A 58-year-old woman comes to the office for follow-up for smoking cessation. Four weeks ago, the patient asked to be started on nicotine replacement therapy and was prescribed a maximal-dose nicotine transdermal patch with nicotine gum. Since then, smoking has been reduced from 2 packs a day to less than a pack a day. Medical history includes hypertension, type 2 diabetes mellitus, and peripheral artery disease. Blood pressure is 132/84 mm Hg and pulse is 86/min. BMI is 32 kg/m². She is determined to quit smoking and requests that varenicline be added to her therapy. In combining these two therapies, this patient is at increased risk for which of the following serious complications?

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Explanation: 11ec2b69_c062_49b0_8f63_f9fb6a966f41_MD0005_00 The most commonly used pharmacotherapies for smoking cessation include nicotine replacement, varenicline, and bupropion. Nicotine replacement therapy (NRT) can be used in smoking cessation to decrease withdrawal symptoms and reduce nicotine cravings. Combining a long-acting NRT (eg, patch) with a short-acting NRT (eg, gum, lozenge, nasal spray), termed a "patch-plus regimen," is more effective than either modality alone. Typically, NRT produces no significant adverse effects other than skin irritation from the patch. Varenicline, a partial nicotine receptor agonist, also reduces nicotine cravings and withdrawal symptoms. Varenicline is generally well tolerated, with mild adverse effects (eg, nausea, insomnia, unusual dreams). In the past, the drug carried a black-box FDA warning for suicide/depression, but the warning was removed in 2016 after more data became available (Choice C). In head-to-head randomized trials, varenicline was more effective than buproprion, nicotine patch, or placebo. A number of randomized control studies have looked at the combination of varenicline and NRT, and most have shown increased effectiveness of the combination therapy, without increase of serious adverse effects. Combination therapy is associated with mild adverse effects, such as nausea, insomnia, and mild skin reactions. (Choice A) Initially, varenicline was thought to increase the frequency of cardiovascular events, but later studies have shown no significant link (alone or in combination with NRT), and there is no evidence that the combination of varenicline and NRT increases the risk for angina. Furthermore, the benefits of smoking cessation likely outweigh any increase in risk. (Choices B and D) Bupropion is an antidepressant frequently used for smoking cessation; it increases the risk for seizures and can worsen hypertension. However, there is no evidence that varenicline, NRT, or their combination affects blood pressure or seizure threshold. Educational objective: Varenicline is the most effective pharmacologic intervention for smoking cessation; combination of varenicline with nicotine replacement therapy increases its effectiveness even further, without serious adverse effects. References: . (http://www.ncbi.nlm.nih.gov/pubmed/1)

A 58-Year-Old Woman Comes to the Office for Follow-Up for Smoking