This study evaluated whether continuing dual antiplatelet therapy (DAPT) beyond one year after drug-eluting stent placement reduces adverse events. It was a large randomized controlled trial comparing aspirin + thienopyridine to aspirin + placebo in patients who had completed one year of standard DAPT. Continuing thienopyridine therapy until 30 months reduced stent thrombosis and major adverse cardiovascular events, but increased moderate or severe bleeding risks compared to placebo. The study provides evidence that prolonging DAPT to 30 months may benefit patients who complete one year of standard therapy without adverse events.

1. Dual antiplatelet therapy with a thieno-
pyridine, such as clopidogrel or prasugrel, and
aspirin is the current standard of care after
vascular occlusion requiring stent placement.
When a drug-eluting stent is used, the current
recommended length of therapy is at least one
year to prevent stent thrombosis, which is as-
sociated with myocardial infarction. Although
there still may be a risk of stent thrombosis
even after one year of treatment it has been
controversial if treatment with dual antiplatelet
therapy beyond one year reduces the risk of
myocardial infarction, or if risk reduction was
present if it would outweigh the risk of bleed-
ing. There have not been adequately powered,
randomized trials to look into this until now.
Mauri, et al. conducted an internation-
al, multi-center, randomized, placebo-
controlled trial looking at aspi-
rin+thienopyridine vs. aspirin+placebo after the
standard of therapy for one year had been
completed until thirty months after placement
of the drug-eluting stent. Eligible patients to be
included in the study were those that complet-
ed one year of dual antiplatelet therapy with
clopidogrel dosed at 75mg daily or prasugrel
dosed at 10mg daily, unless the patient
weighed less than 60kg in which case a dose
of 5mg daily was used, alongside aspirin dosed
at 75-162mg daily. During the year of standard
therapy, patients could not have had a major
adverse cardiovascular or cerebrovascular
event, repeat revascularization, or moderate or
severe bleeding and must have been adherent
to thienopyridine therapy.
After completion of the study, results
of the primary endpoints of stent thrombosis
and major adverse cardiovascular/
cerebrovascular events were determined. Look-
ing at stent thrombosis, the group randomized
to continue thienopyridine therapy with asprin
had a lower incidence than placebo (0.4% vs.
1.4%; hazard ratio 0.29; 95% CI 0.17-0.48;
p<0.001). Comparing major adverse cardio/
cerebrovascular events, thienopyridine treat-
ment had a lower incidence compared to pla-
cebo (4.3% vs 5.9%; hazard ratio 0.71; 95% CI
0.59-0.85; p<0.001). Thienopyridine therapy
also had lower incidence of myocardial infarc-
tion. The rate of death from both cardiac and
vascular causes and the rate of stroke were
similar for the two groups. The rate of death
from any cause was higher in the thieno-
pyridine group (2.0% vs. 1.5%; hazard ratio
1.36; 95% CI 1.00-1.85; p=0.05). The com-
bined safety endpoint of moderate or severe
bleeding during the randomized part of the trial
found that the thienopyridine group had this
occurrence at a higher frequency (2.5% vs.
1.6%; hazard ratio 1.61; 95% CI 1.21-2.16;
p=0.001) although this was not significant with
respect to fatal bleeding or severe bleeding
alone.
When assessing this study some limi-
tations should be considered. First, patients
had to make it through a year of the standard
therapy without thombosis or moderate to se-
vere bleeding. This may have selected for pa-
tients who were at a lower risk of adverse
events. Also, it did not randomize between
drugs or stents used which could confound
comparisons. Another point to look at is the
rate of deaths from any cause, being higher in
the thienopyridine group. This was attributed
to bleeding, mainly from fatal trauma, and can-
cer-related deaths mediated by bleeding - with
more deaths coming from the cancer cohort.
The authors attributed this to an imbalance of
patients with history of cancer randomly as-
signed to the thenopyridine group by 22 pa-
tients but this difference is not statistically sig-
nificant [488(9.8%) vs. 466(9.5%);p=0.63].
This study was a large, randomized,
placebo-controlled trial looking at the differ-
ence in length of dual antiplatelet therapy after
drug-eluting stent placement. It was of good
design and adequate power. After reviewing
this study, I would recommend prolonging dual
antiplatelet therapy to 30 months in all pa-
tients completing a year of therapy that do not
have a history of cancer.
Written By: Steven Apa
Reference:
Mauri L, Kereiakes DJ, Yeh RW, et al. Twelve or 30
Months of Dual Antiplatelet Therapy after Drug-
Eluting Stents. NEJM. 2014. 371(23): 2155-2166
Duration of Dual Antiplatelet Therapy after Drug-Eluting Stent Placement: 12 versus 30 Months
NorthCrest Medical Center
February 2015
Volume 28, Number 22
Pharmacy & Therapeutics
B♦U♦L♦L♦E♦T♦I♦N
FORMULARY UDATE
The Pharmacy and
Therapeutics Committee will
meet on February 24th in the
ABC Conference room.
Full Documentation from
meetings are available upon
request.
 Approved Additions —
none
 Deletions — see agenda
 MUE—
Sedation of mechanically
ventilated patients in CCU
Mycamine
Inside this issue:
Drug-Eluting Stents 1
Drug Shortages: Causes
and Management
2
Impact of Increasing Rates of
Neonatal Absentee Syndrome
3
P&T Agenda 4
Current Drug Shortages 5

2. Shortages of drugs pose a significant public health
threat, delaying or denying critically needed care for patients.
The number of drug shortages quadrupled from 2005 to
2011, jumping from 61 to 2511. In 2010 and 2011, almost
75% of shortages were sterile injectable drugs, which are the
foundation of life-saving cancer treatments, antibiotics, emer-
gency room medications and electrolytes needed for IV feed-
ing. Beginning in 2012, the number of drug shortages has
started to decline thanks to the FDA Safety and Innovation Act
(FDASIA), which gave the agency new authority to deal with
drug shortages by requiring early notification from manufac-
turers. In 2011, the FDA was able to help prevent 195 drug
shortages, and in 2012, 282 drug shortages were prevented2.
In spite of these improvements, shortages involving sterile
injectable drugs are still a problem.
According to most recent ASHP Guidelines on Manag-
ing Drug Product Shortages in Hospitals and Health Systems
(2009), there are many contributing factors to shortages: raw
and bulk material unavailability, manufacturing difficulties
and regulatory issues, voluntary recalls, changes in formula-
tions, manufacturer’s production economics, industry consoli-
dations, restricted drug product distribution, inventory practic-
es, unexpected increases in demand, and shifts in clinical
practice3. Discontinuation is a major contributor to drug short-
ages. Older drugs are discontinued by companies in favor of
newer, more profitable drugs. When one manufacturer discon-
tinues a drug, the remaining manufacturers have a hard time
increasing production quickly and a shortage occurs. The sup-
pliers of raw material are also limited in the amount they can
make due to capacity issues at their facilities. The small num-
ber of manufacturers and limited production capacity for ster-
ile injectables, combined with the complexity of the manufac-
turing injectable drugs, results in exacerbation of drug short-
ages.
Just as we plan for worst scenarios in case of fires,
storms, code blue or pink, etc., we also need to plan for drug
shortages to minimize the impact on patient care and phar-
macy operations. The ASHP has put in place a three-phase
approach to effectively manage and also prevent shortages
(see figure below). The first phase consists of the identifica-
tion of shortages by the purchasing agent and the assess-
ment of the extent and potential effects of these shortages.
Figuring out the inventory usage patterns is useful at this
stage. In the second phase, hospital pharmacies should iden-
tify therapeutic alternatives, communicate with other clinical
staff, establish a collaborative agreement with other health
systems, if appropriate, and prioritize the drugs for a specific
patient population. In the last phase, pharmacies should pre-
pare for potential litigation from patients who might have suf-
fered an adverse event as a result of delays or alternative
therapies. Finally, hospital pharmacies should also consider
the financial implications of expensive alternatives and budg-
et for similar future expenditures.
Managing drug shortages is a complex task for health
systems pharmacies. However, the pharmacy department
must take a leadership role in developing and implementing
appropriate steps to minimize the impact on patient care and
contain costs.
Written by Florentina Eller
References:
1. FDA, DHHS. A Review of FDA’s Approach to Medical Product Shortages.
9/2011. http://www.fda.gov/downloads/AboutFDA/ReportsManualsForms/
Reports/UCM277755.pdf. Accessed 1/24/2015
2. US Food and Drug Administration. Frequently Asked Questions about the
Drug Shortages Program. http://www.fda.gov/Drugs/DrugSafety/
DrugShortages/ucm050796.htm. Accessed 1/24/2015
3. Fox E, Birt A, James K, et al. ASHP Guidelines on Managing Drug Product
Shortages in Hospitals and Health Systems. Am J Health-Syst Pharm. 2009;
66:1399-406.
Drug Shortages: Causes and Management
Page 2 Pharmacy & Therapeutics

3. Impact of Increasing Rates of Neonatal Abstinence Syndrome
Page 3
The incidence of Neonatal Abstinence
Syndrome (NAS) has increased dramatically
over the past 15 years. Once recent study
in the Journal of Pediatrics found that in
>5% of births, mothers tested positive for
opiates on UDS. There has been almost a 3
fold increase in incidents of NAS in the past
5 years according the data from the Cincin-
nati Children’s Hospital. Among other is-
sues opiate use in expecting mothers has
been linked to premature birth, respiratory
complications, GI dysfunction, and
CNS irritability.
Tools for assessing withdrawal
manifestations are used to quantify severity
and determine the initiation of pharmalogic
therapy and drug titrations. Examples of
some tools are the Finnegan scoring
system, Lipsitz Tool, Neonatal Narcotic
Withdrawal Index, Ostrea System, and
Neonatal Withdrawal Inventory. Every insti-
tution should have a chosen assessment
tool and nurses should be trained to ade-
quately and routinely preform these
assessments.
Another complicating issue is that
management of NAS can vary greatly
because of the lack of evidence for one
clear treatment strategy and lack of a
control population. As of right now either
morphine or methadone is the
recommended treatment for NAS.
Traditionally there have been other options
but paregoric and tincture of opium are
falling out of favor due to their unwanted
adverse effects and other safety concerns.
The pharmacokinetic issue of methadone,
which has a long and variable half-life,
makes it less preferred compared to
morphine.
Other treatment options that are lacking
evidence but are promising include
clonidine and buprenorphine. Both are
viable options for neonates that are failing
treatment of NAS with morphine.
Traditionally, phenobarbital was used as
adjunct therapy and in some institutions is
still the primary drug of choice but as new
evidence emerges a trend to adopt
alternative therapies can be seen.
Therapies including benzodiazepines have
been studied as well because they
suppress neurological excitability.
Diazepam is the most common
benzodiazepine studied as of now.
The use of non-pharmalogical therapy is an
adjunctive imperative treatment that has
evidence to support its use. As new
evidence emerges, drug therapies will
change and although studies are
lacking, there has been a sharp rise in
interest in NAS because of the quick rise in
the incidence of NAS in the past few years.
Wexelblatt SL, Ward LP, Torok K, Tisdale E, Meinzen-derr JK,
Greenberg JM. Universal Maternal Drug Testing in a High-
Prevalence Region of Prescription Opiate Abuse. J Pediatr.
2014
Parlier AB, Fagan B, Ramage M, Galvin S. Prenatal care,
pregnancy outcomes, and postpartum birth control plans
among pregnant women with opiate addictions. South Med J.
2014;107(11):676-83.
Volume 28, Number 22

4. Pharmacy & TherapeuticsPage 4
PHARMACY & THERAPEUTICS
COMMITTEE
AGENDA
February 24th
2015 12:00 noon
1. Review and approval of October 28, 2014 minutes
Old Business (yellow tab) – PowerPoint
NPSG3 Compliance – warfarin/enoxaparin dosing guidelines – pharmacy
Renal Dosing Report – pharmacy interventions
New Business (red tab) – PowerPoint unless noted
Formulary Additions and Deletions
Additions – none
Deletions:
Uroblue
Tetracyline
Moduretic
Minocycline
Carbamazepine suspension
Cefaclor 250mg po
Candida albicans skin test
Aminocaproic acid 500mg
Amiloride & HCTZ tablet 5-50mg
Chlorzoxazone tablet 500mg
Aridol (PFT testing-no longer available)
Phophasal
PNU-23 (pneumonia vaccine)
Large Volume Fluid Shortage – attached
Propofol Shortage
MUE Propofol (Diprivan)
Micafungin (Mycamine)
Protocols (green tab) – attached *
PNU-23 and Flu vaccine admission protocol
COPD
Policies (blue tab) *
Adult Massive Transfusion
Therapeutic Hypothermia
Order Reconciliation
Approval of Outsource Pharmacies

5. NorthCrest—Current Drug Shortages (1/28/15)
Volume 28, Number 21 Page 5
Out of Stock/Unavailable Legend
added new
RED Restriction:
ER/CCU/OR
Yellow Order with Caution
Green Good Supply
Out of Stock/Unavailable Out
Atropine Pediatric 0.5mg/5ml PFS
Caffeine/sodium benzoate 2 ml vial
Calcium Gluconate
Chloroprocaine 20mg/ ml 20ML
Digoxin 0.5mg / 2ml inj
Diltiazem ADD-VANTAGE 100mg
Epinephrine 1:1000 (PF) 1ml inj
Indigo Carmine -
Morrhuate inj 50mg/1ml
Pancuronium inj
Protonix IV
Phentolamine 5mg/ 1ml
Vecuronium 20mg inj
Restricted Use
Tuberculin Skin Test
Critical Low
2000 ml Sterile Water
0.9% Sodium Chloride 250ADV added new
0.9% Sodium Chloride 3000ml
Hydralazine 20mg/1ml inj
HydrOXYzine injection 50mg /1ml
Ketorolac Injection added new
Multitrace injection
Multivitamin 10 ml inj
Phenylephrine Opth Drops 10%
Phenylephrine Opth Drops 2.5 %
Proparacaine 0.5% /15 ml
0.9% Sodium Chloride 250 ml added new
Vancomycin
Good Supply
https://www.ashp.org/menu/Drug
Shortages/CurrentShortages

6. Volume 28, No 22February 2015
This publication is produced by the
Department of Pharmacy
Services and the Pharmacy and
Therapeutics Committee at
NorthCrest.
Editor Jeremy Felker, PharmD. and
Brian Barnes, PharmD.
Director of Pharmacy Services
Keith Kuboske, PharmD. DPh
Chairman, Pharmacy &
Therapeutics Committee
Ronnie Jackson, MD
100 NorthCrest Drive
Springfield, TN 32610-0316
Phone: 615-384-1553
NorthCrest Medical Center
Department of Pharmacy
Drug Information Questions?
Contact the Pharmacy:
Call 384-1523 or
1-800-599-8870 after hours
This service for physicians and other healthcare
professionals taking care of NorthCrest Medical
Center patients.
All answers are thoroughly researched
and referenced