Cardiovascular Benefits and Diabetes Risks of Statin Therapy in Primary Prevention

By P. Ridker, A. Pradhan, Jean G Macfadyen, Peter Libby, Robert J. Glynn. The Lancet, 2012

801 citations recorded by the source corpus.

Background As statin therapy increases risks of diabetes, the balance of benefit and risk in primary prevention for these agents has become controversial. We undertook an analysis of participants from the JUPITER trial to address the balance of vascular benefits and diabetes hazard of statin use. Methods In the randomized, double-blind JUPITER trial, 17,603 men and women without prior cardiovascular disease or diabetes were randomly allocated to rosuvastatin 20 mg or placebo and followed for up to 5 years for the trial primary endpoint (myocardial infarction, stroke, hospitalization for unstable angina, arterial revascularization, or cardiovascular death) and the protocol pre-specified secondary endpoints of venous thromboembolism (VTE), all-cause mortality, and incident diabetes. To address balance of vascular benefits and diabetes hazard, participants were stratified on the basis of having none or at least one of the following major risk factors for developing diabetes: metabolic syndrome, impaired fasting glucose, body mass index >30 kg/m2, or HbA1c > 6 percent. Findings Trial participants with one or more major diabetes risk factor (N=11,508) were at higher risk of developing diabetes; for such individuals, statin allocation was associated with a 39 percent reduction in the primary endpoint (P=0.0001), a 36 percent reduction in VTE (P=0.08), a 17 percent reduction in total mortality (P=0.15) and a 28 percent increase in diabetes (P=0.01). Thus, for those with diabetes risk factors, 93 vascular events or deaths were avoided for every 54 new cases of diabetes diagnosed. For trial participants with no major diabetes risk factor (N=6,095), statin allocation was associated with a 52 percent reduction in the primary endpoint (P=0.0001), a 53 percent reduction in VTE (P=0.05), a 22 percent reduction in total mortality (P=0.08) and no increase in diabetes (HR 0.99, P= 0.99). For such individuals, a total of 86 vascular events or deaths were avoided with no new cases of diabetes diagnosed. In analysis limited to the 486 participants who developed diabetes during follow-up (270 on rosuvastatin vs. 216 on placebo group, P=0.01), the point estimate of cardiovascular risk reduction associated with statin therapy (hazard ratio 0.63) was consistent with that observed for the trial as a whole (hazard ratio 0.56). As compared to placebo, statin allocation accelerated the average time to diagnosis of diabetes by 5.4 weeks. Interpretation In the JUPITER primary prevention trial, the cardiovascular and mortality benefits of statin therapy exceed the diabetes hazard, including among those at higher risk for developing diabetes

Subfields: Cardiology and Cardiovascular Medicine, Endocrinology, Diabetes and Metabolism, Surgery

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Citations in the corpus

2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. (2014, background): “year have been observed for high-intensity statins (52,82).”
Interpretation of the evidence for the efficacy and safety of statin therapy. (2016, background): “elevated BMI or HbA1c, or impaired fasting glucose), and did not appear to get larger as treatment continued.(47,224,226,227) Prior to these reports from randomized trials, adverse associations had not been reported between statin therapy and diabetes incidence in observational studies, although sev”
Atherosclerotic Cardiovascular Disease and Heart Failure in Type 2 Diabetes – Mechanisms, Management, and Clinical Considerations (2016, neutral): “00 mmol/L]), BMI 30 kg/m(2) or higher, or HbA 1c >6%.(190) As expected, incident diabetes mellitus was 28% higher those with than without any major diabetes mellitus risk factor, and statins accelerated the average time to diagnosis of diabetes mellitus by 5.”
National Lipid Association Recommendations for Patient-Centered Management of Dyslipidemia: Part 2. (2015, background): “diabetes hazard in all patients, including those at high risk for developing diabetes.(344,465) Because the incidence of diabetes increases with age, periodic glucose monitoring, and when appropriate, glycated hemoglobin measurement, should be performed when administering statins to older patients.”
Reprint: 2013 ACC/AHA Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults. (2014, background): “3 exces s cases of diabetes 100 statin-treated individuals per year have been observed for high-intensity statins (52,82).”
Statin Safety and Associated Adverse Events: A Scientific Statement From the American Heart Association (2019, positive): “However, fasting glucose levels at 24 months did not differ among the rosuvastatin and placebo groups.(112) In 2010, a meta-analysis of study-level data from 91 140 participants in 13 randomized trials (limited to CVD outcome trials with >1000 participants and follow-up of >1 year) indicated that st”