Statin treatment is not associated with an increased risk of adrenal insufficiency in real-world setting.

Introduction: Statins could reduce the synthesis of steroid hormones, thereby could cause adrenal insufficiency. We investigated this risk in a large nationwide database. Methods: We conducted a nested case-control study using a cohort of individuals affiliated to the French health insurance system in 2010, ≥18y and without adrenal insufficiency history. Each case had a first event of adrenal insufficiency between 2015 and 2017 and was matched to up to ten controls on age, sex, and prior treatment with corticosteroids. Statin exposure was measured over the five years preceding the index date, considering a six-month censoring lag-time. Association was estimated using a conditional logistic regression adjusted for confounders included in a disease risk score. Analyses were stratified on age, sex and corticosteroid history of use. Results: 4 492 cases of adrenal insufficiency were compared with 44 798 controls (median age 66y, 58% women), of which 39% vs. 33% were exposed to statins, respectively. No association between statin use and adrenal insufficiency was found when adjusting the model for confounders (adjusted odds ratio 0.98; 95% confidence interval 0.90-1.05). These results were consistent regardless of the exposure definition and stratifications considered. Conclusion: Statin-related adrenal insufficiency risk, if any, seems to be very limited and does not compromise the benefit of statin treatment.

Cost-utility analysis of focal high-intensity focussed ultrasound vs active surveillance for low- to intermediate-risk prostate cancer using a Markov multi-state model.

OBJECTIVES: To estimate the relative cost-effectiveness of focal high-intensity focussed ultrasound (F-HIFU) compared to active surveillance (AS) in patients with low- to intermediate-risk prostate cancer, in France. PATIENTS AND METHODS: A Markov multi-state model was elaborated for this purpose. Our analyses were conducted from the French National Health Insurance perspective, with a time horizon of 10 years and a 4% discount rate for cost and effectiveness. A secondary analysis used a 30-year time horizon. Costs are presented in 2016 Euros (€), and effectiveness is expressed as quality-adjusted life years (QALYs). Model parameters' value (probabilities for transitions between health states, and cost and utility of health states) is supported by systematic literature reviews (PubMed) and random effect meta-analyses. The cost of F-HIFU in our model was the temporary tariff attributed by the French Ministry of Health to the overall treatment of prostate cancer by HIFU (€6047). Our model was analysed using Microsoft Excel 2010 (Microsoft Corp., Redmond, WA, USA). Uncertainty about the value of the model parameters was handled through probabilistic analyses. RESULTS: The five health states of our model were as follows: initial state (AS or F-HIFU), radical prostatectomy, radiation therapy, metastasis, and death. Transition probabilities from the initial F-HIFU state relied on four articles eligible for our meta-analyses. All were non-comparative studies. Utilities relied on a single cohort in San Diego, CA, USA. For a fictive cohort of 1000 individuals followed for 10 years, F-HIFU would be €207 520 more costly and would yield 382 less QALYs than AS, which means that AS is cost-effective when compared to F-HIFU. For a threshold value varying from €0 to 100 000/QALY, the probability of AS being cost-effective compared to F-HIFU varied from 56.5% to 60%. This level of uncertainty was in the same range with a 30-year time horizon. CONCLUSION: Given existing published data, our results suggest that AS is cost-effective compared to F-HIFU in patients with low- and intermediate-risk prostate cancer, but with high uncertainty. This uncertainty must be scaled down by continuing to supply the model with new published data and ideally through a randomised clinical trial that includes cost-effectiveness analyses.