ABC | Volume 113, Nº4, October 2019

Updated Updated Cardiovascular Prevention Guideline of the Brazilian Society Of Cardiology – 2019 Arq Bras Cardiol. 2019; 113(4):787-891 Effectiveness - placebo compared - RR = 2.0 (95% CI 1.8-2.2). 6-Month abstinence rate - RR = 24.2 (95% CI 22.2-26.4). • Presentation: 150-mg prolonged-release lozenges. • Route of administration: oral. • Dose schedule: 1 tablet daily for 4 days, then increase to 1 tablet twice daily with a minimum interval of 8 hours. • Care in administration: Avoid night administration to minimize the risk of insomnia. • Adverse reactions: dry mouth, insomnia (interrupted sleep), constipation, epigastric pain, dizziness. • Contraindications: Absolute: risk of seizure (history of seizure, epilepsy, childhood febrile seizure, known electroencephalogram abnormalities); alcoholism; use of monoamine oxidase inhibitors (MAOI) in the last 14 days; cerebrovascular disease; central nervous system tumor, head trauma. • Warnings/precautions: The combination of bupropion with nicotine replacement, especially patches, may increase BP; for this reason, it should be evaluated at all doctor visits. Alcohol use may predispose to seizure, so patient should be advised to restrict alcohol consumption during use. • Overdose (toxicity): convulsions. 5. Varenicline tartrate (Chart 7.2) Varenicline 268,277 it is a partial nicotinic receptor agonist in the central nervous system. The substance is the most effective medication among the first-line drugs in treating smoking. 278,279 Effectiveness - compared to placebo - RR = 3.1 (95% CI 2.5-3.8). 6-Month abstinence rate - RR = 33.2 (95% CI 28.9-37.8). • Doses: 0.5- and 1-mg varenicline tartrate tablets. • Route of administration: Oral use. • Dose schedule: Start with 0.5 mg once a day. On the 4 th day, prescribe 0.5 mg twice a day. On the 7 th day, prescribe 1 mg 2 times a day. Prescribe for 12 to 24 weeks. Varenicline therapy does not require immediate cessation of smoking. It is recommended to stop smoking from the 14 th day after starting the medication. • Care in administration: take after meal with water (between 150 and 250 ml to reduce nausea). • Adverse reactions: The most expected side effect with this substance is nausea (30%of patients). This effect is minimized by taking themedication after meals and with a glass of water. Less than 6% of patients discontinue medication because of this effect. Other effects reported to a lesser extent are insomnia (14%), headache (10%), constipation (6%), abnormal dreams (dream recall and actual content) and flatulence, which in some circumstances require dose reduction (1 mg/ day), but rarely cause discontinuation of medication. • Contraindications: Absolute - terminal renal failure, pregnancy and breastfeeding. Dose adjustment in patients with severe renal failure (see adjustment table). • Precaution for use: Caution should be exercised when using in patients with a history of psychiatric illness such as severe depression, bipolar disorder and panic syndrome. Although the causal connection has not been demonstrated, and considering that smokers have a higher risk of depression and suicidal ideation, 280 the US Food and Drug Administration (FDA) in 2009, 281 warned about the possibility of mood swings, restlessness and suicidal ideation among users of varenicline, and is therefore not recommended in patients with non-stabilized psychiatric disorders. In 2011, Singh et al. 271 conducted a meta-analysis with some varenicline studies warning of possible risks of CV events among users. After careful analysis of the study, it was concluded that a significant number of patients who used varenicline in randomized trials were not included in the meta- analysis and did not present with any CV event. 282 Prochaska and Hilton 283 performed a more comprehensive meta-analysis, including all varenicline studies, and found no risk of increased CV event in the varenicline versus placebo group. The safety of varenicline was assessed by Rigotti et al., 284 when they analyzed, in a randomized, placebo-controlled manner, the efficacy and safety of varenicline in patients with CVD. The authors found no additional CV risk in the varenicline group. • Overdose (toxicity): nausea, feeling sick, vomiting. Second line medicine: 1. Nortriptyline Nortriptyline is a tricyclic antidepressant that blocks the reuptake of norepinephrine into the central nervous system. It is a 2 nd line drug in the treatment of smoking. The FDA has not yet approved its use for treatment because, although its efficacy is similar to that obtained with NRT or bupropion, there is a greater risk of side effects from the medication. 268,281 The recommended dose is 25 mg/day, as a single dose, gradually increasing to 75 to 100 mg per day. Use is not recommended in patients with structural heart disease of any nature because of the risk of inducing conduction disorders and arrhythmia. 7.5. Anti-Smoking Drug Combinations The effectiveness of first-line anti-smoking drugs is between 20 and 25% for nicotine replacement and bupoprione, and does not exceed 35%with varenicline. 268 Thus, we can imagine that out of 10 patients treated, about 3 will quit and 7 will not. The combination of anti-smoking drugs seems to be a reasonable application option to improve success rates. Despite the increase in cost, it should be considered that quitting smoking has an substantial cost-benefit ratio, so the proposal is perfectly viable, leaving the perspective of dealing with the possible increase in side effects as the main factor to be managed. Some studies with the combination of patches and oral nicotine have shown improved results. Meta-analysis of 9 studies 277 that combined a nicotine patch with a nicotine rapid-release drug (gum, spray, lozenge) proved to be more effective than a single type of NRT (RR 1.34, 95% confidence interval 1.18 to 1.51). The combination of NRT and bupropion was more effective than bupropion alone in the meta-analysis of 4 studies. 277 (RR 1,24; 95% confidence interval 1.06 to1.45). 825