title: Evaluation of a pharmacist-managed amiodarone monitoring program.
abstract: BACKGROUND
  Because of the potential for serious adverse effects, patients treated with amiodarone must be carefully screened and routinely monitored for potential liver, thyroid, and pulmonary toxicity. However, laboratory and pulmonary monitoring rates have been found to be substantially lower than recommended in guidelines, including those of the North American Society of Pacing and Electrophysiology (NASPE, 2007).
  
  
  OBJECTIVE
  To (a) assess rates of laboratory monitoring of liver, thyroid, and pulmonary function and adverse events in a pharmacist-managed amiodarone monitoring program compared with usual care in an integrated health care system and (b) estimate return on investment (ROI) from this intervention.
  
  
  METHODS
  This retrospective cohort study used clinic and enrollment data to identify those patients in the pharmacist-managed program and usual care who received at least 100 days of amiodarone therapy with the first prescription for amiodarone (index) from June 1, 2007, through May 31, 2009 (index date). Laboratory test monitoring was recorded at baseline (up to 6 months before the index date), from 1-6 months after the index date, 7-12 months after the index date, and at any time during the year (months 1-12). Alanine aminotransferase (ALT) was evaluated for liver function. Thyroid-stimulating hormone (TSH) and, for patients with abnormal TSH ( less than 0.4 micro international units [uIU] per mL or greater than 4.0 uIU per mL), free thyroxine (T4) were evaluated for thyroid function. Rates of pulmonary function testing (PFT) were measured by the diffusion capacity of carbon monoxide tests (DLCO) and annual chest x-rays (CXR); electrocardiograms were not counted. Monitoring rates were compared using Pearson chi-square tests, and logistic regression was used to compare the odds of testing (ALT, TSH, T4, CXR, PFT) between the 2 groups at any time during the year after the index date. Concomitant uses of amiodarone with high-dose statins and of amiodarone with digoxin were compared using Pearson chi-square tests. Hospitalizations and emergency room (ER) visits during the 12-month follow-up period were counted for (a) interstitial lung disease; (b) rhabdomyolysis for patients who received amiodarone with high-dose statins (either lovastatin greater than 40 mg per day or greater than 20 mg per day of simvastatin or atorvastatin); and (c) for patients with abnormal digoxin, ALT, TSH, or T4 levels, if the hospitalization occurred within 2 days of the abnormal laboratory value.
  
  
  RESULTS
  There were 2,292 patients who received at least 100 days of amiodarone therapy and met the other inclusion criteria, of whom 181 patients (7.9%) were in the pharmacist-managed group and 2,111 received usual care. There were 90 (49.7%) new amiodarone users in the pharmacist-managed group and 990 (46.9%) in usual care. The 2 groups had similar demographic characteristics except race, with more whites and fewer African Americans, Asians, and Hispanics in usual care. Laboratory monitoring rates for ALT, TSH, and T4 were significantly higher in the pharmacist-managed group than usual care at the first and second 6 months and at baseline for ALT and TSH but not T4. Baseline CXR rates were significantly higher for the pharmacist-managed group than usual care (59.1% vs. 49.3%; P=0.011). Few patients in either group received PFT tests at baseline, 6.6% versus 3.6% (P=0.042). After controlling for covariates (age, gender, race, new vs. continuing use, and comorbidities), pharmacist-managed patients were significantly more likely to have at least 1 ALT test within the year after the index prescription (odds ratio [OR]=3.13, 95% CI=1.12-8.71), as well as a TSH test (OR=8.13, 95% CI=3.27-20.21) and T4 (OR=2.51, 95% CI=1.67-3.75). PFTs were also more likely to be given to these patients (OR=5.89, 95% CI=3.86-8.99). A higher percentage of patients in the pharmacist-managed group than in usual care were taking a high-dose statin during the 12-month follow-up period (47.5% vs. 36.2%, P=0.003), but of those patients, a greater proportion were switched to another statin (14.0% [n=12] vs. 7.5% [n=57], P=0.037) or a lower dose (9.3% [n=8] vs. 3.9% [n=30], P=0.022). Six patients in the usual care group (0.79% of patients on high-dose statins) developed rhabdomyolysis, and 5 (0.24% of all patients in usual care) had an admission for interstitial lung disease. The proportions of patients using amiodarone and digoxin concomitantly were similar in the 2 groups (35.9% vs. 31.3%, P=0.197). Among patients with abnormal laboratory results for ALT, TSH, and T4, or digoxin, there were 2 all-cause hospitalizations and 1 ER visit in the pharmacist-managed group and 34 all-cause hospitalizations and 18 ER visits in the usual care group during the follow-up year. Assuming that all hospitalizations and ER visits incurred in the usual care group were avoid- able, approximately $2.14 could be saved for every dollar spent on the pharmacist-managed amiodarone monitoring program.
  
  
  CONCLUSIONS
  Pharmacist management of patients treated with amiodarone was associated with improved monitoring of recommended laboratory tests and PFTs.
authors.affiliation: Kaiser Permanente, Pharmacy Outcomes Research Group, 12254 Bellflower Blvd., Downey, CA 90242, USA. michele.m.spence@kp.org
authors.forename: Michele M
authors.initials: MM
authors.lastname: Spence
authors.forename: Jennifer K
authors.initials: JK
authors.lastname: Polzin
authors.forename: Calvin L
authors.initials: CL
authors.lastname: Weisberger
authors.forename: John P
authors.initials: JP
authors.lastname: Martin
authors.forename: Jay P
authors.initials: JP
authors.lastname: Rho
authors.forename: Giselle H
authors.initials: GH
authors.lastname: Willick
mesh_terms: D000638:Amiodarone / Q000009:adverse effects* / Q000191:economics* / Q000627:therapeutic use; D000889:Anti-Arrhythmia Agents / Q000009:adverse effects* / Q000191:economics* / Q000627:therapeutic use; D015415:Biomarkers / Q000032:analysis; D015331:Cohort Studies; D016903:Drug Monitoring / Q000191:economics* / Q000379:methods; D005260:Female; D017048:Health Care Costs; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use; D008297:Male; D010595:Pharmacists; D012129:Respiratory Function Tests; D012189:Retrospective Studies
chemical_list: D000889:Anti-Arrhythmia Agents; D015415:Biomarkers; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D000638:Amiodarone