scholarly journals Thrombotic Events with NovoSeven® RT in Approved Indications Are Rare (0.2%) and Associated with Older Age (>= 65 y), Cardiovascular Disease, and Concomitant Use of aPCCs

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 1203-1203
Author(s):  
Madhvi Rajpurkar ◽  
Stacy E. Croteau ◽  
Lisa N Boggio ◽  
David L Cooper

Abstract Introduction: Recombinant activated factor VII (NovoSeven®RT, Novo Nordisk A/S) is approved for treatment of bleeding and perioperative management in congenital hemophilia with inhibitors (CHwI), acquired hemophilia (AH), congenital factor VII (FVII) deficiency, and Glanzmann thrombasthenia (GT) with refractoriness to platelets. Serious thrombotic events (TEs) have been reported in clinical trials and postmarketing surveillance; however, the incidence of this risk (rate of thrombosis) is considered to be low within labeled indications. While many general risk factors are noted in the prescribing information (PI), the association of reported TEs with certain risk factors noted in the PI has not been established. Methods: A retrospective safety assessment of clinical trials and registries, used to support licensure and postmarketing surveillance, was performed from which the rate of thrombosis could be calculated in the 4 indicated disorders. Further, all postmarketing TE case reports in the Novo Nordisk safety database (including from registries, spontaneous reports, and the literature) were assessed to identify any of the risk factors listed in the PI and the temporal relationship to NovoSeven®RT use (defined as within 48 h given 2- to 3- hour half-life). Results: In clinical trials and registries used to support licensure and in postmarketing surveillance, overall rate of thrombosis was 0.17% of 12,288 bleeding and surgical episodes. There were 21 TEs identified (12 CHwI, 5 AH, 3 FVII deficiency, 1 GT). The specific risk by indication (Table 1) was 0.11% for CHwI (11,121 episodes), 0.19% for GT (518 episodes), 0.82% for FVII deficiency (367 episodes) and 1.77% for AH (282 episodes). Analysis of all postmarketing databases (Table 2) revealed 213 TEs (88 CHwI, 61 AH, 53 FVII deficiency, 11 GT). The majority were reported spontaneously (141), with fewer reported in the literature (47) or solicited in registries or investigator-sponsored studies (25). Of 213 TE cases, temporal relationship was assessed as plausible in 188 (88%) if NovoSeven®RT use was reported within 48 hours prior to TE or timing unknown; timing was more than 48 hours in 25 (12%) of cases. Overall, the most common associated risk factor was "elderly," defined in the PI as age ≥65 years (29%), and was particularly common in patients with AH and TE (67%). Another common factor was concomitant use of activated prothrombin complex concentrates (aPCC), identified in 18% of all TEs and 34% of TEs in CHwI. Broadly defined cardiovascular disease (including arrhythmias) was noted in 18% of all TEs (36% AH, 15% FVII deficiency, 9% CHwI) and was much more common than specific note of atherosclerotic disease (2%). Other risk factors listed in the PI were uncommon and, in some cases, never identified in TE reports (eg, postoperative immobilization, sepsis, liver disease, disseminated intravascular coagulation, neonates, pregnancy, postpartum hemorrhage, crush injury). Conclusions: Data show that the rate of TEs within licensed indications is low (0.17%), as was originally described in the US PI from 1999-2009. It has remained stable over time during postapproval surveillance in multiple US and global registries, with active surveillance for safety information across the 4 approved indications. In postmarketing safety report assessments of patients with CHwI receiving concomitant treatment with aPCCs, older patients, particularly those with AH who are receiving other hemostatic agents, and patients with a history of cardiac and vascular disease may have an increased risk of developing TE. Disclosures Rajpurkar: HEMA biologics: Honoraria; Bristol Myers Squibb: Research Funding; Shire: Honoraria; Pfizer: Honoraria, Research Funding; Novonordisk: Honoraria. Croteau:CSL-Behring: Consultancy; Catalyst Biosciences: Consultancy; Genetech: Consultancy, Research Funding; Novo Nordisk: Consultancy; Octapharma: Consultancy, Honoraria, Research Funding; Pfizer: Research Funding; Spark Therapeutics: Research Funding; Tremeau Pharmaceuticals: Consultancy; Bioveritiv: Consultancy; Biomarin: Consultancy; Bayer: Consultancy; Baxalta/Shire: Consultancy, Research Funding. Boggio:Novo Nordisk: Honoraria. Cooper:Novo Nordisk: Employment.

2018 ◽  
Vol 36 (26) ◽  
pp. 2710-2717 ◽  
Author(s):  
Dawn L. Hershman ◽  
Cathee Till ◽  
Sherry Shen ◽  
Jason D. Wright ◽  
Scott D. Ramsey ◽  
...  

Background Cardiovascular disease is the primary cause of death among patients with breast cancer. However, the association of cardiovascular-disease risk factors (CVD-RFs) with long-term survival and cardiac events is not well studied. Methods We examined SWOG (formerly the Southwest Oncology Group) breast cancer trials from 1999 to 2011. We identified baseline diabetes, hypertension, hypercholesterolemia, and coronary artery disease by linking trial records to Medicare claims. The primary outcome was overall survival. Patients with both baseline and follow-up claims were examined for cardiac events. Cox regression was used to assess the association between CVD-RFs and outcomes. Results We identified 1,460 participants older than 66 years of age from five trials; 842 were eligible for survival outcomes analysis. At baseline, median age was 70 years, and median follow-up was 6 years. Hypertension (73%) and hypercholesterolemia (57%) were the most prevalent conditions; 87% of patients had one or more CVD-RF. There was no association between any of the individual CVD-RFs and overall survival except for hypercholesterolemia, which was associated with improved overall survival (hazard ratio [HR], 0.73; 95% CI, 0.57 to 0.93; P = .01). With each additional CVD-RF, there was an increased risk of death (HR, 1.23; 95% CI, 1.08 to 1.40; P = .002), worse progression-free survival (HR, 1.12; 95% CI, 1.00 to 1.25; P = .05), and marginally worse cancer-free survival (HR, 1.15; 95% CI, 0.99 to 1.34; P = .07). The relationship between baseline CVD-RFs and cardiac events was analyzed in 736 patients. A strong linear association between the number of CVD-RFs and cardiac event was observed (HR per CVD-RF, 1.41; 95% CI, 1.17 to 1.69; P < .001). Conclusion Among participants in clinical trials, each additional baseline CVD-RF was associated with an increased risk of cardiac events and death. Efforts to improve control of modifiable CVD-RFs are needed, especially among those with multiple risk factors.


Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 3277-3277
Author(s):  
Brian Wiley ◽  
Kristin Erlandson ◽  
Katherine Tassiopoulos ◽  
Yizhe Song ◽  
Rachel Presti ◽  
...  

Abstract Introduction An estimated 1.2 million individuals in the United States are living with HIV (www.hiv.gov). Thanks to modern antiretroviral therapies (ART), the life expectancies of individuals living with HIV now approach those of people without HIV (Marcus 2020). But with this, an increase in the proportion of deaths due to non-infectious causes has occurred including, predominately, cardiovascular disease (CVD). Multiple studies have shown that HIV infection is an independent risk factor for cardiovascular disease. This increased risk is multifactorial due to an increased prevalence of traditional CVD risk factors and HIV-specific risk factors including ART, chronic inflammation and immune activation (Hsue 2010). Clonal Hematopoiesis, characterized by the expansion of blood cells stemming from a mutant hematopoietic stem/progenitor cell (HSPCs) is an emerging risk factor for cardiovascular disease. Mechanistically, this is thought to be driven, at least in part, by CH-induced proinflammatory circulating leukocytes (Jaiswal 2017, Bick 2020). Recent data suggest that inflammatory states may also promote the expansion of DNMT3A and TET2 CH mutant HSPCs suggesting a potential feedback loop (Zheng 2019, King 2019). CH has been recently reported to be increased among individuals living with HIV (Dharan 2021). Whether CH is a risk factor for HIV-associated CVD is not known. Given evidence of an increased prevalence of CH among those with HIV, we hypothesized that CH would predict risk of CVD. Methods We performed a nested case-control study drawn from the AIDS Clinical Trials Group Longitudinal Linked Randomized Trials (ALLRT) observational study which was a long-term study of individuals with newly diagnosed HIV receiving ART (N=4,371). Cases who developed a cardiovascular event were matched to controls with no event based on age at blood draw and sex. Peripheral blood mononuclear cells (PMBCs) were isolated from the blood draw closest to the time of CVD event or time of censoring, for cases and controls respectively. Extracted DNA was subjected to whole exome sequencing (WES) at a median depth of 500x. We also included WES data from 267 children sequenced using the same platform as a technical panel of normal (PON). Mutation calling was performed using Mutect2, VarDict and Varscan2. We retained variants that met the following criteria: 1) passed by at least two callers 2) showed statistically significant higher variant allele fraction (VAF) compared to our PON 3) had VAF between 2-35% 4) at least 6 reads supporting the variant 5) passed additional post-calling filters for germline variants and sequencing artifacts 6) were annotated as a putative driver of CH based on previously defined criteria. Results Over 13 years of follow-up we observed 83 cardiovascular events: 4 cases of ASC, 14 of stroke, 25 of cerebrovascular accident, 37 of myocardial infarction, 2 of peripheral artery disease, and 1 heart failure. The mean age of our participants was 51.6 years, 81% were male, 35% percent were African-American, 17% were Hispanic and 2% were Asian. Among 161 participants (83 cases and 78 controls) we observed at least one CH mutation in 14% of participants (18% of cases and 10% of controls). The median VAF was 3.5% with 23 individuals harboring a median of 1 mutation (range 1-2). In a conditional logistic regression model adjusted for race, Atherosclerotic Cardiovascular Disease (ASCVD) Risk Score and stratified by case-control matched pairs, CH was significantly associated with CVD (OR=3.70, 95% CI 1.03-13.23 p=0.045). Because of the possible confounding effects of classes of ART therapy on the CH-CVD association, we explored whether the prevalence of CH differed based on prior exposure to ART sub-class(es). We did not observe differences in the frequency of CH among individuals with prior exposure to different ART regimens (Non-Nucleoside Reverse Transcriptase Inhibitors 14%, Nucleoside reverse transcriptase inhibitors 17%, Protease inhibitors 20%, Integrase inhibitors 18%) Conclusions Among individuals with HIV, CH is associated with a nearly four-fold increased risk of CVD. These findings highlight the relevance of CH to HIV-associated CVD and provide support for interventions targeting potential CH-induced pro-inflammatory states among patients with HIV. Disclosures Erlandson: Gilead Sciences: Consultancy, Research Funding; Viiv Pharmaceuticals: Consultancy; Janssen Pharmaceuticals: Consultancy. Bolton: bristol myers squibb: Research Funding.


1970 ◽  
Vol 11 (2) ◽  
pp. 108-114 ◽  
Author(s):  
Ratan Das Gupta ◽  
Muhibur Rahman ◽  
HAM Nazmul Ahasan ◽  
Md Billal Alam ◽  
Md Titu Miah ◽  
...  

Background: Compared with general population mortality rates are 10-20 times higher among patients with endstage renal disease, with 50% of this excess burden being attributable to cardiovascular disease. This excess risk is notentirely explained by elevation of traditional risk factors. Elevation of several Non-traditional risk factors associatedwith an increased risk for cardiovascular disease in CKD and haemodialysis dependent patients.Methods: It was a case control study which included total 96 subjects, 48 were non-dialysis CKD patients, 22Heamodialysis dependent patients and 26 healthy controls. Non-traditional risk factors homocysteine, fibrinogen,CRP, factor VII activity and haemoglobin estimated and compared with normal control population.Results: The study revealed that homocysteine , fibrinogen , CRP, factor VII significantly increased and haemoglobinwas significantly low in both non-dialysis CKD and haemodialysis dependent patients in comparison to control group.Mean homocysteine 15.38, 27.30, 23.76 μmol/L in control, non-dialysis CKD and haemodialysis dependent patientrespectively. Fibrinogen in control , non-dialysis CKD and haemodialysis dependent patient were 180.25 , 264.10 ,259.59 mg/dl respectively. CRP level in control, non-dialysis CKD and haemodialysis dependent patient were 3.90,52.59, 17.31 mg/L respectively. Factor VII activity in control was 94.18%, whereas in non-dialysis CKD it was103.97%, and 106.18 % in haemodialysis dependent patient. haemoglobin was 13.85 gm/dl in control , but in nondialysisCKD it was 8.08 gm/dl, and in haemodialysis dependent patients 9.46 gm/dl .cardiovascular disease in nondialysisCKD 54.56% and haemodialysis dependent patients 59.4%Conclusion: Haemoglobin is low and levels of homocysteine, fibrinogen, CRP, factor-VII activity are increasedamong the patients with CKD and haemodialysis dependent patients.Key words: Non-traditional; Cardiovascular; Chronic Kidney DiseaseDOI: 10.3329/jom.v11i2.5450J MEDICINE 2010; 11 : 108-114


2020 ◽  
Vol 30 (Supplement_5) ◽  
Author(s):  
E Leiter ◽  
K L Greenberg ◽  
M Donchin ◽  
O Keidar ◽  
S Siemiatycki ◽  
...  

Abstract Background Women from low socio-economic, culturally insular populations are at increased risk for cardiovascular disease (CVD). The ultra-Orthodox Jewish (UOJ) community in Israel is a difficult to access, rapidly growing low socio-economic, insular minority with numerous obstacles to health. The current study investigates CVD-related risk factors (RF) in a sample of OUJ women, comparing sample characteristics with the general population. Addressing the questions, 'Are UOJ women at increased risk for CVD?', 'Which RFs should be addressed beyond the general population's?', this study can inform public health initiatives (PHI) for this and similar populations. Methods Self-administered questionnaires completed by a cluster randomized sample of 239 women from a UOJ community included demographics, fruit, vegetables, and sweetened drink consumption, secondhand smoke exposure, physical activity (PA) engagement, and BMI. Population statistics utilized for comparison of demographic and cardiovascular risk factors were obtained from government-sponsored national surveys. Results Compared with the general population, UOJ women were less likely to consume 5 fruits and vegetables a day (12.7% vs. 24.3%, p&lt;.001) and more likely to consume &gt; 5 cups of sweetened beverages a day (18.6% vs. 12.6%, p=.019). UOJ women also reported less secondhand smoke exposure (7.2% vs. 51.4%, p&lt;.001) and higher rates of PA recommendation adherence (60.1% vs. 25.6%, p&lt;.0001) than the general population. Obesity was higher in UOJ women (24.3% vs. 16.1%, p&lt;.0001). Conclusions This study suggests that PHIs in this population target healthy weight maintenance, nutrition, and PA. As a consequence of this study, the first CVD prevention intervention has been implemented in this population, targeting the identified RFs. Utilizing a mixed methods and community-based participatory approach, this innovative 3-year intervention reached over 2,000 individuals. Key messages This study identified nutrition risk behaviors and high levels of obesity in a difficult to access, minority population. This study informed the planning and implementation of a community-based PHI.


2021 ◽  
Vol 14 ◽  
pp. 117954412110287
Author(s):  
Mir Sohail Fazeli ◽  
Vadim Khaychuk ◽  
Keith Wittstock ◽  
Boris Breznen ◽  
Grace Crocket ◽  
...  

Objective: To scope the current published evidence on cardiovascular risk factors in rheumatoid arthritis (RA) focusing on the role of autoantibodies and the effect of antirheumatic agents. Methods: Two reviews were conducted in parallel: A targeted literature review (TLR) describing the risk factors associated with cardiovascular disease (CVD) in RA patients; and a systematic literature review (SLR) identifying and characterizing the association between autoantibody status and CVD risk in RA. A narrative synthesis of the evidence was carried out. Results: A total of 69 publications (49 in the TLR and 20 in the SLR) were included in the qualitative evidence synthesis. The most prevalent topic related to CVD risks in RA was inflammation as a shared mechanism behind both RA morbidity and atherosclerotic processes. Published evidence indicated that most of RA patients already had significant CV pathologies at the time of diagnosis, suggesting subclinical CVD may be developing before patients become symptomatic. Four types of autoantibodies (rheumatoid factor, anti-citrullinated peptide antibodies, anti-phospholipid autoantibodies, anti-lipoprotein autoantibodies) showed increased risk of specific cardiovascular events, such as higher risk of cardiovascular death in rheumatoid factor positive patients and higher risk of thrombosis in anti-phospholipid autoantibody positive patients. Conclusion: Autoantibodies appear to increase CVD risk; however, the magnitude of the increase and the types of CVD outcomes affected are still unclear. Prospective studies with larger populations are required to further understand and quantify the association, including the causal pathway, between specific risk factors and CVD outcomes in RA patients.


2021 ◽  
Vol 8 (1) ◽  
pp. e000515
Author(s):  
Isak Samuelsson ◽  
Ioannis Parodis ◽  
Iva Gunnarsson ◽  
Agneta Zickert ◽  
Claes Hofman-Bang ◽  
...  

ObjectivePatients with SLE have increased risk of myocardial infarction (MI). Few studies have investigated the characteristics of SLE-related MIs. We compared characteristics of and risk factors for MI between SLE patients with MI (MI-SLE), MI patients without SLE (MI-non-SLE) and SLE patients without MI (non-MI-SLE) to understand underlying mechanisms.MethodsWe identified patients with a first-time MI in the Karolinska SLE cohort. These patients were individually matched for age and gender with MI-non-SLE and non-MI-SLE controls in a ratio of 1:1:1. Retrospective medical file review was performed. Paired statistics were used as appropriate.ResultsThirty-four MI-SLE patients (88% females) with a median age of 61 years were included. These patients had increased number of coronary arteries involved (p=0.04), and ≥50% coronary atherosclerosis/occlusion was numerically more common compared with MI-non-SLE controls (88% vs 66%; p=0.07). The left anterior descending artery was most commonly involved (73% vs 59%; p=0.11) and decreased (<50%) left ventricular ejection fraction occurred with similar frequency in MI-SLE and MI-non-SLE patients (45% vs 36%; p=0.79). Cardiovascular disease (44%, 5.9%, 12%; p<0.001) and coronary artery disease (32%, 2.9%, 0%; p<0.001), excluding MI, preceded MI/inclusion more commonly in MI-SLE than in MI-non-SLE and non-MI-SLE patients, respectively. MI-SLE patients had lower plasma albumin levels than non-MI-SLE patients (35 (29–37) vs 40 (37–42) g/L; p=0.002).ConclusionIn the great majority of cases, MIs in SLE are associated with coronary atherosclerosis. Furthermore, MIs in SLE are commonly preceded by symptomatic vascular disease, calling for attentive surveillance of cardiovascular disease and its risk factors and early atheroprotective treatment.


2021 ◽  
Vol 36 (3) ◽  
pp. 299-309 ◽  
Author(s):  
Joshua Elliott ◽  
Barbara Bodinier ◽  
Matthew Whitaker ◽  
Cyrille Delpierre ◽  
Roel Vermeulen ◽  
...  

AbstractMost studies of severe/fatal COVID-19 risk have used routine/hospitalisation data without detailed pre-morbid characterisation. Using the community-based UK Biobank cohort, we investigate risk factors for COVID-19 mortality in comparison with non-COVID-19 mortality. We investigated demographic, social (education, income, housing, employment), lifestyle (smoking, drinking, body mass index), biological (lipids, cystatin C, vitamin D), medical (comorbidities, medications) and environmental (air pollution) data from UK Biobank (N = 473,550) in relation to 459 COVID-19 and 2626 non-COVID-19 deaths to 21 September 2020. We used univariate, multivariable and penalised regression models. Age (OR = 2.76 [2.18–3.49] per S.D. [8.1 years], p = 2.6 × 10–17), male sex (OR = 1.47 [1.26–1.73], p = 1.3 × 10–6) and Black versus White ethnicity (OR = 1.21 [1.12–1.29], p = 3.0 × 10–7) were independently associated with and jointly explanatory of (area under receiver operating characteristic curve, AUC = 0.79) increased risk of COVID-19 mortality. In multivariable regression, alongside demographic covariates, being a healthcare worker, current smoker, having cardiovascular disease, hypertension, diabetes, autoimmune disease, and oral steroid use at enrolment were independently associated with COVID-19 mortality. Penalised regression models selected income, cardiovascular disease, hypertension, diabetes, cystatin C, and oral steroid use as jointly contributing to COVID-19 mortality risk; Black ethnicity, hypertension and oral steroid use contributed to COVID-19 but not non-COVID-19 mortality. Age, male sex and Black ethnicity, as well as comorbidities and oral steroid use at enrolment were associated with increased risk of COVID-19 death. Our results suggest that previously reported associations of COVID-19 mortality with body mass index, low vitamin D, air pollutants, renin–angiotensin–aldosterone system inhibitors may be explained by the aforementioned factors.


Antioxidants ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 146
Author(s):  
Vittoria Cammisotto ◽  
Cristina Nocella ◽  
Simona Bartimoccia ◽  
Valerio Sanguigni ◽  
Davide Francomano ◽  
...  

Oxidative stress may be defined as an imbalance between reactive oxygen species (ROS) and the antioxidant system to counteract or detoxify these potentially damaging molecules. This phenomenon is a common feature of many human disorders, such as cardiovascular disease. Many of the risk factors, including smoking, hypertension, hypercholesterolemia, diabetes, and obesity, are associated with an increased risk of developing cardiovascular disease, involving an elevated oxidative stress burden (either due to enhanced ROS production or decreased antioxidant protection). There are many therapeutic options to treat oxidative stress-associated cardiovascular diseases. Numerous studies have focused on the utility of antioxidant supplementation. However, whether antioxidant supplementation has any preventive and/or therapeutic value in cardiovascular pathology is still a matter of debate. In this review, we provide a detailed description of oxidative stress biomarkers in several cardiovascular risk factors. We also discuss the clinical implications of the supplementation with several classes of antioxidants, and their potential role for protecting against cardiovascular risk factors.


2006 ◽  
Vol 154 (1) ◽  
pp. 131-139 ◽  
Author(s):  
Lenora M Camarate S M Leão ◽  
Mônica Peres C Duarte ◽  
Dalva Margareth B Silva ◽  
Paulo Roberto V Bahia ◽  
Cláudia Medina Coeli ◽  
...  

Background: There has been a growing interest in treating postmenopausal women with androgens. However, hyperandrogenemia in females has been associated with increased risk of cardiovascular disease. Objective: We aimed to assess the effects of androgen replacement on cardiovascular risk factors. Design: Thirty-seven postmenopausal women aged 42–62 years that had undergone hysterectomy were prospectively enrolled in a double-blind protocol to receive, for 12 months, percutaneous estradiol (E2) (1 mg/day) combined with either methyltestosterone (MT) (1.25 mg/day) or placebo. Methods: Along with treatment, we evaluated serum E2, testosterone, sex hormone-binding globulin (SHBG), free androgen index, lipids, fibrinogen, and C-reactive protein; glucose tolerance; insulin resistance; blood pressure; body-mass index; and visceral and subcutaneous abdominal fat mass as assessed by computed tomography. Results: A significant reduction in SHBG (P < 0.001) and increase in free testosterone index (P < 0.05; Repeated measures analysis of variance) were seen in the MT group. Total cholesterol, triglycerides, fibrinogen, and systolic and diastolic blood pressure were significantly lowered to a similar extent by both regimens, but high-density lipoprotein cholesterol decreased only in the androgen group. MT-treated women showed a modest rise in body weight and gained visceral fat mass relative to the other group (P < 0.05), but there were no significant detrimental effects on fasting insulin levels and insulin resistance. Conclusion: This study suggests that the combination of low-dose oral MT and percutaneous E2, for 1 year, does not result in expressive increase of cardiovascular risk factors. This regimen can be recommended for symptomatic postmenopausal women, although it seems prudent to perform baseline and follow-up lipid profile and assessment of body composition, especially in those at high risk of cardiovascular disease.


2018 ◽  
Vol 12 ◽  
pp. 117954681881516 ◽  
Author(s):  
Josefine Rönnqvist ◽  
Pär Hallberg ◽  
Qun-Ying Yue ◽  
Mia Wadelius

Background: Statins are widely used lipid-lowering drugs used for the prevention of cardiovascular disease. Statins are known to cause myopathy, an adverse drug reaction with various clinical features rhabdomyolysis. Objective: To describe clinical characteristics of statin-treated individuals who experienced myopathy and identify risk factors of statin-associated myopathy. Methods: A retrospective study was conducted on cases of statin-associated myopathy reported to the Swedish Medical Products Agency. Clinical factors were compared between cases and statin-treated controls not diagnosed with myopathy. Statistical methods were univariate and multivariate logistic regression and results were presented as odds ratio (OR) with 95% confidence interval (CI). To correct for multiple comparisons, the cutoff for statistical significance was set to P < .0017. Results: In total, 47 cases of statin-associated myopathy were compared with 3871 treated controls. Rhabdomyolysis was diagnosed in 51% of the cases. Markers for cardiovascular disease were more common in cases than controls. Statistical analysis revealed the following independent risk factors for myopathy: high statin dose (OR = 1.54, calculated using the standard deviation 19.82, 95% CI = 1.32-1.80, P < .0001), and concomitant treatment with fusidic acid (OR = 1002, 95% CI = 54.55-18 410, P < .0001), cyclosporine (OR = 34.10, 95% CI = 4.43-262.45, P = .0007), and gemfibrozil (OR = 12.35, 95% CI = 2.38-64.10, P = .0028). Conclusions: The risk of myopathy increases with statin dose and cotreatment with cyclosporine and gemfibrozil. Concomitant fusidic acid has previously only been noted in a few case reports. Considering that use of fusidic acid may become more frequent, it is important to remind of this risk factor for statin-associated myopathy.


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