Statin Users Research Articles

Statins decrease the risk of hepatocellular carcinoma in metabolic dysfunction-associated steatotic liver disease: A systematic review and meta-analysis

BACKGROUND Metabolic dysfunction-associated steatotic liver disease (MASLD) is a leading cause of chronic liver disease with a significant risk of developing hepatocellular carcinoma (HCC). Recent clinical evidence indicates the potential benefits of statins in cancer chemoprevention and therapeutics. However, it is still unclear if statins can lower the specific risk of HCC among patients with MASLD. AIM To investigate the impact of statin use on the risk of HCC development in patients with MASLD. METHODS A systematic review and meta-analysis of all the studies was performed that measured the effect of statin use on HCC occurrence in patients with MASLD. The difference in HCC risk between statin users and non-users was calculated among MASLD patients. We also evaluated the risk difference between lipophilic versus hydrophilic statins and the effect of cumulative dose on HCC risk reduction. RESULTS A total of four studies consisting of 291684 patients were included. MASLD patients on statin therapy had a 60% lower pooled risk of developing HCC compared to the non-statin group [relative risk (RR) = 0.40, 95%CI: 0.31-0.53, I2 = 16.5%]. Patients taking lipophilic statins had a reduced risk of HCC (RR = 0.42, 95%CI: 0.28-0.64), whereas those on hydrophilic statins had not shown the risk reduction (RR = 0.57, 95%CI: 0.27-1.20). The higher (> 600) cumulative defined daily doses (cDDD) had a 70% reduced risk of HCC (RR = 0.30, 95%CI: 0.21-0.43). There was a 29% (RR = 0.71, 95%CI: 0.55-0.91) and 43% (RR = 0.57, 95%CI: 0.40-0.82) decreased risk in patients receiving 300-599 cDDD and 30-299 cDDD, respectively. CONCLUSION Statin use lowers the risk of HCC in patients with MASLD. The higher cDDD and lipophilicity of statins correlate with the HCC risk reduction.

Coronary artery calcium and atherosclerotic cardiovascular disease risk scores in patients with calcium pyrophosphate deposition disease.

Calcium pyrophosphate deposition (CPPD) disease is associated with an increased risk for cardiovascular (CV) events. We examined the atherosclerotic burden by coronary artery calcium scores (Agatston score) and compared 10-year atherosclerotic CV (ASCVD) risk scores in patients with vs without chondrocalcinosis, a radiographic marker of CPPD. We performed a cross-sectional analysis at an academic medical center, 1991-2022. Among all patients with an Agatston score in routine care, we defined a cohort with chondrocalcinosis detected before the coronary artery calcium scan. Comparators without chondrocalcinosis were matched 2:1 on age and sex-the primary analysis excluded statin users. We compared Agatston scores between the chondrocalcinosis cohort and comparators. We also tested for differences between cohorts in 10-year ASCVD risk score frequencies (low, borderline/intermediate, or high). 756 patients with chondrocalcinosis were matched to 1554 comparators (mean age 68 years, 53% female). CV risk factor burden was high in both cohorts, and statin use was infrequent. The unadjusted Agatston score was non-significantly higher in the chondrocalcinosis cohort (mean 359.1, SD 737.9) than in matched comparators (mean 297.1, SD 644.9) (p= 0.08). High 10-year ASCVD risk scores were significantly more common in the chondrocalcinosis cohort than comparators (p< 0.01). Coronary atherosclerosis burden by CAC was not significantly different between patients with chondrocalcinosis and matched comparators, though 10-year ASCVD risk scores were higher in the chondrocalcinosis cohort, suggesting that factors beyond coronary artery calcification contribute to the increased CV event rate in patients with CPPD disease.

Serum vitamin D concentration and anthropometric indicators of adiposity in adults without or with low dose statin users: a cross-sectional study

BackgroundThis study sought to determine the accuracy of several anthropometric parameters in association with serum Vit. D concentrations and to compare the novel indices with the conventional ones.MethodsA total of 947 individuals referred to the cardiology clinic who have not used statin or take low-dose statin were evaluated through a cross-sectional study. Data on demographic information, anthropometric indices, and biochemical measurements were gathered using a checklist. Both the multivariable regression modeling and the area under the receiver-operating characteristic (ROC) were employed for the analysis.ResultsConsidering novel indices, BRI (Body Roundness Index) showed the most powerful correlation with serum Vit. D levels among both genders. Among conventional ancient indices, WC (Waist Circumference) had the strongest association in both men and women groups. Based on the confounding factors-adjusted model, the highest odds ratio (OR) for the presence of Vit. D deficiency belonged to WHtR (Waist to Height Ratio) in women (OR, 0.347 (0.171–0.704), P = 0.003). None of the indices predicted Vit. D deficiency significantly among men. A Vit. D concentration of 4.55 ng/ml was found as a cutoff based on the metabolic syndrome status.ConclusionThe most powerful association with serum Vit. D levels were detected for BRI in both genders among newly developed indices. In addition, WHtR predicted Vit. D deficiency independent of confounding factors among women.

Muscle contractile properties and perceived fatigue in the general and diseased population.

Knowledge of muscle contractile properties, physical fitness, and their associations with perceived fatigue may provide insights into mechanisms inducing fatigue and treatment targets. We aimed to identify differences in contractile properties and physical fitness between populations, and examine associations with perceived fatigue. We pooled data on perceived fatigue, physical fitness, and contractile properties from six studies, including a control group (n = 90), cancer survivors (n = 27), patients with chronic obstructive pulmonary disease (COPD; n = 16), chronic myeloid leukemia (CML; n = 20), and statin users (n = 64). We evaluated differences between populations, and associations of contractile properties and physical fitness with perceived fatigue. Compared with the control group, we found differences in contractile properties of patients with COPD (larger muscle force decline: β = -10.5%, 95% CI = -16.7; -4.2, increase in early relaxation time (Rt): β = 84.4%, 95% CI = 51.7; 117.0, increase in half Rt: β = 83.1%, 95% CI = 45.5; 120.7, muscle force rise (MFR): β = 0.2%/ms, 95% CI = 0.1; 0.3, and decrease in MFR: β = -24.3%, 95% CI = -35.7; -13.0) and statin users (early Rt: β = -5.4 ms, 95% CI = -10.0; -0.8, increase in early Rt: β = 19.8%, 95% CI = 2.5; 37.1). Associations between contractile properties and perceived fatigue varied across populations. Longer relaxation times were associated with higher perceived fatigue in hemato-oncological populations. To conclude, contractile properties were impaired in patients with COPD and statin users. Associations between contractile properties and perceived fatigue varied across populations. In hemato-oncological populations, impaired muscle relaxation was associated with higher perceived fatigue.

Abstract 4137922: Cardiovascular Prognosis of Statin Users Developing Diabetes in Secondary Prevention: A Prospective Multicenter Study

Background: In primary prevention, statin use with new-onset diabetes mellitus (DM) was associated with increased atherosclerotic cardiovascular disease (ASCVD) risk. In high-risk and secondary prevention settings, the cardiovascular prognosis of statin users progressing to new-onset DM remains unclear. Methods: We collected data from inpatients with or without baseline ASCVD from four medical centers affiliated to Qingdao University. Patients were categorized into 4 phenotypes: (1) statin non-users without diabetes; (2) statin users with incident diabetes; (3) statin users with pre-existing diabetes; and (4) statin users without diabetes. The primary outcome was ASCVD events. The stratified Cox proportional hazard model was used to investigate the association between the four distinct phenotypes and the risk of ASCVD. Results: Among 12,800 high-risk patients, over a median follow-up of 118 days (interquartile range, 48-379 days), 1447 ASCVD events were documented. Compared with statin non-users without diabetes, statin users without diabetes (hazard ratio [95% confidence interval], 0.77 [0.65, 0.91], P=0.001) and statin users with pre-existing diabetes (0.80 [0.66, 0.99], P=0.035) were associated with lower risk of ASCVD, whereas statin users with new-onset diabetes were not (0.91 [0.70, 1.19], P=0.50), overall P for trend =0.013.( Figure 1 ) In patients with baseline ASCVD (i.e., secondary prevention settings), we observed similar findings ( Figure 2 ) Conclusions: In high-risk patients with pre-existing ASCVD, new-onset diabetes after statin use was likely associated with compromised cardiovascular benefits of statins.

Effect of statin on long-term outcomes in persistent tobacco users receiving percutaneous coronary intervention: A longitudinal, retrospective cohort study.

The role of statins in improving cardiovascular outcomes is well established, but little is known about their impacts on long-term outcomes in persistent tobacco users with stable coronary artery disease (CAD) who receive percutaneous coronary intervention (PCI). A population of persistent smokers with CAD treated by PCI was analyzed. From 2012 through 2019, a cohort of 907 persistent tobacco users with stable CAD undergoing PCI were enrolled from the inpatient department of Taichung Tzu Chi Hospital, Taiwan. We surveyed statin users and non-statin users after index PCI, and general characteristics, major risk factors, angiographic findings, and long-term clinical outcome were compared. Kaplan-Meier curve was used to compare the survival difference and Cox proportional hazard model was used to analyze the predictors for all-cause mortality and major adverse cardiovascular events, including cardiovascular (CV) mortality, myocardial infarction, and repeated PCI procedures. The statin group had a higher average total cholesterol (P < .01) and low-density lipoprotein cholesterol (LDL-C) level (P < .01) and was younger (P < .01) than the non-statin group. Ninety-six point one percent patients in the statin group had a LDL-C level below 100 mg/dL after treatment. They also had a more frequent history of acute coronary syndrome and lower prevalence of chronic kidney disease than the non-statin group (both P < .01). Freedom from all-cause and CV mortality were lower in the non-statin group than the statin group (both P < .01). After adjustment for age and chronic kidney disease, statin treatment no longer reduced the risk of CV mortality (hazard ratio: 0.32, 95% confidence interval = 0.07-1.49), but was still associated with a reduction in all-cause mortality (hazard ratio: 0.27, 95% confidence interval = 0.10-0.75). In persistent tobacco users undergoing PCI, patients treated with statin for LDL-C values above 100 mg/dL had a similar level of cardiovascular protection as those with LDL-C below 100 mg/dL and without statin treatment. Therefore, smoking attenuates pleiotropic effect of statin. Nevertheless, statin therapy was still associated with a reduction of all-cause mortality.

The association of statin use with in-hospital mortality in patients with acute kidney injury during hospitalization: A retrospective analysis.

Acute kidney injury (AKI) is a severe condition in hospitalized patients and carries high mortality. The influence of statin use on the outcomes of AKI patients remains inconsistent. We aimed to discover the association between statin use and in-hospital mortality. This retrospective study screened all adult admissions in Peking University First Hospital between 1 January 2018 and 31 December 2020, and patients with AKI during hospitalization were included. Exposure was defined as any statin prescription prior to AKI onset. Patients were followed up until death or discharge. The primary outcome was in-hospital all-cause mortality; secondary outcomes included cardiovascular- and sepsis-related mortality, elevated transaminases, rhabdomyolysis and kidney nonrecovery at discharge. A total of 2034 AKI patients were included. 551 (27%) patients were statin users. During a median of 10 days of follow-up, we documented 283 (14%) in-hospital deaths. Compared with statin nonusers, statin users experienced a significantly lower risk in in-hospital all-cause mortality (adjust hazard ratio [aHR], 0.54; 95% CI, 0.35-0.84) and cardiovascular-related mortality (aHR, 0.48; 95% CI, 0.24-0.97) after covariate adjustment. The survival benefit of statin use was consistent across subgroups, that is, age, sex, initial AKI stage and major surgery (all P for heterogeneity >.05). For sepsis-related mortality, elevated transaminases, rhabdomyolysis and kidney nonrecovery, the association was no longer significant in the fully adjusted model. For any type of statins, a statistically significant association was only observed in atorvastatin (aHR, 0.49; 95% CI, 0.30-0.81). Statin use may improve survival, and atorvastatin may be preferred in patients with AKI.

Effects of statins in patients with coronary artery spasm: A nationwide population-based study.

Controversies regarding the benefits of statin treatment on clinical outcomes in coronary artery spasm (CAS) without obstructive coronary artery disease (CAD) persist due to limited data. In this retrospective nationwide population-based cohort study from the Taiwan National Health Insurance Research Database during the period 2000-2012, the matched cohorts consisted of 12,000 patients with CAS. After propensity score matching with 1:1 ratio, 2216 patients were eligible for outcome analysis in either statin or nonstatin group, with the mean follow-up duration of 4.8 and 4.6 years, respectively. Statin users versus nonusers had a significantly reduced risk of major adverse cardiovascular events (MACEs) (6.7% vs. 9.5%, hazard ratio [HR] 0.68; 95% confidence interval [CI] 0.55-0.84) and all-cause mortality (6.0% vs. 7.6%; HR 0.77; 95% CI 0.61-0.96). While the results of MACEs were mainly contributed by cardiovascular death (1.9% vs. 3.2%; HR 0.56; 95% CI 0.38-0.83) and ischemic stroke (3.8% vs. 5.4%; subdistribution HR 0.69; 95% CI 0.52-0.91), they were primarily driven by reductions in ischemic but not hemorrhagic stroke. The benefit of statins was significantly pronounced in patients with hypertension and diabetes. Nevertheless, the effect on MACEs was consistent irrespective of age, sex, dyslipidemia, and mental disorder. Statins significantly reduced the risk of MACEs and all-cause mortality in CAS patients. The benefit of statin therapy in reducing MACEs appeared to be linear, with greater risk reduction with higher doses and longer duration without upper threshold, reflecting the dose-dependent relationship of statins with MACEs in CAS patients.

Baseline inflammatory status affects the prognostic impact of statins in patients with peripheral arterial disease

BackgroundStatins bring favourable effects on the clinical prognosis of patients with atherosclerotic disease partly through their anti-inflammatory properties. However, this effect has not been fully verified in patients with peripheral arterial disease (PAD). We aimed to test whether statins exert different prognostic effects depending on the degrees of inflammation in patients with PAD. MethodsThis study was a sub-analysis of a multicenter prospective cohort of 2321 consecutive patients with PAD who received endovascular therapy (EVT). After excluding patients without information on C-reactive protein (CRP) levels at the time of index EVT, 1974 patients (1021 statin users and 953 non-users) were classified into four groups depending on CRP levels: low CRP (<0.1 mg/dL), intermediate-low CRP (0.1–0.3 mg/dL), intermediate-high CRP (0.3–1.0 mg/dL), and high CRP (>1.0 mg/dL). A composite of death, stroke, myocardial infarction, and major amputation as the primary endpoint was compared between statin users and non-users in each CRP category. ResultsDuring the median observation period of 316 days, the primary composite endpoint occurred in 112 (11.0 %) statin users and 178 (18.7 %) non-users (log-rank test, p < 0.001). However, statin therapy was associated with significantly lower event rates only in the intermediate-high- and high-CRP categories (p = 0.02 and p = 0.008, respectively). Multivariable Cox regression analysis revealed that statin use was independently associated with the primary endpoint only in the high-CRP category (adjusted hazard ratio: 0.64 [95 % confidence interval: 0.41–0.98]). ConclusionStatins may exert favourable prognostic effects in patients with PAD and highly elevated CRP levels.

The Effect of Statin Usage on Survival in Metastatic Colorectal Cancer Patients Receiving Regorafenib.

Regorafenib is an oral multikinase inhibitor used in later lines for metastatic colorectal carcinoma (mCRC) treatment, but its efficacy and tolerability are low. To improve the response rates and ameliorate adverse effects, different strategies have been implemented. In our study, we examined the effect of statin usage in patients with mCRC treated with regorafenib. This single-center retrospective study included patients with mCRC who were treated with regorafenib between January 2015 and December 2023. The primary outcomes were progression-free survival (PFS) and overall survival (OS), and the secondary outcomes were adverse effects and the tolerability of regorafenib. The data of 105 patients were collected retrospectively. The median age of the patients was 66 years, and 60 patients were male. Seventeen patients (16.1%) were receiving statins. Statin-using patients were significantly older than non-users (72 years vs. 66.5 years, p=0.05). Comorbid diseases were more common in patients using statins. The median PFS was 1.9 months for statin users and 4.2 months for statin non-users (p<0.001), and the median OS was 4.7 vs. 6.7 months (p=0.01). Cox regression revealed that statin usage was significantly associated with a higher hazard ratio (HR) for PFS (2.53) and OS (2.06) (both p<0.01 and p=0.02, respectively). Statins are associated with decreased survival and response rates in patients with mCRC treated with regorafenib. However, further studies are needed to confirm these results.

The long-term usage of statin prevents adverse events in patients with atrial fibrillation

Abstract Background The effectiveness of statins in preventing adverse cardiovascular events in individuals with atrial fibrillation (AF) has remained uncertain. This study aimed to assess whether statin use could lead to better outcomes among individuals with AF. Purpose Our study aimed to investigate the relationship between statin use and cardiovascular outcomes in patients with newly-diagnosed AF. Methods This study used the National Health Insurance Research Database (NHIRD) in Taiwan. We enrolled 397,787 patients with AF from January 1st, 2012, to December 31st, 2020. Patients with AF were divided into 2 groups (statin user and statin non-user), and the risks of composite outcomes (ischemic stroke, hemorrhagic stroke and transient ischemic attack [TIA]), all-cause death and major adverse cardiovascular events (MACEs, which encompassed cardiovascular death, non-fatal myocardial infarction and heart failure hospitalization) were analyzed. Propensity score matching with time-dependent analysis was examined. Results We analyzed 288,958 patients with newly diagnosed AF (mean age, 73 years; 44% women; mean CHA2DS2-VASc score, 3.5). Compared with patients without statin use, statin user had a lower risk of composite endpoint, which included ischemic stroke, hemorrhagic stroke and TIA. (adjusted hazard ratio, 0.92; 95% confidence interval, 0.88-0.95; p &amp;lt; 0.01) after adjusting for patients’ age, gender, CHA2DS2-VASc score, cardiovascular medications, and comorbidities. In regard to all-cause mortality, statin users exhibited a 62% risk reduction compared to statin non-users (hazard ratio, 0.38; 95% confidence interval, 0.37-0.39; p &amp;lt; 0.01). Statin use was also associated with reduced incidence of MACEs (hazard ratio, 0.70, 95% confidence interval, 0.68-0.71; p &amp;lt; 0.01). In the subgroups stratified by CHA2DS2 VASc score, statin therapy was particularly effective for patients with CHA2DS2-VASc scores 0-3 for composite endpoints but consistently reduced all-cause mortality and MACEs across all score categories. Conclusions Among patients with newly diagnosed AF, statin use was associated with a lower risk of ischemic stroke, hemorrhagic stroke, TIA, all-cause mortality and MACEs.

Statin use before acute coronary syndrome and coronary risk factors, clinical presentation, interventions, and outcomes: ACC-NCDR-CathPCI Registry in India

Abstract Background Statins are used for coronary artery disease (CAD) primary and secondary prevention. Limited studies on the association of statin use before acute coronary syndrome (ACS) with clinical presentation and outcomes are available. Purpose We compared statin-user and statin-naïve ACS patients for clinical and angiographic findings and in-hospital and 3-year outcomes following percutaneous coronary intervention (PCI). Methods Successive patients with ACS who underwent PCI from Sep’17 to Dec’23 were enrolled in the ACC-NCDR-CathPCI registry in India. Details of risk factors, clinical presentation, coronary angiography, interventions and in-hospital were recorded. Follow-up data in a sub-cohort recruited from Apr’19 to Mar’22 were obtained for incident major cardiovascular events (MCE) (cardiovascular deaths, recurrent ACS, PCI and bypass surgery). Results 8296 ACS patients were enrolled; prior statin use was in 3149 (38%) and statin naïve were 5147 (62%). Statin-user vs statin-naïve patients were older (61.6+10 vs 59.7+11y), with more hypertension (60.1 vs 48.6%), diabetes (35.8 vs 31.8%), pre-existing CAD (PCI 20.9 vs 9.1%; CABG 5.0 vs 2.3%) and lower mean total, LDL, and NHDL cholesterol (p&amp;lt;0.001). Statin users had less ST-elevation myocardial infarction (STEMI) (28.4% vs 45.2%), more non-STEMI (65.2 vs 50.8%), better LVEF (46.3+10 vs 44.5+10%), &amp;gt;2 coronary stents (35.5 vs 29.5%), lower mechanical circulatory support (2.2 vs 3.9%) and lower median hospitalization (66.1 vs 68.5h) (p&amp;lt;0.001). In statin-users incidence of in-hospital CAD deaths was 29 (0.92%) vs 78 (1.52%) (odds ratio, OR 0.61, 95% confidence intervals 0.39-0.93) and all-cause deaths 33 (1.05) vs 91(1.77%) (OR 0.59, 95%CI 0.39-0.88) (p&amp;lt;0.01). ORs attenuated following multivariate adjustments for risk factors, clinical presentation and interventions. In the follow up cohort (n=3813, high-intensity statins 99.6%), among baseline statin-users incident MCE was 98 (6.9%) vs 214 (8.9%) (hazard ratio, HR 0.76, 95%CI 0.59-0.97) and CVD deaths were in 46 (3.2%) vs 113 (4.7%) (HR 0.68, 95%CI 0.48-0.96) with attenuation following adjustment for baseline clinical variables and interventions. Conclusions Acute coronary syndrome patients taking pre-admission statins have significantly lower in-hospital and long-term cardiovascular and all-cause mortality following PCI.

Lipoprotein(a) cardiovascular disease risk not captured by low density lipoprotein cholesterol and apolipoprotein B

Abstract Background Elevated lipoprotein(a) affects 1 in 5 individuals and is considered a causal risk factor for atherosclerotic cardiovascular disease (ASCVD) and aortic valve stenosis (AVS). However, lipoprotein(a) measurements are not widely implemented in clinical practice. Low-density lipoprotein (LDL) cholesterol and apolipoprotein B (ApoB) measurements include contributions from lipoprotein(a), yet whether these measurements can replace measurements of lipoprotein(a) in assessing cardiovascular disease risk from this causal risk factor is unknown. Purpose We tested the hypotheses that lipoprotein(a) risk of ASCVD and AVS is captured by LDL cholesterol or ApoB. Methods We included 70,189 individuals from a prospective contemporary cohort study of the general population. Mediated risk by LDL cholesterol and ApoB in the association between lipoprotein(a) and risk of ASCVD and AVS was examined using four-way decomposition analyses stratified by statin treatment at baseline. Results During a median follow-up of 10.8 years, 7,127 developed ASCVD and 1,516 AVS. Per 50 mg/dL higher lipoprotein(a), multivariable adjusted hazard ratios were 1.22 (95% CI: 1.18-1.26) for ASCVD and 1.36 (1.28-1.46) for AVS. In individuals without statin use, LDL cholesterol mediated 19% (15%-24%) of the risk of ASCVD from lipoprotein(a) and 7.7% (1.5%-14%) of the risk of AVS from lipoprotein(a) (Figure 1). Corresponding values for ApoB were 14.0% (11%-18%) and 6.6% (2.8%-10%). In statin users (n=9,570), LDL cholesterol did not mediate risk of ASCVD from lipoprotein(a) but mediated 8.0% (0.8%-15%) of the risk of AVS from lipoprotein(a). Correspondingly, ApoB mediated 9.8% (2.2%-17%) of the risk of ASCVD and 4.2% (0.4%-8.0%) of the risk of AVS from lipoprotein(a). Conclusion Lipoprotein(a) risk of ASCVD and AVS is not adequately captured by LDL cholesterol and ApoB. Therefore, lipoprotein(a) measurement is needed in all individuals to capture the cardiovascular disease risk from this causal risk factor.

Risk of Opioid Overdose Associated with Concomitant Use of Methadone and Statins.

Methadone has a high potential for risky drug-drug interactions that can lead to opioid overdose, yet evidence on the magnitude of this risk remains limited. Since methadone is transported via P-glycoprotein (P-gp), the use of statins that inhibit P-gp may elevate methadone plasma concentrations, potentially leading to opioid overdose. We explored this hypothesis by examining whether concomitant use of methadone and P-gp-inhibiting statins was associated with opioid overdose. Using Medicaid claims data from 2003 to 2020, we conducted a cohort study among new concomitant users of methadone and statins. We compared overdose rates among individuals exposed to P-gp-inhibiting statins (simvastatin, atorvastatin, or lovastatin) vs. those exposed to rosuvastatin (negative control), adjusting for baseline covariates. We identified 69,263 individuals newly exposed to methadone and a statin of interest; the overall incidence rate of opioid overdose was 26.0 per 1,000 person-years. Adjusted hazard ratios (HRs) for methadone + P-gp-inhibiting statins consistently showed no association, ranging from 0.76 (95% CI = 0.48-1.22) for atorvastatin to 0.78 (95% CI = 0.50-1.22) for simvastatin, compared with methadone + rosuvastatin. Similar results were observed in sensitivity analysis that treated all P-gp-inhibiting statins as a single exposure group, as well as analyses stratified by baseline diagnosis of opioid use disorder or overdose, the duration of baseline methadone use, and calendar year intervals. Our findings suggest that concomitant use of methadone with simvastatin, atorvastatin, or lovastatin is not associated with the risk of opioid overdose compared to concomitant use of methadone and rosuvastatin.

Statin Therapy Reduces Radiation-Induced Cardiotoxicity in Patients With Breast Cancer Receiving Adjuvant Radiotherapy.

To evaluate the efficacy of statin therapy in reducing major adverse cardiovascular event (MACE) risk among patients with breast cancer undergoing breast-conserving surgery and adjuvant whole breast radiotherapy. A retrospective cohort study was conducted using data from the Taiwan Cancer Registry Database linked to the National Health Insurance Research Database. Patients diagnosed with left-sided early breast invasive ductal carcinoma between 2016 and 2019 were included. Propensity score matching was employed to compare MACE risk between statin users and nonusers. Cox regression models were used to estimate adjusted hazard ratios (aHRs) for MACE, considering cumulative defined daily doses and daily defined doses of statins. Among 1481 patients undergoing breast-conserving surgery and adjuvant whole breast radiotherapy, statin use significantly reduced MACE risk (aHR, 0.34 [95% CI, 0.25-0.44]). Hydrophilic statins, particularly rosuvastatin and pravastatin, demonstrated the greatest risk reduction. Higher cumulative defined daily doses and daily intensity doses of statins were associated with lower MACE risk, indicating a dose-response relationship. The 5-year cumulative incidence of MACE was significantly lower in statin users compared with nonusers (12.24% versus 31.70%). Statin therapy is associated with a reduced risk of MACE in patients with breast cancer undergoing breast-conserving surgery and adjuvant whole breast radiotherapy. Hydrophilic statins rosuvastatin and pravastatin exhibit the most pronounced cardioprotective effects. These findings suggest a potential role for statins in mitigating cardiovascular complications in this population and highlight the need for further research to optimize statin therapy in survivors of breast cancer undergoing radiotherapy.

Beyond low-density lipoprotein cholesterol levels: Impact of prior statin treatment on ischemic stroke outcomes

Although essential for cardiovascular therapy, the pleiotropic effects of statins on ischemic stroke lack clinical evidence. This study examined the effects of statins beyond low-density lipoprotein cholesterol (LDL-C) levels on mortality and stroke severity. A total of 825,874 patients with ischemic stroke were included in this study, of whom 125,650 statin users were 1:1 matched with non-users based on their LDL-C levels (±0.05mmol/L), forming the LDL-C-matched cohort. Associations between preceding statin treatment, in-hospital mortality, and stroke severity (National Institutes of Health Stroke Scale score ≥16) were estimated by multivariate and conditional logistic regression models in overall cohort and LDL-C-matched cohort, respectively. The overall statin effects reduced in-hospital mortality (odds ratio [OR]: 0.72, 95% confidence interval [CI]: 0.65-0.79, p<0.001) and moderate-to-severe stroke (OR: 0.93, 95% CI: 0.90-0.96, p<0.001). After matching for LDL-C levels, the reduction in mortality persisted (OR: 0.63, 95% CI: 0.52-0.77, p<0.001) but not for moderate-to-severe stroke (OR: 0.96, 95% CI: 0.90-1.02, p= 0.215). Stratified by LDL-C levels, the effects of statin beyond LDL-C in reducing mortality remained consistent across all LDL-C ranges but increased with LDL-C reduction for stroke severity and achieved statistical significance at LDL-C <2.60mmol/L. Mediation analyses showed that LDL-C reduction explained 0.35% (95% CI: 0.23-0.93, p= 0.235) of the statin treatment-mortality relationship and 12.47% (95% CI: 6.78-18.16, p<0.001) for moderate-to-severe stroke. When examining the overall statin efficacy, LDL-C <2.60mmol/L was not necessary for mortality reduction but for reducing stroke severity. The efficacy of statins in ischemic stroke outcomes is primarily derived from their effects beyond the LDL-C levels, suggesting that their neuroprotective effects should be considered in addition to their lipid-lowering effects.

Statin use is associated with less ST-elevation versus non-ST-elevation myocardial infarction in a nationwide study

Background and aimsStatin therapy reduces myocardial infarction rate but whether it is associated with a shift of ST-elevation myocardial infarction (STEMI) towards non-ST-elevation myocardial infarction (non-STEMI) remains unknown. Thus, we tested the hypothesis that statin use is associated with less STEMI relative to non-STEMI in first-time myocardial infarction. MethodsIn a nationwide study, including 66,896 patients with first-time myocardial infarction between 2010 and 2021, we obtained multivariable risk estimates for STEMI versus non-STEMI according to any statin use, cumulated statin use, and daily statin dose. Furthermore, we obtained hazard ratios for 60-day mortality (5545 deaths) following myocardial infarction according to type of infarction. ResultsOdds ratios for STEMI versus non-STEMI were 0.81 (95 % CI:0.77–0.85) and 1.07 (1.01–1.13) in current and previous statin users compared to never statin users. Cumulated statin exposure yielded odds ratios of 0.96 (0.87–1.07) for <2 statin-years, 0.87 (0.79–0.95) for 2–4.9 statin-years, 0.80 (0.74–0.87) for 5–10 statin-years, and 0.75 (0.70–0.80) for >10 statin-years compared to never users. Corresponding odds ratios for statin dose intensity were 0.89 (0.84–0.95) for low-intensity, 0.77 (0.73–0.82) for moderate-intensity, and 0.70 (0.63–0.77) for high-intensity. Results were similar in multiple sensitivity analyses and using a cohort design. The hazard ratio for 60-day mortality after first-time STEMI versus non-STEMI was 2.24 (2.13–2.37). ConclusionsIn this nationwide study, prior statin use is associated with less STEMI relative to non-STEMI in a dose dependent manner. This indicates that statin therapy, in addition to reducing myocardial infarction event rates, also result in a less severe presentation of myocardial infarctions.

Association between statin use and immune-related adverse events in patients treated with immune checkpoint inhibitors: analysis of the FAERS database.

Understanding the risk relationship between statin use and immune-related adverse events (irAEs) in patients undergoing immune checkpoint inhibitors (ICIs) therapy is crucial for optimizing oncological management. This study aimed to investigate whether the use of statins increases the risk of irAEs in patients receiving ICI therapy. This study primarily utilized data from FAERS database. Multivariable logistic regression was the principal method of analysis, and the Benjamini-Hochberg procedure was employed to adjust for multiple hypothesis testing. In a group of 145,214 patients undergoing ICI therapy, 9,339 reported using statin medications. Multivariable analysis indicated an increased risk of irAEs among statin users (OR 1.199, 95% CI: 1.141-1.261; FDR p < 0.001) in comparison to those not using statins. Notably, increased risks were observed particularly in patients diagnosed with lung, pancreatic, and renal cancers. The link between statin usage and increased irAEs risk remained consistent across various ICIs treatments. Statin medication usage is linked to an elevated probability of experiencing irAEs in patients enrolled in ICI therapy. In cancer patients receiving immune checkpoint inhibitors, careful consideration of statin use is essential to avoid potentially increased irAEs risk. These findings provide critical guidance for clinicians in developing treatment strategies that balance therapeutic efficacy and safety in oncological management.

Association between statin usage and mortality outcomes in aging U.S. cancer survivors: a nationwide cohort study

BackgroundThe population of Aging cancer survivors in the United States has surged to over 16.9 million. Research on the relationship between statin usage and post-cancer survival rates remains limited.AimsThis study aims to investigate the association between statin use and various causes of mortality among aging cancer survivors.MethodsWe analyzed NHANES data from 1999 to 2018, Statin usage, both hydrophilic and lipophilic, was derived from NHANES prescription records. We utilized Cox proportional hazards models to associate statin utilization with mortality, differentiating causes of death according to statin type and patterns of use.ResultsWithin a cohort of 2,968 participants, statin usage was categorized into non-users (1,738), hydrophilic statin users (216), and lipophilic statin users (982). Compared to those who did not use statins, individuals prescribed hydrophilic statins did not show a reduced risk of all-cause mortality (adjusted hazard ratio [HR] 1.01; 95% confidence interval [CI] 0.72–1.41; P = 0.960), as outlined in Model 3. In contrast, the group receiving lipophilic statins exhibited a notable decrease in all-cause mortality risk (adjusted HR, 0.77; P = 0.003). Nonetheless, both hydrophilic and lipophilic statins were effective in diminishing the risk associated with cancer from its onset until death, with hydrophilic statins showing a greater level of efficacy.DiscussionThe potential of statins to reduce cancer-related mortality may provide avenues for targeted clinical interventions and management strategies.ConclusionsOur study reveals that the use of lipophilic statins is significantly associated with lower all-cause and cancer-cause mortality risks among aging cancer survivors.

Association of PCSK9 inhibitors with mortality: insights from a retrospective cohort analysis.

Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors are effective in reducing cardiovascular events, but their impact on all-cause mortality and medical utilization compared to statins is unclear. This study investigated PCSK9 inhibitor use and its impact on mortality and medical utilization vs. statins, using TriNetX database data with up to 9 years of follow-up. This retrospective cohort study analysed TriNetX data spanning 1 July 2015, to 31 December 2023, including 79194 PCSK9 inhibitor users (alirocumab, evolocumab, inclisiran) and 5437513 statin users with hyperlipidaemia. The primary outcomes were all-cause mortality and medical utilization, including hospital inpatient services, emergency department visits, critical care, and mechanical ventilation. Propensity score matching showed that PCSK9 inhibitor use was associated with a 28.3% lower risk of all-cause mortality [adjusted hazard ratio (aHR) 0.717, 95% confidence interval (CI): 0.673-0.763] and significant reductions in medical utilization (hospital inpatient services usage: aHR 0.692, 95% CI: 0.664-0.721; emergency department services: aHR 0.756, 95% CI: 0.726-0.788; critical care services: aHR 0.619, 95% CI: 0.578-0.664; and mechanical ventilation: aHR 0.537, 95% CI: 0.484-0.596) compared to statins. These findings were consistent across various demographics and clinical subgroups. The sensitivity analyses supported the robustness of the findings. PCSK9 inhibitors significantly reduced all-cause mortality and medical utilization compared to statins, suggesting their important role in dyslipidaemia management, particularly for statin-naïve or intolerant patients. Further research, including randomized controlled trials, is needed to confirm these findings and explore the underlying mechanisms.