RAMB Julho/Agosto 2015

ernardi

376

ssoc

ras

2015; 61(4):375-380

alists’ (CTT) collaboration, which included data on ap-

proximately 170,000 individuals from 26 randomized tri-

als (statin

. placebo, or high-dose

. low-dose statin).

This meta-analysis showed a cardiovascular risk reduction

of approximately 20% for each 39mg/dL decrease in LDLc.

This risk reduction is achieved with a low incidence of ad-

verse effects. The main side effects with their use are my-

opathy and myalgia. In extreme cases, there may be rhab-

domyolysis, particularly simvastatin 80mg, a dosage already

banned in some countries. Treatment with statins was

shown to be generally safe and without significant effects

on deaths due to cancer or other non-vascular causes.

For

these reasons, this class of drugs has become the most

commonly prescribed in the world. In the United States,

over 25% of adults aged at least 45 years (30 million indi-

viduals) received statins between 2005 and 2008,

and an

estimated 56 million may be eligible for treatment with

statins under the new American guidelines.

12,13

In recent years, some evidence suggests that the use of

statins may be associated with the emergence of new cas-

es of diabetes, leading to new questions about the safety

of these drugs. Data from a meta-analysis of prospective

studies,

14,15

as well as population-based study data confirm

this finding.

16-18

In this review, we try to show the most re-

cent evidence on this subject, but reinforcing the current

concept that the benefit in reducing cardiovascular risk

with the use of statins in patients eligible for the treatment

outweighs the possible risk of developing diabetes.

tatins

and

risk

type

diabetes

Despite the efficacy and adequate safety profile, current ev-

idence suggests the association between the use of statins

and the risk of developing type 2 diabetes. Greater atten-

tion to the issue has been given since the publication of the

Justification for the Use of Statins in Primary Prevention: an Inter-

vention Trial Evaluation Rosuvastatin

(JUPITER study),

which

showed significant benefit of rosuvastatin compared to pla-

cebo in reducing cardiovascular risk in adults without car-

diovascular disease or diagnosed diabetes with LDLc <130

mg/dL and PCR ≥2 mg/L. In this study, we observed an in-

creased number of patients with newly diagnosed diabetes

in the group that received statin. This absolute increase was

small but statistically significant in the number of report-

ed cases of diabetes. These results of the JUPITER study dif-

fered from a post

hoc

analysis performed by

The West of Scot-

land Coronary Prevention Study

(Woscops),

which involved

men with significant hypercholesterolemia in primary pre-

vention. In this analysis, there was an absolute decrease of

about 1%, and 30% decrease in relative risk for developing

diabetes associated with pravastatin 40 mg/day compared

with placebo. The apparently consistent protective effect

was attributed by the authors to the possible anti-inflam-

matory effects of statin. It is true that the number of dia-

betes cases in the Woscops was relatively small, only 139

new cases, and the diabetes diagnostic criteria were not in

accordance with current guidelines. Analysis of studies con-

ducted after the Woscops showed inconsistent relationship

between statin use and diabetes.

21,22

However, more recent

analyzes corroborated the findings of the JUPITER study.

In a meta-analysis of 13 studies on statins including

over 90,000 individuals, the risk of developing diabetes as-

sociated with the use of statins as compared to placebo

was 9% (odds ratio [OR] 1.09; 95CI 1.02–1.17).

Moreover,

a meta-regression analysis showed that the risk of devel-

oping diabetes with statins is higher in studies with older

individuals. In this study, the authors estimated that the

treatment of 255 patients with statins for 4 years would

result in one extra case of diabetes (number needed to harm

– NNH).

In all of the studies involved in the meta-analy-

sis, the population of long-term or recent onset diabetics

has the same benefit of decreased cardiovascular morbid-

ity and mortality than the individuals treated with statins

who were not pre-diabetic or insulin resistant.

A subsequent meta-analysis evaluated the influence of

statin dosage on the incidence of type 2 diabetes, evaluat-

ing studies that compared intensive statin therapy and

moderate dose therapy.

Five studies andmore than 32,000

participants without diagnosed diabetes were included.

2,749 cases of diabetes were identified, 1,449 cases from

the group receiving intensive care and 1,300 in the group

receiving a moderate treatment, with two additional cases

in the intensive treatment group per 1000 patient-years. It

is interesting to note that of the 6,684 individuals present-

ing cardiovascular events, 3,134 were in the intensive group

and 3,550 belonged to the moderate treatment group, rep-

resenting 6.5 cases less in the intensive group per 1000 pa-

tient-years in a follow-up of 4.9 years. Thus, in this meta-

analysis that included patients with manifest coronary

disease, intensive therapy was associated with increased

risk of type 2 diabetes compared with moderate therapy

(OR 1.12, 95CI 1.04-1.22), but also lower cardiovascular

risk (OR 0.84, 95CI 0.75-0.94).

In another meta-analysis, published in 2014, the inci-

dence of type 2 diabetes associated with the use of statin

was evaluated once again. 129,170 participants were in-

cluded from 20 randomized trials with statins (statin

control, and high-dose

. low-dose statin) without a diag-

nosis of type 2 diabetes at baseline. In this study, the chance

of a new diagnosis of type 2 diabetes with the use of statin

was 12% (OR 1.12, 95CI 1.06-1.18).