title: Practice-based evidence: profiling the safety of cilostazol by text-mining of clinical notes.
abstract: BACKGROUND
  Peripheral arterial disease (PAD) is a growing problem with few available therapies. Cilostazol is the only FDA-approved medication with a class I indication for intermittent claudication, but carries a black box warning due to concerns for increased cardiovascular mortality. To assess the validity of this black box warning, we employed a novel text-analytics pipeline to quantify the adverse events associated with Cilostazol use in a clinical setting, including patients with congestive heart failure (CHF).
  
  
  RESULTS
  We analyzed the electronic medical records of 1.8 million subjects from the Stanford clinical data warehouse spanning 18 years using a novel text-mining/statistical analytics pipeline. We identified 232 PAD patients taking Cilostazol and created a control group of 1,160 PAD patients not taking this drug using 1:5 propensity-score matching. Over a mean follow up of 4.2 years, we observed no association between Cilostazol use and any major adverse cardiovascular event including stroke (OR = 1.13, CI [0.82, 1.55]), myocardial infarction (OR = 1.00, CI [0.71, 1.39]), or death (OR = 0.86, CI [0.63, 1.18]). Cilostazol was not associated with an increase in any arrhythmic complication. We also identified a subset of CHF patients who were prescribed Cilostazol despite its black box warning, and found that it did not increase mortality in this high-risk group of patients.
  
  
  CONCLUSIONS
  This proof of principle study shows the potential of text-analytics to mine clinical data warehouses to uncover 'natural experiments' such as the use of Cilostazol in CHF patients. We envision this method will have broad applications for examining difficult to test clinical hypotheses and to aid in post-marketing drug safety surveillance. Moreover, our observations argue for a prospective study to examine the validity of a drug safety warning that may be unnecessarily limiting the use of an efficacious therapy.
authors.affiliation: Division of Vascular Surgery and Cardiovascular Medicine, Stanford University, Stanford, California, United States of America.
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Leeper
authors.forename: Anna
authors.initials: A
authors.lastname: Bauer-Mehren
authors.forename: Srinivasan V
authors.initials: SV
authors.lastname: Iyer
authors.forename: Paea
authors.initials: P
authors.lastname: Lependu
authors.forename: Cliff
authors.initials: C
authors.lastname: Olson
authors.forename: Nigam H
authors.initials: NH
authors.lastname: Shah
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000077407:Cilostazol; D015331:Cohort Studies; D057225:Data Mining; D005260:Female; D006333:Heart Failure / Q000188:drug therapy*; D006801:Humans; D008297:Male; D016555:Matched-Pair Analysis; D008875:Middle Aged; D058729:Peripheral Arterial Disease / Q000188:drug therapy*; D058987:Phosphodiesterase 3 Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use; D010975:Platelet Aggregation Inhibitors / Q000009:adverse effects / Q000627:therapeutic use; D057216:Propensity Score; D012306:Risk; D013777:Tetrazoles / Q000009:adverse effects* / Q000627:therapeutic use; D016896:Treatment Outcome; D014665:Vasodilator Agents / Q000009:adverse effects / Q000627:therapeutic use
chemical_list: D058987:Phosphodiesterase 3 Inhibitors; D010975:Platelet Aggregation Inhibitors; D013777:Tetrazoles; D014665:Vasodilator Agents; D000077407:Cilostazol