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OBJECTIVE: To study the occurrence of torsades de pointes (TdP) ventricular tachycardia in relation to use of drugs labelled with TdP risk, using two nationwide Swedish registers. DESIGN: Prospective register-based cohort study. SETTING: Entire Sweden. PARTICIPANTS: Persons aged ≥18 years prescribed and dispensed any drug classified with TdP risk during 2006-2017, according to CredibleMeds. Persons with a registered TdP diagnosis during the study period, using drugs labelled with known (TdP 1), possible (TdP 2) or conditional (TdP 3) risk at the incident of TdP were examined. PRIMARY OUTCOME MEASURES: Occurrence of TdP in relation to exposure rates for individual drugs with TdP risk. SECONDARY OUTCOME MEASURES: Concurrent use of more than one TdP-labelled drug in a person with a TdP diagnosis. RESULTS: During the study period, 410 TdP cases using drugs with TdP risk labels at the incident were registered; 205 women and 205 men, mean age 74.0 and 71.5 years, respectively. Antidepressants dominated (129/410, 30%), followed by antiarrhythmics (17%). Diuretics and gastric acid-secretion inhibitors, with TdP risk related to induction of hypokalaemia or hypomagnesaemia, were used in 56% and 32% of the 410 TdP cases, respectively. Among the most used antidepressants, citalopram with known TdP 1 risk was associated with both a higher absolute number and incidence of TdP per 100 000 users (two to four times), compared with mirtazapine with possible (TdP 2), and sertraline with conditional (TdP 3) risk. Multiple risk factors, including advanced age, cardiovascular disease and treatment with more than one TdP-classified drug, were frequently observed. CONCLUSIONS: Antidepressants followed by antiarrhythmics dominated among TdP risk drugs used by adults with TdP diagnosis, the majority being ≥65 years. TdP risk class and concomitant medication should be considered when prescribing antidepressants to older patients.
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Antiarrítmicos/efectos adversos , Antidepresivos/efectos adversos , Torsades de Pointes/epidemiología , Adulto , Anciano , Estudios de Cohortes , Femenino , Humanos , Masculino , Persona de Mediana Edad , Factores de Riesgo , SueciaRESUMEN
OBJECTIVE: The aim of the study was to assess the risk of venous thromboembolism (VTE) associated with systemic hormone therapy according to type and to route of administration and the risk of VTE associated with locally administered estrogen. METHODS: In this case-control study, conducted in Sweden between 2003 and 2009, we included 838 cases of VTE and 891 controls with a mean age of 55 years. Controls were matched by age to the cases and randomly selected from the population. We used logistic regression to calculate odds ratios (ORs) with 95% CIs and adjusted for smoking, body mass index, and immobilization. RESULTS: Current use of any hormone therapy was associated with an increased risk of VTE (OR 1.72, 95% CI 1.34-2.20). For estrogen in combination with progestogen the OR was 2.85 (95% CI 2.08-3.90), and for estrogen only the OR was 1.31 (95% CI 0.78-2.21). In orally administered estrogen combined with progestogen, the OR was slightly, but not significantly, higher among users of medroxyprogesterone acetate (OR 2.94, 95% CI 1.67-5.36) than among norethisterone acetate users (OR 2.55, 95% CI 1.50-3.40). Transdermal estrogen combined with progestogen was not associated with VTE risk (crude and imprecise ORs ranging from 0.87 to 1.16). For local effect of estrogen, there was no association with VTE risk (OR 0.69, 95% CI 0.43-1.10). CONCLUSIONS: The risk of VTE risk is higher in users of systemic combined estrogen-progestogen treatment than in users of estrogen only. Furthermore, the risk of VTE was lower for women who used local estrogen than among those using oral estrogen only. Transdermal estrogen only treatment and estrogen for local effect seem not to be related to an increased risk of VTE.
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Terapia de Reemplazo de Estrógeno/efectos adversos , Terapia de Reemplazo de Estrógeno/métodos , Estrógenos/administración & dosificación , Menopausia , Progestinas/administración & dosificación , Tromboembolia Venosa/inducido químicamente , Administración Cutánea , Administración Oral , Estudios de Casos y Controles , Estrógenos/efectos adversos , Femenino , Humanos , Modelos Logísticos , Acetato de Medroxiprogesterona/administración & dosificación , Acetato de Medroxiprogesterona/efectos adversos , Persona de Mediana Edad , Noretindrona/administración & dosificación , Noretindrona/efectos adversos , Noretindrona/análogos & derivados , Acetato de Noretindrona , Oportunidad Relativa , Perimenopausia , Posmenopausia , Progestinas/efectos adversos , Factores de Riesgo , Suecia , Vagina/efectos de los fármacos , Tromboembolia Venosa/epidemiologíaRESUMEN
Genetic associations for the reoccurrence of venous thromboembolism (VTE) are not well described. Our aim was to investigate if common genetic variants, previously found to contribute to the prediction of first time thrombosis in women, were associated with risk of recurrence. The Thromboembolism Hormone Study (TEHS) is a Swedish nationwide case-control study (2002-2009). A cohort of 1,010 women with first time VTE was followed up until a recurrent event, death or November 2011. The genetic variants in F5 rs6025, F2 rs1799963, ABO rs514659, FGG rs2066865, F11 rs2289252, PROC rs1799810 and KNG1 rs710446 were assessed together with clinical variables. Recurrence rate was calculated as the number of events over the accumulated patient-time. Cumulative recurrence was calculated by Kaplan-Meier curve. Cox proportional-hazard model was used to estimate hazard ratios (HR) and 95% confidence intervals (95% CI) between groups. A total of 101 recurrent events occurred during a mean follow-up time of five years. The overall recurrence rate was 20 per 1,000 person-years (95% CI; 16-24). The recurrence rate was highest in women with unprovoked first event and obesity. Carriers of the risk alleles of F5 rs6025 (HR=1.7 (95% CI; 1.1-2.6)) and F11 rs2289252 (HR=1.8 (95% CI; 1.1-3.0)) had significantly higher rates of recurrence compared to non-carriers. The cumulative recurrence was 2.5-fold larger in carriers of both F5 rs6025 and F11 rs2289252 than in non-carriers at five years follow-up. In conclusion, F5 rs6025 and F11 rs2289252 contributed to the risk of recurrent VTE and the combination is of potential clinical relevance for risk prediction.
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Factor V/genética , Factor XI/genética , Tromboembolia Venosa/sangre , Adolescente , Adulto , Alelos , Estudios de Casos y Controles , Factor V/metabolismo , Factor XI/metabolismo , Femenino , Estudios de Seguimiento , Predisposición Genética a la Enfermedad , Humanos , Estimación de Kaplan-Meier , Persona de Mediana Edad , Análisis Multivariante , Polimorfismo de Nucleótido Simple , Modelos de Riesgos Proporcionales , Estudios Prospectivos , Recurrencia , Factores de Riesgo , Suecia , Tromboembolia Venosa/diagnóstico , Tromboembolia Venosa/genéticaRESUMEN
OBJECTIVES: To assess the prevalence of concomitant use of two or more antipsychotic drugs and other psychotropic drugs in the Swedish population. METHODS: Data for this observational cohort study were collected from the Swedish Prescribed Drug Register including all dispensed drugs to the entire Swedish population (9.4 million inhabitants). We identified all individuals with at least one dispensed prescription of antipsychotic drug during January to June 2008. After 12 months, a second exposure period was chosen. Individuals who were dispensed two or more antipsychotic drugs in both periods were considered long-time users of antipsychotic polypharmacy. RESULTS: In 2008, 1.5% of the Swedish population was dispensed antipsychotic drugs, the majority (75%) using only one antipsychotic drug. Out of individuals who were dispensed 2 or more antipsychotic drugs during the first period, 62% also was also dispensed at least 2 antipsychotic drugs during the second period. A total of 665 different unique combinations were used in 2008. Individuals prescribed two or more antipsychotic drugs during both periods were more often dispensed anxiolytics and sedatives than those who were dispensed only one antipsychotic drug. Elderly were dispensed antipsychotic drugs much more often than younger persons. CONCLUSIONS: In Sweden, 25% of patients dispensed antipsychotic drugs receive a combination of two or more antipsychotic drugs. Individuals who are dispensed antipsychotic polypharmacy are more often dispensed anxiolytics and sedatives than those prescribed only one antipsychotic drug. Long-term observational studies are needed to assess the efficacy and safety of such combinations.
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OBJECTIVE: To investigate associations between combined hormonal contraception and progestogen-only contraception and risks of venous thromboembolism by progestogen and carriership of genetic hemostatic variations. METHODS: This was a case-control study in Sweden carried out between 2003 and 2009, which included 948 patients with venous thromboembolism and 902 individuals in a control group, all aged 18-54 years. Information was obtained by telephone interviews and DNA analyses of blood samples. Radiologic referrals were used for case ascertainment. For comparisons, odds ratios were estimated by unconditional logistic regression analysis adjusting for smoking, body mass index (BMI), and immobilization. RESULTS: The odds ratio (OR) for current use of combined hormonal contraception was 5.3 (95% confidence interval [CI] 4.0-7.0). Desogestrel combinations had the highest OR (11.4, 95% CI 6.0-22.0). The OR for injection of medroxyprogesterone acetate was 2.2 (95% CI 1.3-4.0). In users of combined hormonal contraception with the factor V Leiden mutation, the OR was 20.6 (95% CI 8.9-58). In women who used progestogen-only contraception and carried the factor V Leiden mutation, the OR was 5.4 (95% CI 2.5-13). CONCLUSION: Risks of venous thromboembolism in association with combined hormonal contraception vary by type of progestogen and independently of BMI and smoking. Thrombophilic genotypes such as factor V Leiden increase risks of venous thromboembolism in users of combined hormonal contraception. Except for injection of medroxyprogesterone acetate, progestin-only contraception seems to be the least thrombogenic hormonal contraception for women carrying genetic hemostatic variations. LEVEL OF EVIDENCE: II.
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Desogestrel , Progestinas , Trombofilia , Tromboembolia Venosa , Adulto , Índice de Masa Corporal , Anticoncepción/métodos , Anticonceptivos Orales Combinados/efectos adversos , Anticonceptivos Orales Combinados/uso terapéutico , Anticonceptivos Hormonales Orales/efectos adversos , Anticonceptivos Hormonales Orales/uso terapéutico , Desogestrel/efectos adversos , Desogestrel/uso terapéutico , Factor V/genética , Femenino , Humanos , Persona de Mediana Edad , Mutación Puntual , Progestinas/efectos adversos , Progestinas/uso terapéutico , Medición de Riesgo , Factores de Riesgo , Fumar/epidemiología , Suecia/epidemiología , Trombofilia/complicaciones , Trombofilia/epidemiología , Trombofilia/genética , Tromboembolia Venosa/epidemiología , Tromboembolia Venosa/etiología , Tromboembolia Venosa/prevención & controlRESUMEN
INTRODUCTION: We investigated whether genetic variations robustly associated with coronary artery disease are also associated with risk of venous thromboembolism in a well-defined, female case-control study (n=2753) from Sweden. MATERIALS AND METHODS: 39 single nucleotide polymorphisms in 32 loci associated with coronary artery disease in genome-wide association studies were identified in a literature search and genotyped in the ThromboEmbolism Hormone Study (TEHS). Association with venous thromboembolism was assessed by logistic regression. RESULTS: Only rs579459 in the ABO locus demonstrated a significant association with VTE. A tentative association between ANRIL and VTE in the discovery analysis failed to replicate in a meta-analysis of 4 independent cohorts (total n=7181). CONCLUSIONS: It appears that only the ABO locus is a shared risk factor for coronary artery disease and VTE.
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Enfermedad de la Arteria Coronaria/genética , Tromboembolia Venosa/genética , Sistema del Grupo Sanguíneo ABO/genética , Adolescente , Adulto , Estudios de Casos y Controles , Femenino , Sitios Genéticos , Predisposición Genética a la Enfermedad , Variación Genética , Estudio de Asociación del Genoma Completo , Humanos , Modelos Logísticos , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple , ARN Largo no Codificante/genética , Factores de Riesgo , Adulto JovenRESUMEN
BACKGROUND: It is a matter of debate whether women with an episode of VTE associated with estrogen have a lower risk of recurrence than women with an unprovoked VTE. OBJECTIVES: To identify risk factors for recurrent VTE in women and to assess the risk of recurrent VTE associated with combined oral contraceptives (CHC) or menopausal hormone treatment (HT), compared to surgery-related and unprovoked VTE. PATIENTS/METHODS: A cohort of 974 women aged 18-64 years with a first episode of VTE were followed-up for a median time of 5.2 years. All women were previously included as cases in the Swedish nation-wide case-control study "Thrombo Embolism Hormone Study" (TEHS). Hazard ratios for recurrence were calculated using univariable and multivariable Cox proportional hazards model. RESULTS: A total of 102 patients (10%) suffered from recurrent VTE. The annual rate of recurrence was 1.0% in patients with surgery/cast, 2.0% in patients with CHC/HT and 3.2% in patients with unprovoked first VTE. Adjusted hazards ratio (HRa) for recurrence was 0.35 (95% CI 0.20-0.61) in women with VT provoked by surgery/cast while women with estrogen-associated VTE had a HRa of 0.70 (95% CI 0.43-1.20) compared to women with unprovoked VTE. CONCLUSION: Women 18-64 years are at low risk of recurrent VTE. Women with hormone associated VTE had a lower risk of recurrence than women with unprovoked VTE, but not as low as surgery/cast provoked VTE.
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Estrógenos/efectos adversos , Tromboembolia Venosa/epidemiología , Adolescente , Adulto , Factores de Edad , Estudios de Cohortes , Femenino , Humanos , Persona de Mediana Edad , Recurrencia , Factores de Riesgo , Suecia/epidemiología , Adulto JovenRESUMEN
BACKGROUND: Combined hormonal contraceptives, menopause hormone treatment and surgery/cast in orthopedic patients are important risk factors for venous thromboembolism (VTE) in women. OBJECTIVES: To evaluate whether self-reported family history can be used for risk assessment concerning hormone and surgery /cast related VTE in women. PATIENTS/METHODS: 1288 women 18-64 years with a first event of VTE and 1327 age-matched controls were included in a nation-wide population-based case-control study in Sweden. Odds ratios were calculated by comparing occurrence of VTE in women with and without a positive family history in combination with hormones or surgery/cast. RESULTS: The risk of hormone-associated VTE was doubled in women with a family history of VTE as compared to women with hormones and negative family history. The risk was more than tripled in women with surgery/cast and a positive family history, as compared to surgery/cast patients with negative family history. Women with a positive family history and combined hormonal contraceptive or menopause hormone treatment had an OR of 15.3 (95% CI 6.1-38) and 5.9 (95% CI 3.3-11) respectively compared to women without hormones or family history. The corresponding OR in women with surgery/cast and a positive family history was 67 (95% CI 21-213) compared to women without surgery/cast treatment and a negative family history. CONCLUSION: Self-reported family history is associated with increased odds of developing VTE on combined hormonal contraceptives, menopause hormone treatment and in connection with surgery or plaster. We believe that assessing family history of VTE can be helpful in identifying high risk patients.
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Anticonceptivos Orales/administración & dosificación , Tromboembolia Venosa/epidemiología , Adolescente , Adulto , Estudios de Casos y Controles , Anticonceptivos Orales/efectos adversos , Salud de la Familia , Femenino , Genotipo , Humanos , Entrevistas como Asunto , Persona de Mediana Edad , Complicaciones Posoperatorias/epidemiología , Factores de Riesgo , Autoinforme , Suecia/epidemiología , Tromboembolia Venosa/genética , Adulto JovenRESUMEN
BACKGROUND: Non-steroidal anti-inflammatory drugs (NSAIDs) might increase the risk of venous thromboembolism (VTE), and risks might differ by type of NSAID. Compared with men, women have a higher incidence of VTE at younger age, and they more often use NSAIDs. OBJECTIVES: To assess risks of VTE in young and middle-aged women in association with use of NSAIDs. PATIENTS/METHODS: In a nationwide casecontrol study (Thrombo Embolism Hormone Study) performed in Sweden 20032009, we included as cases 1433 women, 18 to 64 years of age with a first time VTE. Controls were 1402 randomly selected women, frequency matched by age. Information was obtained by telephone interviews and DNA analyses of blood samples. We calculated adjusted odds ratios (ORs) with 95% confidence intervals (CIs) adjusting for degree of immobilization, chronic disease, smoking, body mass index, use of hormonal contraception, hormone therapy or other NSAIDs. RESULTS: Use of NSAIDs was not associated with increased risks of VTE (OR = 0.98, 95% CI 0.801.19). The OR was 0.88 for propionic acid derivatives (95% CI 0.721.10), 1.18 for acetic acid derivatives (95% CI 0.821.70) and 1.76 for coxibs (95% CI 0.734.27). For users of acetic acid derivatives and coxibs, the ORs increased by cumulative dose. Carriership of the prothrombin gene mutation or factor V Leiden had only minor effects on the results. CONCLUSIONS: We found no increased risks of VTE in association with use of NSAIDs. Users of high cumulative doses of acetic acid derivatives and coxibs had the highest risks, suggesting a relationship with cyclooxygenase selectivity and dose.
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Antiinflamatorios no Esteroideos/efectos adversos , Tromboembolia Venosa/inducido químicamente , Tromboembolia Venosa/epidemiología , Adolescente , Adulto , Índice de Masa Corporal , Estudios de Casos y Controles , Femenino , Humanos , Incidencia , Modelos Logísticos , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple , Sistema de Registros , Suecia , Tromboembolia Venosa/genética , Adulto JovenAsunto(s)
Moldes Quirúrgicos/efectos adversos , Anticonceptivos Orales Combinados/efectos adversos , Anticonceptivos Hormonales Orales/efectos adversos , Procedimientos Quirúrgicos Operativos/efectos adversos , Tromboembolia Venosa/etiología , Adulto , Anticoagulantes/uso terapéutico , Estudios de Casos y Controles , Factor V/genética , Femenino , Heparina de Bajo-Peso-Molecular/uso terapéutico , Humanos , Inmovilización/efectos adversos , Persona de Mediana Edad , Obesidad/complicaciones , Protrombina/genética , Factores de Riesgo , Fumar/efectos adversos , Encuestas y Cuestionarios , Tromboembolia Venosa/tratamiento farmacológico , Tromboembolia Venosa/genética , Tromboembolia Venosa/prevención & controlRESUMEN
INTRODUCTION: Hemostasis in women is affected by changes of estrogen levels. The role of endogenous estrogens on risk of venous thromboembolism (VTE) remains unclear. The aim of this study was to investigate the importance of acquired and genetic risk factors for VTE in pre-and postmenopausal women. METHOD: In a nationwide case-control study we included as cases 1470 women, 18 to 64years of age with a first time VTE. The 1590 controls were randomly selected and matched by age to the cases. Information on risk factors was obtained by interviews and DNA-analyses. We used unconditional logistic regression to calculate odds ratios (ORs) with 95% confidence intervals (CIs). RESULTS: The ORs were generally of similar magnitude in pre- and postmenopausal women. The highest risk was for the combination of surgery and cast (adjusted OR 54.12, 95% CI 16.62-176.19) in postmenopausal women. The adjusted OR for use of menopausal hormone therapy was 3.73 (95% CI 1.86-7.50) in premenopausal and 2.22 (95% CI 1.54-3.19) in postmenopausal women. Overweight was linked to an increased risk and exercise to a decreased risk, regardless of menopausal status. CONCLUSION: Menopausal status had only minor influence on the risk levels. Acquired transient risk factors conveyed the highest risks for VTE.
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Tromboembolia Venosa/epidemiología , Tromboembolia Venosa/genética , Adolescente , Adulto , Estudios de Casos y Controles , ADN/genética , Femenino , Predisposición Genética a la Enfermedad , Terapia de Reemplazo de Hormonas/efectos adversos , Humanos , Persona de Mediana Edad , Oportunidad Relativa , Sobrepeso/complicaciones , Posmenopausia , Premenopausia , Factores de Riesgo , Adulto JovenRESUMEN
OBJECTIVE: To assess the current knowledge concerning progestogen-only contraception (POC) and risks of venous thromboembolism (VTE). DESIGN AND SETTING: Systematic review of the literature on observational and analytical studies reporting risk estimates for VTE in women exposed to POCs. METHODS AND MAIN OUTCOME MEASURES: We performed a computerized literature search in the Pub Med, Embase, and the Cochrane Library for studies published between 1966 and February 13, 2008. Based on the evaluated studies we calculated an overall risk estimate for VTE in association with POC. RESULTS: Four case-control studies and one cohort study were included. Of the case-control studies, three reported an increased risk and one a decreased risk of VTE. The cohort study found divergent results depending on the type of statistical analysis used. None of the results was statistically significant. The overall odds ratio for POC-associated VTE in the four case-control studies was 1.45 (95% CI=0.92-2.26). CONCLUSIONS: The risk of VTE associated with use of POCs is poorly investigated. The slightly elevated overall risk estimate might suggest an association between POC and an increased risk for VTE. The results must, however, be interpreted with caution due to the possibility of residual confounding. Well-designed studies with sufficient statistical power to evaluate risks of VTE with POC are warranted.