The Risk of Venous Thromboembolism (VTE) in Men with Benign Prostatic Hyperplasia Treated with 5-Alpha Reductase Inhibitors (5ARIs)

Background: Many men receive 5-alpha reductase inhibitors (5ARIs) for ongoing treatment of benign prostatic hyperplasia (BPH). The increased risk of cardiovascular complications with 5ARIs has been documented in BPH studies and the occurrence of cerebral venous thrombosis, presumably due to increased estrogen level following 5ARI use, was described in multiple case reports. The objective of this study was to determine if 5ARIs with or without alpha blockers (AB) were associated with an increased risk of venous thromboembolism (VTE) in males with BPH. Methods: We conducted a nested case-control study among a population of men ages 40-79 who received at least one 5ARI or AB prescription for treatment of BPH between 1995 and 2015 in the UK-based Clinical Practice Research Datalink GOLD. Cases of incident VTE (pulmonary embolism [PE] or deep venous thrombosis [DVT]) and matched controls were identified from this population. We used descriptive analyses and conditional logistic regression to evaluate the risk of VTE in users of 5ARIs compared to users of ABs. Results: For 5ARI only users, the adjusted odds ratios (aORs), (95% CI) for VTE were 1.51 (0.98-2.32) in current 5ARI users and 1.23 (0.70-2.17) in recent/distant past, compared to AB only users. However, the aOR (95% CI) in men who had 50 or more current 5ARI prescriptions compared to users of ABs only was higher: 2.29 (1.14-4.63). For 5ARI with AB use, the aORs, (95% CI) for VTE were 1.16 (0.64-2.10) in current 5ARI+AB users and 1.93 (0.71-5.25) in recent/distant past, compared to AB only users. The aOR (95% CI) in men who had 50 or more current 5ARI+AB prescriptions compared to users of ABs only was 1.65 (0.64-4.26). Conclusion: Current use of 5ARI, particularly long-term use, is associated with an increased risk of incident idiopathic VTE compared to patients treated with AB use only

Estimation of Health State Utility Values in Fabry Disease Using Vignette Development and Valuation

**Background:** Health state utilities are measures of health-related quality of life that reflect the value placed on improvements in patients’ health status and are necessary for estimation of quality-adjusted life-years. Health state utility data on Fabry disease (FD) are limited. In this study we used vignette (scenario) construction and valuation to develop health state utilities. **Objectives:** The aim of this study was to use vignette construction and valuation to estimate health state utility values suitable for inclusion in economic models of FD treatments. **Methods:** Health state vignettes were developed from semistructured qualitative telephone interviews with patients with FD and informed by published literature and input from an expert. Each vignette was valued in an online survey by members of the United Kingdom (UK) general population using the composite time trade-off (TTO) method, which aims to determine the time the respondent would trade to live in full health compared with each impaired health state. **Results:** Eight adults (50% women) with FD from the UK were interviewed. They were recruited via various approaches, including patient organizations and social media. The interviewees' responses, evidence from published literature, and input from a clinical expert informed the development of 6 health state vignettes (pain, moderate clinically evident FD $$CEFD$$, severe CEFD, end-stage renal disease $$ESRD$$, stroke, and cardiovascular disease $$CVD$$) and 3 combined health states (severe CEFD + ESRD, severe CEFD + CVD, and severe CEFD + stroke). A vignette valuation survey was administered to 1222 participants from the UK general population who were members of an external surveying organization and agreed to participate in this study; 1175 surveys were successfully completed and included in the analysis. Responses to TTO questions were converted into utility values for each health state. Pain was the highest valued health state (0.465), and severe CEFD + ESRD was the lowest (0.033). **Discussion:** Overall, mean utility values declined as the severity of the vignettes increased, indicating that respondents were more willing to trade life-years to avoid a severe health state. **Conclusions:** Health state vignettes reflect the effects of FD on all major health-related quality-of-life domains and may help to support economic modeling for treatment of FD

The use of pharmacologic agents and venous thromboembolic outcomes

Venous thromboembolism (VTE) which includes pulmonary embolism (PE), or deep venous thrombosis (DVT) poses an important disease burden, however, much remains unknown about the risk factors that cause it. In recent years, more attention has focused on medications that play a role in the development of drug-induced venous thrombosis. The three studies in this dissertation explore the risk of VTE in relation to the use of specific pharmacologic agents; glucocorticoids, 5ARIs and statins in three distinct patient populations with; asthma, benign prostatic hyperplasia (BPH) and hypercholesterolemia, using different approaches to address the inevitable confounding present in etiologic pharmacoepidemiologic research. Using a nested case-control design for the first two studies and cohort design for the last, we assessed the risk of VTE in relation to timing of drug exposure, duration of use, number, and dose of prescriptions. The base populations comprised subjects who received at least one prescription for any of the pharmacologic agents of interest (during 1995–2015 for study 1 and 2 and 1995–2018 for study 3) in the UK-based Clinical Practice Research Datalink. We used descriptive analyses as well as conditional logistic regression and Poisson regression models to evaluate the relationship between these drugs and the risk of VTE. Study 1 examined the relationship between glucocorticoid use and venous thromboembolism among asthma patients age 20–59. We found that current and systemic glucocorticoid use was associated with an increased risk of VTE, with a dose-response relationship. Study 2 explored the relationship between VTE and 5ARI use compared to alpha blocker use among patients, age 40–79, with BPH. We observed that cumulatively high doses of 5ARI+/-AB increases the risk of incident VTE. In study 3, we examined the relationship between VTE and statin use compared to fibrate use among 40–79-year-old patients with hypercholesterolemia. We observed that statin use decreases the risk of incident VTE. These three studies in a large population-based database of high quality, efficiently evaluate the safety/unintended benefit of glucocorticoids, 5ARIS and statins, with the hope to guide the development of guidelines for their use in prolonged care of asthma, BPH and hypercholesterolemia, respectively.2023-08-25T00:00:00