Statin Benefits Offset Diabetes Risk

The cardiovascular benefits of statin treatment for primary prevention outweighed the risk of developing diabetes, even among those at risk for the condition, an analysis of the JUPITER trial showed.

Taking into account several outcomes, statin therapy prevented 134 cardiovascular events or deaths for every 54 cases of new-onset diabetes among participants with at least one risk factor for diabetes, Paul Ridker, MD, of Brigham and Women’s Hospital in Boston, and colleagues determined.

And among those who were not at risk for developing diabetes, statin therapy prevented 86 cardiovascular events or deaths with no additional cases of new-onset diabetes, the researchers reported in the Aug. 11 issue ofThe Lancet.

“As the increase in risk of diabetes associated with statin therapy seems limited to patients with major risk factors for diabetes, monitoring of glucose concentrations when starting statin therapy might not be needed in those who have normal pretreatment glucose concentrations or who do not have multiple characteristics of metabolic syndrome,” Ridker and colleagues wrote.

“For our patients, we hope these data ease concern about risks associated with statin therapy when these drugs are appropriately prescribed for cardiovascular risk reduction as an adjunct to dietary discretion, increased exercise, and smoking cessation.”

Trial data and meta-analyses have indicated that statins increase the risk of developing diabetes, possibly in a dose-response fashion. In the JUPITER trial, for example, patients taking rosuvastatin (Crestor) had a 27% increased risk of new-onset diabetes compared with those taking placebo.

And earlier this year, the FDA added a warning about the diabetes risk to all statin labels. There remains some concern that when statins are used for primary prevention, the cardiovascular benefits may not outweigh the diabetes risk.

To explore the issue, Ridker and colleagues examined data from 17,603 participants in the JUPITER trial. All were free from previous cardiovascular disease and diabetes at baseline. The main study results showed that rosuvastatin reduced the rate of MI, stroke, hospitalization for unstable angina, arterial revascularization, or cardiovascular death by a relative 44%.

In the current analysis, the researchers divided the participants into two groups — those with at least one of four major risk factors for diabetes (metabolic syndrome, impaired fasting glucose, obesity, or a glycated hemoglobin greater than 6%) and those with none of those risk factors.

Most of the patients (63%) had at least one of the risk factors and, as expected, they were more likely to develop diabetes during the study (rate of 1.88 versus 0.18 per 100 person-years).

Overall, the risk of diabetes was greater in the rosuvastatin group (HR 1.25, 95% CI 1.05 to 1.49), a relationship confined to those participants who were already at risk for developing the disease. The average time from randomization to diagnosis of diabetes was shorter in the statin group (84.3 versus 89.7 weeks).

Among those at risk for diabetes, rosuvastatin was associated with:

• 39% reduction in the primary endpoint (HR 0.61, 95% CI 0.47 to 0.79)
• 36% reduction in venous thromboembolism (HR 0.64, 95% CI 0.39 to 1.06)
• 17% reduction in total mortality (HR 0.83, 95% CI 0.64 to 1.07)
• 28% increase in diabetes (HR 1.28, 95% CI 1.07 to 1.54)

 

Among those with no risk factors for diabetes, statin therapy was associated with:

• 52% reduction in the primary endpoint (HR 0.48, 95% CI 0.33 to 0.68)
• 53% reduction in venous thromboembolism (HR 0.47, 95% CI 0.21 to 1.03)
• 22% reduction in total mortality (HR 0.78, 95% CI 0.59 to 1.03)
• No increase in diabetes (HR 0.99, 95% CI 0.45 to 2.21).

 

Taken together, those findings indicate a net benefit for statin treatment in both groups of participants.

“A major take-home message for the clinician involved in either primary or secondary prevention of cardiovascular disease is that all individuals on a statin who have major risk factors for diabetes, particularly impaired fasting glucose, need to be informed about the risk, monitored regularly for hyperglycemia, and advised to lose weight and take regular physical exercise to mitigate the emergence of diabetes,” Gerald Watts, DSc, PhD, and Esther Ooi, PhD, of the University of Western Australia in Perth, wrote in an accompanying editorial.

Ridker and colleagues noted some limitations of their analysis, including the use of a single statin at a single dose, the fact that all participants had elevated high-sensitivity C-reactive protein, and the relatively short duration of follow-up (median 2 years), which precludes a long-term assessment of the risk-benefit balance.

 

The JUPITER trial was an investigator-initiated project funded by AstraZeneca.

Ridker is the principal investigator of the trial and received grant support from AstraZeneca for its conduct. He has served as a consultant to Merck, ISIS, Vascular Biogenics, Boehringer Ingelheim, Abbott, and Genzyme; receives additional research grant support from Novartis; and is listed as a co-inventor on patents held by the Brigham and Women’s Hospital related to inflammatory biomarkers in cardiovascular disease and diabetes that have been licensed to Siemens and AstraZeneca. His co-authors reported relationships with AstraZeneca, GlaxoSmithKline, Merck, Novartis, Pfizer, ProNova, Sigma-Tau, Athera Biotechnologies, Carolus Therapeutics, Interleukin Genetics, and BIND Biosciences.

Watts has received honoraria or lecture fees from AstraZeneca, Pfizer, Merck Sharp & Dohme, Sanofi, Amgen, Abbott, and Glaxo Wellcome. Ooi reported that she had no conflicts of interest.

 

From the American Heart Association:

• AHA: JUPITER Results Point to Role of Statins for ‘Apparently Healthy’ Patients
• Triglycerides and Cardiovascular Disease

 

Primary source: The Lancet
Source reference:
Ridker P, et al “Cardiovascular benefits and diabetes risks of statin therapy in primary prevention: an analysis from the JUPITER trial” Lancet 2012; 380: 565-571.

Additional source: The Lancet
Source reference:
Watts G, Ooi E “Balancing the cardiometabolic benefits and risks of statins” Lancet 2012; 380: 541-543.