Effect of fitness on incident diabetes from statin use in primary prevention

Background: Statins are first line therapy for hyperlipidemia and the preferred treatment for primary and secondary prevention of cardiovascular disease (CVD). Meta-analyses of prior statin studies suggest an association of statin use with incident diabetes (DM). It is unknown whether incident co-morbid disease plays a role in this observed increase in incident DM amongst statin users. We examined the risk of incident DM using a competing risk of time to first event model. Method: Patients from an integrated health care system were included if they were > 45 years of age, had no prior history of either CVD or DM and who were started on a statin medication for primary prevention. Patients were followed from January 2002 to November 2012 and assessed at 1, 5, and 10 years (n=14736, 10305, and 2541 respectively) for the association of continuous statin use and incident DM or CV event (MI, CVA, AF, CHF, or coronary revascularization). Time until first event was examined using a competing risks statistical model, where the outcome was incident DM a first CV event, or neither. Risk estimates were adjusted using propensity scores of sex, age, hypertension, hyperlipidemia, renal failure, or tobacco use. Results: Patients averaged 55±6 years and were 56% male. Though not statistically significant, 1 -yr follow-up of statin use trended toward an association with incident DM (HR=1.68, 95% CI (0.978, 2.89), p=0.06). 5-yr follow-up of statin use was significantly associated with incident DM (HR=1.48, 95% CI (1.11, 1.97), p =0.008). 10-yr follow-up of statin use was not significantly associated with incident DM (HR=1.01, 95% CI (0.687, 1.47), p =0.97). Conclusion: Using a competing risks model, an association between continuous statin use at 5-years and incident DM was observed, with a trend toward an association at 1-year. Although continuous statin treatment through 5 years was associated with risk of DM , these results do not reveal whether that risk outweighs the expected benefit of statin therapy for primary prevention.

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Statin use in postmenopausal women is associated with an increased risk of incident diabetes mellitus

Evidence-Based Medicine ◽

10.1136/eb-2012-100676 ◽

2012 ◽

Vol 17 (6) ◽

pp. 192-193

Author(s):

Sarah H Wild ◽

Christopher D Byrne

Keyword(s):

Diabetes Mellitus ◽

Postmenopausal Women ◽

Incident Diabetes ◽

Increased Risk ◽

Statin Use

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Abstract 05: Assessing Population Impact of Statin Treatment for Primary Prevention of Atherosclerotic Cardiovascular Diseases in US

Circulation ◽

10.1161/circ.131.suppl_1.05 ◽

2015 ◽

Vol 131 (suppl_1) ◽

Author(s):

Quanhe Yang ◽

Yuna Zhong ◽

Catheen Gillespie ◽

Robert Merritt ◽

Barbara Bowman ◽

...

Keyword(s):

Primary Prevention ◽

Adverse Effects ◽

Randomized Clinical Trials ◽

Statin Treatment ◽

Population Based ◽

Number Needed To Treat ◽

Atherosclerotic Cardiovascular Disease ◽

Population Impact ◽

New Guidelines ◽

Statin Use

Introduction: American College of Cardiology/American Heart Association (ACC/AHA) new cholesterol treatment guidelines recommend consideration of statin treatment for a larger proportion of population for the primary prevention of atherosclerotic cardiovascular disease (ASCVD). It is important to assess the population impact of statin treatment under these new guidelines. Hypothesis: We assessed the hypothesis that increased statin use for the primary prevention of ASCVD might be accompanied by adverse effects among population. Methods: We used 2010 US Census, Multiple Cause Mortality, Third National Health and Nutrition Examination Survey Linked Mortality File (NHANES III 1988-2006, n=7095) and NHANES 2005-2010 (n=3178) participants 40-75 years of age to estimate prevalence of statin use, annual ASCVD deaths prevented and excess adverse effects by age, sex, and race/ethnicity if everyone followed updated guidelines. Results: Among 33.0 million adults aged 40-75 years meeting new guidelines for primary prevention of ASCVD (12.4 million with diabetes and 20.6 without diabetes but with a predicted 10-year ASCVD risk ≥7.5% and 70 ≤ low-density lipoprotein (LDL) ≤189 mg/dL), 26.9% (8.8 million) were on statins, indicating an additional 24.2 million potentially eligible for statin treatment (7.7 million with diabetes and 16.5 million without). Among the 7.7 million with diabetes, assuming 100% statin use, expected annual ASCVD deaths prevented were 2,514 (95% CI 592-4,142) and number-needed-to-treat (NNT) was 3,063 (1,860-13,017). The additional cases of myopathy based on estimates from randomized clinical trials (RCT) was 482 (0-2239) and number-needed-to-harm (NNH) was 15,992 (3,440-∞), and was 11,801 (9,251-14,916) and NNH 653 (516-833) based on estimates from population-based studies. Among 16.5 million without diabetes, ASCVD deaths prevented were 5,425 (1,276-8,935) with NNT 3,039 (1,845-12,914). The additional diabetes cases were 16,406 (4,922-26,250) with NNH 1,005 (628-3,349). Additional cases of myopathy was 1,030 (0-4,791) with NNH 15,996 3,441-∞) based on RCT estimates, and 24,302 (19,363-30,292) with NNH 678 (544-851) for population-based studies. ASCVD deaths prevented increased with age and >70% of ASCVD deaths prevented would occur among adults aged ≥60 years. Conclusions: Under ACC/AHA new guidelines for primary prevention of ASCVD by statin, assuming all those eligible took a statin, up to 12.6% of annual ASCVD deaths could be prevented, but could be accompanied by additional cases of diabetes and myopathy.

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Global variation of risk thresholds for initiating statins for primary prevention of cardiovascular disease: a benefit-harm balance modelling study

BMC Cardiovascular Disorders ◽

10.1186/s12872-020-01697-6 ◽

2020 ◽

Vol 20 (1) ◽

Author(s):

Henock G. Yebyo ◽

Sofia Zappacosta ◽

Hélène E. Aschmann ◽

Sarah R. Haile ◽

Milo A. Puhan

Keyword(s):

Cardiovascular Disease ◽

Primary Prevention ◽

Assessment Method ◽

Competing Risk ◽

Net Benefit ◽

Cvd Risk ◽

Risk Threshold ◽

Risk Thresholds ◽

Statin Use ◽

Country Specific

Abstract Background We previously showed that the 10-year cardiovascular disease (CVD) risk threshold to initiate statins for primary prevention depends on the baseline CVD risk, age, sex, and the incidence of statin-related harm outcome and competing risk for non-CVD death. As these factors appear to vary across countries, we aimed in this study to determine country-specific thresholds and provide guidelines a quantitative benefit-harm assessment method for local adaptation. Methods For each of the 186 countries included, we replicated the benefit-harm balance analysis using an exponential model to determine the thresholds to initiate statin use for populations aged 40 to 75 years, with no history of CVD. The analyses took data inputs from a priori studies, including statin effect estimates (network meta-analysis), patient preferences (survey), and baseline incidence of harm outcomes and competing risk for non-CVD (global burden of disease study). We estimated the risk thresholds above which the benefits of statins were more likely to outweigh the harms using a stochastic approach to account for statistical uncertainty of the input parameters. Results The 5th and 95th percentiles of the 10-year risk thresholds above which the benefits of statins outweigh the harms across 186 countries ranged between 14 and 20% in men and 19–24% in women, depending on age (i.e., 90% of the country-specific thresholds were in the ranges stated). The median risk thresholds varied from 14 to 18.5% in men and 19 to 22% in women. The between-country variability of the thresholds was slightly attenuated when further adjusted for age resulting, for example, in a 5th and 95th percentiles of 14–16% for ages 40–44 years and 17–21% for ages 70–74 years in men. Some countries, especially the islands of the Western Pacific Region, had higher thresholds to achieve net benefit of statins at 25–36% 10-year CVD risks. Conclusions This extensive benefit-harm analysis modeling shows that a single CVD risk threshold, irrespective of age, sex and country, is not appropriate to initiate statin use globally. Instead, countries need to carefully determine thresholds, considering the national or subnational contexts, to optimize benefits of statins while minimizing related harms and economic burden.

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