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2.
Gene ; 725: 144163, 2020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-31639433

RESUMO

BACKGROUND: Previous studies have established that coronary artery disease is associated with excess inflammation. These studies have shown an elevation of both pro and anti-inflammatory cytokines in sufferers of coronary artery disease. There is increasing interest in the role played by the inflammasome Nod Like Receptor family pyrin domain containing 3 (NLRP3) in the aetiology of coronary artery disease. Increased severity of coronary artery disease correlates with higher levels of expression of NLRP3. Does NLRP3 polymorphisms play a role in the aetiology of coronary artery disease? METHOD: In a cohort of Vietnam War (n-299) veterans who have been previously exposed to trauma, NLRP3 polymorphisms were analysed for association with coronary calcium scores using analyses of variance. Independent t-test was used to analyse genotypes. In samples with a small representation of minor homozygotes, genotypes were combined and analysed using independent t-test. If any of the genotype analysis suggested the potential for a dominant or a recessive model the model was further explored. Hardy-Weinberg Equilibrium was calculated using Hardy-Weinberg equilibrium calculator including analysis for ascertainment bias. RESULTS: The NLRP3 polymorphism, rs10159239 was significantly associated (p = 0.001) with a higher raised coronary calcium score. The Single Nucleotide Polymorphism rs10159239 was examined by logistic regression with known risk factors for Coronary artery disease and remained significant (0.035). This is the first time rs10159239 A-allele has been associated with raised coronary calcium score. CONCLUSIONS: This is the first time rs10159239 A-allele has been associated with raised coronary calcium score. Further research is needed to replicate our results in larger well-characterised cohorts.


Assuntos
Doença da Artéria Coronariana/genética , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Idoso , Idoso de 80 Anos ou mais , Alelos , Proteínas de Transporte/genética , Estudos de Coortes , Doença da Artéria Coronariana/metabolismo , Citocinas/genética , Grupo com Ancestrais do Continente Europeu/genética , Feminino , Frequência do Gene/genética , Predisposição Genética para Doença/genética , Genótipo , Humanos , Inflamação/genética , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único/genética , Fatores de Risco , Veteranos , Guerra do Vietnã
4.
Heart Lung Circ ; 28(10): 1571-1579, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31104887

RESUMO

Proprotein convertase subtilisin/kexin type 9 (PCSK9) monoclonal antibodies (mAb) have progressed from showing marked low density lipoprotein cholesterol lowering in early phase trials through to reducing cardiovascular events in large clinical outcome trials. Recently in Australia, the indication for evolocumab has been expanded to include both heterozygous and homozygous familial hypercholesterolaemia under the Pharmaceutical Benefits Scheme (PBS). With prices remaining high currently their use in non-familial hypercholesterolaemia in Australia remains by private prescription only at this stage. This manuscript summarises the major outcomes trials of the PCSK9 mAbs and the secondary analyses that have assessed their benefits in high risk patient groups, and describes the consensus of authors on which patients would most likely benefit from PCSK9 mAb therapy.


Assuntos
Anticorpos Monoclonais Humanizados/farmacologia , Anticorpos Monoclonais/farmacologia , Doenças Cardiovasculares/tratamento farmacológico , Pró-Proteína Convertase 9/imunologia , Anticolesterolemiantes/farmacologia , Austrália/epidemiologia , Doenças Cardiovasculares/epidemiologia , Humanos , Incidência , Pró-Proteína Convertase 9/antagonistas & inibidores , Resultado do Tratamento
5.
J Clin Sleep Med ; 14(9): 1577-1586, 2018 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-30176975

RESUMO

STUDY OBJECTIVES: Recent results from the PTSD Initiative, a cross-sectional cohort study in Australian Vietnam veterans (VV) with and without posttraumatic stress disorder (PTSD), demonstrated an increased prevalence of self-reported sleep disturbances in those with PTSD. This study aimed to objectively assess the prevalence of sleep disorders in the same cohort using detailed polysomnography (PSG). METHODS: Participants from the PTSD Initiative were recruited to undergo PSG. PTSD status was determined with the Clinician Administered PTSD Scale for DSM-5 (CAPS-5). Subjective sleep information was attained via structured questionnaires. Data from single night PSG were compared between trauma-exposed VV with and without PTSD. RESULTS: A total of 74 trauma-exposed male VV (40 with PTSD) underwent PSG (prospective n = 59, retrospective n = 15). All PSG parameters were similar between groups. No difference was seen in PSG-diagnosed obstructive sleep apnea (OSA) or periodic limb movements of sleep (PLMS). VV with PTSD showed a trend toward increased duration of sleep with oxygen saturations < 90% (10% versus 1.8%; P = .07). VV with PTSD reported increased sleep onset latency (42.4 versus 13.3 minutes; P < .01); were less likely to report sleeping well (32.5% versus 67.5%; P < .01); had higher OSA risk using Berlin Questionnaire (BQ) (70% versus 38.2%; P < .01); and had higher rates of partner-reported limb movements (56.4% versus 17.6%; P < .01). No association between PSG-diagnosed OSA and PTSD severity was evident. CONCLUSIONS: In Australian VV with and without PTSD, no difference was seen across all PSG parameters including the diagnosis and severity of OSA and PLMS. However, VV with PTSD demonstrated an increased perception of sleep disturbances.


Assuntos
Polissonografia/métodos , Transtornos do Sono-Vigília/diagnóstico , Transtornos do Sono-Vigília/epidemiologia , Transtornos de Estresse Pós-Traumáticos/epidemiologia , Veteranos/estatística & dados numéricos , Idoso , Austrália/epidemiologia , Estudos de Coortes , Comorbidade , Estudos Transversais , Humanos , Masculino , Prevalência , Índice de Gravidade de Doença , Guerra do Vietnã
6.
Australas Psychiatry ; 26(5): 524-530, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30113869

RESUMO

OBJECTIVES: There are some psychosocial factors that have similar importance to biological factors in the genesis of coronary diseases. However, reasons for high rates of coronary heart disease in individuals with post-traumatic stress disorder (PTSD) are yet to be fully elucidated. Using a meta-analysis, we investigated the longitudinal relationship between PTSD and coronary heart disease (CHD) as an independent factor in the aetiology of CHD. METHODS: The databases of Medline, EBSCOhost and Psychoinfo were electronically searched for relevant articles. RESULTS: The pooled hazard ratio (HR) for the magnitude of the relationship between PTSD and CHD was an HR of 1.61, and p-value of p < 0.0005, 95% confidence interval (CI) [1.46-1.77] before adjustment for depression in nine studies ( N = 151,144) that met inclusion criteria. The HR estimates for the seven depression-adjusted estimates was 1.46, and a p-value of p < 0.0005, 95% CI[0.26-1.69]. CONCLUSIONS: This study demonstrates an association between CHD and PTSD.


Assuntos
Comorbidade , Doença da Artéria Coronariana , Transtorno Depressivo , Transtornos de Estresse Pós-Traumáticos , Doença da Artéria Coronariana/epidemiologia , Doença da Artéria Coronariana/etiologia , Transtorno Depressivo/epidemiologia , Transtorno Depressivo/etiologia , Humanos , Transtornos de Estresse Pós-Traumáticos/epidemiologia , Transtornos de Estresse Pós-Traumáticos/etiologia
7.
R Soc Open Sci ; 5(3): 180100, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29658963

RESUMO

[This corrects the article DOI: 10.1098/rsos.171085.].

8.
Australas Psychiatry ; 26(1): 60-64, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-28994620

RESUMO

OBJECTIVES: Several studies have demonstrated a link between post-traumatic stress disorder and myocardial infarction. We aim to determine what phenotypic features or symptom profile associated with cardiovascular disease may help with early detection and intervention. METHODS: This is a cross-sectional study. The study population comprises trauma-exposed Vietnam War veterans. RESULTS: Variables significantly associated with myocardial infarction from the bivariate analysis were avoidance memories, avoidance reminders and sleep disturbance. These variables were put into a logistic regression with known risk factors for myocardial infarction. Only sleep disturbance retained its effect, with a p-value of 0.015. CONCLUSIONS: It is concluded that sleep disturbance may be a modifiable risk factor in the treatment and prevention of myocardial infarction.


Assuntos
Infarto do Miocárdio/epidemiologia , Transtornos do Sono-Vigília/epidemiologia , Transtornos de Estresse Pós-Traumáticos/epidemiologia , Veteranos/estatística & dados numéricos , Idoso , Idoso de 80 Anos ou mais , Comorbidade , Estudos Transversais , Humanos , Masculino , Pessoa de Meia-Idade , Queensland/epidemiologia , Fatores de Risco , Guerra do Vietnã
9.
Nature ; 551(7682): 557-559, 2017 11 30.
Artigo em Inglês | MEDLINE | ID: mdl-29189798
10.
BMJ ; 358: j3975, 2017 08 30.
Artigo em Inglês | MEDLINE | ID: mdl-28855153
11.
Int J Cardiol ; 248: 361-368, 2017 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-28728851

RESUMO

BACKGROUND: Coronary heart disease is a major cause of heart failure. Availability of risk-prediction models that include both clinical parameters and biomarkers is limited. We aimed to develop such a model for prediction of incident heart failure. METHODS: A multivariable risk-factor model was developed for prediction of first occurrence of heart failure death or hospitalization. A simplified risk score was derived that enabled subjects to be grouped into categories of 5-year risk varying from <5% to >20%. RESULTS: Among 7101 patients from the LIPID study (84% male), with median age 61years (interquartile range 55-67years), 558 (8%) died or were hospitalized because of heart failure. Older age, history of claudication or diabetes mellitus, body mass index>30kg/m2, LDL-cholesterol >2.5mmol/L, heart rate>70 beats/min, white blood cell count, and the nature of the qualifying acute coronary syndrome (myocardial infarction or unstable angina) were associated with an increase in heart failure events. Coronary revascularization was associated with a lower event rate. Incident heart failure increased with higher concentrations of B-type natriuretic peptide >50ng/L, cystatin C>0.93nmol/L, D-dimer >273nmol/L, high-sensitivity C-reactive protein >4.8nmol/L, and sensitive troponin I>0.018µg/L. Addition of biomarkers to the clinical risk model improved the model's C statistic from 0.73 to 0.77. The net reclassification improvement incorporating biomarkers into the clinical model using categories of 5-year risk was 23%. CONCLUSION: Adding a multibiomarker panel to conventional parameters markedly improved discrimination and risk classification for future heart failure events.


Assuntos
Síndrome Coronariana Aguda/diagnóstico , Síndrome Coronariana Aguda/epidemiologia , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/epidemiologia , Síndrome Coronariana Aguda/sangue , Adulto , Idoso , Biomarcadores/sangue , Feminino , Insuficiência Cardíaca/sangue , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Prospectivos , Distribuição Aleatória , Fatores de Risco
12.
Heart ; 103(23): 1860-1866, 2017 12.
Artigo em Inglês | MEDLINE | ID: mdl-28652315

RESUMO

BACKGROUND: A single assessment of psychological distress, which includes depression and anxiety, has been associated with increased mortality in patients with coronary heart disease, but the prognostic importance of persistence of distress symptoms is less certain. AIM: To determine whether intermittent and/or persistent psychological distress is associated with long-term cardiovascular (CV) and total mortality in patients with stable coronary artery disease. METHODS: 950 participants in the Long-Term Intervention with Pravastatin in Ischaemic Disease (LIPID) trial completed at least four General Health Questionnaires (GHQ-30) at baseline and after ½, 1, 2 and 4 years. In a landmark analysis from 4 years, Cox proportional hazards models evaluated the risk of CV and total mortality by increasing levels of psychological distress: never distressed, sometimes any severity (GHQ score >5), persistent mild (GHQ score >5 on three or more occasions) and persistent moderate distress (GHQ score >10) on three or more occasions, over a median of 12.1 (IQR 8.6-12.5) years. The models were both unadjusted and adjusted for known baseline risk factors. RESULTS: Persistent moderate or greater psychological stress was reported on three or more assessments by 35 (3.7%) subjects. These patients had a higher risk of both CV death (adjusted HR 3.94, 95% CI 2.05 to 7.56, p<0.001) and all-cause mortality (adjusted HR 2.85, 95% CI 1.74 to 4.66, p<0.001) compared with patients with no distress. In contrast, patients who reported persistent mild distress (n=73, 7.7%) on three or more visits, and those who met criteria for distress on only one or two assessments (n=255, 26.8%), did not have an increased risk of CV or all-cause mortality during follow-up. CONCLUSION: In patients with stable coronary artery disease, persistent psychological distress of at least moderate severity is associated with a substantial increase in CV and all-cause mortality.


Assuntos
Angina Instável/mortalidade , Doença da Artéria Coronariana/mortalidade , Infarto do Miocárdio/mortalidade , Estresse Psicológico/mortalidade , Adulto , Idoso , Angina Instável/diagnóstico por imagem , Angina Instável/tratamento farmacológico , Angina Instável/psicologia , Austrália , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/tratamento farmacológico , Doença da Artéria Coronariana/psicologia , Feminino , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Estimativa de Kaplan-Meier , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/diagnóstico por imagem , Infarto do Miocárdio/tratamento farmacológico , Infarto do Miocárdio/psicologia , Nova Zelândia , Razão de Chances , Pravastatina/uso terapêutico , Prognóstico , Modelos de Riscos Proporcionais , Medição de Risco , Fatores de Risco , Índice de Gravidade de Doença , Estresse Psicológico/diagnóstico , Estresse Psicológico/psicologia , Inquéritos e Questionários , Fatores de Tempo
13.
BMJ ; 357: j2425, 2017 05 19.
Artigo em Inglês | MEDLINE | ID: mdl-28526742
14.
Curr Med Res Opin ; 33(7): 1337-1341, 2017 07.
Artigo em Inglês | MEDLINE | ID: mdl-28425296

RESUMO

OBJECTIVE: Long-term anticoagulant therapy with non-valvular atrial fibrillation (AF) is essential to prevent thromboembolic complications, especially ischemic stroke. This study examines medium-term persistence in AF patients using a non-vitamin-K antagonist oral anticoagulant drug (NOAC). RESEARCH DESIGN AND METHODS: We assessed national Pharmaceutical Benefit Scheme records December 2013 through September 2016 for initial prescription of a NOAC in a 10% random sample of concessional patients. Key outcome measures were: (a) proportions filling first repeat prescription, (b) proportions persisting with NOAC over 12 and 30 months and (c) proportions switching to another NOAC or warfarin. RESULTS: A total of 8656 patients with AF initiated a NOAC (3352 apixaban, 1340 dabigatran, 3964 rivaroxaban). Mean age was 77 years, 53% male; 91% collected the first repeat prescription for any NOAC, 70% and 57% collected any NOAC or subsequent warfarin prescription over 12 months and 30 months respectively; 8.9% had switched to warfarin. The proportions switching from apixaban, dabigatran and rivaroxaban to a different NOAC were 14%, 31% and 17% respectively. In a regression model adjusting for age, gender and comorbidity, apixaban-initiated patients over 30 months were 28% more likely to persist with any anticoagulant therapy compared with dabigatran-initiated patients (hazard ratio [95% CI] 1.28 [1.16-1.42]) and 15% more likely to persist compared with rivaroxaban-initiated (1.15 [1.06-1.24]). Rivaroxaban-initiated patients were 12% more likely to persist compared with dabigatran-initiated patients (1.12 [1.02-1.24]). CONCLUSIONS: Long-term persistence with anticoagulation in patients with AF remains a concern, even with NOACs. Patients initiated to apixaban appear to experience better medium-term persistence compared with rivaroxaban or dabigatran.


Assuntos
Anticoagulantes/administração & dosagem , Fibrilação Atrial/tratamento farmacológico , Acidente Vascular Cerebral/prevenção & controle , Varfarina/administração & dosagem , Administração Oral , Idoso , Idoso de 80 Anos ou mais , Anticoagulantes/uso terapêutico , Austrália , Comorbidade , Dabigatrana/uso terapêutico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pirazóis/administração & dosagem , Piridonas/administração & dosagem , Rivaroxabana/uso terapêutico , Varfarina/uso terapêutico
15.
Med J Aust ; 206(6): 251-257, 2017 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-28359007

RESUMO

OBJECTIVE: To determine whether the prevalence of physical comorbidities in Australian Vietnam War veterans with post-traumatic stress disorder (PTSD) is higher than in trauma-exposed veterans without PTSD. DESIGN, SETTING AND PARTICIPANTS: Cross-sectional analysis of the health status (based on self-reported and objective clinical assessments) of 298 Australian Vietnam War veterans enrolled by the Gallipoli Medical Research Institute (Brisbane) during February 2014 - July 2015, of whom 108 were confirmed as having had PTSD and 106 served as trauma-exposed control participants.Main outcomes and measures: Diagnostic psychiatric interview and psychological assessments determined PTSD status, trauma exposure, and comorbid psychological symptoms. Demographic data, and medical and sleep history were collected; comprehensive clinical examination, electrocardiography, spirometry, liver transient elastography, and selected pathology assessments and diagnostic imaging were performed. Outcomes associated with PTSD were identified; regression analysis excluded the effects of potentially confounding demographic and risk factors and comorbid symptoms of depression and anxiety. RESULTS: The mean total number of comorbidities was higher among those with PTSD (17.7; SD, 6.1) than in trauma-exposed controls (14.1; SD, 5.2; P < 0.001). For 24 of 171 assessed clinical outcomes, morbidity was greater in the PTSD group, including for conditions of the gastrointestinal, hepatic, cardiovascular, and respiratory systems, sleep disorders, and laboratory pathology measures. In regression analyses including demographic factors, PTSD remained positively associated with 17 adverse outcomes; after adjusting for the severity of depressive symptoms, it remained significantly associated with ten. CONCLUSION: PTSD in Australian Vietnam veterans is associated with comorbidities in several organ systems, independent of trauma exposure. A comprehensive approach to the health care of veterans with PTSD is needed.


Assuntos
Doenças Cardiovasculares/epidemiologia , Doenças do Sistema Digestório/epidemiologia , Transtornos Mentais/epidemiologia , Doenças Respiratórias/epidemiologia , Transtornos de Estresse Pós-Traumáticos/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Austrália/epidemiologia , Doenças Cardiovasculares/psicologia , Estudos de Casos e Controles , Comorbidade , Estudos Transversais , Doenças do Sistema Digestório/psicologia , Humanos , Masculino , Transtornos Mentais/psicologia , Pessoa de Meia-Idade , Doenças Profissionais/epidemiologia , Doenças Profissionais/psicologia , Exposição Ocupacional , Prevalência , Análise de Regressão , Doenças Respiratórias/psicologia , Transtornos de Estresse Pós-Traumáticos/etiologia , Veteranos/psicologia , Veteranos/estatística & dados numéricos , Guerra do Vietnã
16.
R Soc Open Sci ; 4(12): 171085, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29308247

RESUMO

We wish to answer this question: If you observe a 'significant' p-value after doing a single unbiased experiment, what is the probability that your result is a false positive? The weak evidence provided by p-values between 0.01 and 0.05 is explored by exact calculations of false positive risks. When you observe p = 0.05, the odds in favour of there being a real effect (given by the likelihood ratio) are about 3 : 1. This is far weaker evidence than the odds of 19 to 1 that might, wrongly, be inferred from the p-value. And if you want to limit the false positive risk to 5%, you would have to assume that you were 87% sure that there was a real effect before the experiment was done. If you observe p = 0.001 in a well-powered experiment, it gives a likelihood ratio of almost 100 : 1 odds on there being a real effect. That would usually be regarded as conclusive. But the false positive risk would still be 8% if the prior probability of a real effect were only 0.1. And, in this case, if you wanted to achieve a false positive risk of 5% you would need to observe p = 0.00045. It is recommended that the terms 'significant' and 'non-significant' should never be used. Rather, p-values should be supplemented by specifying the prior probability that would be needed to produce a specified (e.g. 5%) false positive risk. It may also be helpful to specify the minimum false positive risk associated with the observed p-value. Despite decades of warnings, many areas of science still insist on labelling a result of p < 0.05 as 'statistically significant'. This practice must contribute to the lack of reproducibility in some areas of science. This is before you get to the many other well-known problems, like multiple comparisons, lack of randomization and p-hacking. Precise inductive inference is impossible and replication is the only way to be sure. Science is endangered by statistical misunderstanding, and by senior people who impose perverse incentives on scientists.

17.
J Gen Physiol ; 148(2): 79-88, 2016 08.
Artigo em Inglês | MEDLINE | ID: mdl-27432998
18.
Curr Med Res Opin ; 32(11): 1857-1861, 2016 11.
Artigo em Inglês | MEDLINE | ID: mdl-27463735

RESUMO

OBJECTIVE: Long-term anticoagulant therapy in patients with non-valvular atrial fibrillation (AF) is essential to prevent thromboembolic complications, especially ischemic stroke, but treatment persistence with warfarin is poor. This study examines Australian nationwide persistence in AF patients using a non-vitamin-K oral anticoagulant (NOAC) drug. RESEARCH DESIGN AND METHODS: We assessed national Pharmaceutical Benefit Scheme records November-December 2013 through March 2015 for prescription of NOAC drugs in a 10% random sample of long-term concession card holders. An historical comparison was made with patients prescribed warfarin in 2008. Key outcome measures were (i) the proportion not filling first repeat prescription and (ii) discontinuation within 12 months. RESULTS: A total of 1471 patients with AF were new users of a NOAC drug (228 apixaban, 645 dabigatran, 598 rivaroxaban) and 1348 were new users of warfarin. Mean age on a NOAC was 76 years (58% male), on warfarin 74 years (54% male). Only 9% (95% CI 7-10) failed to collect the first repeat prescription on a NOAC, 30% (27-32) discontinued within 12 months; corresponding proportions on warfarin were 14% (12-16) and 62% (60-65). In a regression model adjusted for age, gender, heart failure, hypertension and diabetes, warfarin-treated patients were 2.5 times more likely to discontinue over 12 months than those who were NOAC treated (hazard ratio =2.47 [95% CI 2.19-2.79]). CONCLUSIONS: Persistence with NOAC drugs in patients with AF appears to be superior to warfarin. If continued long-term, this alone will be of clinical importance in the prevention of stroke and death.


Assuntos
Anticoagulantes/uso terapêutico , Fibrilação Atrial/tratamento farmacológico , Varfarina/uso terapêutico , Administração Oral , Idoso , Idoso de 80 Anos ou mais , Dabigatrana/uso terapêutico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pirazóis/uso terapêutico , Piridonas/uso terapêutico , Rivaroxabana/uso terapêutico
19.
Cardiovasc Drugs Ther ; 30(3): 297-304, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26936841

RESUMO

PURPOSE: Recent evidence suggests that statin intolerance may be more common than reported in randomized trials. However, the statin-intolerant population is not well characterized. The goal of this report is to characterize the population enrolled in the phase 3 Goal Achievement after Utilizing an anti-PCSK9 antibody in Statin Intolerant Subjects Study (GAUSS-2; NCT 01763905). METHODS: GAUSS-2 compared evolocumab, a fully human monoclonal antibody to proprotein convertase subtilisin/kexin type 9 (PCSK9) to ezetimibe in hypercholesterolemic patients who discontinued statin therapy due to statin-associated muscle symptoms (SAMS). GAUSS-2 was a 12-week, double-blind, placebo-controlled, randomized study that enrolled patients with elevated LDL-C who were either not on a statin or able to tolerate only a low-dose due to SAMS. Patients had received ≥2 statins and were unable to tolerate any statin dose or increase in dose above a specified weekly dose due to SAMS. RESULTS: Three hundred seven patients (mean [SD] age, 62 [10] years; 54 % males) were randomized 2:1 (evolocumab:ezetimibe). Mean (SD) LDL-C was 4.99 (1.51) mmol/L. Patients had used ≥2 (100 %), ≥3 (55 %), or ≥4 (21 %) statins. Coronary artery disease was present in 29 % of patients. Statin-intolerant symptoms were myalgia in 80 % of patients, weakness in 39 %, and more serious complications in 20 %. In 98 % of patients, SAMS interfered with normal daily activity; in 52 %, symptoms precluded moderate exertion. CONCLUSION: Evaluation of the GAUSS-2 trial population of statin-intolerant patients demonstrates that most patients were high risk with severely elevated LDL-C and many had statin-associated muscle symptoms that interfered with their quality of life.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Anticolesterolemiantes/uso terapêutico , Ezetimiba/uso terapêutico , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Hipercolesterolemia/tratamento farmacológico , Doenças Musculares/induzido quimicamente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Humanizados , LDL-Colesterol/sangue , Método Duplo-Cego , Feminino , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Hipercolesterolemia/sangue , Masculino , Pessoa de Meia-Idade , Pró-Proteína Convertase 9/antagonistas & inibidores , Adulto Jovem
20.
Circulation ; 133(19): 1851-60, 2016 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-27016105

RESUMO

BACKGROUND: We aimed to assess the long-term effects of treatment with statin therapy on all-cause mortality, cause-specific mortality, and cancer incidence from extended follow-up of the Long-term Intervention with Pravastatin in Ischemic Disease (LIPID) trial. METHODS AND RESULTS: LIPID initially compared pravastatin and placebo over 6 years in 9014 patients with previous coronary heart disease. After the double-blind period, all patients were offered open-label statin therapy. Data were obtained over a further 10 years from 7721 patients, by direct contact for 2 years, by questionnaires thereafter, and from mortality and cancer registries. During extended follow-up, 85% assigned pravastatin and 84% assigned placebo took statin therapy. Patients assigned pravastatin maintained a significantly lower risk of death from coronary heart disease (relative risk [RR] 0.89; 95% confidence interval [CI], 0.81-0.97; P=0.009), from cardiovascular disease (RR, 0.88; 95% CI, 0.81-0.95; P=0.002), and from any cause (RR, 0.91; 95% CI, 0.85-0.97; absolute risk reduction, 2.6%; P=0.003).Cancer incidence was similar by original treatment group during the double-blind period (RR, 0.94; 95% CI, 0.82-1.08; P=0.41), later follow-up (RR, 1.02; 95% CI, 0.91-1.14; P=0.74), and overall (RR, 0.99; 95% CI, 0.91-1.08; P=0.83). There were no significant differences in cancer mortality, or in the incidence of organ-specific cancers. Cancer findings were confirmed in a meta-analysis with other large statin trials with extended follow-up. CONCLUSIONS: In LIPID, the absolute survival benefit from 6 years of pravastatin treatment appeared to be maintained for the next 10 years, with a similar risk of death among survivors in both groups after the initial period. Treatment with statins does not influence cancer or death from noncardiovascular causes during long-term follow-up.


Assuntos
Doença da Artéria Coronariana/tratamento farmacológico , Doença da Artéria Coronariana/mortalidade , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Pravastatina/uso terapêutico , Doença da Artéria Coronariana/diagnóstico , Método Duplo-Cego , Feminino , Seguimentos , Humanos , Estudos Longitudinais , Masculino , Estudos Multicêntricos como Assunto , Ensaios Clínicos Controlados Aleatórios como Assunto , Taxa de Sobrevida/tendências , Fatores de Tempo
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