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Lipids in Health and Disease Nov 2023Statins are routinely prescribed to lower cholesterol and have been demonstrated to have significant benefits in atherosclerotic cardiovascular disease. However, whether... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Statins are routinely prescribed to lower cholesterol and have been demonstrated to have significant benefits in atherosclerotic cardiovascular disease. However, whether statin therapy has effects on cancer risk remains controversial. In this study, we investigated the influence of statin therapy on cancer incidence and mortality by conducting a comprehensive meta-analysis of randomized controlled trials.
METHODS
Systematic searches by Cochrane, Embase, Medline, and PubMed were performed to locate data from eligible randomized controlled trials related to statin therapy and oncology. Our main endpoints were cancer incidence and mortality. Fixed-effects models were used in this study.
RESULTS
This meta-analysis comprised thirty-five randomized controlled studies. Twenty-eight included studies reported cancer incidence, and eighteen reported cancer mortality. The pooled results indicated no reduction in cancer incidence with statins compared to placebo [OR = 0.99, 95% CI (0.95, 1.03)]. In addition, statins did not decrease cancer mortality [OR = 0.99, 95% CI (0.91, 1.07)]. This study also performed a number of subgroup analyses, which showed no effect of statins on cancer subtypes such as genitourinary and breast cancer. Neither the type of statin nor long-term treatment with statins had an effect on cancer incidence and mortality.
CONCLUSION
Through comprehensive analysis, we found that statin therapy does not reduce cancer incidence or mortality while protecting the cardiovascular system.
TRIAL REGISTRATION
Prospero CRD42022377871.
Topics: Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Cholesterol; Atherosclerosis; Neoplasms; Risk
PubMed: 37950285
DOI: 10.1186/s12944-023-01955-4 -
Annals of Hematology Mar 2024The VEXAS syndrome, a genetically defined autoimmune disease, associated with various hematological neoplasms has been attracting growing attention since its initial...
The VEXAS syndrome, a genetically defined autoimmune disease, associated with various hematological neoplasms has been attracting growing attention since its initial description in 2020. While various therapeutic strategies have been explored in case studies, the optimal treatment strategy is still under investigation and allogeneic cell transplantation is considered the only curative treatment. Here, we describe 2 patients who achieved complete molecular remission of the underlying UBA1 mutant clone outside the context of allogeneic HCT. Both patients received treatment with the hypomethylating agent azacitidine, and deep molecular remission triggered treatment de-escalation and even cessation with sustained molecular remission in one of them. Prospective studies are necessary to clarify which VEXAS patients will benefit most from hypomethylating therapy and to understand the variability in the response to different treatment strategies.
Topics: Humans; Antimetabolites, Antineoplastic; Prospective Studies; Myelodysplastic Syndromes; Azacitidine; Pathologic Complete Response; Skin Diseases, Genetic
PubMed: 38214707
DOI: 10.1007/s00277-023-05611-w -
JAMA Network Open Nov 2023Several studies have reported an association between the use of statins and breast cancer (BC) mortality. However, most of these studies did not take into account the...
IMPORTANCE
Several studies have reported an association between the use of statins and breast cancer (BC) mortality. However, most of these studies did not take into account the underlying cholesterol level.
OBJECTIVE
To investigate the association between serum cholesterol, statin use, and BC mortality.
DESIGN, SETTING, AND PARTICIPANTS
This cohort study included females with invasive BC that was newly diagnosed between January 1, 1995, and December 31, 2013, in Finland. The cohort had available hormone receptor data and at least 1 cholesterol measurement. All data were obtained from Finnish national registries. Statistical analyses were performed from January to May 2022.
EXPOSURE
Use of statins; statin dose; and serum cholesterol, low-density lipoprotein, high-density lipoprotein, and triglyceride levels measured separately before and after BC diagnosis.
MAIN OUTCOMES AND MEASURES
Breast cancer mortality and overall mortality between date of BC diagnosis and December 31, 2015.
RESULTS
A total of 13 378 female patients with BC (median [IQR] age, 62 [54-69] years) participated in the study. The median (IQR) follow-up was 4.5 (2.4-9.8) years after BC diagnosis, during which 16.4% of patients died and 7.0% died of BC. Prediagnostic statin use was a risk factor for BC death even after adjustment for total cholesterol level (hazard ratio [HR], 1.22; 95% CI, 1.02-1.46; P = .03). Reduced risk for BC death was seen for postdiagnostic statin use (HR, 0.85; 95% CI, 0.73-1.00; P = .05). The risk reduction was robust in participants whose cholesterol level decreased after starting statins (HR, 0.49; 95% CI, 0.32-0.75; P = .001) but was nonsignificant if cholesterol level did not subsequently decrease (HR, 0.69; 95% CI, 0.34-1.40; P = .30). Reduced BC mortality among statin users was also observed in females with estrogen receptor-positive tumors (HR, 0.82; 95% CI, 0.68-0.99; P = .03). Overall mortality was lower among statin users vs nonusers when adjusted for serum cholesterol level (HR, 0.80; 95% CI, 0.72-0.88; P < .001).
CONCLUSIONS AND RELEVANCE
Results of this cohort study showed that postdiagnostic use of statins was associated with reduced BC mortality compared with nonuse, and the risk was associated with subsequent change in serum cholesterol level. This finding suggests that cholesterol-lowering interventions with statins may be beneficial for patients with BC.
Topics: Humans; Female; Middle Aged; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Cohort Studies; Breast Neoplasms; Proportional Hazards Models; Cholesterol
PubMed: 37976058
DOI: 10.1001/jamanetworkopen.2023.43861 -
Journal of the American Heart... Nov 2023Background Information on the real-world use of proprotein convertase subtilisin kexin 9 inhibitors (PCKS9is) in familial hypercholesterolemia are limited. We evaluated...
Real-World Effectiveness of PCSK9 Inhibitors in Reducing LDL-C in Patients With Familial Hypercholesterolemia in Italy: A Retrospective Cohort Study Based on the AIFA Monitoring Registries.
Background Information on the real-world use of proprotein convertase subtilisin kexin 9 inhibitors (PCKS9is) in familial hypercholesterolemia are limited. We evaluated the pattern of prescription and the long-term efficacy of alirocumab and evolocumab in Italian patients with familial hypercholesterolemia in clinical practice. Methods and Results The data set for analysis was extracted from the PCKS9i Italian Medicines Agency (AIFA) registry and included 2484 patients with heterozygous familial hypercholesterolemia (HeFH) and 62 patients with homozygous familial hypercholesterolemia (HoFH) who were prescribed PCKS9is from February 2017 to December 2021. As the follow-up schedules were not prespecified and could vary, persistence and adherence as well as low-density lipoprotein cholesterol (LDL-C) changes during 2 years of treatment were analyzed in a final cohort of 1299 patients with familial hypercholesterolemia. At baseline, 53.8% of patients with HeFH and 69.4% of patients with HoFH were receiving maximally tolerated lipid-lowering therapies, while 45.9% of patients with HeFH and 30.7% of patients with HoFH reported statin intolerance; mean LDL-C was 197.7±52.3 mg/dL in HeFH and 252.0±106.2 mg/dL in HoFH. The 6-month persistence and adherence to therapy were >85%, and LDL-C reduction reached 58.6% (to 79.7 mg/dL) in HeFH and 57.6% (to 95.1 mg/dL) in HoFH after 24 months of treatment. The European Atherosclerosis Society/European Society of Cardiology LDL-C goals were achieved in 43.3% of patients with HeFH and 37.5% of patients with HoFH. Conclusions PCKS9i prescribed to patients with familial hypercholesterolemia in clinical practice showed LDL-C-lowering efficacy similar to that observed in controlled trials. However, 2 of 5 HeFH cases and 2 of 6 HoFH cases achieved the recommended LDL-C goals. The full achievement of European Atherosclerosis Society/European Society of Cardiology LDL-C goals should require a lower threshold for PCKS9i initiation and a combination of multiple therapies.
Topics: Humans; PCSK9 Inhibitors; Cholesterol, LDL; Proprotein Convertase 9; Homozygous Familial Hypercholesterolemia; Retrospective Studies; Hyperlipoproteinemia Type II; Hypercholesterolemia; Atherosclerosis; Anticholesteremic Agents
PubMed: 37850449
DOI: 10.1161/JAHA.122.026550 -
JAMA Network Open Aug 2023Many patients with coronary artery disease (CAD) do not achieve the guideline-directed goals for low-density lipoprotein cholesterol (LDL-C) levels. (Observational Study)
Observational Study
IMPORTANCE
Many patients with coronary artery disease (CAD) do not achieve the guideline-directed goals for low-density lipoprotein cholesterol (LDL-C) levels.
OBJECTIVE
To estimate reductions in the rates of adverse events associated with CAD in a large US military veteran population that may be achieved through use of optimized statin therapy alone or with ezetimibe compared with the prevailing lipid-lowering therapy (LLT).
DESIGN, SETTING, AND PARTICIPANTS
In this observational cohort study, US military veterans with CAD were identified by coronary angiography between June 2015 and September 2020 across 82 US Department of Veterans Affairs health care facilities.
EXPOSURES
The exposures were observed LLT, LLT with an optimized statin regimen, and LLT with optimized statin and ezetimibe.
MAIN OUTCOMES AND MEASURES
Observed rates of death, myocardial infarction, stroke, and coronary revascularization, and potential reductions in those outcomes with optimized LLT based on expected further reductions in LDL-C levels and application of formulas from The Cholesterol Treatment Trialists' Collaboration.
RESULTS
The analysis cohort comprised 111 954 veterans (mean [SD] age, 68.4 [8.8] years; 109 390 men [97.7%]; 91 589 White patients [81.8%]; 17 592 Black patients [15.7%]). The median (IQR) observation period for this study was 3.4 (2.1-4.0) years. At the time of index angiography, 66 877 patients (59.7%) were treated with statin therapy, and 623 patients (0.6%) were treated with ezetimibe. At 6 months, the number of patients with statin prescriptions increased to 74 400 (68.7%), but the number of patients with high-intensity statin prescriptions was only 57 297 (52.9%). At 6 months, ezetimibe use remained low (n = 1168 [1.1%]), and LDL-C levels were 70 mg/dL or more in 56 405 patients (52.1%). At 4 years, observed incidences of death, myocardial infarction, stroke, and coronary revascularization were 21.6% (95% CI, 21.3%-21.8%), 5.0% (95% CI, 4.9%-5.2%), 2.2% (95% CI, 2.1%-2.3%), and 15.4% (95% CI, 15.2%-15.7%), respectively. With optimized statin treatment, projected absolute reductions in these incidences were 1.3% (95% CI, 0.9%-1.7%), 0.8% (95% CI, 0.7%-1.0%), 0.2% (95% CI, 0.1%-0.3%), and 2.3% (95% CI, 2.0%-2.7%), respectively. With optimized statin and ezetimibe treatment, projected absolute reductions were 1.8% (95% CI, 1.2%-2.4%), 1.1% (95% CI, 0.9%-1.3%), 0.3% (95% CI, 0.2%-0.4%), and 3.1% (95% CI, 2.6%-3.6%), respectively.
CONCLUSIONS AND RELEVANCE
In this cohort study of veterans with CAD, suboptimal LLT was prevalent in the clinical setting. Optimization of statin therapy was projected to produce clinically relevant reductions in the risks of death and cardiovascular events. Despite a lesser lipid-lowering efficacy of ezetimibe, its widespread use on a population level in conjunction with optimized statin therapy may be associated with further meaningful reductions in cardiovascular risk.
Topics: United States; Male; Humans; Aged; Coronary Artery Disease; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Veterans; Cholesterol, LDL; Cohort Studies; Myocardial Infarction; Ezetimibe
PubMed: 37638630
DOI: 10.1001/jamanetworkopen.2023.29066 -
Current Medicinal Chemistry 2024Previous studies have found a potential role for statins in liver cancer prevention. (Meta-Analysis)
Meta-Analysis
BACKGROUND
Previous studies have found a potential role for statins in liver cancer prevention.
OBJECTIVE
This study aimed to explore the effect of different types of statins on the incidence of liver cancer.
METHODS
Relevant articles were systematically retrieved from PubMed, EBSCO, Web of Science, and Cochrane Library databases from inception until July 2022 to explore the relationship between lipophilic statins or hydrophilic statins exposure and the incidence of liver cancer. The main outcome was the incidence of liver cancer.
RESULTS
Eleven articles were included in this meta-analysis. The pooled results showed a reduced incidence of liver cancer in patients exposed to lipophilic statins (OR=0.54, p < 0.001) and hydrophilic statins (OR=0.56, p < 0.001) compared with the non-exposed cohort. Subgroup analysis showed that both exposures to lipophilic (Eastern countries: OR=0.51, p < 0.001; Western countries: OR=0.59, p < 0.001) and hydrophilic (Eastern countries: OR=0.51, p < 0.001; Western countries: OR=0.66, p=0.019) statins reduced the incidence of liver cancer in Eastern and Western countries, and the reduction was most significant in Eastern countries. Moreover, atorvastatin (OR=0.55, p < 0.001), simvastatin (OR=0.59, p < 0.001), lovastatin (OR=0.51, p < 0.001), pitavastatin (OR=0.36, p=0.008) and rosuvastatin (OR=0.60, p=0.027) could effectively reduce the incidence of liver cancer, unlike fluvastatin, cerivastatin and pravastatin.
CONCLUSION
Both lipophilic and hydrophilic statins contribute to the prevention of liver cancer. Moreover, the efficacy was influenced by the region and the specific type of statins used.
Topics: Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Incidence; Simvastatin; Lovastatin; Liver Neoplasms
PubMed: 37393552
DOI: 10.2174/0929867330666230701000400 -
Stroke Aug 2023Whether a strategy to target an LDL (low-density lipoprotein) cholesterol <70 mg/dL is more effective when LDL is reduced >50% from baseline rather than <50% from... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Whether a strategy to target an LDL (low-density lipoprotein) cholesterol <70 mg/dL is more effective when LDL is reduced >50% from baseline rather than <50% from baseline has not been investigated.
METHODS
The Treat Stroke to Target trial was conducted in France and South Korea in 61 sites between March 2010 and December 2018. Patients with ischemic stroke in the previous 3 months or transient ischemic attack within the previous 15 days and evidence of cerebrovascular or coronary artery atherosclerosis were randomly assigned to a target LDL cholesterol of <70 mg/dL or 100±10 mg/dL, using statin and/or ezetimibe as needed. We used the results of repeated LDL measurements (median, 5 [2-6] per patient) during 3.9 years (interquartile range, 2.1-6.8) of follow-up. The primary outcome was the composite of ischemic stroke, myocardial infarction, new symptoms requiring urgent coronary or carotid revascularization, and vascular death. Cox regression model including lipid-lowering therapy as a time-varying variable, after adjustment for randomization strategy, age, sex, index event (stroke or transient ischemic attack), and time since the index event.
RESULTS
Among 2860 patients enrolled, patients in the lower target group who had >50% LDL cholesterol reduction from baseline during the trial had a higher baseline LDL cholesterol and a lower LDL cholesterol achieved as compared to patients who had <50% LDL cholesterol reduction (155±32 and 62 mg/dL versus 121±34 and 74 mg/dL, respectively, <0.001 for both). In the <70 mg/dL target group, patients with >50% LDL reduction had a significant reduction in the primary outcome as compared to the higher target group (hazard ratio, 0.61 [95% CI, 0.43-0.88]; =0.007) and patients with <50% LDL reduction from baseline had little reduction (hazard ratio, 0.96 [95% CI, 0.73-1.26]; =0.75).
CONCLUSIONS
In this post hoc analysis of the TST trial, targeting an LDL cholesterol of <70 mg/dL reduced the risk of primary outcome compared with 100±10 mg/dL provided LDL cholesterol reduction from baseline was superior to 50%, thereby suggesting that the magnitude of LDL cholesterol reduction was as important to consider as the target level to achieve.
REGISTRATION
URL: https://www.
CLINICALTRIALS
gov; Unique identifier: NCT01252875. URL: https://clinicaltrialsregister.eu; Unique identifier: EUDRACT2009-A01280-57.
Topics: Humans; Cholesterol, LDL; Ischemic Attack, Transient; Stroke; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Ischemic Stroke; Anticholesteremic Agents; Treatment Outcome
PubMed: 37376989
DOI: 10.1161/STROKEAHA.123.042621 -
The Korean Journal of Internal Medicine Nov 2023Dyslipidemia is a significant risk factor for atherosclerotic cardiovascular disease (ASCVD), and statins are the primary therapeutic options for reducing low-density... (Review)
Review
Dyslipidemia is a significant risk factor for atherosclerotic cardiovascular disease (ASCVD), and statins are the primary therapeutic options for reducing low-density lipoprotein cholesterol (LDL-C) levels. However, it can be challenging to achieve optimal LDL-C goals with statin monotherapy. Ezetimibe, a cholesterol absorption inhibitor, offers a potential non-statin therapy to optimize LDL-C management. Key clinical trials, such as IMPROVE-IT and RACING, have demonstrated that the addition of ezetimibe to statin therapy leads to further decreases in LDL-C or significant decreases in major adverse cardiovascular events (MACEs), particularly in patients with high ASCVD risk. Subsequent meta-analyses and clinical trials have further supported the beneficial effect of ezetimibe, suggesting additive decreases in LDL-C and MACEs, as well as pleiotropic effects. This review provides a comprehensive analysis of the clinical implications of ezetimibe for managing dyslipidemia; it also evaluates the available evidence that supports the role of ezetimibe as an adjunct non-statin therapy for long-term use. However, the long-term pleiotropic effects of ezetimibe remain controversial because of limited clinical data. Therefore, additional research is needed to clarify its potential benefits beyond LDL-C reduction. Nonetheless, an understanding of the role of ezetimibe in dyslipidemia management will help clinicians to develop effective treatment strategies.
Topics: Humans; Ezetimibe; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Cholesterol, LDL; Anticholesteremic Agents; Dyslipidemias; Drug Therapy, Combination; Treatment Outcome
PubMed: 37866817
DOI: 10.3904/kjim.2023.243 -
Drugs Feb 2024Increased plasma levels of low-density lipoprotein cholesterol (LDL-C) are causally associated with atherosclerotic cardiovascular disease (ASCVD), and statins that... (Review)
Review
Increased plasma levels of low-density lipoprotein cholesterol (LDL-C) are causally associated with atherosclerotic cardiovascular disease (ASCVD), and statins that lower LDL-C have been the cornerstone of ASCVD prevention for decades. However, guideline-recommended LDL-C targets are not achieved in about 60% of statin users. Proprotein convertase subtilisin/kexin type 9 (PCSK9)-targeted therapy effectively lowers LDL-C levels and has been shown to reduce ASCVD risk. A growing body of scientific and clinical evidence shows that PCSK9-targeted therapy offers an excellent safety and tolerability profile with a low incidence of side effects in the short term. In this review, we present and discuss the current clinical and scientific evidence pertaining to the long-term efficacy and tolerability of PCSK9-targeted therapy.
Topics: Humans; Proprotein Convertase 9; Cholesterol, LDL; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Atherosclerosis; Anticholesteremic Agents
PubMed: 38267805
DOI: 10.1007/s40265-024-01995-9 -
Cancer Immunology, Immunotherapy : CII Nov 2023Concomitant medications may potentially affect the outcome of cancer patients. In this sub-analysis of the ARON-2 real-world study (NCT05290038), we aimed to assess the...
Use of concomitant proton pump inhibitors, statins or metformin in patients treated with pembrolizumab for metastatic urothelial carcinoma: data from the ARON-2 retrospective study.
BACKGROUND
Concomitant medications may potentially affect the outcome of cancer patients. In this sub-analysis of the ARON-2 real-world study (NCT05290038), we aimed to assess the impact of concomitant use of proton pump inhibitors (PPI), statins, or metformin on outcome of patients with metastatic urothelial cancer (mUC) receiving second-line pembrolizumab.
METHODS
We collected data from the hospital medical records of patients with mUC treated with pembrolizumab as second-line therapy at 87 institutions from 22 countries. Patients were assessed for overall survival (OS), progression-free survival (PFS), and overall response rate. We carried out a survival analysis by a Cox regression model.
RESULTS
A total of 802 patients were eligible for this retrospective study; the median follow-up time was 15.3 months. PPI users compared to non-users showed inferior PFS (4.5 vs. 7.2 months, p = 0.002) and OS (8.7 vs. 14.1 months, p < 0.001). Concomitant PPI use remained a significant predictor of PFS and OS after multivariate Cox analysis. The use of statins or metformin was not associated with response or survival.
CONCLUSIONS
Our study results suggest a significant prognostic impact of concomitant PPI use in mUC patients receiving pembrolizumab in the real-world context. The mechanism of this interaction warrants further elucidation.
Topics: Humans; Proton Pump Inhibitors; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Metformin; Carcinoma, Transitional Cell; Retrospective Studies; Urinary Bladder Neoplasms
PubMed: 37676282
DOI: 10.1007/s00262-023-03518-z