OBJECTIVE PROBLEM INTERVENTION COMPARISON OUTCOME REFERENCE

To Coronary artery -They searched the They identified 37 randomized controlled trials involving 11,948 This Cochrane review >http://www.cochra
determine disease is a Cochrane Central Register participants. These trials compared lidocaine versus placebo or no found evidence of ne.org/CD008553/V
the clinical major public of Controlled Trials intervention, disopyramide, mexiletine, tocainide, propafenone, low quality to ASC_prophylactic-
effectivenes health problem (CENTRAL) (2015, Issue amiodarone, dimethylammonium chloride, aprindine and pirmenol. suggest that lidocaine-
s and safety affecting both 3), MEDLINE Ovid (1946 Overall, trials were underpowered and had high risk of bias. Ninety-seven prophylactic myocardial-
of developed and to 13 April per cent of trials (36/37) were conducted without an a priori sample size lidocaine has very infarction
prophylactic developing 2015), EMBASE (1947 to estimation. Ten trials were sponsored by the pharmaceutical industry. little or no effect on
countries. Acute c 13 April 2015) and Latin
lidocaine in Trials were conducted in 17 countries, and intravenous intervention was mortality or AUTHORS:
oronary American Caribbean
preventing the most frequent route of administration. ventricular fibrillation Martí-Carvajal AJ,
syndromes Health Sciences Literature
death include unstable (LILACS) (1986 to 13 April In trials involving participants with proven or non-proven acute myocardial in people with acute Simancas-Racines D,
among angina and 2015). We also searched infarction, lidocaine versus placebo or no intervention showed no myocardial Anand V,
people with myocardial Web of Science (1970 to significant differences regarding all-cause mortality (213/5879 (3.62%) vs infarction. The safety Bangdiwala S
myocardial infarction with or 13 April 2013) and hand 199/5848 (3.40%); RR 1.02, 95% CI 0.82 to 1.27; participants = 11727; profile is unclear.
infarction. without ST- searched the reference studies = 18; I2 = 15%); low-quality evidence), cardiac mortality (69/4184 This conclusion is Published:
segment lists of included papers. (1.65%) vs 62/4093 (1.51%); RR 1.03, 95% CI 0.70 to 1.50; participants = based on randomised 21 August 2015
elevation We applied no language 8277; studies = 12; I2 = 12%; low-quality evidence) and prophylaxis of controlled trials with
(electrocardiogra restriction in the search. ventricular fibrillation (76/5128 (1.48%) vs 103/4987 (2.01%); RR 0.78, 95% high risk of bias.
m sector is higher -They included randomized CI 0.55 to 1.12; participants = 10115; studies = 16; I2 = 18%; low-quality However
than baseline). controlled trials assessing evidence). In terms of sinus bradycardia, lidocaine effect is imprecise (disregarding the risk
Ventricular the effects of prophylactic compared with effects of placebo or no intervention (55/1346 (4.08%) vs of bias), trial
arrhythmia after lidocaine for myocardial 49/1203 (4.07%); RR 1.09, 95% CI 0.66 to 1.80; participants = 2549; studies sequential analysis
myocardial infarction. They considered = 8; I2 = 21%; very low-quality evidence). In trials involving only suggests that
infarction is all-cause mortality, cardiac participants with proven acute myocardial infarction, lidocaine versus additional trials may
associated with mortality and overall placebo or no intervention showed no significant differences in all-cause not be needed to
high risk of mortal survival at 30 days after
mortality (148/2747 (5.39%) vs 135/2506 (5.39%); RR 1.01, 95% CI 0.79 to disprove an
ity. The evidence myocardial infarction as
1.30; participants = 5253; studies = 16; I2 = 9%; low-quality evidence). No intervention effect of
is out of date, and primary outcomes.
considerable -We performed study significant differences were noted between lidocaine and any other 20% relative risk
uncertainty selection, risk of bias antiarrhythmic drug in terms of all-cause mortality and ventricular reduction. Smaller
remains about the assessment and data fibrillation. Data on overall survival 30 days after myocardial infarction risk reductions might
effects of extraction in duplicate. We were not reported. Lidocaine compared with placebo or no intervention require additional
prophylactic use estimated risk ratios (RRs) for increased risk of asystole (35/3393 (1.03%) vs 14/3443 (0.41%); RR 2.32, higher trials.
of lidocaine on dichotomous outcomes and 95% CI 1.26 to 4.26; participants = 6826; studies = 4; I2 = 0%; very low-
all- measured statistical quality evidence) and dizziness/drowsiness (74/1259 (5.88%) vs 16/1274
cause mortality, (1.26%); RR 3.85, 95% CI 2.29 to 6.47; participants = 2533; studies = 6; I2 =
heterogeneity using I2. We
in particular, in 0%; low-quality evidence). Overall, safety data were poorly reported and
used a random-effects model
patients with adverse events may have been underestimated. Trial sequential analyses
suspected and conducted trial
sequential analysis. suggest that additional trials may not be needed for reliable conclusions to
myocardial be drawn regarding these outcomes.
infarction.
 NOTRE DAME UNIVERSITY
COLLEGE OF HEALTH SCIENCES
COTABATO CITY

REQUIREMENTS
IN
PHARMACOLOGY
“Prophylactic lidocaine for myocardial infarction”

SUBMITTED TO: PROF. DONNAVILLA YAP, RM, MAN

SUBMITTED BY: HORON-AIN E. MOMEN
BSN2A
 NOTRE DAME UNIVERSITY
COLLEGE OF HEALTH SCIENCES
COTABATO CITY

REQUIREMENTS
IN
PHARMACOLOGY
“Use of nitroglycerin to deliver a retained placenta”

SUBMITTED TO: PROF. DONNAVILLA YAP, RM, MAN

SUBMITTED BY: NORHAFIZA DATUMANONG
BSN2A
 OBJECTIVE PROBLEM INTERVENTION COMPARISON OUTCOME REFERENCE
To evaluate Retained -They searched the They included three randomised controlled trials (RCTs) with In cases of retained >http://www.cochrane.org/CD0
the benefits placenta affects Cochrane Pregnancy and 175 women. The three published RCTs compared NTG alone placenta, currently available 07708/PREG_use-nitroglycerin-
and harms of 0.5% to 3% of Childbirth Group’s Trials versus placebo. The detachment status of retained placenta data showed that the use of deliver-retained-placenta
NTG as a women Register (14 January was unknown in all three RCTs. Collectively, among the three NTG alone did not reduce
tocolytic, following 2015), reference lists of included trials, two were judged to be at low risk of bias and the need for manual Authors:
either alone delivery, with retrieved studies and the third trial was judged to be at high risk of bias for two removal of placenta. This Abdel-Aleem H, Abdel-Aleem
or in addition considerable contacted experts in the domains: incomplete outcome data and selective reporting. intervention did not MA, Shaaban OM
to morbidity if left field. The three trials reported seven out of 23 of the review's pre- increase the incidence of Published:
uterotonics, in untreated. Use -Any adequately specified outcomes. severe postpartum 12 November 2015
the of nitroglycerin randomised controlled The primary outcome "manual removal of the placenta" was haemorrhage nor the need
management (NTG), either trial (RCT) comparing the reported in all three studies. No differences were seen for blood transfusion.
of retained alone or in use of NTG, either alone between NTG and placebo for manual removal of the placenta Haemodynamically, NTG
placenta. combination or in combination with (average risk ratio (RR) 0.83, 95% confidence interval (CI) 0.47 had a significant though
with uterotonics, uterotonics, with no to 1.46; women = 175; I² = 81%). A random-effects model was mild effect on both pulse
may be of value intervention or with used because of evidence of substantial heterogeneity in the rate and blood pressure.
to minimise the other interventions in analysis. There were also no differences between groups for
need for manual the management of risk of severe postpartum haemorrhage (RR 0.93, 95% CI 0.62
removal of the retained placenta. All to 1.39; women = 150; studies = two; I² = 0%). Blood
placenta in women having a vaginal transfusion was only reported in one study (40 women) and
theatre under delivery with a retained again there was no difference between groups (RR 1.00, 95%
anaesthesia placenta, regardless of CI 0.07 to 14.90; women = 40; I² = 0%). Mean blood loss (mL)
the management of the was reported in the three studies and no differences were
third stage of labour observed (mean difference (MD) -115.31, 95% CI -306.25 to
(expectant or active). 75.63; women = 169; I² = 83%). Nitroglycerin administration
We included all trials was not associated with an increase in headaches (RR 1.09,
with haemodynamically 95% CI 0.80 to 1.47; women = 174; studies = three; I² = 0%).
stable women in whom However, nitroglycerin administration was associated with a
the placenta was not significant, though mild, decrease in systolic and diastolic
delivered at least within blood pressure and a significant increase in pulse rate (MD -
15 minutes after 3.75, 95% CI -7.47 to -0.03) for systolic blood pressure, and
delivery of the baby. (MD 6.00, 95% CI 3.07 to 8.93) for pulse rate (beats per
-Two review authors minute) respectively (reported by only one study including 24
independently assessed participants). Maternal mortality and addition of therapeutic
trials for inclusion and uterotonics were not reported in any study.
risk of bias, extracted
data and checked them
for accuracy.
 NOTRE DAME UNIVERSITY
COLLEGE OF HEALTH SCIENCES
COTABATO CITY

REQUIREMENTS
IN
PHARMACOLOGY
“Nitrates for reducing death and cardiac complications in
participants during non-cardiac surgery”
SUBMITTED TO: PROF. DONNAVILLA YAP, RM, MAN
SUBMITTED BY: EILLYSSAH ASHER MATABALAO
BSN2A
OBJECTIVE PROBLEM INTERVENTION COMPARISON OUTCOME REFERENCE
• To assess Cardiac -They searched the Cochrane They included 27 randomized controlled trials (RCTs) (8244 This systematic review suggests >http://www.c
effects of complications are not Central Register of Controlled participants analysed). Investigators reported 12 different that nitroglycerin or isosorbide ochrane.org/CD
nitrates as uncommon in Trials (CENTRAL), MEDLINE, comparisons of three different nitrates (nitroglycerin, dinitrate is not associated with 010726/ANAES
compared patients undergoing EMBASE and the Chinese isosorbide dinitrate and nicorandil) versus no treatment, improvement in mortality and TH_nitrates-
with other non-cardiac surgery, BioMedical Database until June placebo or other pharmacological interventions. All cardiac complications among reducing-
interventions especially in patients 2014. We also searched relevant participants were older than 15 years of age. More than half of patients undergoing non- death-and-
or placebo in with coronary artery conference abstracts of important the trials used general anaesthesia. Surgical procedures in cardiac surgery. Limited cardiac-
reducing disease (CAD) or at anaesthesiology or cardiology most trials were at low to moderate risk for perioperative evidence suggests that complications-
cardiac risk high risk of CAD. scientific meetings, the database cardiac complications. Only two comparisons including three nicorandil may reduce the risk participants-
(such as Perioperative cardiac of ongoing trials and Google studies reported the primary outcome - all-cause mortality up of cardiac ischaemia in during-non-
death caused complications can Scholar. They reran the search in to 30 days post operation. Researchers reported other participants undergoing non- cardiac-surgery
by cardiac lead to mortality and January 2016. We added three morbidity outcomes and adverse events in a variable and cardiac surgery. Additional
factors, morbidity, as well as potential new studies of interest heterogeneous way, resulting in limited available data for studies are needed to
angina higher costs for to the list of ‘Studies awaiting inclusion in the meta-analysis. We determined that the overall consolidate the evidence. Authors:
pectoris, patient care. classification' and will incorporate methodological quality of included studies was fair to low, in However, the data included in Zhao N, Xu J,
acute Nitrates, which are them into our formal review accordance with risk of bias in most domains. many of the analyses in this Singh B, Yu X,
myocardial among the most findings for the review update. In summary, we found no difference in the primary outcome - review are sparse - that is, Wu T, Huang Y
infarction, commonly used -They included randomized all-cause mortality up to 30 days post operation - when adequate data are few -
acute heart cardiovascular drugs, controlled trials (RCTs) comparing nitroglycerin was compared with no treatment (one study, 60 resulting in very low power to
failure and perform the function nitrates versus no treatment, participants, 0/30 vs 1/30; (risk ratio (RR) 0.33, 95% confidence detect differences between Published:
cardiac of decreasing cardiac placebo or other pharmacological interval (CI) 0.01 to 7.87, very low-quality evidence based on nitrates and comparators.
arrhythmia) preload while interventions in participants (15 GRADE criteria) or with placebo (two studies, 89 participants, Thus, a more objective 4 August 2016
in patients improving cardiac years of age and older) 1/45 vs 0/44; RR 2.81, 95% CI 0.12 to 63.83, very low-quality conclusion would state that
undergoing blood perfusion. undergoing non-cardiac surgery evidence). Regarding our secondary outcomes, we noted no available evidence is
non-cardiac Sometimes, nitrates under any type of anaesthesia. statistically significant differences in angina pectoris, acute insufficient to show whether
surgery. are administered to -They used standard myocardial infarction, acute heart failure, cardiac arrhythmia nitrates are associated with
patients undergoing methodological procedures as or cardiac arrest in any comparisons. In comparisons versus improvement in mortality and
non-cardiac surgery expected by Cochrane. Two nitroglycerin, although more events of cardiac ischaemia were cardiac complications among
• To identify to reduce the review authors selected trials, observed in participants receiving no treatment or placebo, we patients undergoing non-
the influence incidence of cardiac extracted data from included found no statistically significant differences in any cardiac surgery.
of different complications, studies and assessed risk of bias. comparisons, except the comparison of nicorandil versus Over the past decade, no high-
routes and especially for We resolved differences by placebo. One study revealed a potential dose-dependent quality studies have focused on
dosages of patients with CAD. discussion and, when necessary, protective effect of nicorandil for cardiac ischaemia. association of cardiac mortality
nitrates on However, their sought help and suggestions from Adverse events were reported in a heterogeneous way among and morbidity with use of
patient effects on patients' a third review author. We used a the comparisons. In general, more participants treated with nitrates during non-cardiac
outcomes. relevant outcomes random-effects model for data nitrates had hypotension, tachycardia and headache, but surgery. This review underlines
remain controversial. analysis. investigators reported no statistically significant differences the need for well-designed
between groups in any comparisons. trials in this field.
 NOTRE DAME UNIVERSITY
COLLEGE OF HEALTH SCIENCES
COTABATO CITY

REQUIREMENTS
IN
PHARMACOLOGY
“Digoxin for preventing or treating neonatal respiratory
distress syndrome”
SUBMITTED TO: PROF. DONNAVILLA YAP, RM, MAN
SUBMITTED BY: PRINCESS ALISSAH UNTONG
BSN2A
 OBJECTIVE PROBLEM INTERVENTION COMPARISON OUTCOME REFERENCE
To assess the Lendrum 1955 -Searches were made of the Two randomized controlled trials have Although hemodynamic >http://www.cochrane.org/CD001
effect of digoxin suggested that Oxford Database of Perinatal studied the effects of digoxin in the disturbances play a role in the 080/NEONATAL_digoxin-for-
on mortality in pulmonary edema Trials, Medline (MeSH terms: prevention and treatment of RDS. No overall pathogenesis of respiratory preventing-or-treating-neonatal-
premature secondary to digoxin; limits: age groups, improvement in respiratory status or distress syndrome, the specific respiratory-distress-syndrome
infants at risk for congestive heart newborn infants; publication mortality was noted. Meta-analysis of contribution of early congestive
or with RDS. failure may contribute type, clinical trial), previous the effect of digoxin given to infants at heart failure (unrelated to Authors:
to neonatal reviews including cross risk of or with RDS on mortality does hemodynamically significant Soll R, Özek E
respiratory distress references, abstracts, not suggest any benefit of digoxin patent ductus arteriosus) does not
syndrome (RDS). conference and symposia treatment (typical relative risk 1.27 appear to be a significant factor in Published:
Based on this proceedings, expert 95% CI 0.78 to 2.07; typical risk RDS. Treatment with digoxin has 19 January 2011
hypothesis, informants, and journal difference 0.06, 95% CI -0.06 to 0.17). no proven value in infants solely
investigators began to handsearching in the English affected with RDS.
use digitalis glycosides language.
to improve myocardial When updated in December
contractility and 2008, the search was expanded
decrease congestive to include Medline, CINHAL,
heart failure. The first and Embase (MeSH terms and
use of digitalis text words: digoxin or digitalis;
glycosides in infants limits: age group, all infants;
with RDS was publication type: clinical trial).
reported by Stahlman -Randomized and quazi-
1959. Stahlman randomized controlled trials of
reported a reduction digoxin in either the prevention
in mortality in an or treatment of RDS are
uncontrolled trial of included in this overview.
digitalis in infants with -Data regarding clinical
RDS. outcomes were excerpted from
the trial reports by one review
author (RS) and checked by the
second review author (EO).
Data were analyzed according
to the standards of the
Cochrane Neonatal Review
Group.
 NOTRE DAME UNIVERSITY
COLLEGE OF HEALTH SCIENCES
COTABATO CITY

REQUIREMENTS
IN
PHARMACOLOGY
“”
SUBMITTED TO: PROF. DONNAVILLA YAP, RM, MAN
SUBMITTED BY: MISCHAELLE ANSOL
BSN2A
 OBJECTIVE PROBLEM
To evaluate the Venous
efficacy of a 10- thromboembolism (VTE) is
mg warfarin a common condition in
nomogram hospital patients.
compared with a Considerable controversy
5-mg warfarin is ongoing regarding
nomogram optimal initial warfarin
among patients dosing for patients with
with VTE. acute deep venous
thrombosis (DVT) and
pulmonary embolism (PE).
Achieving a therapeutic
international normalized
ratio (INR) with warfarin
as soon as possible is
important because this
minimizes the duration of
parenteral medication
necessary to attain
immediate
anticoagulation, and it
potentially decreases the
cost and inconvenience of
treatment. Although a 5-
mg loading-dose
nomogram tends to
prevent excessive
anticoagulation, a 10-mg
loading-dose nomogram
may achieve a therapeutic
INR more quickly. This is
an update of a review first
published in 2013.
INTERVENTION COMPARISON OUTCOME REFERENCE
-For this update the Four trials involving 494 participants were included. In patients with acute >http://www.cochrane.org/
Cochrane Vascular Three studies involving 383 participants provided data thromboembolism (DVT or CD007699/PVD_warfarin-
Trials Search Co- on the proportion of participants who had achieved a PE) aged 18 years or older, initiation-nomograms-5-mg-
ordinator searched the therapeutic INR by day five. Significant benefit of a 10- considerable uncertainty and-10-mg-venous-
Specialised Register mg warfarin nomogram was observed (risk ratio (RR) surrounds the use of a 10-mg thromboembolism
(last searched 1.27, 95% confidence interval (CI) 1.05 to 1.54; or a 5-mg loading dose for
September 2015) and moderate quality evidence), although with substantial initiation of warfarin to Authors:
the Cochrane Register heterogeneity (I2 = 90%). The review authors analyzed achieve an INR of 2.0 to 3.0 Garcia P, Ruiz W, Loza
of Studies (CENTRAL each study separately because it was not possible to on the fifth day of therapy. Munárriz C
(2015, Issue 8). Clinical perform a subgroup analysis by inpatient or outpatient Heterogeneity among
trials databases were status. One study showed significant benefit of a 10- analyzed studies, mainly Published:
also searched. The mg warfarin nomogram for the proportion of caused by differences in 29 January 2016
review authors outpatients with VTE who had achieved a therapeutic types of study participants
searched PubMed (last INR by day five (RR 1.78, 95% CI 1.41 to 2.25), with the and length of follow-up,
searched 11 June 2015) number needed to treat for an additional beneficial limits certainty surrounding
and LILACS (last outcome (NNTB = 3, 95% CI 2 to 4); another study optimal warfarin initiation
searched 11 June showed significant benefit of a 5-mg warfarin nomograms.
2015). In addition, the nomogram in outpatients with VTE (RR 0.58, 95% CI
review authors 0.36 to 0.93) with NNTB = 5 (95% CI 3 to 28); a third
contacted study, consisting of both inpatients and outpatients,
pharmaceutical showed no difference (RR 1.08, 95% CI 0.65 to 1.80).
companies.
-Randomized No difference was observed in recurrent venous
controlled studies thromboembolism at 90 days when the warfarin
comparing warfarin nomogram of 10 mg was compared with the warfarin
initiation nomograms nomogram of 5 mg (RR 1.48, 95% CI 0.39 to 5.56; 3
of 10 and 5 mg in studies, 362 participants, low quality evidence); no
patients with VTE. difference was observed in major bleeding at 14 to 90
-Two review authors days (RR 0.97, 95% CI 0.27 to 3.51; 4 studies, 494
independently participants, moderate quality evidence). No
assessed trial quality difference was observed in minor bleeding at 14 to 90
and extracted data. days (RR 0.52, 95% CI 0.15 to 1.83; 2 studies, 243
The review authors participants, very low quality evidence) or in length of
contacted study hospital stay (mean difference (MD) -2.3 days, 95% CI -
authors for additional 7.96 to 3.36; 1 study, 111 participants, low quality
information. evidence).
 NOTRE DAME UNIVERSITY
COLLEGE OF HEALTH SCIENCES
COTABATO CITY

REQUIREMENTS
IN
PHARMACOLOGY
“Effect of atorvastatin on cholesterol”
SUBMITTED TO: PROF. DONNAVILLA YAP, RM, MAN
SUBMITTED BY: RINDELLE ALEXANDRIAH NICOLE KASILAG
BSN2A
 OBJECTIVE PROBLEM INTERVENTION COMPARISON OUTC REFERENCE
OME
To quantify the This represents -They searched the In this update, we found an additional 42 trials and added This update resulted in no >http://www.cochrane.or
effects of various the first update of Cochrane Central them to the original 254 studies. The update consists of change to the main conclusions g/CD008226/HTN_effect-
doses of atorvastatin this review, which Register of Controlled 296 trials that evaluated dose-related efficacy of of the review but significantly atorvastatin-cholesterol
on serum total was published in Trials (CENTRAL) (Issue atorvastatin in 38,817 participants. Included are 242 increases the strength of the
cholesterol, low- 2012. 11, 2013), MEDLINE before-and-after trials and 54 placebo-controlled RCTs. evidence. Studies show that Published:
density lipoprotein Atorvastatin is (1966 to December Log dose-response data from both trial designs revealed atorvastatin decreases blood 11 March 2015
(LDL)-cholesterol, one of the most Week 2 2013), EMBASE linear dose-related effects on blood total cholesterol, total cholesterol and LDL-
high-density widely prescribed (1980 to December LDL-cholesterol, HDL-cholesterol and triglycerides. The cholesterol in a linear dose- Authors:
lipoprotein (HDL)- drugs and the Week 2 2013), Web of Summary of findings table 1 documents the effect of related manner over the Adams SP, Tsang M,
cholesterol and most widely Science (1899 to atorvastatin on LDL-cholesterol over the dose range of 10 commonly prescribed dose Wright JM
triglycerides in prescribed statin December Week 2 to 80 mg/d, which is the range for which this systematic range. New findings include
individuals with and in the world. It is 2013) and BIOSIS review acquired the greatest quantity of data. Over this that atorvastatin is more than
without evidence of therefore Previews (1969 to range, blood LDL-cholesterol is decreased by 37.1% to three-fold less potent than
cardiovascular important to December Week 2 51.7% (Summary of findings table 1). The slope of dose- rosuvastatin, and that the
disease. The primary know the dose- 2013). We applied no related effects on cholesterol and LDL-cholesterol was cholesterol-lowering effects of
focus of this review related language restrictions. similar for atorvastatin and rosuvastatin, but rosuvastatin atorvastatin are greater in
was determination magnitude of -Randomised controlled is about three-fold more potent. Subgroup analyses females than in males and
of the mean per cent effect of and uncontrolled suggested that the atorvastatin effect was greater in greater in non-familial than in
change from atorvastatin on before-and-after trials females than in males and was greater in non-familial familial hypercholesterolaemia.
baseline of LDL- blood lipids. evaluating the dose than in familial hypercholesterolaemia. Risk of bias for This review update does not
cholesterol. response of different the outcome of withdrawals due to adverse effects provide a good estimate of the
fixed doses of (WDAEs) was high, but the mostly unclear risk of bias was incidence of harms associated
atorvastatin on blood judged unlikely to affect lipid measurements. with atorvastatin because
lipids over a duration of Withdrawals due to adverse effects were not statistically included trials were of short
three to 12 weeks. significantly different between atorvastatin and placebo duration and adverse effects
-Two review authors groups in these short-term trials (risk ratio 0.98, 95% were not reported in 37% of
independently assessed confidence interval 0.68 to 1.40). placebo-controlled trials.
eligibility criteria for
studies to be included
and extracted data. We
collected information
on withdrawals due to
adverse effects from
placebo-controlled
trials.
 NOTRE DAME UNIVERSITY
COLLEGE OF HEALTH SCIENCES
COTABATO CITY

REQUIREMENTS
IN
PHARMACOLOGY
“Allopurinol for chronic gout”
SUBMITTED TO: PROF. DONNAVILLA YAP, RM, MAN
SUBMITTED BY: BAI JULY FATMA SULTAN
BSN2A
OBJECTIVE PROBLEM INTERVENTION
To assess Allopurinol, -They searched the
the efficacy a xanthine Cochrane Central Register of
and safety oxidase Controlled Trials (CENTRAL),
of inhibitor, is MEDLINE and EMBASE on 14
allopurinol considered January 2014. We also
compared one of the handsearched the 2011 to
with most 2012 American College of
placebo and effective Rheumatology (ACR) and
other urate- urate- European League against
lowering lowering Rheumatism (EULAR)
therapies drugs and is abstracts, trial registers and
for treating frequently regulatory agency drug
chronic used in the safety databases.
gout. treatment of -All randomised controlled
chronic trials (RCTs) or quasi-
gout. randomised controlled
clinical trials (CCTs) that
compared allopurinol with a
placebo or an active therapy
in adults with chronic gout.
-They extracted and
analysed data using
standard methods for
Cochrane reviews. The
major outcomes of interest
were frequency of acute
gout attacks, serum urate
normalisation, pain,
function, tophus regression,
study participant withdrawal
due to adverse events (AE)
and serious adverse events
(SAE). We assessed the
quality of the body of
evidence for these outcomes
using the GRADE approach.
COMPARISON OUTCOME REFERENCE
They included 11 trials (4531 participants) that compared allopurinol Our review found low- to >http://www.co
(various doses) with placebo (two trials); febuxostat (four trials); moderate-quality evidence chrane.org/CD0
benzbromarone (two trials); colchicine (one trial); probenecid (one trial); indicating similar effects on 06077/MUSKEL_
continuous versus intermittent allopurinol (one trial) and different doses of withdrawals due to AEs and SAEs allopurinol-for-
allopurinol (one trial). Only one trial was at low risk of bias in all domains. and incidence of acute gout chronic-gout
We deemed allopurinol versus placebo the main comparison, and attacks when allopurinol (100 to
allopurinol versus febuxostat and versus benzbromarone as the most 600 mg daily) was compared with Published:
clinically relevant active comparisons and restricted reporting to these placebo, benzbromarone (100 to 14 October 2014
comparisons here. 200 mg daily) or febuxostat (80
Moderate-quality evidence from one trial (57 participants) indicated mg daily). There was moderate- Authors:
allopurinol 300 mg daily probably does not reduce the rate of gout attacks quality evidence of little or no Seth R, Kydd
(2/26 with allopurinol versus 3/25 with placebo; risk ratio (RR) 0.64, 95% difference in the proportion of ASR, Buchbinder
confidence interval (CI) 0.12 to 3.52) but increases the proportion of participants achieving target R, Bombardier C,
participants achieving a target serum urate over 30 days (25/26 with serum urate when allopurinol Edwards CJ
allopurinol versus 0/25 with placebo, RR 49.11, 95% CI 3.15 to 765.58; was compared with
number needed to treat for an additional beneficial outcome (NNTB) 1). In benzbromarone. However,
two studies (453 participants), there was no significant increase in allopurinol seemed more
withdrawals due to AE (6% with allopurinol versus 4% with placebo, RR successful than placebo and may
1.36, 95% CI 0.61 to 3.08) or SAE (2% with allopurinol versus 1% with be less successful than
placebo, RR 1.93, 95% CI 0.48 to 7.80). One trial reported no difference in febuxostat (80 mg daily) in
pain reduction or tophus regression, but did not report outcome data or achieving a target serum urate
measures of variance sufficiently and we could not calculate the differences level (6 mg/dL or less; 0.36
between groups. Neither trial reported function. mmol/L or less) based on
Low-quality evidence from three trials (1136 participants) indicated there moderate- to low-quality
may be no difference in the incidence of acute gout attacks with allopurinol evidence. Single studies reported
up to 300 mg daily versus febuxostat 80 mg daily over eight to 24 weeks no difference in pain reduction
(21% with allopurinol versus 23% with febuxostat, RR 0.89, 95% CI 0.71 to when allopurinol (300 mg daily)
1.1); however more participants may achieve target serum urate level (four was compared with placebo over
trials; 2618 participants) with febuxostat 80 mg daily versus allopurinol 300 10 days, and no difference in
mg daily (38% with allopurinol versus 70% with febuxostat, RR 0.56, 95% CI tophus regression when
0.48 to 0.65, NNTB with febuxostat 4). Two trials reported no difference in allopurinol (200 to 300 mg daily)
tophus regression between allopurinol and febuxostat over a 28- to 52- was compared with febuxostat
week period; but as the trialists did not provide variance, we could not (80 mg daily). None of the trials
calculate the mean difference between groups. The trials did not report reported on function, health-
pain reduction or function. Moderate-quality evidence from pooled data related quality of life or
from three trials (2555 participants) comparing allopurinol up to 300 mg participant global assessment of
daily versus febuxostat 80 mg daily indicated no difference in the number treatment success, where further
of withdrawals due to AE (7% with allopurinol versus 8% with febuxostat, research would be useful.
RR 0.89, 95% CI 0.62 to 1.26) or SAE (4% with allopurinol versus 4% with
febuxostat, RR 1.13, 95% CI 0.71 to 1.82) over a 24- to 52-week period.
Low-quality evidence from one trial (65 participants) indicated there may
be no difference in the incidence of acute gout attacks with allopurinol up
to 600 mg daily compared with benzbromarone up to 200 mg daily over a
four-month period (0/30 with allopurinol versus 1/25 with benzbromarone,
RR 0.28, 95% CI 0.01 to 6.58). Based on the pooled results of two trials (102
participants), there was moderate-quality evidence of no probable
difference in the proportion of participants achieving a target serum urate
level with allopurinol versus benzbromarone (58% with allopurinol versus
74% with benzbromarone, RR 0.79, 95% CI 0.56 to 1.11). Low-quality
evidence from two studies indicated there may be no difference in the
number of participants who withdrew due to AE with allopurinol versus
benzbromarone over a four- to nine-month period (6% with allopurinol
versus 7% with benzbromarone, pooled RR 0.80, 95% CI 0.18 to 3.58). There
were no SAEs. They did not report tophi regression, pain and function.
All other comparisons were supported by small, single studies only, limiting
conclusions.