10 years. Interestingly, the relative increase in cardiovascular risk associated with diabetes is greater in women than in men. This abrogates the normal premenopausal gender-related difference in CVD mortality (figure 1).
(Enlarge Image)
Cardiovascular mortality in diabetic (D) and non-diabetic control (C) populations, 15 years from time of diagnosis. Diabetes abrogates the normal premenopausal gender-related difference in incidence of cardiovascular mortality[8]
In the UKPDS - one of the largest studies of patients with type 2 diabetes to date - strict glycaemic control led to a 25% reduction in the risk of microvascular complications (p=0.010). However, the effect of this intervention on macrovascular events was less clear: there was a trend for reduced risk of myocardial infarction with intensive blood glucose control (RR=16%) but it did not reach statistical significance (p=0.052). This result indicates that a multifaceted approach to macrovascular disease prevention is likely to be of value in patients with type 2 diabetes. Ideally, the chosen therapeutic regimen should address all other major risk factors for CVD in type 2 diabetes, including dyslipidaemia, hypertension, endothelial dysfunction, increased vascular oxidative stress, and abnormalities of platelet function, coagulation and fibrinolysis.
Current guidelines recommend that people with type 2 diabetes should be considered as CHD risk equivalents, and that dyslipidaemia should be a key therapeutic target in these patients, irrespective of baseline LDL-C level or age.
Diabetes increases cardiovascular risk, and is recognised as a cardiovascular disease equivalent. Effective reduction of cardiovascular risk factors in diabetes patients is therefore vital. Several landmark clinical trials, including the Heart Protection Study, showed that statins reduce cardiovascular risk, even in patients with pretreatment low-density lipoprotein cholesterol (LDL-C) below 3 mmol/L. The Collaborative Atorvastatin Diabetes Study demonstrated that statin therapy significantly reduces LDL-C and major coronary events in patients with type 2 diabetes. Several studies have assessed which statins are most effective at reducing LDL-C. In patients with diabetes, rosuvastatin 10 mg and atorvastatin 10 mg bring 94% and 79% of patients, respectively, to European LDL-C goals. The benefits of more effective lipid lowering using high-dose statin therapy are being investigated in trials such as Treating to New Targets. Furthermore, studies indicate that combining a fibrate or niacin with a statin may offer more comprehensive lipid control in diabetes patients.
The prevalence of type 2 diabetes continues to rise. More than 5% of adults (32 million people) in the International Diabetes Federation European Region are currently affected by the condition, and it is estimated that the prevalence of type 2 diabetes will increase by approximately 20% between 2000 and 2036 in the UK. In the US, between 30% and 40% of individuals born in 2000 are likely to develop the condition. The rising prevalence of type 2 diabetes stems from several interrelated factors: an ageing population, excessive dietary energy intake and a sedentary lifestyle. Obesity, often the result of such factors, is also increasing in prevalence and is a significant risk factor for diabetes.
Diabetes leads to a 2- to 8-fold increase in the risk of vascular disease. The underlying pathologies in patients with type 2 diabetes are often more diffuse and severe than in non-diabetic subjects, and mortality rates are higher. Overall, up to 80% of patients with type 2 diabetes die from cardiovascular complications and average life expectancy is reduced by approximately 10 years. Interestingly, the relative increase in cardiovascular risk associated with diabetes is greater in women than in men. This abrogates the normal premenopausal gender-related difference in CVD mortality (figure 1).
(Enlarge Image)
Cardiovascular mortality in diabetic (D) and non-diabetic control (C) populations, 15 years from time of diagnosis. Diabetes abrogates the normal premenopausal gender-related difference in incidence of cardiovascular mortality[8]
In the UKPDS - one of the largest studies of patients with type 2 diabetes to date - strict glycaemic control led to a 25% reduction in the risk of microvascular complications (p=0.010). However, the effect of this intervention on macrovascular events was less clear: there was a trend for reduced risk of myocardial infarction with intensive blood glucose control (RR=16%) but it did not reach statistical significance (p=0.052). This result indicates that a multifaceted approach to macrovascular disease prevention is likely to be of value in patients with type 2 diabetes. Ideally, the chosen therapeutic regimen should address all other major risk factors for CVD in type 2 diabetes, including dyslipidaemia, hypertension, endothelial dysfunction, increased vascular oxidative stress, and abnormalities of platelet function, coagulation and fibrinolysis.
Current guidelines recommend that people with type 2 diabetes should be considered as CHD risk equivalents, and that dyslipidaemia should be a key therapeutic target in these patients, irrespective of baseline LDL-C level or age.
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