Abstract TP439: Statin Treatment and Prevalent Cerebral Microbleeds: A Systematic Review and Meta-Analysis

Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Aristeidis H Katsanos ◽  
Vasileios-Arsenios Lioutas ◽  
Andreas Charidimou ◽  
Luciana Catanese ◽  
Kelvin K Ng ◽  
...  

Introduction: Statins have been reported to increase the risk of intracererbral hemorrhage, however their effects on cerebral microbleeds (CMBs) formation is not well understood. We systematically reviewed previously published studies to pool adjusted and unadjusted estimates of the association between prevalent CMBs and current statin use. Methods: We performed a systematic search in MEDLINE and SCOPUS databases on July 28 th , 2019 to identify all cohorts from randomized clinical trials or observational studies reporting CMB prevalence and statin use. We extracted cross-sectional data on CMBs presence, as provided by each study, in association to the history of current statin use. Associations are reported as odds ratios (ORs) with corresponding 95% confidence intervals (95%CI). Random effects model was used to calculate the pooled estimates. Results: We included 7 studies (n=3671 participants): unselected general population [n=1965], ischemic stroke [n=770], hemorrhagic stroke [n=252], hypertension [n=605] or neuroimaging based studies [n=72]. Statin use was not associated with CMBs presence in either unadjusted (OR=1.15, 95%CI: 0.76-1.74) or adjusted analyses (OR=1.01, 95%CI: 0.62-1.64). Statin use was more strongly related to lobar CMB presence (OR=2.01, 95%CI: 1.48-2.72) in unadjusted analysis. The effect size of this association was consistent, but no longer statistically significant in adjusted analysis that was confined to two eligible studies (OR=2.26, 95%CI: 0.86-5.91). Except for the analysis on the unadjusted probability of CMBs presence, considerable heterogeneity was present in all other analyses (I 2 >60%). Conclusion: Our findings suggest that statin treatment is not associated with CMBs overall, but may increase the risk of lobar CMB formation. This hypothesis deserves further investigation within magnetic resonance imaging ancillary studies of randomized trials.

BMJ ◽  
2021 ◽  
pp. n48
Author(s):  
Yuanxi Jia ◽  
Jiajun Wen ◽  
Riaz Qureshi ◽  
Stephan Ehrhardt ◽  
David D Celentano ◽  
...  

Abstract Objective To identify redundant clinical trials evaluating statin treatment in patients with coronary artery disease from mainland China, and to estimate the number of extra major adverse cardiac events (MACEs) experienced by participants not treated with statins in those trials. Design Cross sectional study. Setting 2577 randomized clinical trials comparing statin treatment with placebo or no treatment in patients with coronary artery disease from mainland China, searched from bibliographic databases to December 2019. Participants 250 810 patients with any type of coronary artery disease who were enrolled in the 2577 randomized clinical trials. Main outcome measures Redundant clinical trials were defined as randomized clinical trials that initiated or continued recruiting after 2008 (ie, one year after statin treatment was strongly recommended by clinical practice guidelines). The primary outcome is the number of extra MACEs that were attributable to the deprivation of statins among patients in the control groups of redundant clinical trials—that is, the number of extra MACEs that could have been prevented if patients were given statins. Cumulative meta-analyses were also conducted to establish the time points when statins were shown to have a statistically significant effect on coronary artery disease. Results 2045 redundant clinical trials were identified published between 2008 and 2019, comprising 101 486 patients in the control groups not treated with statins for 24 638 person years. 3470 (95% confidence interval 3230 to 3619) extra MACEs were reported, including 559 (95% confidence interval 506 to 612) deaths, 973 (95% confidence interval 897 to 1052) patients with new or recurrent myocardial infarction, 161 (132 to 190) patients with stroke, 83 (58 to 105) patients requiring revascularization, 398 (352 to 448) patients with heart failure, 1197 (1110 to 1282) patients with recurrent or deteriorated angina pectoris, and 99 (95% confidence interval 69 to 129) unspecified MACEs. Conclusions Of more than 2000 redundant clinical trials on statins in patients with coronary artery disease identified from mainland China, an extra 3000 MACEs, including nearly 600 deaths, were experienced by participants not treated with statins in these trials. The scale of redundancy necessitates urgent reform to protect patients.


Circulation ◽  
2014 ◽  
Vol 129 (suppl_1) ◽  
Author(s):  
Elena Salmoirago-Blotcher ◽  
Kathleen M Hovey ◽  
Judith K Ockene ◽  
Chris A Andrews ◽  
Jennifer Robinson ◽  
...  

Background: Statin therapy is recommended for treatment of hypercholesterolemia and prevention of cardiovascular events. Concerns have been raised about a potentially higher risk of hemorrhagic stroke in statin users; however, there is limited information in women and in older populations. We evaluated whether statin treatment was associated with increased risk of hemorrhagic stroke among women enrolled in the Women’s Health Initiative (WHI). Methods: This secondary data analysis was conducted among 68,132 women enrolled in the WHI Clinical Trials (CTs). Participants were 50 to 79 yrs old; postmenopausal; and were followed through 2005 (parent study) and for an additional 5 yrs (through September 30, 2010) in the WHI extension study. Statin use was assessed at baseline and at follow-up (FU) visits at 1, 3, 6, and 9 years. Women brought all medications in original containers for inventory. Strokes were self-reported annually and adjudicated by medical record review. Risk of hemorrhagic stroke by statin use (modeled as a time-varying covariate, with the “no use” category as the referent) was estimated from Cox proportional hazard regression models adjusted for age (model 1); risk factors for hemorrhagic stroke (model 2); and possible confounders by indication (model 3). All models adjusted for enrollment in the different CTs and in the extension study. Participants were censored at the date of last contact or loss to FU. Pre-specified subgroup analyses were conducted according to use or non-use of antiplatelet medications (including aspirin) or anticoagulants, and prior history of stroke. Results: Final models included 67,882 women (mean age at baseline 63 ± 7 yrs). Over a mean FU of 12 yrs, incidence rates of hemorrhagic stroke were 6.4/10,000 person-years among women on statins and 5.0/10,000 person-years among women not taking statins. The unadjusted risk of hemorrhagic stroke in statin users vs. non-users was 1.21 (CI: 0.96, 1.53). The HR was attenuated to 0.98 (CI: 0.76, 1.26) after adjusting for age, hypertension, and other risk factors for hemorrhagic stroke. Planned subgroups analyses showed that women taking both statins and antiplatelet agents had a higher risk of hemorrhagic stroke than women taking antiplatelet medications without statins (HR: 1.59; CI: 1.02, 2.46), whereas women not taking antiplatelet medications had no risk elevation with statins (HR=0.79; CI: 0.58-1.08); P for interaction = .01. No significant interactions were found for anticoagulant use or prior history of stroke, but the statistical power for these analyses was low. Conclusion: Statin use was not associated with an overall increased risk of hemorrhagic stroke among older community-dwelling women. However, women taking statins in conjunction with antiplatelet medications had elevated risk; a finding that warrants further study and potential incorporation into clinical decision making.


2021 ◽  
Vol 8 ◽  
Author(s):  
Shuang Wang ◽  
Yun-Feng Cao ◽  
Xiao-Yu Sun ◽  
Mo Hong ◽  
Zhong-Ze Fang ◽  
...  

Objective: The objective of the study was to investigate the relationship of amino acid metabolism with hypertriglyceridemia in diabetic patients under statins free of prior cardiovascular diseases.Methods: Two independent cross-sectional hospital based cohorts, i.e., Liaoning Medical University First Affiliated Hospital (LMUFAH, n = 146) and the Second Affiliated Hospital of Dalian Medical University (SAHDMU, n = 294) were included in the current analysis. Hypertriglyceridemia was defined as triglyceride ≥1.7 mmol/L, and well-controlled LDL-C was defined as <2.6 mmol/L. The adjusted ORs (95% CI) of circulating metabolic measures for hypertriglyceridemia were assessed using logistic regression. Pooled results of metabolites with the same direction of association in both cohorts were combined using inverse variance-weighted fixed-effect meta-analysis. Difference of identified metabolites in patients with and without hypertriglyceridemia were also obtained in the context of LDL-C.Results: Patients, 86 and 106, were with hypertriglyceridemia in LMUFAH and SAHDMU, respectively. We observed that elevated alanine, asparagine, leucine, and valine were consistently associated with increased hypertriglyceridemia in both cohorts. In fixed-effect pooled analysis, the OR (95% CI) per SD increase was 1.71 (1.32–2.20) for alanine, 1.62 (1.20–2.19) for asparagine, 1.64 (1.22–2.20) for leucine, and 1.62 (1.22–2.13) for valine (all P values ranged from 0.0018 to <0.0001); adjusting for C-peptide attenuated effect sizes of Ala, Leu, and Val for hypertriglyceridemia. The difference were robust in groups with well- or bad-controlled LDL-C.Conclusion: Among 23 amino acids, alanine, asparagine, leucine, and valine were positively associated with increased residual risk of hypertriglyceridemia in diabetic patients with statin treatment.


Circulation ◽  
2015 ◽  
Vol 131 (suppl_1) ◽  
Author(s):  
Quanhe Yang ◽  
Yuna Zhong ◽  
Catheen Gillespie ◽  
Robert Merritt ◽  
Barbara Bowman ◽  
...  

Introduction: American College of Cardiology/American Heart Association (ACC/AHA) new cholesterol treatment guidelines recommend consideration of statin treatment for a larger proportion of population for the primary prevention of atherosclerotic cardiovascular disease (ASCVD). It is important to assess the population impact of statin treatment under these new guidelines. Hypothesis: We assessed the hypothesis that increased statin use for the primary prevention of ASCVD might be accompanied by adverse effects among population. Methods: We used 2010 US Census, Multiple Cause Mortality, Third National Health and Nutrition Examination Survey Linked Mortality File (NHANES III 1988-2006, n=7095) and NHANES 2005-2010 (n=3178) participants 40-75 years of age to estimate prevalence of statin use, annual ASCVD deaths prevented and excess adverse effects by age, sex, and race/ethnicity if everyone followed updated guidelines. Results: Among 33.0 million adults aged 40-75 years meeting new guidelines for primary prevention of ASCVD (12.4 million with diabetes and 20.6 without diabetes but with a predicted 10-year ASCVD risk ≥7.5% and 70 ≤ low-density lipoprotein (LDL) ≤189 mg/dL), 26.9% (8.8 million) were on statins, indicating an additional 24.2 million potentially eligible for statin treatment (7.7 million with diabetes and 16.5 million without). Among the 7.7 million with diabetes, assuming 100% statin use, expected annual ASCVD deaths prevented were 2,514 (95% CI 592-4,142) and number-needed-to-treat (NNT) was 3,063 (1,860-13,017). The additional cases of myopathy based on estimates from randomized clinical trials (RCT) was 482 (0-2239) and number-needed-to-harm (NNH) was 15,992 (3,440-∞), and was 11,801 (9,251-14,916) and NNH 653 (516-833) based on estimates from population-based studies. Among 16.5 million without diabetes, ASCVD deaths prevented were 5,425 (1,276-8,935) with NNT 3,039 (1,845-12,914). The additional diabetes cases were 16,406 (4,922-26,250) with NNH 1,005 (628-3,349). Additional cases of myopathy was 1,030 (0-4,791) with NNH 15,996 3,441-∞) based on RCT estimates, and 24,302 (19,363-30,292) with NNH 678 (544-851) for population-based studies. ASCVD deaths prevented increased with age and >70% of ASCVD deaths prevented would occur among adults aged ≥60 years. Conclusions: Under ACC/AHA new guidelines for primary prevention of ASCVD by statin, assuming all those eligible took a statin, up to 12.6% of annual ASCVD deaths could be prevented, but could be accompanied by additional cases of diabetes and myopathy.


Stroke ◽  
2020 ◽  
Vol 51 (6) ◽  
pp. 1662-1666 ◽  
Author(s):  
Damianos G. Kokkinidis ◽  
Nikos Zareifopoulos ◽  
Christina A. Theochari ◽  
Angelos Arfaras-Melainis ◽  
Christos A. Papanastasiou ◽  
...  

Background and Purpose— Atrial fibrillation (AF) is the most common chronic arrhythmia. Dementia and cognitive impairment (CI) are major burdens to public health. The prevalence of all 3 entities is projected to increase due to population aging. Previous reports have linked AF with a higher risk of CI and dementia in patients without prior stroke. Stroke is known to increase the risk for dementia and CI. It is unclear if AF in patients with history of stroke can further increase the risk for dementia or CI. Our purpose was to evaluate the impact of AF on risk for dementia or CI among patients with history of stroke. Methods— Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines were followed. Pubmed, Scopus, and Cochrane central were searched. The outcomes of interest were dementia, CI, and the composite end point of dementia or CI. A random-effect model meta-analysis was performed. Meta-regression analysis was also performed. Publication bias was assessed with the Egger test and with funnel plots. Results— Fourteen studies and 14 360 patients (1363 with AF) were included in the meta-analysis. In the meta-analysis of adjusted odds ratio, AF was associated with increased risk of CI (odds ratio, 1.60 [95% CI, 1.20–2.14]), dementia (odds ratio, 3.11 [95% CI, 2.05–4.73]), and the composite end point of CI or dementia (odds ratio, 2.26 [95% CI, 1.61–3.19]). The heterogeneity for the composite end point of dementia or CI was moderate (adjusted analysis). The heterogeneity for the analysis of the end point of CI only was substantial in the unadjusted analysis and moderate in the adjusted analysis. The heterogeneity for the end point of dementia only was moderate in the unadjusted analysis and zero in the adjusted analysis. Conclusions— Our results indicate that an association between AF and CI or dementia is patients with prior strokes is possible given the persistent positive associations we noticed in the unadjusted and adjusted analyses. The heterogeneity levels limit the certainty of our findings.


2019 ◽  
Vol 34 (8) ◽  
pp. 1607-1614 ◽  
Author(s):  
Morten Rix Hansen ◽  
Asbjørn Hróbjartsson ◽  
Anton Pottegård ◽  
Per Damkier ◽  
Kasper Søltoft Larsen ◽  
...  

2020 ◽  
Vol 14 ◽  
pp. 175346662093719
Author(s):  
Ching-Yi Chen ◽  
Wang-Chun Chen ◽  
Chi-Hsien Huang ◽  
Yi-Ping Hsiang ◽  
Chau-Chyun Sheu ◽  
...  

Background: Long-acting muscarinic antagonist (LAMA) monotherapy is recommended for chronic obstructive pulmonary disease (COPD) patients with high risk of exacerbations. It is unclear whether long-acting β2-agonist (LABA)/LAMA fixed-dose combinations (FDCs) are more effective than LAMAs alone in preventing exacerbations. The aim of this study was to systematically review the literature to investigate whether LABA/LAMA FDCs are more effective than LAMA monotherapy in preventing exacerbations. Methods: We searched several databases and manufacturers’ websites to identify relevant randomized clinical trials comparing LABA/LAMA FDC treatment with LAMAs alone ⩾24 weeks. Outcomes of interest were time to first exacerbation and rates of moderate to severe, severe and all exacerbations. Results: We included 10 trials in 9 articles from 2013 to 2018 with a total of 19,369 patients for analysis in this study. Compared with LAMA monotherapy, LABA/LAMA FDCs demonstrated similar efficacy in terms of time to first exacerbation [hazard ratio, 0.96; 95% confidence interval (CI) 0.79–1.18; p = 0.71], moderate to severe exacerbations [risk ratio (RR), 0.96; 95% CI 0.90–1.03; p = 0.28], severe exacerbations (RR, 0.92; 95% CI 0.81–1.03; p = 0.15), and a marginal superiority in terms of all exacerbations (RR, 0.92; 95% CI 0.86–1.00; p = 0.04). The incidence of all exacerbation events was lower in the LABA/LAMA FDC group for the COPD patients with a history of previous exacerbations and those with a longer treatment period (52–64 weeks). Conclusion: This study provides evidence that LABA/LAMA FDCs are marginally superior in the prevention of all exacerbations compared with LAMA monotherapy in patients with COPD. The reviews of this paper are available via the supplemental material section.


2019 ◽  
Vol 7 (1) ◽  
pp. 21 ◽  
Author(s):  
Mohammad Imani ◽  
Hamid Mozaffari ◽  
Mazaher Ramezani ◽  
Masoud Sadeghi

Nickel and chromium ions released from fixed orthodontic appliances may act as allergens. This study aimed to systematically review the effect of fixed orthodontic treatment on salivary levels of these ions by doing a meta-analysis on cross-sectional and cohort studies. The Web of Science, Scopus, Cochrane Library, and PubMed databases were searched for articles on salivary profile of nickel or chromium in patients under fixed orthodontic treatment published from January 1983 to October 2017. A random-effect meta-analysis was done using Review Manager 5.3 to calculate mean difference (MD) and 95% confidence interval (CI), and the quality of questionnaire was evaluated by the Newcastle–Ottawa scale. Fourteen studies were included and analyzed in this meta-analysis. Salivary nickel level was higher in periods of 10 min or less (MD = −11.5 µg/L, 95% CI = −16.92 to −6.07; P < 0.0001) and one day (MD = −1.38 µg/L, 95% CI = −1.97 to −0.80; P < 0.00001) after initiation of treatment compared to baseline (before the insertion of appliance). Salivary chromium level was higher in periods of one day (MD = −6.25 µg/L, 95% CI = −12.00 to −0.49; P = 0.03) and one week (MD = −2.07 µg/L, 95% CI = −3.88 to −0.26; P = 0.03) after the initiation of treatment compared to baseline. Corrosion of fixed orthodontic appliances leads to elevated salivary nickel and chromium concentrations early after initiation of orthodontic treatment. Randomized clinical trials controlling for factors affecting the saliva composition are recommended on a higher number of patients and among different ethnicities.


2021 ◽  
Vol 17 (1) ◽  
Author(s):  
Saad Alhumaid ◽  
Abbas Al Mutair ◽  
Zainab Al Alawi ◽  
Ali A. Rabaan ◽  
Raghavendra Tirupathi ◽  
...  

Abstract Background Currently there is no systematic review and meta-analysis of the global incidence rates of anaphylactic and nonanaphylactic reactions to SARS-CoV-2 vaccines in the general adult population. Objectives To estimate the incidence rates of anaphylactic and nonanaphylactic reactions after COVID-19 vaccines and describe the demographic and clinical characteristics, triggers, presenting signs and symptoms, treatment and clinical course of confirmed cases. Design A systematic review and meta-analysis. Preferred Reporting Items for Systematic Reviews and Meta-Analyses [PRISMA] statement was followed. Methods Electronic databases (Proquest, Medline, Embase, Pubmed, CINAHL, Wiley online library, and Nature) were searched from 1 December 2020 to 31 May 2021 in the English language using the following keywords alone or in combination: anaphylaxis, non-anaphylaxis, anaphylactic reaction, nonanaphylactic reaction, anaphylactic/anaphylactoid shock, hypersensitivity, allergy reaction, allergic reaction, immunology reaction, immunologic reaction, angioedema, loss of consciousness, generalized erythema, urticaria, urticarial rash, cyanosis, grunting, stridor, tachypnoea, wheezing, tachycardia, abdominal pain, diarrhea, nausea, vomiting and tryptase. We included studies in adults of all ages in all healthcare settings. Effect sizes of prevalence were pooled with 95% confidence intervals (CIs). To minimize heterogeneity, we performed sub-group analyses. Results Of the 1,734 papers that were identified, 26 articles were included in the systematic review (8 case report, 5 cohort, 4 case series, 2 randomized controlled trial and 1 randomized cross-sectional studies) and 14 articles (1 cohort, 2 case series, 1 randomized controlled trial and 1 randomized cross-sectional studies) were included in meta-analysis. Studies involving 26,337,421 vaccine recipients [Pfizer-BioNTech (n = 14,505,399) and Moderna (n = 11,831,488)] were analyzed. The overall pooled prevalence estimate of anaphylaxis to both vaccines was 5.0 (95% CI 2.9 to 7.2, I2 = 81%, p =  < 0.0001), while the overall pooled prevalence estimate of nonanaphylactic reactions to both vaccines was 53.9 (95% CI 0.0 to 116.1, I2 = 99%, p =  < 0.0001). Vaccination with Pfizer-BioNTech resulted in higher anaphylactic reactions compared to Moderna (8.0, 95% CI 0.0 to 11.3, I2 = 85% versus 2.8, 95% CI 0.0 to 5.7, I2 = 59%). However, lower incidence of nonanaphylactic reactions was associated with Pfizer-BioNTech compared to Moderna (43.9, 95% CI 0.0 to 131.9, I2 = 99% versus 63.8, 95% CI 0.0 to 151.8, I2 = 98%). The funnel plots for possible publication bias for the pooled effect sizes to determine the incidence of anaphylaxis and nonanaphylactic reactions associated with mRNA COVID-19 immunization based on mRNA vaccine type appeared asymmetrical on visual inspection, and Egger’s tests confirmed asymmetry by producing p values < 0.05. Across the included studies, the most commonly identified risk factors for anaphylactic and nonanaphylactic reactions to SARS-CoV-2 vaccines were female sex and personal history of atopy. The key triggers to anaphylactic and nonanaphylactic reactions identified in these studies included foods, medications, stinging insects or jellyfish, contrast media, cosmetics and detergents, household products, and latex. Previous history of anaphylaxis; and comorbidities such as asthma, allergic rhinitis, atopic and contact eczema/dermatitis and psoriasis and cholinergic urticaria were also found to be important. Conclusion The prevalence of COVID-19 mRNA vaccine-associated anaphylaxis is very low; and nonanaphylactic reactions occur at higher rate, however, cutaneous reactions are largely self-limited. Both anaphylactic and nonanaphylactic reactions should not discourage vaccination.


2022 ◽  
Vol 22 (1) ◽  
Author(s):  
Duygu Bozkaya ◽  
Heng Zou ◽  
Cindy Lu ◽  
Nicole W. Tsao ◽  
Byron L. Lam

Abstract Background Choroideremia is a rare inherited retinal disease that leads to blindness. Visual acuity (VA) is a key outcome measure in choroideremia treatment studies, but VA decline rates change with age. An accurate understanding of the natural deterioration of VA in choroideremia is important to assess the treatment effect of new therapies in which VA is the primary outcome measure. We conducted a meta-analysis of data on individuals with choroideremia to determine the rate of VA deterioration between the better- and worse-seeing eye (BSE and WSE, respectively). Methods Data were collected from the prospective Natural History of the Progression of Choroideremia (NIGHT) study (613 eyes, baseline data only), studies included in a recent meta-analysis, and studies identified in a targeted literature search performed on March 25, 2020, including individual best-corrected VA (BCVA) and age data in male individuals with choroideremia. Best-corrected VA decline rates (measured by logMAR units) by age and trends in BCVA decline rates in the BSE and WSE were evaluated.  Results Data from 1037 males (1602 eyes; mean age, 41.8 years) were included. Before and after an age cutoff of 33.8 years, BCVA decline rates for the WSE were 0.0086 and 0.0219 logMAR per year, respectively. Before and after an age cutoff of 39.1 years, BCVA decline rates for the BSE were 0.00001 and 0.0203 logMAR per year, respectively. Differences in absolute BCVA and decline rates increased between the 2 eyes until age ~ 40; thereafter, differences in absolute BCVA and decline rates were similar between eyes. Conclusions Using the largest choroideremia data set to date, this analysis demonstrates accelerated BCVA decline beginning between 30 and 40 years of age. Disparate interocular progression rates were observed before the transition age, with similar interocular progression rates after the transition age.


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