Practice-Based Evidence: Profiling the Safety of Cilostazol by Text-Mining of Clinical Notes

Abstract

BackgroundPeripheral 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).Methods and ResultsWe 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.ConclusionsThis 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.

A cilostazol hatékony és biztonságos lehetőség a claudicatio intermittens kezelésére. A NOCLAUD vizsgálat eredményei

“…2013-ban az Európai Gyógyszer Ügynökség (EMA) a cilostazol használatát korlátozó ajánlást tett közzé, mivel egyes európai országokban a cardiovascularis események gyakoribb előfordulását regisztrálták cilostazolkezelés mellett. Adatbányászat [16], illetve prospektív regiszteradatok [17] alapján a cilostazolkezelés nem növeli a cardiovascularis események előfordulását, illetve a halálozást. Vizsgálatunkban az EMA-ajánlásnak megfelelően kialakított alkalmazási elő-irat ellenjavallatait figyelembe vett cilostazolkezelés biztonságosnak bizonyult az 1405 beválasztott, hat hóna-pig kezelt beteg megfigyelése során.…”

Detecting Unplanned Care From Clinician Notes in Electronic Health Records

“…Our hypothesis is that information extraction techniques can significantly improve the ability to use EHR data to measure outcomes related to postdiagnosis morbidity in patients with cancer. We evaluate the performance of information extraction on two tasks-identifying external ED visits and identifying the most significant symptoms at the visit-using a text-processing framework that has been previously used to monitor for adverse drug events, 16 learn drug-drug interactions, 17 identify off-label drug use, 18 test clinical hypotheses, 19 identify new medical insights, 20 and generate phenotypic fingerprints 21 as well as build predictive models. 22 For the purpose of our study, we defined "unplanned care" as an emergent medical event that results in ED care, unplanned inpatient care, or a trip to an outpatient urgent care center.…”

Prevention of Femoropopliteal In-Stent Restenosis With Cilostazol

“…29,39 In addition, although cilostazol has a black box warning recommending against its use in patients with heart failure based on increased mortality with other phosphodiesterase inhibitors (eg, milrinone), newer information from retrospective studies and registries suggest no increased mortality. 40,41 There is a paucity of data regarding cost effectiveness of cilostazol for in-stent restenosis. In a study by Meng et al, in the United Kingdom, comparing the cost of vasoactive drugs in patients with PAD, the estimated cost of cilostazol was £964.…”