Consider Using Statin Therapy for Most Diabetics

Statin therapy is a safe and cost-effective option for reducing the risk of major vascular events in patients with diabetes and should be considered for almost all diabetics, findings from a recent meta-analysis show.

In all, 14 randomized trials of statin therapy involving 18,686 individuals with diabetes and 17,220 without diabetes were included in the meta-analysis, which was conducted by the Cholesterol Treatment Trialists' Collaborators.

During more than 4 years of follow-up, 3,247 major vascular events, which were defined as the composite outcome of myocardial infarction, coronary death, stroke, or coronary revascularization, occurred in the trial participants.

Statin therapy in the diabetic patients was associated with a 9% proportional reduction in all-cause mortality per mmol/L reduction in LDL cholesterol, and was associated with a statistically similar 13% reduction in all-cause mortality in those without diabetes. This finding was due mainly to a significant reduction in vascular mortality (rate ratio of 0.87) in those with diabetes; there was no apparent effect on nonvascular mortality (rate ratio of 0.97) in this population, the investigators reported (Lancet 2008;371:117–25).

Furthermore, both those with and without diabetes had a 21% proportional reduction in major vascular events per mmol/L reduction in LDL cholesterol. In the diabetic patients, the effects of statin therapy were similar regardless of whether they had a history of vascular disease and regardless of other baseline characteristics, including type of diabetes, age, sex, treated hypertension, body mass index, systolic or diastolic blood pressure, smoking status, and estimated glomerular filtration rate.

In addition, reductions in major coronary events, coronary revascularization, and stroke were seen in those with diabetes (rate ratios of 0.78, 0.75, and 0.79, respectively), and the effect of statins on each of these outcomes was similar in diabetic and nondiabetic patients.

At 5 years, 42 fewer diabetic patients per 1,000 treated with statins had major vascular events, the collaborators found.

Statin therapy given in moderate doses over the 5 years was not associated with an increased risk of cancer or nonvascular causes of death in the study participants.

The findings, which “show convincingly” the benefits of statin therapy for reducing the risk of major vascular events in a wide range of individuals with and without diabetes, indicate that “the cost effectiveness of treatment for a person at a specific absolute level of risk of major vascular events, irrespective of whether diabetes is present, will be much the same,” the investigators wrote.

In a previous meta-analysis of 14 statin trials involving more than 90,000 patients, the researchers showed that a generic statin regimen producing a mean reduction of about 1 mmol/L was cost effective in those with as low as 1% risk of a major vascular event—suggesting that statin treatment would be cost effective in almost all diabetic patients, they noted.

Furthermore, “standard doses of a statin reduce LDL cholesterol by about 40%, which translates into a reduction of at least 1.5 mmol/L for many people with diabetes, so our results suggest that such an absolute reduction in LDL cholesterol would prevent about a third of patients from having a major vascular event,” they wrote. They concluded that statin therapy is likely to be inappropriate only in those in whom there are safety concerns (such as in pregnant women) or when there is a low short-term absolute risk of vascular disease (such as in children with type 1 diabetes).

Because the benefit seen with statin therapy is related mainly to the absolute reduction in LDL cholesterol achieved, it may be necessary to revise guidelines on statin therapy to ensure that a regimen sufficient to reduce LDL cholesterol substantially is considered for those with diabetes, they added.

In a commentary on the findings, Dr. Bernard M.Y. Cheung of the University of Birmingham, England, calls the collaborators' findings reassuring, but notes that statins “are not a panacea, and patients on statins are liable to other causes of morbidity and mortality” (Lancet 2008;321:94–5).

Treatment decisions should be based on the reduction in absolute risk—or the number needed to treat, rather than on relative risk reduction, he states, noting that in those with a high absolute cardiovascular risk, even a modest reduction in relative risk will provide meaningful clinical benefit. But he adds that other factors, such as life expectancy, concomitant disease, and quality of life also should be taken into consideration, and he stresses the continued importance of lifestyle.

“Apart from drug treatment, one must not forget the importance of lifestyle changes, such as cessation of smoking, healthy diet, and regular exercise,” Dr. Cheung wrote.