Cardiovascular Event Reduction Versus New-Onset Diabetes During Atorvastatin Therapy

Waters, David D.; Ho, Jennifer E.; Boekholdt, S. Matthijs; DeMicco, David A.; Kastelein, John J.P.; Messig, Michael; Breazna, Andrei; Pedersen, Terje R.

doi:10.1016/j.jacc.2012.09.042

Cited by 166 publications

(132 citation statements)

References 23 publications

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“…A recent post-hoc analysis of data from the Treating to New Targets (TNT) (N ¼ 7595) and IDEAL (N ¼ 7461) trials showed that the statin-mediated development of T2D is associated with raised FPG levels (>100 mg/dL) and by the presence of components of the metabolic syndrome, including elevated levels of fasting TGs (>150 mg/dl), BMI >30 kg/m 2 , and hypertension [41,78]. Among patients with 0e1 T2D risk factors at baseline, the risk of developing T2D during a median 5 years follow up was similar among patients treated with high-dose statins (atorvastatin 80 mg or simvastatin 40 mg) and moderate-dose statins (atorvastatin 10 mg or simvastatin 20 mg) (3.22% vs. 3.35%, respectively; HR: 0.97; 95% CI: 0.77e1.22).…”

Section: Peoplementioning

confidence: 99%

“…They should then discuss the possible consequences of statin therapy with their patients and encourage them to reduce both their CV and T2D risk through intensive lifestyle changes. Overall, available evidence suggests that the short-term risk of developing statin-mediated T2D in patients without any risk factors for T2D is low irrespective of statin dose and that the risk gradually increases with increasing numbers of T2D risk factors [35,41,78,79] (Section 4). In our opinion, all patients with high CV risk considered for statins should have their risk for T2D assessed initially using a validated risk score.…”

Section: Recommendations For the Use Of Statins In Patients With Ormentioning

confidence: 99%

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The use of statins in people at risk of developing diabetes mellitus: Evidence and guidance for clinical practice

Sattar¹,

Ginsberg

Ray

et al. 2014

Atherosclerosis Supplements

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Reducing low-density lipoprotein cholesterol (LDL-C) levels using statins is associated with significant reductions in cardiovascular (CV) events in a wide range of patient populations. Although statins are generally considered to be safe, recent studies suggest they are associated with an increased risk of developing Type 2 diabetes (T2D). This led the US Food and Drug Administration (FDA) to change their labelling requirements for statins to include a warning about the possibility of increased blood sugar and HbA1c levels and the European Medicines Agency (EMA) to issue guidance on a small increased risk of T2D with the statin class. This review examines the evidence leading to these claims and provides practical guidance for primary care physicians on the use of statins in people with or at risk of developing T2D. Overall, evidence suggests that the benefits of statins for the reduction of CV risk far outweigh the risk of developing T2D, especially in individuals with higher CV risk. To reduce the risk of developing T2D, physicians should assess all patients for T2D risk prior to starting statin therapy, educate patients about their risks, and encourage risk-reduction through lifestyle changes. Whether some statins are more diabetogenic than others requires further study. Statin-treated patients at high risk of developing T2D should regularly be monitored for changes in blood glucose or HbA1c levels, and the risk of conversion from pre-diabetes to T2D should be reduced by intensifying lifestyle changes. Should a patient develop T2D during statin treatment, physicians should continue with statin therapy and manage T2D in accordance with relevant national guidelines.

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Section: Peoplementioning

confidence: 99%

Section: Recommendations For the Use Of Statins In Patients With Ormentioning

confidence: 99%

The use of statins in people at risk of developing diabetes mellitus: Evidence and guidance for clinical practice

Sattar¹,

Ginsberg

Ray

et al. 2014

Atherosclerosis Supplements

Self Cite

View full text Add to dashboard Cite

show abstract

“…The underlying mechanism remains to be elucidated, but the issue was considered sufficiently important for the US FDA to change their labeling requirements for statins to include a warning about the possibility of increased blood sugar and glycated hemoglobin (HbA 1c ) levels. The risk of new-onset diabetes is relatively circumscribed to patients who already have one or more risk factors for developing this disease [24,25] and seems to be higher with intensive statin therapy than with moderate-dose therapy [26]. Although some drugs may be more harmful than others [27,28], the current evidence is insufficient to recommend specific statins based on their diabetogenic potential [29,30].…”

Section: Side Effects Of Statinsmentioning

confidence: 99%

Defining the Place of Ezetimibe/Atorvastatin in the Management of Hyperlipidemia

Ferreira

Silva

2016

Am J Cardiovasc Drugs

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Statin-ezetimibe combinations are a potentially advantageous therapeutic option for high-risk patients who need additional lowering of low-density lipoprotein cholesterol (LDL-C). These combinations may overcome some of the limitations of statin monotherapy by blocking both sources of cholesterol. Recently, a fixed-dose combination with atorvastatin, one of the most extensively studied statins, was approved and launched in several countries, including the USA. Depending on atorvastatin dose, this combination provides LDL-C reductions of 50-60%, triglyceride reductions of 30-40%, and highdensity lipoprotein cholesterol (HDL-C) increases of 5-9%. Studies comparing the lipid-lowering efficacy of the atorvastatin-ezetimibe combination with the alternatives of statin dose titration or switching to a more potent statin consistently showed that combination therapy provided greater LDL-C reduction, translating into a greater proportion of patients achieving lipid goals. Simvastatinezetimibe combinations have been shown to reduce the incidence of major atherosclerotic events in several clinical settings to a magnitude that seems similar to that observed with statins for the same degree of absolute LDL-C lowering. The atorvastatin-ezetimibe combination has also been shown to induce the regression of coronary atherosclerosis measured by intravascular ultrasound in a significantly greater proportion of patients than atorvastatin alone. Atorvastatin-ezetimibe combinations are generally well tolerated. Previous concerns of a possible increase in the incidence of cancer with ezetimibe were dismissed in large trials with long follow-up periods. In this paper, we examine the rationale for an atorvastatin-ezetimibe combination, review the evidence supporting it, and discuss its potential role in the management of dyslipidemia. Key PointsStatin-ezetimibe combinations are a realistic treatment option for patients who do not achieve low-density lipoprotein cholesterol (LDL-C) targets while receiving statin monotherapy and for patients prone to dose-dependent statin side effects.The IMPROVE-IT trial was the first to demonstrate a reduction in cardiovascular events with ezetimibe.Recently, combination therapy with atorvastatin plus ezetimibe was also associated with greater coronary plaque regression than atorvastatin alone.

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“…Although an increase in new-onset diabetes has been observed in subjects with one or more risk factors for diabetes, the cardiovascular benefits from statin use exceed the risk for development of diabetes [13]. Memory problems leading to statin discontinuation were identified among only 0.06% of statin users in a large cohort study [14].…”

mentioning

confidence: 99%

Statin intolerance: more questions than answers

Guyton¹,

Campbell²,

Lakey³

2013

Expert Review of Clinical Pharmacology

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Cardiovascular Event Reduction Versus New-Onset Diabetes During Atorvastatin Therapy

Cited by 166 publications

References 23 publications

The use of statins in people at risk of developing diabetes mellitus: Evidence and guidance for clinical practice

The use of statins in people at risk of developing diabetes mellitus: Evidence and guidance for clinical practice

Defining the Place of Ezetimibe/Atorvastatin in the Management of Hyperlipidemia

Statin intolerance: more questions than answers

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