Risk of rheumatoid arthritis diagnosis in statin users in a large nationwide US study

Objective To evaluate the association between statin use and the risk of developing rheumatoid arthritis (RA) in a large, US case-control study. Methods Using the OptumLabs Data Warehouse, RA cases were identified as patients aged ≥18 years with ≥2 RA diagnoses between January 1, 2010 and June 30, 2019 and ≥1 prescription fills for methotrexate within 1 year of the first RA diagnosis. The first RA diagnosis was the index date. Cases were matched 1:1 to controls on age, sex, region, year of index date, and length of baseline coverage. Statin users were defined by having ≥2 statin prescription fills at least 90 days pre-index. Patients identified as statin users were further classified by statin user status (current or former), statin use duration, and intensity of statin exposure. Odds ratios for RA risk with statin use were estimated using logistic regression. Results 16,363 RA cases and 16,363 matched controls were identified. Among RA cases, 5509 (33.7%) patients were statin users compared to 5164 (31.6%) of the controls. Statin users had a slightly increased risk of RA compared to non-users (OR 1.12, 95% CI 1.06–1.18), and former statin users had an increased RA risk compared to current users (OR 1.21, 95% CI 1.13–1.28). However, risk was eliminated following adjustment for hyperlipidemia. The risk estimates for statin use duration and intensity did not reach significance. Conclusion This study demonstrates no significant increase in the risk of developing RA for statin users compared to non-users after adjustment for hyperlipidemia in addition to other relevant confounders. However, more information from prospective studies would be necessary to further understand this relationship.

Association between Statins and Retinal Vascular Occlusion: A Population-Based Cohort Study

Retinal vascular occlusion (RVO), including retinal arterial occlusion and retinal vein occlusion, is a common retinal vascular disease that causes visual disturbance. The exact pathogenesis of RVO remains unclear. In all types of RVO patients, hyperlipidemia is more than twofold more common than in controls. Statins have been used to control blood cholesterol levels and have been found to reduce the risk of cardiovascular morbidity and mortality. Moreover, the immunomodulatory functions of statins may play a role in treating inflammatory diseases. This study aimed to evaluate whether patients taking statins have a lower risk of developing RVO compared to patients not taking statins. Adult patients with statins usage on the index date identified from the Taiwan National Health Insurance Research Database (NHIRD) between 2000 and 2013 were included. A threefold matched group was selected using age, sex, and year of index date for comparison. During the mean follow-up period of 12.87 ± 1.88 years, the cumulative incidence of RVO was significantly lower in the statin-user group (29.96 per 105 person-years [PYs]) than in the non-statin-user group (39.35 per 105 PYs). The results showed a lower cumulative incidence rate of RVO in patients prescribed statins than in those not prescribed statins (log-rank test, p = 0.020). The adjusting hazard ratio (HR) was significantly greater for RVO in the statin-user group (adjusted HR, 0.704; 95% CI, 0.591–0.873). Statin users had a decreased risk for all types of RVO development, including central retinal artery occlusion, arterial branch occlusion, central retinal vein occlusion, and branch retinal vein occlusion. In conclusion, patients undergoing statin treatment have a lower risk of developing RVO compared to patients not taking statins.

Primary and Secondary Effects of Statin on Cerebro-Cardiovascular Disease Using the Nationwide Health Screening Data

Background and Purpose Dyslipidemia is a significant risk factor for cerebro-cardiovascular diseases (CVD). Limited evidence is available on the prevention effect of statin in a nationwide large population. We aim to verify the primary and secondary prevention effects of statin on CVD among not only the general adult population but also elderly over 60 years.Methods This study is a big data cohort study using propensity score-matched data from the Korean National Health Screening Cohort. Differences in the cumulative incidence of major adverse cerebro-cardiovascular events and hazard ratio between the statin-user and the non-statin-user groups were investigated.Results A propensity score-matched pairs of statin-user and non-statin-user identified 64,182 population of 40–75 years old without CVD and 24,688 with accompanying diseases. In this group, statin showed both primary (HR 0.76, 95% CI 0.70–0.83, p<0.001) and secondary (HR 0.87, 95% CI 0.79–0.95, p=0.004) prevention effect. In the elderly over 60 years, statin only showed primary prevention effect (HR 0.85, 95% CI 0.76–0.96, p=0.008) in the 26,836 propensity score-matched pairs.Conclusions Statin use in the elderly showed the primary prevention effect on CVD. Taking statin is desirable for both general population of dyslipidemia patients and elders over 60 years with CVD risk factors.

Evaluating the Effect of Statins on Prognosis in Patients Undergoing Liver Transplantation for Hepatocellular Carcinoma

IntroductionThe anti-cancer effect of statins is drawing attention. However, it is unclear whether statin use reduces the risk of hepatocellular carcinoma (HCC) recurrence in patients who undergo liver transplantation (LT) for HCC.MethodsConsecutive patients who underwent LT for HCC between 1995 and 2019 were enrolled. The effect of statins were compared between statin non-user and statin user groups. The primary endpoint was HCC recurrence. All-cause and HCC-related mortality were also evaluated. We also performed multivariable-stratified and sensitivity analyses for HCC recurrence. ResultsA total of 430 patients was enrolled, among whom 323 (75.1%) were statin non-users and 107 (24.9%) were statin users. During a median of 64.9 months (IQR, 26.1–122.6) of follow-up, 79 patients (18.4%) had HCC recurrence and 111 (25.8%) died. Among those who died, 53 (47.7%) were identified as HCC-related mortalities. Statin use was associated with a significantly lower risk of HCC recurrence (adjusted HR = 0.26, 95% CI, 0.11–0.60; P = 0.002) compared to that in statin non-users. Statin users also had significantly lower all-cause and HCC-related mortality than did statin non-users (P < 0.001 & P = 0.040, respectively). There was a dose-dependent relationship between statin use and HCC recurrence. The anti-cancer effect of statins on HCC recurrence was consistently significant across multivariable-stratified and sensitivity analyses. ConclusionsStatin use significantly reduced the risk of HCC recurrence and improved the survival of patients who underwent LT for HCC.

Statins for the Treatment of Pulmonary Hypertension in Patients with Chronic Obstructive Pulmonary Disease

Background: Patients with chronic obstructive pulmonary disease (COPD) are at risk for pulmonary hypertension (PH). The aim of our study was to investigate the benefit of statins for PH in patients with COPD.Methods: The study enrolled 23 million individuals from Taiwan’s population database from January 1, 2002, to December 31, 2017. COPD patients who met the inclusion criteria were enrolled, and patients with lung cancer, less than one year of observation, specific drug therapy for PH and lung transplantation were excluded.Results: A total of 643,131 COPD patients were included in the study, and only 12,308 patients developed PH during follow-up. Based on the inclusion and exclusion criteria, 8,577 PH patients were included in the cohort of patients with PH related to COPD for analysis. According to the definition of statin exposure, the final study population had 1,487 statin users and 7,090 statin non-users. The statin user group had a lower mortality related to PH than the non-user group (3.87 vs. 5.55 per 100 person-years, p &lt; 0.001). The mortality rate for PH in the multivariate analysis (aHR = 0.78, 95% CI = 0.62–0.98, p = 0.046) was significantly lower for statin users than for non-users.Conclusion: Statins seem to benefit patients with PH and COPD.

Association between statin use and osteoporotic fracture in patients with chronic obstructive pulmonary disease: a population-based, matched case-control study

Background In the recent years, chronic obstructive pulmonary disease (COPD) has been found to be associated with a higher risk of new-onset osteoporotic fracture (NOF). However, the existence of such an association in the COPD patients receiving statin treatment remains unknown. The present study aimed to investigate the association between COPD and NOF in statin-treated patients. Methods The present study was conducted over a period of 10 years (January 2004 to December 2013) in Taiwan. COPD patients receiving statin treatment were included in the statin user group, whereas the randomly selected statin non-users, with 1:1 matching for sex, age, index date, and Charlson Comorbidity Index, were included in the statin non-user group. The hazard ratio (HR) of NOFs in COPD patients was estimated between statin user and non-user groups. Results A total of 86,188 cases were identified as the statin-treated patients, and 86,188 subjects were included in the control group of statin non-users. Initially, the risk of NOF was found to be higher among the statin users as compared to non-users [HR, 1.12; 95% confidence interval (CI), 1.01–1.25]. However, the calculation of risk for NOFs after the adjustment for age, sex, comorbidities, and concurrent medications indicated no association of NOF (HR, 0.81; 95% CI, 0.55–1.21) with COPD in patients receiving statin treatment as compared to statin non-users. Conclusion The results of the study provided first evidence for the absence of any association between COPD and NOFs in statin-treated patients during a follow-up period of 10 years. Thus, the findings of this study might support the hypothesis stating the potent pleiotropic effects of statins. In clinical practice, these drugs might prove beneficial for the patients with COPD.

Statin use and risk of joint replacement due to osteoarthritis and rheumatoid arthritis: a propensity-score matched longitudinal cohort study

Objective Statins are reported to have a potential benefit on progression of OA and on disease activity in RA, but existing evidence is conflicting. Our objective was to examine whether statins associate with reduction in the risk for joint replacement due to OA and RA. Methods This was a propensity score-matched cohort study. Electronic health records from the UK Clinical Practice Research Datalink were used. We selected people prescribed statins and people never prescribed statins. Each statin user was matched to a non-user by age, gender, practice and propensity score for statin prescription. The main outcome measures were knee or hip joint replacement overall, and specifically because of OA or RA. The association between statins and risk of joint replacement was assessed using Cox proportional hazard regression. Statin exposure was categorized according to the potency of reducing low-density lipoprotein as low (21–28%), medium (32–38%) or high (42–55%) intensity. Results A total of 178 467 statin users were matched with 178 467 non-users by age, gender, practice and propensity score. Overall, statin was not associated with reduced risk of knee or hip replacement (hazard ratio 0.99, 95% CI: 0.97, 1.03), unless prescribed at high strength (0.86, 0.75–0.98). The reduced risk was only observed for joint replacement due to RA (0.77, 0.63–0.94) but not OA (0.97, 0.94–1.01). Conclusion Statins at high intensity may reduce the risk of hip or knee replacement. This effect may be RA specific. Further studies to investigate mechanisms of risk reduction and the impact in people with RA are warranted.

Inverse Association between Statin Use and Stomach Cancer Incidence in Individuals with Hypercholesterolemia, from the 2002–2015 NHIS-HEALS Data

Purpose: To investigate the association between statin use and stomach cancer incidence in individuals with hypercholesterolemia. Materials and methods: To examine the cumulative effect of statins, we defined a statin user as one who used statins during 2002–2003 at baseline. Statin users were further classified into high and low users according to the medication possession rate. Statin non-users consisted of participants who had never used statins during the entire period of 2002–2015, despite having hypercholesterolemia (total cholesterol level ≥250 mg/dL at baseline). Ultimately, 17,737 statin users and 13,412 statin non-users were used in the analysis. We performed survival analyses, considering the diagnosis of stomach cancer as an event of interest. Results: Median follow-up duration was 12.9 years. The cumulative incidence rates of stomach cancer were lowest in high users (1.90% in men and 0.98% in women). Compared to non-users, hazard ratios (95% confidential intervals) for stomach cancer of low users and high users were 0.953 (0.755–1.203) and 0.526 (0.399–0.693) in men and 0.629 (0.457–0.865) and 0.370 (0.256–0.535) in women, respectively, after adjusting for possible confounders. Conclusions: We observed an inverse association between statin use and stomach cancer incidence in participants with hypercholesterolemia.

Statin treatment and the risk of depression

ABSTRACTThe effect of statin treatment on the risk of developing depression remains unclear. Therefore, we aimed to assess the association between statin treatment and depression in a nationwide register-based cohort study with up to 20 years of follow up. We identified all statin users among all individuals born in Denmark between 1920 and 1983. One non-user was matched to each statin user based on age, sex and a propensity score taking several potential confounders into account. Using Cox regression we investigated the association between statin use and: I) redemption of prescriptions for antidepressants, II) redemption of prescriptions for any other drug, III) depression diagnosed at psychiatric hospitals, IV) cardiovascular mortality and V) all-cause mortality. A total of 193,977 statin users and 193,977 non-users were followed for 2,621,282 person-years. Statin use was associated with I) increased risk of antidepressant use (hazard rate ratio (HRR)=1.33; 95% confidence interval (95%-CI)=1.31-1.36), II) increased risk of any other prescription drug use (HRR=1.33; 95%-CI=1.31-1.35), III) increased risk of receiving a depression diagnosis (HRR=1.22, 95%-CI=1.12-1.32) - but not after adjusting for antidepressant use (HRR=1.07, 95%-CI=0.99- 1.15), IV) reduced cardiovascular mortality (HRR=0.92, 95%-CI=0.87-0.97) and V) reduced all-cause mortality (HRR=0.90, 95%-CI=0.88-0.92). These results suggest that the association between statin treatment and antidepressant use was unspecific (equivalent association between statins and other drugs) and that the association between statin use and depression diagnoses was mediated by antidepressant use. Thus, statin users and non-users appear to be equally likely to develop depression, but the depression is more often detected/treated among statin users.