Evaluation of the effectiveness of cytisine for the treatment of smoking cessation: A systematic review and meta-analysis.

BACKGROUND AND AIMS: Smoking is considered the main cause of preventable death world-wide. This study aimed to review the efficacy and safety of cytisine for smoking cessation. METHODS: This review included an exhaustive search of databases to identify randomized controlled trials (RCTs) in health centers of any level with smokers of any age or gender investigating the effects of cytisine at standard dosage versus placebo, varenicline or nicotine replacement therapy (NRT). RESULTS: We identified 12 RCTs. Eight RCTs compared cytisine with placebo at the standard dose covering 5922 patients, 2996 of whom took cytisine, delivering a risk ratio (RR) of 2.25 [95% confidence interval (CI) = 1.42-3.56; I2  = 88%; moderate-quality evidence]. The greater intensity of behavioral therapy was associated directly with the efficacy findings (moderate-quality evidence). The confirmed efficacy of cytisine was not evidenced in trials conducted in low- and middle-income countries. We estimate a number needed to treat (NNT) of 11. Two trials compared the efficacy of cytisine versus NRT, and the combination of both studies yields modest results in favor of cytisine. Three trials compared cytisine with varenicline, without a clear benefit for cytisine. Meta-analyses of all non-serious adverse events in the cytisine group versus placebo groups yielded a RR of 1.24 (95% CI = 1.11-1.39; participants = 5895; studies = 8; I2 = 0%; high-quality evidence). CONCLUSIONS: Cytisine increases the chances of successful smoking cessation by more than twofold compared with placebo and has a benign safety profile, with no evidence of serious safety concerns. Limited evidence suggests that cytisine may be more effective than nicotine replacement therapy, with modest cessation rates.

Tabagismo na pandemia de Covid-19: aspectos neurobiológicos do abuso de drogas em condições de estresse prolongado / Smoking on Covid-19 pandemic: neurobiological aspects of drug abuse in lasting stress conditions / Fumar en la pandemia de Covid-19: aspectos neurobiológicos del abuso de drogas en condiciones de estrés duradero

No fim de 2019 iniciou-se uma das maiores crises da saúde pública global em Wuhan, China. Essa emergência foi o aparecimento do SARS-CoV-2 e da doença COVID-19, uma síndrome respiratória aguda de alta transmissibilidade. A declaração da pandemia pela OMS em março de 2020 fez com que o mundo tomasse diversas medidas para o combate e contenção da doença. Inicialmente o isolamento social e lockdown foram as principais iniciativas, já que não havia formas de tratamento ou prevenção da doença. Essas medidas restritivas geraram uma mudança de hábito da população que deflagrou sérios comprometimentos físicos e psicológicos. Uma das consequências foi o aumento do uso de substâncias de abuso e, consequentemente, do transtornos por uso de substâncias, dentre elas o tabaco. Durante a pandemia o consumo de cigarro aumentou de 10 a 30% no mundo, o tabagismo é a principal causa de morte evitável e fator de risco para diversas doenças. Conjuntamente ao álcool, a nicotina têm um poder aditivo superior a muitas drogas ilícitas. A combinação dos transtornos por uso de substâncias e a COVID-19 acabam por ter um efeito sinérgico, dessa forma, buscamos integrar aspectos neuroquímicos, cognitivos e comportamentais que levaram ao aumento do consumo e/ou recaída nicotina e a terapêutica utilizada.

One of the biggest global public health crisis began in Wuhan, China at the end of 2019. That emergency was the emergence of SARS-CoV-2 and the disease COVID-19, a highly transmissible acute respiratory syndrome. The pandemic declaration by the WHO in March 2020 caused the world to take on several measures to combat and contain the virus. Initially, social isolation and lockdown were the main initiatives, as there were no forms of treatment or prevention of the disease. These restrictive measures generate a change in the habit of the population that triggered serious physical and psychological impairments. One of the consequences was the increase in the use of substances of abuse and, consequently, substance use disorder, including tobacco. During the pandemic, cigarette consumption increased from 10 to 30% worldwide, whereas smoking is the main cause of preventable death and a risk factor for several diseases. Along with alcohol, nicotine has a greater addictive power than illicit drugs. Substance use disorders and COVID-19 have a synergistic effect, in this way, we seek to integrate neurochemical, cognitive and behavioral aspects that led to increased consumption and/or relapse in nicotine consumption and the used therapy.

Una de las mayores crisis mundiales de salud pública comenzó en Wuhan (China) a finales de 2019. Esa emergencia fue la aparición del SARS-CoV-2 y la enfermedad COVID-19, un síndrome respiratorio agudo altamente transmisible. La declaración de pandemia por parte de la OMS en marzo de 2020 hizo que el mundo adoptara varias medidas para combatir y contener el virus. Inicialmente, el aislamiento social y el encierro fueron las principales iniciativas, ya que no existían formas de tratamiento o prevención de la enfermedad. Estas medidas restrictivas generaron un cambio en los hábitos de la población que desencadenó graves alteraciones físicas y psicológicas. Una de las consecuencias fue el aumento del consumo de sustancias de abuso y, en consecuencia, el trastorno por consumo de sustancias, incluido el tabaco. Durante la pandemia, el consumo de cigarrillos aumentó del 10 al 30% en todo el mundo, mientras que el tabaquismo es la principal causa de muerte evitable y un factor de riesgo de varias enfermedades. Junto con el alcohol, la nicotina tiene un mayor poder adictivo que las drogas ilícitas. Los trastornos por uso de sustancias y la COVID-19 tienen un efecto sinérgico, de esta manera, buscamos integrar los aspectos neuroquímicos, cognitivos y conductuales que llevaron al aumento del consumo y/o recaída en el consumo de nicotina y la terapia utilizada.

Varenicline for Tobacco-Dependent Adults Who Are Not Ready to Discontinue Use: A Systematic Review and Meta-Analysis.

Rationale: Not all individuals with tobacco dependence are ready to give up smoking. Research reveals behavioral differences between adults ready to discontinue tobacco use and those who are not. Thus, the interventions applied to these populations might differ. However, the evidence of using varenicline in individuals who are not ready to discontinue tobacco use is uncertain. Objectives: To determine if, in tobacco-dependent adults who report not being ready to discontinue tobacco use, clinicians should begin treatment with varenicline or wait until subjects are ready to discontinue tobacco use. Methods: We conducted a systematic review to assess the effectiveness and safety of treatment with varenicline in tobacco-dependent adults who are not ready to discontinue tobacco use. We systematically searched the Cumulative Index to Nursing and Allied Health Literature, Embase, MEDLINE, and the Cochrane Central Register of Controlled Trials to identify randomized controlled trials comparing varenicline versus placebo for individuals who were not ready to discontinue tobacco use. Outcomes of interest include point prevalence abstinence during treatment or at six months or longer, smoking reduction, motivation to quit, adverse events, and withdrawal symptoms. Two authors independently extracted data and assessed eligibility and risk of bias using a standardized data collection form. We followed the Grading of Recommendations, Assessment, Development and Evaluations approach to assess the certainty of evidence. Results: Five trials met our inclusion criteria. All 2,616 participants were adults who were not ready to discontinue tobacco use at study entry. For 7-day point prevalence abstinence at six months or longer, high-certainty evidence suggested that varenicline increased abstinence compared with placebo (relative risk, 2.00 [95% confidence interval (CI), 1.70-2.35]; absolute risk reduction, 173 more per 1,000 [95% CI, 121 more to 234 more]). We identified moderate-certainty evidence suggesting that varenicline increased serious adverse events (relative risk, 1.75 [95% CI, 0.98-3.13]; absolute risk reduction, 12 more per 1,000 [95% CI, 0 fewer to 35 more]). For withdrawal, low-certainty evidence suggested that varenicline treatment was associated with a lower symptom score (mean difference, 1.54 points lower; 95% CI, 2.15-0.93 points lower; low certainty) assessed using the Brief Questionnaire of Smoking Urges. Conclusions: In tobacco-dependent adults who are not ready to discontinue tobacco use, initiating varenicline treatment results in a large increase in abstinence and likely results in a slight increase in serious adverse events.

Matching-adjusted indirect comparison of phase 3 clinical trial outcomes: OC-01 (varenicline solution) nasal spray and cyclosporine a 0.05% ophthalmic emulsion for the treatment of dry eye disease.

BACKGROUND: Matching-adjusted indirect comparison (MAIC) is a validated and widely accepted statistical method that derives indirect comparisons between treatments when head-to-head studies have not been performed. OBJECTIVE: To compare the efficacy of OC-01 varenicline nasal spray (OC-01 VNS) 0.03 mg to cyclosporine A (CsA) 0.05% ophthalmic emulsion on tear production in patients with dry eye disease based on data from the respective phase 3 clinical trials using the MAIC technique. METHODS: Individual patient data were drawn from the phase 3 registry trial of OC-01 VNS; aggregate data were drawn from 2 phase 3 trials of CsA in the publicly available New Drug Application for CsA 0.05% ophthalmic emulsion (RESTASIS). Using unanchored MAIC methods, the individual patient data were weighted based on 4 clinically relevant baseline variables (age, race, sex, and baseline Schirmer test score [STS]) to produce a weighted OC-01 VNS dataset matched to the key demographics of the CsA dataset. Least-squares mean change from baseline in STS for OC-01 VNS was calculated using the identical analysis of variance model used to calculate the same value for CsA in the RESTASIS New Drug Application, which were then compared. Proportions of subjects with improvement of 10 mm or more from baseline in STS were compared in the weighted OC-01 VNS and CsA dataset. Time points available for comparisons were CsA trials at 3 and 6 months and OC-01 data at 2 and 4 weeks. RESULTS: Data from 511 subjects in the OC-01 VNS phase 3 trial and 585 in the CsA phase 3 trials were analyzed. The least-squares mean STS change from baseline for OC-01 VNS at 2 and 4 weeks was significantly higher than that for CsA at 3 and 6 months (P < 0.0001 for all comparisons). Mean STS improvements were approximately 6-7 mm for OC-01 VNS and approximately 1 mm for CsA. The proportion of subjects with improvement of 10 mm or more from baseline in STS was significantly higher for OC-01 VNS (50.2%) than CsA (11.7 and 17.1% in the 2 CsA studies; P < 0.0001 for both comparisons). CONCLUSIONS: This MAIC analysis demonstrates OC-01 VNS produces significantly greater improvement in mean STS and results in significantly greater numbers of patients with substantial improvement in STS (percentage ≥ 10 mm) compared with CsA. Together, absent more robust data from head-to-head trials, findings may suggest a potentially greater magnitude of improvement achieved with OC-01 VNS compared with CsA for the treatment of dry eye disease within conditions of the analysis methodology. DISCLOSURES: Dr Visco was a consultant for Novartis, Allergan, and Oyster Point, Inc. Ms Hendrix and Drs Macsai and Gibson are employees and shareholders for Oyster Point Pharma, Inc. Drs Sun and Tam participated in clinical research and received funding from Oyster Point Pharma, Inc. Oyster Point Pharma, Inc sponsored the Phase 3 OC-01 (varenicine solution) clinical study from which analysis data are obtained.

Cost-Effectiveness Analysis of Varenicline Versus Currently Funded Smoking Cessation Strategies in Brazil.

OBJECTIVES: To assess the cost-effectiveness of varenicline in comparison to currently funded smoking cessation strategies in Brazil. METHODS: We modeled the lifetime direct costs and health-related quality of life of a hypothetical cohort of smokers with a single attempt to quit smoking using one of the following: (1) cognitive behavioral therapy (CBT) without any pharmacological intervention, (2) varenicline, (3) bupropion, (4) nicotine replacement therapy (NRT) with transdermal patch, (5) bupropion in combination with NRT transdermal patch, and (6) combined NRT (oral plus transdermal). All drug alternatives were considered with concomitant CBT. The analysis relied on a Markov model based on the Benefits of Smoking Cessation and Outcomes study and used different age and sex categories in the consideration of relative risks and incidence rates of the diseases included in the model. The analysis was conducted from the healthcare system perspective, and a 3% discounting rate for costs and outcomes was applied. Model parameter values were sourced from published literature. Probabilistic and deterministic sensitivity analyses assessed robustness. RESULTS: Among the smoking cessation alternatives available in Brazil, varenicline and combined NRT were estimated to have higher effectiveness; varenicline, however, was dominated due to its higher average cost. In the base-case analysis, combined NRT had an incremental gain of 0.25 quality-adjusted life-years (QALYs) in comparison to the second-best option (bupropion in combination with NRT transdermal patch) and an incremental cost-effectiveness ratio of R$2173.47/QALY ($595.45/QALY). CONCLUSIONS: Combination of oral and transdermal NRT (coupled with CBT) was the most effective smoking cessation option and was 100% cost-effective within a conservative willingness-to-pay threshold.

Profile of the Nicotinic Cholinergic Receptor Alpha 7 Subunit Gene Expression is Associated with Response to Varenicline Treatment.

INTRODUCTION: Smoking is considered the leading cause of preventable morbidity and mortality worldwide. Studies have sought to identify predictors of response to smoking cessation treatments. The aim of this study was to analyze a possible association of target gene expression for smoking cessation with varenicline. METHODS: We included 74 smokers starting treatment with varenicline. Gene expression analysis was performed through the custom RT² Profiler qPCR array assay, including 17 genes. Times for sample collection were before the start of therapy (T0) and two weeks (T2) and four weeks (T4) after the start of treatment. RESULTS: For gene expression analysis, we selected 14 patients who had success and 13 patients resistant to varenicline treatment. Success was considered to be when a patient achieved tobacco abstinence until the fourth week of treatment and resistant was when a patient had not stopped smoking as of the fourth week of treatment. We observed a significant difference for CHRNA7 gene expression: in the resistant group, samples from T2 and T4 had lower expression compared with T0 (fold change: 0.38, P = 0.007; fold change: 0.67, P = 0.004; respectively). CONCLUSION: This exploratory clinical study, searching for a possible predictor of effectiveness for varenicline, reaffirmed the association of the α7 nAChR subunit for nicotine dependence and smoking therapy effectiveness with varenicline.

Cytochrome P450 2A6 and 2B6 polymorphisms and smoking cessation success in patients treated with varenicline.

BACKGROUND: The identification of variants in genes involved in nicotine metabolism may have implications for the pharmacological therapy of smoking. In the scenario of precision medicine, the aim of this study was to evaluate a possible association of cytochrome P450 2A6 and 2B6 polymorphisms with varenicline pharmacotherapy. METHODS: The present study included 167 patients treated with varenicline in monotherapy who were from a cohort study of 1049 patients (treated with smoking cessation drugs: nicotine replacement therapy, bupropion, varenicline, or combinations of same). Smoking cessation success was considered for patients who completed 6 months of continuous abstinence. The CYP2A6 rs1801272 and rs28399433 and CYP2B6 rs8109525 polymorphisms were genotyped by real-time PCR using the TaqMan® platform. RESULTS: Patients with AG or GG genotypes for CYP2B6 rs8109525 had a higher success rate of smoking cessation with varenicline (51.2%) compared with carriers of the AA genotypes (33.3%, P = 0.03, n = 167). The AG or GG genotypes were also associated with a higher odds ratio of success, even in a multivariate analysis adjusting for potential confounders (OR = 2.01; 95%CI = 1.01 to 4.00; P = 0.047). CONCLUSION: CYP2B6 rs8109525 was associated with a higher success rate of smoking cessation with varenicline treatment. This finding may be useful in pharmacogenomic strategies for smoking cessation therapy.

Vareniclina para cessação do tabagismo / Varenicline for smoking cessation

INTRODUÇÃO: O tabagismo é fator causal para doenças incapacitantes e fatais, como câncer, doenças cardiovasculares e respiratórias crônicas. Atualmente, o modelo de tratamento adotado no SUS tem como base a abordagem cognitivo-comportamental e apoio farmacoterápico, quando necessário, com reposição de nicotina e cloridrato de bupropiona. TECNOLOGIA: Tartarato de Vareniclina (Champix®). PERGUNTA: O tratamento com vareniclina é mais eficaz, seguro e custo-efetivo para a cessação do tabagismo do que as terapias farmacológicas atualmente disponíveis no SUS? EVIDÊNCIAS CIENTÍFICAS: A vareniclina (período habitual de tratamento de 12 semanas) demonstrou eficácia quando comparada ao grupo placebo, para a cessação do tabagismo - 6 meses ou mais (RR 2,24; IC95% 2,06 - 2,43). Quando comparada com bupropiona, a vareniclina mostrou-se mais eficaz tanto na abstinência aos 6 meses (RR 1,39; IC95% 1,25 ­ 1,54), como na abstinência às 52 semanas (RR 1,52; IC95% 1,22 ­ 1,88), ambas com tratamento usual (12 semanas). Na comparação com TRN isolada, a vareniclina também mostrou uma eficácia maior para abstinência aos 6 meses (RR 1,25; IC95% 1,14 ­ 1,37), ambas com tratamento usual (12 semanas). Contudo, quanto se compara a vareniclina com a combinação de TRN (CTRN), não foi verificada diferença entre os tratamentos (OR 1,06; IC95% 0,75-1,48). Resultado similar foi verificado em um ECR que avaliou a comparação direta entre a CTRN e vareniclina, a taxa de cessação do tabagismo após seis meses foi estatisticamente semelhante entre os grupos, correspondendo a 26,8% e 23,6%, respectivamente. Os eventos adversos moderados significativamente mais frequentes para vareniclina foram: náusea, insônia, sonhos anormais e dor de cabeça. Depressão e ideação suicida não apresentaram associação com o uso de vareniclina. Por fim, observou-se um risco aumentado de 25% de eventos adversos sérios para a utilização de vareniclina em comparação ao placebo (RR 1,25; IC25% 1,04 - 1,49). AVALIAÇÃO ECONÔMICA: O tratamento com vareniclina não se mostrou mais custo-efetivo que o tratamento com CTRN, sendo a vareniclina uma alternativa dominada pela CTRN, com mesma efetividade e custo médio por paciente superior. Os resultados para a simulação probabilística (Monte Carlo de 1ª e 2ª ordem) com 10.000 simulações de 3.000 pacientes foram similares e a razão de custo-efetividade incremental da CTRN quando comparada à alternativa não dominada de monoterapia com bupropiona foi de R$ 2.106,32/QALY. A CTRN apresentou razão de custoefetividade incremental favorável inclusive em limiares de disposição a pagar restritos, apresentando 100% de probabilidade de ser custo-efetiva no limiar de 0,5 PIB perca pita. AVALIAÇÃO DE IMPACTO ORÇAMENTÁRIO: Ambas as tecnologias mostraram grande variação dentro dos diversos cenários simulados em comparação à TRN isolada e à bupropiona. O impacto orçamentário da vareniclina variou entre R$ 14.155.153,65 a R$ 208.083.216,00, e o da CTRN (forma lenta e rápida de liberação de nicotina) variou entre R$ 9.574.166,25 a R$ 290.210.250,00. Tal variação mostra a necessidade de se avaliar as incertezas relacionados ao uso dos medicamentos, como a quantidade média consumida, a estrutura do sistema de saúde, a proporção de pacientes que teriam acesso a prescrição médica e o orçamento disponível, de forma a obter o menor impacto orçamentário com a estratégia mais custo-efetiva. RECOMENDAÇÃO PRELIMINAR: O Plenário, na reunião da CONITEC realizada em 08 de maio de 2019, considerou que o modelo de tratamento para a cessação do tabagismo adotado no Brasil já preconiza e disponibiliza a utilização de farmacoterapia adjuvante pelo SUS (TRN e Cloridrato de Bupropiona). Não há evidência científica, até o momento, da superioridade da vareniclina para a cessação do tabagismo, quando comparada com a combinação de duas TRN (forma lenta e rápida de liberação de nicotina) e a avaliação econômica mostrou a vareniclina como opção dominada em relação à combinação de TRN. Portanto, emitiu-se recomendação preliminar pela não incorporação no SUS da vareniclina (Champix®) para o tratamento do tabagismo. CONSULTA PÚBLICA: Foram recebidas 8 contribuições técnico-científicas e 39 contribuições de experiência ou opinião, a maioria discordante com a recomendação preliminar da CONITEC. Não foram apresentados dados de eficácia, segurança, custo-efetividade e impacto orçamentário, relacionados a comparação da vareniclina com a CTRN, para contra argumentar os dados apresentados nesse relatório. A CONITEC entendeu que não houve argumentação que justificasse a alteração da sua recomendação inicial. RECOMENDAÇÃO FINAL: Os membros da CONITEC em 03/07/2019 deliberaram por recomendar a não incorporação no SUS da vareniclina (Champix®) para dependência à nicotina. Foi assinado o Registro de Deliberação nº 468/2019. DECISÃO: Não incorporar a vareniclina para a cessação do tabagismo, no âmbito do Sistema Único de Saúde - SUS. Dada pela Portaria nº 41, publicada no Diário Oficial da União nº 61, seção 1, página 148, em 25 de julho de 2019.

Predictors of Varenicline Adherence Among Cancer Patients Treated for Tobacco Dependence and its Association With Smoking Cessation.

INTRODUCTION: The degree to which smokers adhere to pharmacotherapy predicts treatment success. The development of interventions to increase adherence requires identification of predictors of treatment adherence, particularly among specific clinical populations. METHODS: Using data from a 12-week open-label phase of a clinical trial of varenicline for tobacco dependence among cancer patients (N = 207), we examined: (1) the relationship between self-reported varenicline adherence and verified smoking cessation and (2) demographic and disease-related variables, and early changes in cognition, affect, withdrawal, the reinforcing effects of smoking, and medication side effects, as correlates of varenicline adherence. RESULTS: At the end of 12 weeks, 35% of the sample had quit smoking and 52% reported taking ≥80% of varenicline. Varenicline adherence was associated with cessation (p < .001): 58% of participants who were adherent had quit smoking versus 11% of those who were not. Participants who experienced early reductions in depressed mood and satisfaction from smoking and experienced an increase in the toxic effects of smoking, showed greater varenicline adherence (p < .05); the relationship between greater adherence and improved cognition, reduced craving, and reduced sleep problems and vomiting approached significance (p < .10). CONCLUSIONS: Among cancer patients treated for tobacco dependence with varenicline, adherence is associated with smoking cessation. Initial changes in depressed mood and the reinforcing effects of smoking are predictive of adherence. IMPLICATIONS: The benefits of varenicline for treating tobacco dependence among cancer patients may depend upon boosting adherence by addressing early signs of depression and reducing the reinforcing dimensions of cigarettes.

Tartarato de vareniclina para tratamento adjuvante da cessação do tabagismo em pacientes adultos com doença pulmonar obstrutiva crônica ou doenças cardiovasculares / Varenicline tartrate for adjunctive treatment of smoking cessation in adult patients with chronic obstructive pulmonary disease or cardiovascular disease

INTRODUÇÃO: A Doença Pulmonar Obstrutiva Crônica (DPOC) é um estado patológico caracterizado por uma limitação do débito aéreo que não é totalmente reversível. A limitação ventilatória é, geralmente, progressiva e está associada a uma resposta inflamatória anómala dos pulmões à inalação de partículas ou gases nocivos. As doenças cardiovasculares (DCV) são alterações no funcionamento do sistema cardíaco, sendo este responsável por transportar oxigênio e nutrientes necessários às células para essas executarem suas tarefas. O tabagismo está associado a 1.147.037 anos potenciais de vida perdidos por morte prematura (APVP) ao ano, concentrados em infarto agudo do miocárdio (IAM) (239.456), câncer de pulmão (187.865), DPOC (177.329) e AVC (164.618). TECNOLOGIA: Champix® (tartarato de vareniclina). PERGUNTA: O uso do tartarato de vareniclina é eficaz e seguro em adultos fumantes com DCV ou DPOC, quando comparado à terapia de reposição de nicotina ou cloridrato bupropiona para o tratamento adjuvante na interrupção do tabagismo? EVIDÊNCIAS CIENTÍFICAS: No estudo observacional de Melzer et al., 2016, a farmacoterapia foi dispensada a uma minoria de fumantes de alto risco admitidos para DPOC e não estava associada à cessação do tabagismo nos 6 a 12 meses. Em comparação com o adesivo de nicotina, a vareniclina estava associada a uma maior probabilidade de cessação, com diminuição da probabilidade de cessação entre os pacientes tratados com TRN de curta ação. Jimenez Ruiz e colaboradores realizaram uma revisão dos registros clínicos de fumantes com DPOC grave ou muito grave. Neste estudo, a vareniclina não difere em eficácia da bupropiona, medicamento disponibilizado no SUS. A taxa de abstinência contínua nas semanas 9-24 para TRN, bupropiona e vareniclina foram 44%, 60% e 61%, respectivamente. No entanto, a diferença entre as taxas só foi significante na comparação de vareniclina e adesivo de nicotina. O estudo EUROACTION PLUS (EA) avaliou a eficácia de um programa de cardiologia preventiva, que oferece terapia intensiva para cessar o tabagismo, além da vareniclina opcional para fumantes com risco elevado de doença cardiovascular, em comparação com os cuidados habituais na prática geral. Dentre as limitações, ressalta-se que o estudo avaliou a eficácia do programa de tratamento, portanto os resultados de efetividade apresentados não refletem a efetividade do fármaco em si. Um mínimo de 6 meses de abstinência prolongada é recomendado como medida para avaliar os ensaios de cessação do tabagismo. Os resultados foram avaliados no final de 16 semanas apenas. AVALIAÇÃO ECONÔMICA: Como resultado da avaliação econômica, o demandante encontrou uma razão de custo-efetividade incremental que, para cada ex-fumante adicional, a vareniclina gera uma necessidade de investimento de R$ 4.156, 70. Em 24 semanas, quando compara da com a bupropiona, e, um RCEI de R$ 3.111,45, quando comparada com terapia de reposição de nicotina. Após o ajuste realizado pela Secretaria Executiva da Conitec, na população e custo dos medicamentos, a razão de custo-efetividade incremental da comparação entre vareniclina e cloridrato de bupropiona em pacientes com DPOC, aponta que, para cada ex-fumante adicional, a vareniclina gera uma necessidade de investimento de R$ 84.925,20. A RCEI da comparação terapia de reposição de nicotina em pacientes com DPOC aponta que, para cada ex-fumante adicional, a vareniclina gera uma necessidade de investimento de R$ 3.784,78. A RCEI da comparação entre tartarato de vareniclina e cloridrato de bupropiona em pacientes com DC, aponta que, para cada ex-fumante adicional, a vareniclina gera uma necessidade de investimento de R$ 2.621,15. AVALIAÇÃO DE IMPACTO ORÇAMENTÁRIO: Ao considerar o cenário, considerando 100% dos pacientes utilizando vareniclina nos cinco anos de impacto, a análise apresentou um AIO de R$ 34 milhões no primeiro ano após a incorporação, chegando a, R$ 181,33 milhões em cinco anos. Após ajustes no modelo, o custo incremental, considerando as mesmas premissas, a AIO foi de 2,7 bilhões em cinco anos, sendo 2,5 bilhões de reais a mais do que o valor apresentado pelo demandante. CONSIDERAÇÕES: Existe incerteza quanto à opção de tratamento mais seguro para pessoas com DCV. Há evidências limitadas sobre o uso de vareniclina em fumantes com DPOC. Faltam dados de manutenção da cessação do tabagismo a longo prazo e de possíveis recaídas. Nenhum estudo randomizado comparou ainda a eficácia da vareniclina com uma combinação de TRN, que, é mais eficaz do que em monoterapia. Existem dados limitados que comparam a eficácia da vareniclina com bupropiona nessa população específica. Sintomas psiquiátricos, incluindo comportamento suicida, foram relatados com vareniclina, mas um nexo de causalidade não foi estabelecido. Eventos cardiovasculares graves foram relatados com vareniclina, mas o tamanho de qualquer risco aumentado é incerto. RECOMENDAÇÃO INICIAL DA CONITEC: A recomendação inicial da Comissão Nacional de Incorporação de Tecnologias no SUS, na 67ª reunião ordinária no dia 13 de junho de 2018, foi por unanimidade, não incorporar o tartarato de vareniclina, entendendo que, faltam evidências robustas de eficácia e segurança no tratamento do tabagismo em pacientes com DPOC ou com doenças cardiovasculares. CONSULTA PÚBLICA: Foram recebidas 62 contribuições, sendo 13 técnico-científicas e 49 contribuições de experiência ou opinião, onde 46% e 64% discordaram da recomendação preliminar da CONITEC, respectivamente. O principal motivo de discordância foi a necessidade de se oferecer mais uma alternativa terapêutica para tratamento do tabagismo. Equivalência terapêutica e eventos adversos foram os principais motivos para concordarem com a recomendação da Conitec. Evidências foram apresentadas e analisadas, porém ainda faltam dados demostrando superioridade da vareniclina em relação aos disponíveis no SUS. DELIBERAÇÃO FINAL DA CONITEC: Os membros da CONITEC presentes na 71ª reunião ordinária da plenária, realizada no dia 07/10/2018, deliberaram por unanimidade recomendar a não incorporação de vareniclina para o tratamento ddo tabagismo em indivíduos com doença cardiovascular ou Doença Pulmonar Obstrutiva Crônica. Foi assinado o Registro de Deliberação nº 380/2018. DECISÃO: A Portaria nº 49, de 16 de outubro de 2017, tornou pública a decisão de não incorporar o tartarato de vareniclina para tratamento adjuvante da cessação do tabagismo em pacientes adultos com doença pulmonar obstrutiva crônica ou doenças cardiovasculares, no âmbito do Sistema Único de Saúde ­ SUS.

Guías de Práctica Clínica para el Tratamiento del Tabaquismo, Chile 2017 / Clinical Practice Guidelines for Smoking Cessation

Considering that a high proportion of the Chilean general population smokes, the Chilean Society of Respiratory Diseases in collaboration with the Chilean Societies of Cardiology and, Endocrinology and Diabetes, formed an interdisciplinary group, who issued a set of recommendations for the treatment of the smoker, methodologically advised by experts. These interventions should be prioritized in high-risk groups. Methods The panel elaborated and graded the recommendations following the GRADE methodology. To assess the effect of each intervention, systematic reviews and randomized clinical trials were identified. In addition, a search of studies done with the Chilean population was carried out. For each of the questions, the panel determined the direction and strength of the recommendation through a decision evidence table. Recommendations For all smokers, the panel recommends using brief counseling ABC on non-intervention, using mobile telephone interventions on non-intervention, using text message on non-intervention, (strong recommendation; moderate certainty in the evidence of the effects). For motivated individuals, with indication for quitting drugs the panel recommends using nicotine replacement therapy on non-intervention, using bupropion on non-intervention, using varenicline on non-intervention. (strong recommendation; moderate certainty in the evidence of the effects). Discussion This clinical practice guide provides recommendations based on the evidence for smoking cessation.

El propósito de esta guía es presentar recomendaciones basadas en evidencia sobre las intervenciones disponibles para dejar de fumar. Su audiencia objetivo corresponde a todos los profesionales de la salud y su población objetivo corresponde a personas fumadoras atendidas en ambientes ambulatorios u hospitalarios, además de poblaciones especiales como embarazadas, adolescentes y pacientes con enfermedad psiquiátrica (compensada por al menos tres meses).

Guías de Práctica Clínica para el Tratamiento del Tabaquismo, Chile 2017 / Clinical Practice Guidelines for Smoking Cessation

RESUMEN Considerando que la población chilena tiene una historia de alto consumo de tabaco la Sociedad Chilena de Enfermedades Respiratorias en colaboración con las Sociedades Chilenas de Cardiología; Endocrinología y Diabetes formó un grupo interdisciplinario que emitió un conjunto de recomendaciones para el enfrentamiento del paciente fumador, asesorado metodológicamente por expertos. Estas intervenciones deben priorizarse en grupos de alto riesgo. Métodos: El panel elaboró y graduó las recomendaciones siguiendo la metodología GRADE. Para estimar el efecto de cada intervención, se identificó revisiones sistemáticas y estudios clínicos aleatorizados. Además, se realizó una búsqueda de estudios realizados con población chilena. Para cada una de las preguntas, el panel determinó la dirección y fuerza de la recomendación mediante una tabla de la Evidencia a la Decisión. Recomendaciones: Para todos los fumadores, el panel recomienda usar consejería breve sobre no intervención, consejería vía telefonía móvil sobre no intervención, y mensajes de texto sobre no intervención (recomendación fuerte; certeza moderada en la evidencia de los efectos). Para los individuos motivados, con indicación de fármacos para dejar de fumar el panel recomienda terapia de reemplazo de nicotina sobre no intervención, bupropión sobre no intervención, vareniclina sobre no intervención (recomendación fuerte; certeza moderada en la evidencia de los efectos). Discusión: Se emiten recomendaciones basadas en la evidencia para el tratamiento del tabaquismo.

Considering that Chilean population has a high tobacco consumption history, the Chilean Society of Respiratory Diseases in collaboration with the Chilean Societies of Cardiology and, Endocrinology and Diabetes, formed an interdisciplinary group, who issued a set of recommendations for the treatment of the smoker, methodologically advised by experts. These interventions should be prioritized in high-risk groups. Methods: The panel elaborated and graded the recommendations following the GRADE methodology. To assess the effect of each intervention, systematic reviews and randomized clinical trials were identified. In addition, a search of studies done with the Chilean population was carried out. For each of the questions, the panel determined the direction and strength of the recommendation through a decision evidence table. Recommendations: For all smokers, the panel recommends using brief counseling ABC on non-intervention, using mobile telephone interventions on non-intervention, using text message on non-intervention, (strong recommendation; moderate certainty in the evidence of the effects). For motivated individuals, with indication for quitting drugs the panel recommends using nicotine replacement therapy on non-intervention, using bupropion on non-intervention, using varenicline on non-intervention. (strong recommendation; moderate certainty in the evidence of the effects). Discussion: This clinical practice guide provides recommendations based on the evidence for smoking cessation.

Vareniclina / Varenicline

Resumen Vareniclina es terapia de primera línea para la cesación del tabaquismo, y presenta la mayor efectividad demostrada ampliamente en ensayos clínicos logrando cifras de abandono al año del orden de 25-35%. En la más reciente revisión de efectividad realizada por la Cochrane se evaluaron 39 ensayos que randomizaban vareniclina contra placebo y en comparación con sustitutos de nicotina (TRN) y bupropión. Con vareniclina se objetivó un RR de 2,24 para abstinencia a 6 meses o más prolongado a dosis standard (2 mg al día) contra placebo. El RR de vareniclina versus placebo comparando con bupropión o TRN fue de 1,3 y 1,25 respectivamente mostrando su superioridad una vez más. Cuando se evaluó el uso de vareniclina por un periodo más prolongado que 12 semanas, se observó que la droga fue bien tolerada sugiriendo que es factible su uso sin intensificar los efectos adversos.

Varenicline is a first-line therapy cessation of smoking, and has the highest effectiveness widely demonstrated in clinical trials with drop-out figures per year of the order of 25-35%. In the most recent effectiveness review conducted by the Cochrane, 39 trials were evaluated that randomized varenicline versus placebo and compared with nicotine substitutes (NRT) and bupropion. With varenicline, a RR of 2.24 was observed for abstinence at 6 months or longer at standard doses (2 mg daily) versus placebo. The RR of varenicline versus placebo compared with bupropion or NRT was 1.3 and 1.25 respectively showing its superiority once again. When the use of varenicline was evaluated for a period longer than 12 weeks, it was observed that the drug was well tolerated suggesting that its use is feasible without intensifying the adverse effects.

[Factors associated with success of a smoking cessation program]. / Factores asociados con el éxito de la terapia antitabaco en pacientes tratados con vareniclina: 10 años de experiencia en un programa multidisciplinario.

BACKGROUND: Smoking cessation therapies include counseling, psychological management and pharmacological therapy. Varenicline is the most effective and safe medication available. AIM: To study risk factors for the failure of pharmacological smoking cessation therapy with varenicline. PATIENTS AND METHODS: Retrospective analysis of 281 patients aged 45 ± 11 years (65% males) with a mean consumption of 31 ± 22 packs/year. They completed a smoking cessation program comprising psychological support and use of varenicline in a private clinic. Patients were followed with telephonic interviews during one year. A complete abstinence during one year was considered as a success of the program. RESULTS: The success rate of the program was 53.4%. The factors associated with failure were a high tobacco dependence rate determined with the Fageström test (Odds ratio (OR) 2.47, 95% confidence intervals (CI) 1.16-5.26, p = 0.02). An instruction level of more than 12 years was associated with a lower failure rate (OR 0.38 95% CI 0.18-0.82). CONCLUSIONS: A high tobacco dependence rate and a lower education were associated with a higher failure rate of this smoking cessation program.

Factores asociados con el éxito de la terapia antitabaco en pacientes tratados con vareniclina: 10 años de experiencia en un programa multidisciplinario / Factors associated with success of a smoking cessation program

Background: Smoking cessation therapies include counseling, psychological management and pharmacological therapy. Varenicline is the most effective and safe medication available. Aim: To study risk factors for the failure of pharmacological smoking cessation therapy with varenicline. Patients and Methods: Retrospective analysis of 281 patients aged 45 ± 11 years (65% males) with a mean consumption of 31 ± 22 packs/year. They completed a smoking cessation program comprising psychological support and use of varenicline in a private clinic. Patients were followed with telephonic interviews during one year. A complete abstinence during one year was considered as a success of the program. Results: The success rate of the program was 53.4%. The factors associated with failure were a high tobacco dependence rate determined with the Fageström test (Odds ratio (OR) 2.47, 95% confidence intervals (CI) 1.16-5.26, p = 0.02). An instruction level of more than 12 years was associated with a lower failure rate (OR 0.38 95% CI 0.18-0.82). Conclusions: A high tobacco dependence rate and a lower education were associated with a higher failure rate of this smoking cessation program.

Effects of aging on the effectiveness of smoking cessation medication.

BACKGROUND: Considering the pharmacokinetic and pharmacodynamic aspects of different medications, it is plausible that the age of a smoker could affect the half-life of these drugs. The aim of this study was to compare the effectiveness of smoking cessation drugs (nicotine replacement therapy, bupropion, and varenicline) used either in isolation or in combination in adults under and over 60 years of age. METHODS: Data were collected from 940 Brazilian patients participating in a smoking cessation program. Participants were prescribed smoking cessation medication to be used for at least 12 weeks and were followed for 52 weeks. RESULTS: Cessation rates were significantly different among younger and older participants who were using nicotine replacement therapy (NRT) alone. Being over 60 years of age was significantly associated with increased cessation success among those who used NRT alone (OR 2.34, 95% CI: 1.36 to 4.04, p = 0.002). The effectiveness of varenicline and bupropion were not significantly different according to age groups. CONCLUSION: Using age as a predictor for tailoring smoking cessation drugs might potentially lead to a more individualized prescription of smoking cessation therapy. These results should be tested in randomized controlled trials.

Influence of smoking cessation drugs on blood pressure and heart rate in patients with cardiovascular disease or high risk score: real life setting.

BACKGROUND: Smoking is the most important reversible cardiovascular risk factor. It is well established that quitting smoking reduces coronary events. However, on several occasions, the cardiovascular safety of smoking cessation drugs has been questioned. Our goal is to evaluate the effects of smoking cessation drugs on blood pressure and heart rate in patients from a smoking cessation service in a cardiology hospital. METHODS: We examined the PAF database (Smoking Cessation Assistance Program database) between January 2008 and March 2014. We analyzed data from 900 patients who were compliant with the treatment (50.5% male, average age 53 ± 17 years). The most frequent clinical diagnoses were coronary artery disease (25.2%), hypertension (57.2%), and diabetes (13.4%). Blood pressure, heart rate, and carbon monoxide (CO) concentration in exhaled air were analyzed at consecutive visits during the first 45 days of treatment (mean visits - 3). Analysis of repeated measures was used for the statistical analysis (p < 0.05). RESULTS: Two hundred seventy one patients used nicotine replacement therapy (NRT) alone, 81 used bupropion alone, 154 used varenicline alone, 283 used NRT plus bupropion and 111 used bupropion plus varenicline. For all smoking cessation drugs, used alone or in combination, no increase occurred in the average value of systolic blood pressure (SBP), diastolic blood pressure (DBP) and heart rate (HR). Significant reductions in CO concentrations occurred in all smoking cessation drug groups. CONCLUSION: Smoking cessation drugs used in monotherapy or in combined regimens did not influence systolic blood pressure (SBP), diastolic blood pressure (DBP) and heart rate (HR) in this group of patients during the observation period.