VA L U E I N H E A LT H 1 9 ( 2 0 1 6 ) A 3 4 7 – A 7 6 6
A639
ranged from 6 weeks to 2 years. Overall, 14 RCTs were placebo-controlled: versus
statins (n= 10), bile acid sequestrants (BAS) (n= 3) and ezetimibe (n= 1). Three stud-
ies compared two active comparators. The range of reported timepoints rendered
a comparison of efficacy challenging; however, all active interventions reduced
TC and LDL-C levels from baseline across all timepoints (from -2.4%/-5.6% with
colevesalam 1.875g daily at 8 weeks to -39.4%/-50.6% with rosuvastatin 20mg daily
at 12 weeks, for TC/ LDL-C, respectively).  Conclusions: Statins were the most
commonly investigated intervention, followed by BAS and ezetimibe. All interven-
tions were found to reduce TC and LDL-C; however, network meta-analysis will yield
greater insight into the comparable efficacy of these interventions. Interestingly,
studies investigating biologics were not identified solely in patients aged ≤ 18 years,
highlighting the potential for future investigation in this patient group.
PCV17
Efectiveness and Inequality Estimation of Antihypertensive
Medicinies` Utilization in Iran According to Observational Data:
2002-2011
Hashemi-Meshkini A1, Farzadfar F2, Kebriaeezadeh A3, Zaboli P1
1Tehran University of Medical Sciences, Tehran, Iran (Islamic Republic of), 2Endocrinology and
Metabolism Research Center, Tehran, Iran (Islamic Republic of), 3Tehran University of Medical
Sciences, Tehran, Iran
Objectives: We aimed to evaluate national and sub-national utilization pattern
of antihypertensive medicines in Iranian population in past decade and evaluate
whether there was any wealth-related inequality in these medicines` utilization
among different provinces. Then, we assessed total and each class effectiveness of
these medicines upon observational data.  Methods: Either fixed effect or random
effect linear panel data model was used to check wealth index effect on all and
each class of antihypertensive medicines utilization, adjusting for other covariates
including years of schooling, urbanization, mean age, and food type of provinces.
The principal component analysis was applied to make summery measures for
covariates using available national datasets. Then we used both Maximum likeli-
hood and Bayesian multilevel modeling on both individual and provincial level
covariates to evaluate antihypertensive medicines utilization effect.  Results: The
wealth category effect on all antihypertensive medicines utilization among Iranian
provinces was positive and significant (0.845; 95% CI: 0.092, 1.598). Accordingly as
subgroup analysis, in BBs and CCBs classes, wealth category effect on medicines
utilization were positive and significant (0.367; 95% CI: 0.127-0.606 and 0.27; 95%
CI: 0.078-0.406, respectively). However in ACEIs and Diuretics classes, wealth cat-
egory effect were positive but not significant. In ARBs class, the effect of wealth
on utilization was negative and not significant (-0.043; p= 0.709). To estimate these
medicines utilization effect, both ML and Bayesian approach indicated almost same
results for all investigated classes and total medicines.  Conclusions: According
to this study, an inequality related to wealth category in total antihypertensive
medicines utilization between provinces could be observed in Iran. Also we observed
a significant effect of total and different antihypertensive classes on systolic blood
pressure of population.
PCV18
Lost in Translation: Randomised Controlled Trial and Systematic
Review Evidence of Intracoronary Versus Intravenous Abciximab in
St-Elevation Myocardial Infarction
Wu O, McMeekin N, Hawkins N
University of Glasgow, Glasgow, UK
Objectives: In the evaluation of healthcare interventions, systematic review and
meta-analysis of randomized controlled trials (RCTs) has been regarded as the
highest level of evidence. However, these methodologies have limitations that are
inherent to potential bias and heterogeneity that may be present in the source
data. In addition, meta-analyses can constitute a form of sequential analysis as in
principle a new systematic review can be conducted each time trial is conducted.
This study seeks to demonstrate the implications for the consideration of find-
ings of statistical significance from meta-analysis via an examination of RCT and
meta-analyses findings of intracoronary with intravenous abciximab in ST-elevation
myocardial infarction (STEMI) patients.  Methods: A systematic review of RCTs and
meta-analyses. Data on mortality were pooled using: (1) cumulative meta-analy-
sis, which does not take into consideration potential false-positive findings ude to
repeatd significance tests as new trials are addded; and (2) sequentail meta-analysis,
which allows for the possibility that the meta-analysis was repeated after each trial
was published.  Results: To date, the efficacy and safety of intracoronary versus
intravenous administration of abciximab in STEMI patients has been evaluated in
eight RCTs, and ten systematic reviews and meta-analyses. None of the trials, with
the exception of one, reported significant benefits associated with intracoronary
abciximab; this is consistent with the findings reported by a recent large trial. Meta-
analyses carried out prior to the publication of this recent trial showed contrasting
results. However, the sequential analysis did not indicate a statistically significant
reduction in mortality at any point.  Conclusions: It is also important to take into
account the essentially sequential nature of the meta-analysis. The total number
of trial that will be conducted is not fixed, and we should allow for the fact that
multiple meta-analyses may be conducted, although not always reported, as trials
are conducted.
PCV19
The Clinical Value of Olmesartan for the Treatment of
Hypertensive Patients: A Systematic Review
Kourlaba G1, Gialama F2, Vellopoulou K1, Tsioufis K3, Maniadakis N4
1EVROSTON LP, Athens, Greece, 2EVROSTON, Athens, Greece, 3University of Athens, Hippocration
Hospital,, Athens, Greece, 4National School of Public Health, Athens, Greece
Objectives: To systematically review the clinical outcomes of olmesartan as
monotherapy or in combination with other antihypertensive agents in the treat-
ment of hypertension.  Methods: We searched the electronic databases PubMed
and Cochrane Library from inception until December 2015, using predetermined
key-words by a group of experts with relevant methodological and clinical exper-
tise. Eligible studies were selected using predetermined inclusion and exclusion
criteria, limiting articles to those published in the English language. The study
selection process proceeded in two main stages. Background information of the
study, participants’ characteristics and study outcomes were collected using data
extraction forms developed specifically to address the review issues in hand.
A quality assessment of the studies was conducted by two reviewers, using the
Detsky method.  Results: The literature search identified a total of 50 full articles
that met the inclusion criteria. In general results from clinical trials evaluating the
efficacy of olmesartan as monotherapy and as combination therapy demonstrated
that olmesartan provided better antihypertensive BP-lowering efficacy compared
with other antihypertensive agents and compared with component monothera-
pies. Furthermore, treatment with olmesartan either as monotherapy or in com-
bination with HCTZ or amlodipine compared with the component monotherapies
or compared with other combination therapies was generally well tolerated, with
similar nature and frequency of adverse events among them.  Conclusions:
Evidence from the present systematic review confirms the antihypertensive effi-
cacy and good safety profile of olmesartan both as monotherapy and as combi-
nation therapy.
PCV20
Evaluation of the Effect of Pharmacogenetic Dosing of Warfarin:
Should Non-Randomized Clinical Studies be Considered?
Janzic A, Locatelli I
University of Ljubljana, Faculty of Pharmacy, Ljubljana, Slovenia
Objectives: Randomized controlled trials (RCTs) are recognized to provide the
highest level of evidence, but non-RCTs may provide additional insight in esti-
mating effectiveness in “real world” which could be valuable for the assessment
process. The aim of this study was to evaluate the effect of pharmacogenetic
dosing of warfarin based on RCTs and non-RCTs.  Methods: A comprehensive
literature search using electronic databases of Medline, Cochrane Library and
ClinicalTrials.gov up to March 2016 was performed. Original studies containing
independent data where at least one cohort initiated warfarin treatment based
on pharmacogenetic dosing algorithm that was compared to the conventional
initiation were selected.  Results: Of the 326 articles found after the initial search,
17 studies met the inclusion criteria. Twelve of them were RCTs which involved a
total of 2,858 patients. Five non-RCT studies included a total of 1,791 patients in
pharmacogenetic arm and additional 5,051 patients for control. The results were
heterogeneous among RCTs as well as among non-RCTs. Five RTCs failed to show
any clinical benefit of pharmacogenetic dosing of warfarin, while 6 RCTs showed
improvement in at least one observed endpoint. Conclusions from 4 out of 5 non-
RCTs indicate that pharmacogenetic dosing of warfarin provides some benefit.
The endpoint studied most often was the percentage of time in therapeutic range
(TTR) which was reported in 13 studies (10 RCTs and 3 non-RCTs). The differ-
ence in TTR was significant in only three RCTs, and varied between 7.1 and 17.0
percentage points. Similar effect size was observed in non-RCTs, where the dif-
ference in TTR ranged from 7.0 to 12.6 percentage points.  Conclusions: RCTs
that showed benefits express similar effect size as non-RCTs. However, there is a
lack of published non-RCTs that did not demonstrate benefits of pharmacogenetic
dosing of warfarin.
PCV21
Comparative Effectiveness of Brand-Name and Generic Warfarin on
Stroke and Bleeding Events in Atrial Fibrillation Patients: A 6-Year
Population-Based Retrospective Cohort Study in Taiwan
Choo DW, Wu FL, Wang J, Chien K, Lin Z
National Taiwan University, Taipei, Taiwan
Objectives: To determine the stroke and bleeding outcome among generic versus
brand name warfarin recipients in a large cohort.  Methods: This is a nationwide
population-based retrospective cohort study using administrative claims data
National Health Insurance Research Database in Taiwan. We identified all patients
who were diagnosed for AF and used generic or brand name warfarin alone between
January 1, 2006, and December 31, 2010 (N= 23,141) from the NHIRD. A propensity
score matching approach is used to create a subgroup for further adjusting poten-
tial selection bias. Cox proportional hazards regressions were performed to esti-
mate the risk of hospitalization for stroke and diagnosis of bleeding associated
with the generic versus brand name warfarin recipients.  Results: We identified
12,944(55.94%) AF patients who received generic warfarin, and 10,197(44.06%) AF
patients who received brand name warfarin. In the matched cohort, the event rate
of hospitalization for stroke was 17.44 per 100 person-years for the generic warfarin
group, as compared to 15.98 for the brand name warfarin group and the multivari-
ate adjusted hazard ratios (HRs) for hospitalization for stroke of generic warfarin
group was 1.15 (95% CI, 1.09-1.20) compared with brand name warfarin group. The
adjusted HRs for critical site bleeding, definite bleeding, intracranial bleeding and
gastrointestinal bleeding of generic warfarin group were 0.92(95% CI, 0.86-0.99),
0.94(95% CI, 0.90-0.99), 0.92(95% CI, 0.76-1.13) and 0.94(95% CI, 0.89-0.99) respectively
in comparison to brand name warfarin group. Generic warfarin group was associ-
ated with statistically significantly higher risk for stroke when the prescribed daily
dose of warfarin was higher than or equal to 2.5, the multivariate adjusted hazard
ratio of generic warfarin group for stroke is 1.14(95% CI, 1.02-1.26).  Conclusions:
The generic warfarin recipients were at slightly but statistically significant higher
risk of hospitalization for stroke and lower risk of bleeding in comparison to brand
name warfarin group.