Frequently Reported Adverse Events With Smoking Cessation Medications: Post Hoc Analysis of a Randomized Trial.

OBJECTIVE: To compare the incidence, severity, and clinical course of frequently reported adverse events (AEs) after treatment with smoking cessation pharmacotherapies. METHODS: This was a multinational, multicenter, post hoc analysis of frequently reported treatment-emergent AEs from a large, phase 4, double-blind, randomized, triple-dummy, placebo-controlled trial (EAGLES), conducted between November 30, 2011, and January 13, 2015, that included smokers with and without psychiatric disorders (N=8144). Treatments were varenicline 1 mg twice daily, bupropion sustained-release 150 mg twice daily, and nicotine patch 21 mg once daily with tapering (12-week treatment, 12-week nontreatment follow-up), with incidence, time to onset, and duration of frequently reported AEs (≥5% of participants in any treatment group) measured. Risk differences for AEs for varenicline and bupropion vs nicotine patch were compared. RESULTS: Across frequently reported AEs, nausea, insomnia, abnormal dreams, anxiety, irritability, dry mouth, fatigue, and application site pruritus differed significantly in active treatment vs placebo groups. Risk differences were as follows: for nausea with varenicline vs nicotine patch, 15.50% (95% CI, 13.20% to 17.80%); for insomnia with bupropion vs nicotine patch, 2.58% (CI, 0.65% to 4.51%); and for abnormal dreams with varenicline and bupropion vs nicotine patch, -2.49% (CI, -4.35% to -0.64%) and -5.60% (CI, -7.27% to -3.93%), respectively. Frequently reported AEs of severe intensity and treatment discontinuation were experienced by less than 1.5% and less than 3% of participants across all groups, respectively. CONCLUSION: Active treatments were well tolerated with comparable AE profiles. Most AEs are not clinically important, and prescribers can reassure patients that those experienced will be manageable. TRIAL REGISTRATION: Clinicaltrials.gov Identifier: NCT01456936.

Effect of varenicline on smoking cessation through smoking reduction: a randomized clinical trial.

IMPORTANCE: Some cigarette smokers may not be ready to quit immediately but may be willing to reduce cigarette consumption with the goal of quitting. OBJECTIVE: To determine the efficacy and safety of varenicline for increasing smoking abstinence rates through smoking reduction. DESIGN, SETTING, AND PARTICIPANTS: Randomized, double-blind, placebo-controlled, multinational clinical trial with a 24-week treatment period and 28-week follow-up conducted between July 2011 and July 2013 at 61 centers in 10 countries. The 1510 participants were cigarette smokers who were not willing or able to quit smoking within the next month but willing to reduce smoking and make a quit attempt within the next 3 months. Participants were recruited through advertising. INTERVENTIONS: Twenty-four weeks of varenicline titrated to 1 mg twice daily or placebo with a reduction target of 50% or more in number of cigarettes smoked by 4 weeks, 75% or more by 8 weeks, and a quit attempt by 12 weeks. MAIN OUTCOMES AND MEASURES: Primary efficacy end point was carbon monoxide-confirmed self-reported abstinence during weeks 15 through 24. Secondary outcomes were carbon monoxide-confirmed self-reported abstinence for weeks 21 through 24 and weeks 21 through 52. RESULTS: The varenicline group (n = 760) had significantly higher continuous abstinence rates during weeks 15 through 24 vs the placebo group (n = 750) (32.1% for the varenicline group vs 6.9% for the placebo group; risk difference (RD), 25.2% [95% CI, 21.4%-29.0%]; relative risk (RR), 4.6 [95% CI, 3.5-6.1]). The varenicline group had significantly higher continuous abstinence rates vs the placebo group during weeks 21 through 24 (37.8% for the varenicline group vs 12.5% for the placebo group; RD, 25.2% [95% CI, 21.1%-29.4%]; RR, 3.0 [95% CI, 2.4-3.7]) and weeks 21 through 52 (27.0% for the varenicline group vs 9.9% for the placebo group; RD, 17.1% [95% CI, 13.3%-20.9%]; RR, 2.7 [95% CI, 2.1-3.5]). Serious adverse events occurred in 3.7% of the varenicline group and 2.2% of the placebo group (P = .07). CONCLUSIONS AND RELEVANCE: Among cigarette smokers not willing or able to quit within the next month but willing to reduce cigarette consumption and make a quit attempt at 3 months, use of varenicline for 24 weeks compared with placebo significantly increased smoking cessation rates at the end of treatment, and also at 1 year. Varenicline offers a treatment option for smokers whose needs are not addressed by clinical guidelines recommending abrupt smoking cessation. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01370356.

Undertreatment of COPD: a retrospective analysis of US managed care and Medicare patients.

BACKGROUND: We investigated a large population of patients with chronic obstructive pulmonary disease (COPD) to determine their frequency of medication use and patterns of pharmacotherapy. METHODS: Medical and pharmacy claims data were retrospectively analyzed from 19 health plans (>7.79 million members) across the US. Eligible patients were aged ≥40 years, continuously enrolled during July 2004 to June 2005, and had at least one inpatient or at least two outpatient claims coded for COPD. As a surrogate for severity of illness, COPD patients were stratified by complexity of illness using predefined International Classification of Diseases, Ninth Revision, Clinical Modification, Current Procedural Terminology, Fourth Edition, and Healthcare Common Procedure Coding System codes. RESULTS: A total of 42,565 patients with commercial insurance and 8507 Medicare patients were identified. Their mean age was 54.7 years and 74.8 years, and 48.7% and 46.9% were male, respectively. In total, 66.3% of commercial patients (n = 28,206) were not prescribed any maintenance COPD pharmacotherapy (59.1% no medication; 7.2% inhaled short-acting ß2-agonist only). In the Medicare population, 70.9% (n = 6031) were not prescribed any maintenance COPD pharmacotherapy (66.0% no medication; 4.9% short-acting ß2-agonist only). A subset of patients classified as high-complexity were similarly undertreated, with 58.7% (5358/9121) of commercial and 68.8% (1616/2350) of Medicare patients not prescribed maintenance COPD pharmacotherapy. Only 18.0% and 9.8% of diagnosed smokers in the commercial and Medicare cohorts had a claim for a smoking cessation intervention and just 16.6% and 23.5%, respectively, had claims for an influenza vaccination. CONCLUSION: This study highlights a high degree of undertreatment of COPD in both commercial and Medicare patients, with most patients receiving no maintenance pharmacotherapy or influenza vaccination.

Identifying and characterizing COPD patients in US managed care. A retrospective, cross-sectional analysis of administrative claims data.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is the fourth leading cause of death among US adults and is projected to be the third by 2020. In anticipation of the increasing burden imposed on healthcare systems and payers by patients with COPD, a means of identifying COPD patients who incur higher healthcare utilization and costs is needed. METHODS: This retrospective, cross-sectional analysis of US managed care administrative claims data describes a practical way to identify COPD patients. We analyze 7.79 million members for potential inclusion in the COPD cohort, who were continuously eligible during a 1-year study period. A younger commercial population (7.7 million) is compared with an older Medicare population (0.115 million). We outline a novel approach to stratifying COPD patients using "complexity" of illness, based on occurrence of claims for given comorbid conditions. Additionally, a unique algorithm was developed to identify and stratify COPD exacerbations using claims data. RESULTS: A total of 42,565 commercial (median age 56 years; 51.4% female) and 8507 Medicare patients (median 75 years; 53.1% female) were identified as having COPD. Important differences were observed in comorbidities between the younger commercial versus the older Medicare population. Stratifying by complexity, 45.0%, 33.6%, and 21.4% of commercial patients and 36.6%, 35.8%, and 27.6% of older patients were low, moderate, and high, respectively. A higher proportion of patients with high complexity disease experienced multiple (≥2) exacerbations (61.7% commercial; 49.0% Medicare) than patients with moderate- (56.9%; 41.6%), or low-complexity disease (33.4%; 20.5%). Utilization of healthcare services also increased with an increase in complexity. CONCLUSION: In patients with COPD identified from Medicare or commercial claims data, there is a relationship between complexity as determined by pulmonary and non-pulmonary comorbid conditions and the prevalence of exacerbations and utilization of healthcare services. Identification of COPD patients at highest risk of exacerbations using complexity stratification may facilitate improved disease management by targeting those most in need of treatment.

Prevalence of cardiovascular comorbidities and utilization of evidence-based treatment strategies among statin users in a Medicare and commercial health plan.

BACKGROUND: Although statins are widely used for the prevention and management of cardiovascular disease in patients with dyslipidemia, the prevalence of cardiovascular comorbidities among statin users has not been well studied. OBJECTIVE: To assess the prevalence of cardiovascular comorbidities, use of concomitant medications, interventions for managing the comorbidities, and hospitalization rates among statin users in Medicare and commercial health plan populations in the United States. RESEARCH DESIGN AND METHODS: This retrospective study assessed pharmacy and medical claims of Medicare and commercial health plan members between 4/1/2005 and 3/31/2006. Patients with at least one claim for a statin were included in the analyses. Comorbidities and procedures were identified based on the presence of at least one diagnosis or procedure code. RESULTS: Of the continuously eligible 238,900 Medicare and 3,258,266 commercial health plan members, 51,818 (21.7%) and 285,820 (8.8%) were statin users. Among the Medicare and commercial statin users, 62.4% and 41.8% were classified with either coronary heart disease (CHD), angina, diabetes mellitus, stroke, transient ischemic attack, or chronic kidney disease. Only 9.2% of Medicare and 29.2% of commercial statin users were not classified with hypertension or any of the comorbidities listed above. Of those with diabetes mellitus, 28.1% of Medicare and 15.9% of commercial statin users appeared to have received no pharmacotherapy for this condition. During the study period, 20.3% of Medicare and 10.3% of commercial statin users were reported to be hospitalized; 24.1% and 30.0% were admitted due to CHD/angina. LIMITATIONS: The study design was descriptive in nature and did not allow for demonstration of cause and effect between diagnoses, treatments, and outcomes. CONCLUSIONS: This study highlights that statin users have a high frequency of cardiovascular comorbidities and are at high risk for cardiovascular events. Comorbidity-related hospitalizations are common, yet interventions for managing many of these comorbidities may be underutilized.

Treatment of hypertension and dyslipidemia or their combination among US managed-care patients.

The authors examined treatment rates in managed-care patients with hypertension (HTN) only or dyslipidemia (DYS) only compared with patients who had both (HTN+DYS). A retrospective, cross-sectional claims analysis was performed in a 2002 US national managed-care database of 1.23 million continuously eligible members aged 18 years or older. Median age was 44.0 years, 8.8% were aged 65 years or older, and 53.2% were women. Study criteria identified 354,324 patients, 32.9% with HTN only, 34.7% with DYS only, and 32.4% with HTN+DYS. Overall, 49.7% of HTN patients had DYS and 48.3% of DYS patients had HTN. Patients with HTN+DYS were significantly older, more likely to have cardiovascular comorbidities, and more likely to use medications and hospital facilities than were patients with HTN only or DYS only (P<.01). About two-thirds of patients with HTN only received 1 or more prescription for an antihypertensive medication, compared with three-quarters of those with HTN+DYS. Fewer than half of patients with DYS only and approximately two-thirds with HTN+DYS received a cholesterol-lowering agent.