研究者根据入组时的糖尿病危险因素将17,603例受试者分成2组，评价瑞舒伐他汀(Crestor) (20 mg/d，连用5年)对心血管和死亡风险及糖尿病风险的影响。
在随刊述评中，西澳大利亚大学的Gerald F. Watts博士和Esther M. Ooi博士指出，该分析结果再次肯定了他汀类药物在心血管疾病一级预防中的净收益。在进行心血管疾病的一级或二级预防时，临床医生需向合并主要糖尿病危险因素的患者(特别是空腹血糖受损的患者)告知他汀类药物的风险，定期监测有无高血糖，并建议患者减肥和规律锻炼，以降低发生糖尿病的风险(Lancet 2012;380:541-3)。
By: DIANA MAHONEY, Cardiology News Digital Network
The cardiovascular benefits of statin treatment outweigh the risk of developing diabetes, even among individuals with multiple diabetes risk factors, according to a new analysis of data from the JUPITER (Justification for the Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin) trial reported online ahead of print in the Lancet on Aug. 9.
In light of recent evidence suggesting a small increased risk of incident type 2 diabetes associated with all statins, Dr. Paul Ridker of Brigham and Women’s Hospital in Boston and his colleagues sought to evaluate the balance of vascular benefits and the diabetes hazard of statin use in JUPITER trial participants.
Toward this end, they divided 17,603 individuals who took part in the randomized, double-blind, placebo-controlled JUPITER trial into two groups based on diabetes risk factors at study entry, and assessed the impact of rosuvastatin (Crestor) allocation (20 mg/day for up to 5 years) on cardiovascular and mortality risk and the risk of developing incident diabetes.
Of the study cohort, 6,095 individuals had no major risk factors for diabetes at study entry, and 11,508 had one or more major risk factors, defined as metabolic syndrome, impaired fasting glucose, body mass index of 30 kg/m2 or higher, and hemoglobin A1c greater than 6%. Subjects in the latter category were more likely to be female; have higher baseline blood pressure, HbA1c, glucose, and triglyceride values; and have lower baseline HDL cholesterol levels, the authors wrote.
Predictably, those patients with one or more diabetes risk factors had an increased risk of developing diabetes during trial follow-up, with an incidence rate of 1.88 per 100 person-years, compared with 0.18 per 100 person-years in those with no diabetes risk factors, the authors reported (Lancet 2012;380:565-71).
Incident diabetes occurred more frequently in the rosuvastatin group than in the placebo group, with a hazard ratio of 1.25 (270 vs. 216 cases, respectively). Among those who developed diabetes, the average time from randomization to diagnosis was shorter in the statin group, at 84.3 weeks vs. 89.7 weeks. "Almost all the excess risk of diabetes associated with rosuvastatin occurred in participants with baseline evidence of impaired fasting glucose," the authors noted.
In participants with and without diabetes risk factors, random allocation to rosuvastatin was associated with 39% and 52% reductions, respectively, in the study’s primary end point (myocardial infarction, stroke, hospital admission for unstable angina, arterial revascularization, or cardiovascular death), the authors wrote. Further, among those with diabetes risk factors, statin use was associated with a 36% reduction in thromboembolism, a 17% reduction in total mortality, and a 28% increase in diabetes, while statin use in the risk-free group led to a 53% reduction in venous thromboembolism, a 22% reduction in total mortality, and no increase in diabetes risk.
In absolute terms, among those with one or more diabetes risks, a total of 134 cardiovascular events or deaths were avoided in the statin users for every 54 new cases of diabetes, and among those with no diabetes risks, 86 total cardiovascular events or deaths were avoided with no excess new cases of diabetes diagnosed.
With respect to the primary cardiovascular end point, "the relative treatment benefits attributable to rosuvastatin were similar in participants with and without diabetes risk factors," the authors wrote. They also noted that the relative benefits and risks of rosuvastatin were generally consistent for all components of the primary and secondary end points and in all subgroups evaluated, and the risks of diabetes associated with rosuvastatin use did not change substantially as the number of diabetes risk factors increased.
The investigators also looked specifically at participants who developed diabetes during the trial and observed that, of the 486 total, 18 primary cardiovascular end points occurred, including 8 among rosuvastatin patients (1.10 per 100 person-years) and 10 in placebo patients (1.73 per 100 person-years). Thus, the authors reported, "the cardiovascular risk reduction associated with rosuvastatin was consistent with that for the trial as a whole."
The findings suggest that the cardiovascular and mortality benefits of statin therapy exceed the diabetes hazard in individuals with and without major diabetes risk, the authors stated.
They acknowledged, however, that the findings are limited by the fact that all of the study participants had elevated serum C-reactive protein (hsCRP) levels, which is a risk marker for both incident type 2 diabetes and incident cardiovascular events. "Thus, care should be used when considering these primary prevention data for those with hsCRP less than 2 mg/L," they cautioned. Other limitations of the findings include the fact that data from this analysis were limited to rosuvastatin at one dose, even though all statins increase diabetes risk, and the fact that the median JUPITER follow-up was 2 years, so "long-term data for benefits and risks cannot be gleaned from this study," they said.
In an accompanying commentary, Dr. Gerald F. Watts and Dr. Esther M. Ooi of the University of Western Australia, Perth, noted that although the findings reaffirm the net value of statins in the primary prevention of cardiovascular disease, "the diabetogenic effect of these drugs is highest in individuals with risk factors for diabetes, including raised C-reactive protein," while the risk of diabetes is negligible in the absence of statins. As such, they wrote, "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" (Lancet 2012;380:541-3).
This analysis and the JUPITER trial were funded by AstraZeneca. Dr. Ridker and some of his coinvestigators disclosed financial relationships with AstraZeneca, Merck, Isis, and other companies. Dr. Watts disclosed receiving honoraria or lecture fees from AstraZeneca, Pfizer, Merck Sharp & Dohme, and other companies. Dr. Ooi declared that she had no financial conflicts of interest.