Long-Term Outcomes and Duration of Dual Antiplatelet Therapy After Coronary Intervention With Second-Generation Drug-Eluting Stents: The Veterans Affairs Extended DAPT Study.

Background Recent guidelines on dual antiplatelet therapy (DAPT) duration after percutaneous coronary intervention (PCI) balance the subsequent risks of major bleeding with ischemic events. Although generally favoring shorter DAPT duration with second-generation drug-eluting stents, the effects on long-term outcomes in the wider population are uncertain. Methods and Results We tracked all patients having PCI with second-generation drug-eluting stents in the Veterans Affairs Healthcare System between 2006 and 2016 for death, myocardial infarction, stroke, and major bleeding up to 13 years. We compared these outcomes with 4 DAPT durations of 1 to 5, 6 to 9, 10 to 12, and 13 to 18 months after the index PCI using hazard ratios (HRs) and 95% CIs from Cox proportional hazards models adjusted by inverse probability weighting. A total of 40 882 subjects with PCI were followed up for a median of 4.3 (25%-75%: 2.4-6.5) years. DAPT discontinuation was rare early after PCI (5.8% at 1-5 months and 6.3% at 6-9 months) but increased (19% and 44%) >9 months. The risk of cardiovascular and noncardiovascular death was higher (HR, 2.03-3.41) with DAPT discontinuation <9 months, likely reflecting premature cessation from factors related to early death. DAPT discontinuation after 9 months following PCI was associated with lower risks of death (HR, 0.93 [95% CI, 0.88-0.99]), cardiac death (HR, 0.79 [95% CI, 0.70-0.90]), myocardial infarction (HR, 0.75 [95% CI, 0.69-0.82]), and major bleeding (HR, 0.82 [95% CI, 0.74-0.91]). Results were similar with an index PCI for an acute coronary syndrome. Conclusions Stopping DAPT after 9 months is associated with lower long-term risks of adverse ischemic and bleeding events and supports recent guidelines of shorter duration DAPT after PCI with second-generation drug-eluting stents.

Risk of community-acquired pneumonia in veteran patients to whom proton pump inhibitors were dispensed.

BACKGROUND: Observational studies linking proton pump inhibitor (PPI) exposure with community-acquired pneumonia (CAP) have reported either modest or no associations. Accordingly, we studied PPI exposure and CAP in veteran patients, using a retrospective, nested case-control design. METHODS: From linked pharmacy and administrative databases of the New England Veterans Healthcare System, we identified 71985 outpatients newly prescribed PPIs between 1998 and 2007; 1544 patients met criteria for CAP subsequent to PPI initiation; 15440 controls were matched through risk-set sampling by age and time under observation. Crude and adjusted odds ratios comparing current with past PPI exposures, as well as tests for interactions, were conducted for the entire and stratified samples. RESULTS: Current PPI use associated with CAP (adjusted odds ratio [OR], 1.29 [95% confidence interval {CI}, 1.15-1.45]). Risks were not substantially altered by age or year of diagnosis. Dementia (n = 85; P = .062 for interaction) and sedative/tranquilizer use (n = 224; P = .049 for interaction) were likely effect modifiers increasing a PPI-CAP association; conversely, for some chronic medical conditions, PPI-associated CAP risks were reversed. PPI exposures between 1 and 15 days increased CAP risks, compared with longer exposures, but PPI initiation also frequently occurred shortly after CAP diagnoses. Prescribed PPI doses >1 dose/day also increased PPI-associated CAP risks. CONCLUSIONS: Among the veterans studied, current compared with past PPI exposures associated modestly with increased risks of CAP. However, our observations that recent treatment initiation and higher PPI doses were associated with greater risks, and the inconsistent PPI-CAP associations between patient subgroups, indicate that further inquiries are needed to separate out coincidental patterns of associations.

Long-term, high-dose benzodiazepine prescriptions in veteran patients with PTSD: influence of preexisting alcoholism and drug-abuse diagnoses.

Databases from the New England Veterans Integrated Service Network were analyzed to determine factors associated with long-term, high-dose anxiolytic benzodiazepine prescriptions dispensed to patients with posttraumatic stress disorder (PTSD) and existing alcoholism and/or drug abuse diagnoses. Among 2,183 PTSD patients, 234 received the highest 10% average daily doses for alprazolam, clonazepam, diazepam, or lorazepam, doses above those typically recommended. Highest doses were more commonly prescribed to patients with existing drug abuse diagnoses. Among patients with PTSD and alcoholism, younger age, drug abuse, and concurrent prescriptions for another benzodiazepine and oxycodone/acetaminophen independently predicted high doses. Results indicate that for veteran patients with PTSD, alcoholism alone is not associated with high-dose benzodiazepines, but existing drug abuse diagnoses do increase that risk.

Characterizations of long-term anxiolytic benzodiazepine prescriptions in veteran patients.

To characterize long-term prescriptions for commonly prescribed anxiolytic benzodiazepines to veteran patients and to identify factors associated with high daily doses, we analyzed the linked pharmacy and administrative databases from New England Veterans Healthcare System (VISN 1). We analyzed treatment episodes of 3 months or longer with the 4 most commonly prescribed agents: alprazolam, clonazepam, diazepam, and lorazepam. Descriptive statistics and univariate and multivariate analyses described the sample and tested associations of pharmacological and clinical variables for patients prescribed the top 5% of average daily doses ("high-dose" prescriptions). From 16,630 full or partial treatment episodes for all 4 agents analyzed within a 42-month window, average daily doses were predominantly moderate, age-sensitive, and stable; refill lag intervals were short. Patients on "high-dose" prescriptions for the 4 agents combined, compared with "middle quartile" dose prescriptions, in adjusted analyses, were younger, more likely to have posttraumatic stress disorder (odds ratio [OR], 2.6; 95% confidence interval [CI], 2.17-3.13), substance abuse (OR, 1.50; 95% CI, 1.25-1.80), and anxiety (OR, 1.33; 95% CI, 1.11-1.60) and were more likely to be receiving concurrent oxycodone/acetaminophen (OR, 2.05; 95% CI, 1.64-2.56), anxiolytic benzodiazepine (OR, 1.51; 95% CI, 1.12-2.03), antidepressant (OR, 2.15; 95% CI, 1.80-2.58), and neuroleptic (OR, 2.03; 95% CI, 1.69-2.44) prescriptions. These results indicate that veteran patients prescribed anxiolytic benzodiazepines typically receive modest, nonincreasing doses over long-term treatment episodes. However, those on the highest average daily doses, typically more than recommended guidelines, are more likely to have clinical diagnoses and concurrent prescriptions for psychoactive medications indicative of more complex and, perhaps, problematic management.

Characterizations of long-term oxycodone/acetaminophen prescriptions in veteran patients.

BACKGROUND: Long-term management of chronic pain with opioids may be stable over time or may be complicated by problematic dose increases, drug dependencies, and toxic effects. To determine clinical contexts in which stability or problems may occur, we examined the pharmacologic and clinical correlates of long-term prescriptions of oxycodone/acetaminophen, a commonly prescribed short-acting opioid formulation. METHODS: We analyzed linked, archival outpatient pharmacy and clinical databases from the New England Veterans Integrated Service Network between January 1, 1998, and June 30, 2001. Durations, doses, and dose changes of oxycodone/acetaminophen prescriptions and concurrent use of long-acting opioids, benzodiazepines, tricyclic antidepressants, and anticonvulsants were determined. RESULTS: In aggregate, 2195 patients (31% with cancer diagnoses per the International Classification of Diseases, Ninth Revision, Clinical Modification) received oxycodone/acetaminophen for more than 9 months at a mean prescribed daily dose of 3.9 tablets per day (range, 0.5-13.0 tablets per day) with minimal changes in daily prescribed mean dose over time. Patients with cancer were more likely than other patients to receive concurrent long-acting opioids. For patients without cancer, a higher mean daily dose was associated with duration, older age, human immunodeficiency virus (HIV) and/or AIDS, and with prescribed benzodiazepines and long-acting opioids; concurrent benzodiazepine prescriptions were associated with anticonvulsant prescriptions and with psychogenic pain and alcohol abuse and/or dependence diagnoses. CONCLUSIONS: In veteran patients who received long-term oxycodone/acetaminophen prescriptions, mean daily doses were typically modest and stable, likely reflecting a selection of patients with successful, long-term management. Among patients without cancer, however, associations of higher oxycodone/acetaminophen doses with benzodiazepine prescriptions, psychogenic pain, alcohol abuse, and HIV/AIDS may portend opioid prescription management problems.

Patterns of dispensed disulfiram and naltrexone for alcoholism treatment in a veteran patient population.

BACKGROUND: Short-term treatment trials indicate that two Food and Drug Administration-approved agents, disulfiram and naltrexone, may each curtail alcohol consumption, but two large 1-year Veterans Administration cooperative studies showed no long-term benefits for these agents over placebo. To assess whether these agents are being prescribed for extended periods, as an indicator of long-term use in nonexperimental settings, we compared dispensing patterns in a veteran patient population. METHODS: The New England Veterans Integrated Service Network outpatient pharmacy files between January 1, 1998, and June 30, 2001, were analyzed; only patients with prescriptions on or after March 1, 1998, were included. Measurements for each patient included data on new and refilled prescriptions of disulfiram, naltrexone, and control medications. Prescription survival curves with right censoring were constructed. Distinct treatment episodes were defined by having six or more months between the end date of a prior prescription and the start date of a new prescription. RESULTS: From eight New England Veterans Integrated Service Network centers, 754 patients were dispensed disulfiram, and 971 were dispensed naltrexone, encompassing 873 and 1075 treatment episodes, respectively. Treatment episode durations were virtually identical for both drugs: more than 35% of episodes were 1 month or shorter, more than 50% were 2 months or shorter, and 75% were 5 months or shorter. Concurrently prescribed neuroleptic or statin medications predicted longer disulfiram and naltrexone treatment episodes. However, for patients newly prescribed common neuroleptic, antidepressant, or statin agents, the risks for discontinuing disulfiram or naltrexone were 1.4 to 2.3 times greater than for discontinuing these other agents. CONCLUSIONS: In clinical settings, veteran patients were likely to be dispensed either disulfiram or naltrexone for only several months or less. The contexts and reasons for these predominantly short-term treatment episodes or the benefits derived were not known and merit further study.