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RxFiles: Objective Comparative Drug Information Trial
Summaries |
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QUICK
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Trial |
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(2010) |
A synopsis
of the purposes, parameters, and outcome evidence for the following trials:
DCCT, DCCT/EDIC, UKPDS-33, UKPDS-34, |
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Prevention Trials Summary (2008) |
An overview of the following drug trials, which focused on the
efficacy in preventing the onset of Diabetes Mellitus: XENDOS(Orlistat), DREAM(Rosiglitazone),
DREAM(Ramipril), STOP-NIDDM(Acarbose), Diabetes Prevention
Program(Metformin, Lifestyle Mods),
IDPP, FDPS |
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(2008) |
Very brief comparison between the results of ACCORD ( |
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(2008) |
An outline
of the methodology and results of the ACCORD T2DM trial examining the
outcomes (Primary = MI, stroke, CV death) of aggressive lowering of
haemoglobin A1C, achieved with various oral hypoglycemics
+/- insulin. Trial halted early due to
increased mortality in intervention group. |
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(2010) |
This trial summary provides an overview of
the blood pressure-lowering and lipid-lowering sub-trials of the ACCORD T2DM
study. While the main trial examining
intensive glucose-lowering was halted early due to safety concerns, these two
sub-trials were permitted to proceed to their conclusion. The lipid-lowering arm compares open-label Simvastatin
20-40mg/day in combination with either masked fenofibrate
or placebo at preventing a first
occurrence of major CV events (non-fatal MI or stroke, death from CV causes)
in patients with T2DM and at a high risk of CVD, over a mean period of 4.7
years. The BP-lowering arm compared
the effects of intensive
therapy targeting (SBP≤120mmHg) vs. standard therapy targeting (SBP≤140mmHg) at preventing these same primary endpoints
for the same duration. Results of these
two sub-studies again seem to emphasize that an aggressive approach to
managing chronic diseases does not always translate into improved patient
outcomes – another reminder that the
target should suit the patient, not vice versa. |
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(2008) |
Summary of
the findings of the ADVANCE T2DM trial that aimed to determine whether there
are any outcome benefits (Primary = nephropathy, retinopathy, CV death,
nonfatal MI/stroke) to intensive glucose control achieved by a gliclazide regimen as compared to a non-gliclazide regimen. |
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(2007) |
A “pros
vs. cons” approach to the growing body of evidence, including the Nissen, Wolski Meta-analysis
(NEJM MAY 2007), linking rosiglitazone to an
increased risk of MI and CV death. Yet
another illustration of the possible harm associated with intensive blood
glucose-lowering therapy. |
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(2007) |
An analysis
of the international DREAM trials, which focused on people with impaired
fasting glucose or impaired glucose tolerance and are at low risk of CV
events. The study aimed to determine
whether the use of rosiglitazone 8mg/day or ramipril 15mg/day showed any benefit in slowing the development and progression of diabetes
in this demographic, when compared to a placebo. |
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GLARGINE & CANCER (2009) |
This
document offers an explanation of the concerns surrounding insulin glargine (Lantus), a
long-acting synthetic insulin analogue.
It also presents the strengths and weaknesses of the studies linking
this drug to cancer, and whether or not these new findings have relevance to
the diabetic population as a whole. (Excerpted with permission from Rapid Rx
July 10, 2009) |
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(2009) |
A
non-inferiority trial whose purpose was to determine whether the addition of rosiglitazone(4-8mg/day)
to a regimen already consisting of either metformin(≤2550mg/day)
or a sulfonylurea(glyburide≤15mg/day; gliclazide≤240mg/day;
glimepiride≤4mg/day) would show a benefit (Primary = CV death or CV
hosp) over a regimen of metformin + a sulfonylurea. |
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Trial |
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(2003) |
An outline
of the purposes and findings of the following trials: AASK, ALLHAT, ALLHAT
LLT, CALM, CAPPP, ELITE II, FACET, HOPE, HOT, IDNT, INSIGHT, IRMA II, LIFE,
NORDIL, OPTIMAAL, PROGRESS, QUIET, RENAAL, SHEP, STOP-Hypertension 2,
SYST-EUR, UKPDS, Val-HeFT |
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(2008) |
To judge efficacy
of ACE Inhibitor (Benazepril 20-40mg/day) + Amlodipine 5-10mg/day vs. Benazepril
20-40mg/day + Hydrochlorothiazide 12.5-25mg/day in preventing CV death,
non-fatal MI, and stroke in high-risk hypertensive patients. |
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(2010) |
This trial
summary provides an overview of the blood pressure-lowering and
lipid-lowering sub-trials of the ACCORD T2DM study. While the main trial examining intensive
glucose-lowering was halted early due to safety concerns, these two
sub-trials were permitted to proceed to their conclusion. The lipid-lowering arm compares open-label Simvastatin 20-40mg/day in combination with either masked
fenofibrate or placebo at preventing a first
occurrence of major CV events (non-fatal MI or stroke, death from CV causes)
in patients with T2DM and at a high risk of CVD, over a mean period of 4.7
years. The BP-lowering arm compared
the effects of intensive therapy targeting (SBP≤120mmHg) vs. standard
therapy targeting (SBP≤140mmHg) at preventing these same primary
endpoints for the same duration.
Results of these two sub-studies again seem to emphasize that an
aggressive approach to managing chronic diseases does not always translate
into improved patient outcomes – another reminder that the target should suit
the patient, not vice versa. |
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(2003) |
Designed
to determine if there were any clinical outcome differences (Primary =
non-fatal MI and fatal CHD) in high-risk hypertensive patients treated with
relatively newer antihypertensive agents (amlodipine,
lisinopril, doxazosin)
versus a low-dose diuretic (chlorthalidone). |
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(2003) |
Compares the
findings of the ANBP2 trial ( |
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(2005) |
Blood
Pressure-Lowering Arm of ASCOT, to determine effect of amlodipine
+/- perindopril vs. atenolol +/- bendroflumethiazide
on ‘non-fatal MI and fatal CHD’ in moderate risk (eg.
diabetes 27%) hypertensive patients without previous heart disease. |
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(2010 Members Only) |
Updated and
condensed summary of the following trials, including the “current knowledge” obtained
from each: AASK, ALLHAT, ASCOT-BPLA, CALM, CAPPP, ELITE II, FACET, HOPE, HOT,
IDNT, INSIGHT, IRMA II, LIFE, NORDIL, OPTIMAAL, PROGRESS, QUIET, RENAAL,
SHEP, STOP-hypertension, SYST-EUR, UKPDS, Val-HeFT |
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Trial |
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(2011) |
Pattern of CVD
changes as CKD progresses: early CKD cholesterol dependent atheromatous coronary disease; late CKD vascular
calcification, LVH. Lipid lowering therapy (statin)
is indicated to prevent atherosclerotic CVD in patients with CKD including
those progressing to ESRD; findings emphasize need to treat early in disease
process, however, point at which patients may no longer benefit remains
unclear, and there is no evidence to support initiation of statin therapy in dialysis patients. Studies confirm that
statin therapy is safe in late stage CKD. Role of ezetimibe is not clear, but unlikely to have contributed
to clinical outcomes. |
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(2011) |
AIM-HIGH
does NOT provide support for the use of ER niacin (NIASPAN) as an add on to statin therapy in a stable 2° prevention population already treated
with ASA, beta-blockers, ACEi or ARB’s & statins. However
likely was not designed appropriately to answer this question since ambitious
estimated risk reduction, and early stop/short duration of the trial. Results
for AIM-HIGH raise questions regarding modifiable nature of residual risk in
patients reaching LDL targets on a statin. |
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(2004) |
Provides a summary
chart and general interpretation of the following lipid trials: 4S, PROVE-IT,
HPS, WOSCOPS, |
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(2010) |
This trial
summary provides an overview of the blood pressure-lowering and
lipid-lowering sub-trials of the ACCORD T2DM study. While the main trial examining intensive
glucose-lowering was halted early due to safety concerns, these two
sub-trials were permitted to proceed to their conclusion. The lipid-lowering arm compares open-label Simvastatin 20-40mg/day in combination with either masked
fenofibrate or placebo at preventing a first
occurrence of major CV events (non-fatal MI or stroke, death from CV causes)
in patients with T2DM and at a high risk of CVD, over a mean period of 4.7
years. The BP-lowering arm compared
the effects of intensive therapy targeting (SBP≤120mmHg) vs. standard
therapy targeting (SBP≤140mmHg) at preventing these same primary endpoints
for the same duration. Results of
these two sub-studies again seem to emphasize that an aggressive approach to
managing chronic diseases does not always translate into improved patient
outcomes – another reminder that the target should suit the patient, not vice
versa. |
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(2003) |
An overview
of the ASCOT-LLA trial, which aimed to determine if there is any benefit to
using atorvastatin(10mg/day)+antihypertensive meds
vs. a placebo +antihypertensive meds in preventing clinical outcomes (Primary
= fatal CHD, non-fatal MI) for high-risk hypertensive patients. |
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(2004) |
The CARDS
trial was designed to judge the efficacy of atorvastatin(10mg/day) vs.
a placebo in preventing CV disease outcomes (Primary = time to 1st occurrence
of: CHD death, non-fatal MI (including silent), hospitalized for unstable angina,
resuscitated cardiac arrest, coronary revascularization or stroke) for
patients with T2DM and at least one other CVD risk
factor. |
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(2008) |
This is a
short(24 month) study comparing the effects of simvastatin(80mg/day)
+ ezetimibe(10mg/day) vs. simvastatin(80mg/day)
+ a placebo by using a surrogate marker (Primary = mean change in
carotid artery intima-media thickness) in patients
with elevated LDL levels and heterozygous familial hypercholesteremia. |
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(2006) |
The IDEAL
trial focuses on a comparison of high-dose atorvastatin(40-80mg/day) vs.
low- to moderate-dose simvastatin(20-40mg/day). It’s aim is to determine whether one
regimen is superior to the other in preventing clinical outcomes (Primary =
coronary death, non-fatal acute MI, or cardiac arrest with resuscitation) for
patients with history of MI. |
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(2008) |
An
international trial that aimed to show the benefit of using rosuvastatin(20mg/day) vs. a placebo in preventing both clinical and surrogate
outcomes (Primary = MI, stroke, arterial revascularization,
hospitalization for unstable angina or death from CV causes) in low- to
moderate-risk older adults with normal LDL and elevated C-reactive protein
levels. |
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(2004) |
PROVE-IT
sought to examine the difference of efficacy in preventing hard clinical
outcomes (Primary = all cause mortality, MI, unstable angina, revascularization,
or stroke) between high-dose atorvastatin(80mg/day) vs. moderate-dose pravastatin(40mg/day)
when either is added to the standard therapy for patients hospitalized with acute coronary syndrome. |
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(2006) |
This study
examines the benefit of using high-dose atorvastatin(80mg/day)
vs. a placebo in preventing clinical outcomes (Primary = non-fatal or fatal stroke)
for patients who have recently suffered a stroke or transient
ischemic attack and have normal LDL and no known history of
coronary heart disease. |
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(2010 Members Only) |
A concise
summary - including comparative graphs, primary/secondary endpoints, results,
and brief analysis – of the following trials: 4S, LIPID, CARE, HPS, BIP,
VA-HIT, CARDS, ASCOT, WOSCOPS, AFCAPS, HHS, WHO-CLOF. |
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Trial |
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(2009) |
The purpose
of the ACTIVE-A trial was to determine whether Aspirin(75-100mg/day)
+ clopidogrel(75mg/day) is superior to
Aspirin(75-100mg/day) + a placebo in preventing a composite of major vascular
outcomes (Primary = stroke, non-CNS systemic embolism, MI, death from any
cause) in patients with atrial fibrillation and at
least one other risk factor for stroke (most pts had CHADS 1-2). Of Note: Over the median 3.6
year follow-up, NNT=42 to prevent 1 stroke, NNH=42 to cause major bleeding. The ACTIVE-W trial focuses on a similar
patient demographic (most CHADS 2), but was designed to determine whether the
combination of Aspirin(75-100mg/day) + clopidogrel(75mg/day) is superior to a Vit K antagonist (warfarin,
titrate to INR 2-3) in preventing similar clinical outcomes. ACTIVE-W trial halted early due to
warfarin showing less harm and more benefit than
the combo of Aspirin + clopidogrel. Together, the ACTIVE trials make a strong
case for the use of ASA only for low-risk patients and
warfarin only for high-risk patients. |
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ARISTOTLE |
Apixiban
vs warfarin in patients
with Atrial Fibrillation. In 18,201 patients over 1.8yrs with a
CHADS2 score of ~2.1, apixapan was superior to warfarin, without the need for INR monitoring. Apixiban is not approved for use in |
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(2006) |
The
CHARISMA trial was also concerned with the comparative efficacy of
ASA(75-162mg/day) + clopidogrel(75mg/day) vs.
ASA(75-162mg/day) + a placebo in preventing clinical outcomes (Primary =
death from any cause, stroke) in patients at high-risk of atherosclerotic events
and who have CVD or multiple CVD risk factors. Of note: Over the 28 month
follow-up, NNT=250 to prevent 1 stroke, while NNH=125 to cause moderate
bleeding (safety endpoint). |
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(2009) |
This
document is a Q&A reflection on some of the recent evidence that shows a
drug-interaction between clopidogrel (Plavix) and proton pump inhibitors, especially omeprazole and esomeprazole. Included are sections offering the proposed
mechanism(s) of this interaction, a discussion of the supporting evidence,
and some tips on managing patients who may be at risk of this interaction. |
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(2010) |
The RE-LY
trial compares the benefits and risks over two years of Dabigatran 110mg BID or 150mg BID vs. dose-adjusted warfarin (INR 2-3) as long-term anticoagulant
agents in patients with atrial fibrillation, who
are also at increased risk of stroke.
Results of this trial show Dabigatran 110mg BID to be non-inferior vs. warfarin
at preventing the primary endpoints (stroke or systemic embolism), while Dabigatran 150mg BID was shown
to be both non-inferior and superior to warfarin
at preventing these endpoints. These
benefits are accompanied by an increased frequency of dyspepsia in patients
receiving either dose of Dabigatran, and the 150mg
BID dose also showed a significantly higher frequency of GI bleeding. However, patients receiving warfarin showed higher rates of life threatening,
intracranial (the primary safety endpoint), and minor bleeding than patients
receiving either dose of Dabigatran. This summary aims to help the reader use
the data provided by RE-LY to make practical choices that lead to the optimal
drug therapy for each individual patient. |
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(2011) |
The
ROCKET-AF trial sought to compare the novel anticoagulant Rivaroxaban 20mg OD (15mg in pts with CrCl=30-49µmol/L) vs. dose-adjusted warfarin
(INR2-3) to reduce stroke or systemic embolism in high-risk patients (avg CHADS2=3.5) with persistent/paroxysmal atrial fibrillation. Over the 1.9 year mean follow-up time, rivaroxaban was found to significantly reduce hemorrhagic stroke
and systemic embolism, with lower rates of intracranial/critical/fatal bleeding
compared with warfarin. However, rivaroxaban showed increased
rates of GI bleed, Hgb decline (≥20g/L), hematuria,
and nosebleeds. The trial
was designed to assess outcomes using both intention-to-treat
as well as per protocol analysis, allowing rivaroxaban
to be compared with warfarin for both
non-inferiority as well as superiority.
While rivaroxaban was shown to be non-inferior compared to warfarin
for the primary endpoint, the data did not reach significance for
superiority. While the
results of the trial are promising, the high cost (~$560/month) and lack of
both an antidote as well as long-term safety data for this new agent seem to
indicate that warfarin will still have a place in
therapy for the foreseeable future. |
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(2010 Members Only) |
A link to
our latest “Oral Antiplatelet & Antithrombotic
Agents” chart from the newly released 8th
Edition Drug Comparison Chart Book (May 2010). Includes most common therapeutic options
and their indications, as well as detailed info on dosing, side effects,
contraindications, and so much more! |
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Trial |
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(1998) |
A brief summary
of the results from the international ATLAS trial, which sought to
distinguish whether an ACE-inhibitor (lisinopril)
was more effective at low doses (2.5-5mg/day) or high doses (32.5-35mg/day)
in preventing clinical outcomes (Primary = death from any cause) for patients
with NYHA Class II-IV congestive heart failure. |
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(2003) |
The CHARM
set of trials are designed to determine whether the use of an Angiotensin Receptor Blocker (candesartan
~24mg/day) along with standard therapy could prevent clinical outcomes
(Primary = death from all causes) in patients with heart failure. CHARM-Alternative focuses on the use of ARB’s in patients that are intolerant of
ACE-inhibitors. The CHARM Added wing
of the study attempts to show a benefit to using ARB’s
in addition to ACE-inhibitors in patients with heart failure. Lastly, the CHARM Preserved arm examines
whether there is any benefit to using ARB’s in
patients with preserved left-ventricular function |
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Trial |
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(2002) |
A findings
summary for the WHI (Women’s Health Initiative) trials, which aims to
determine the long-term effects of conjugated equine estrogen
(Premarin, 0.625mg/day) + medroxyprogesterone
(Provera, 2.5mg/day) in otherwise older, healthy
postmenopausal women. WHI focuses on
clinical outcomes (Primary = CHD, invasive breast cancer) to weigh the
benefits and drawbacks of combination HRT.
The summary also references several findings of the similar HERS/HERS
II study, which focused on patients who already had CHD. All three studies trend toward the same
conclusion – the risks of long-term HRT may in fact outweigh the
benefits in many postmenopausal women. Finally, a chart is included that describes
various approaches to HRT and the evidence (or lack thereof) supporting each,
followed by a sampling of alternative therapeutic options to alleviate
symptoms and risk factors common to postmenopausal women. WHI trial halted early due to
risk-benefit imbalance. |
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(2002) |
A further breakdown
of the WHI trial findings, paying particular attention to how the age of
trial participants may influence an interpretation of the results. Also included is a discussion as to why an
apparently small increase in breast cancer incidence from HRT must be weighed
against other factors to gain a full appreciation of risk vs. benefit. |
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(2002) |
Yet another
analysis of the data provided by the WHI trials, focusing on the primary
study outcomes (CHD, invasive breast cancer) that eventually led to the early
termination of the experiment. Also
includes a useful “Tips in Interpreting Data” section that can (and should!)
be applied to any study. |
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Trials |
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(2010) |
Provides
a brief outline of the various etiologies resulting
in anemia, followed by a summary of the
intervention, population, and results of the following studies: ∙ Iron Trials –
Charytan et al, Van Wyck
et al, DeVita et al, Besarab
et al, Macdougall et al, Fishbane
et al, DRIVE-I, DRIVE-II ∙ ESA Trials
– Revicki et al, Levin et al, CREATE, CHOIR,
Canadian EPO Study Group, Parfrey
et al, Foley et al, Besarab, Tonelli
et al, TREAT Also offers points to
consider for both Iron and ESA therapy of chronic kidney disease, either with
or without dialysis |
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Trials |
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(2006) |
Offers an
overview, with interpretive comments, of the population, intervention, and
results for the following trials: SMART, Wolfe, Rabe,
STAY, GOAL, Concept, Overbeek, START, Ram, Gibson,
Ni, Adams(Cochrane), Lasserson(Cochrane), Masoli(Fluticasone), Masoli(Budesonide), IMPACT |
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Trial |
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CATIE-AD |
This trial
compares the effectiveness of atypical antipsychotics drugs ( risperidone, quetiapine & olanzapine to
placebo) in 421 patients for up to 36 weeks. There was no
significant differences between any atypical agents & placebo for
overall rate of discontinuation. These
agents offer limited efficacy, but differ in their side effect profile. |
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(2001) |
Summary of
several studies that looked at the efficacy of various COX-2 inhibitors,
including: ∙ MELISSA – Meloxicam(7.5mg/day)
vs. Diclofenac(100mg SR/day) ∙ SELECT – Meloxicam(7.5mg/day)
vs. Piroxicam(20mg/day) ∙ CLASS – Celecoxib(800mg/day)
vs. Ibuprofen(2400mg/day) vs. Diclofenac(150mg/day) →
Each class treatment arm was separated into two subgroups, one receiving ASA(≤325mg/day)
and one receiving no ASA ∙ VIGOR – Rofecoxib*(50mg/day)
vs. Naproxen(1000mg/day) |
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(2008) |
This trial
summary looks at a study (Kay et al.) comparing Darifenacin(7.5-15mg/day)
vs. Oxybutynin(10-20mg/day) vs. a placebo in improving
memory recall outcomes (Primary = Name-Face Association Test score) for
otherwise healthy older patients. The
main purpose of the study was to justify the use of Darifenacin
over oxybutynin to treat urinary incontinence based
on the newer drug’s improved side-effect profile (lower cognitive
impairment). This document also offers
some insight into why the limitations of this study design prevent such a
definitive justification. |
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As a
supplement to our newsletter, Q&A summary, and CFP article on opioid use for
chronic non-cancer pain, this trial summary provides an overview of a recent
observational cohort study examining the relative efficacy and safety of NSAID’s, Coxib’s, and opioids in elderly patients (84% women) with arthritis
and <2 comorbidities. The article offers some advice toward
individualizing therapy for this difficult condition, and gives some
interpretation of some of the more ambiguous data presented in the
article. Notably, a comment on the
clinical significance of increased rates for CV events,
mortality, fracture, and GI obstruction within the opioid cohort, and which of these adverse events should
be of primary concern to caregivers. |
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Varenicline & Increased CV Risk (2011) |
In July
2011 there was a meta-analysis published in the CMAJ attributing an increased
risk of serious cardiovascular events to varenicline
(CHAMPIX in |
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With
Health |
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* Note: Rofecoxib withdrawn from market in
2004 due to increased CV risk |
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