-
Pain Medicine (Malden, Mass.) Apr 2020Cumulative evidence suggests an analgesic effect of thiamine, pyridoxine, and cyanocobalamin (TPC) in monotherapy, and also when combined with nonsteroidal... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Cumulative evidence suggests an analgesic effect of thiamine, pyridoxine, and cyanocobalamin (TPC) in monotherapy, and also when combined with nonsteroidal anti-inflammatory drugs (NSAIDs), particularly diclofenac, in a synergistic manner. The aim of this review was to determine the effects of diclofenac combined with TPC compared with diclofenac monotherapy for low back pain (LBP) management.
METHODS
We searched for randomized clinical trials on the MEDLINE, EMBASE, LILACS, and Cochrane databases of records of clinical trials, among other sources. We evaluated the risk of bias regarding randomization, allocation concealment, blinding, incomplete outcome data, selective reporting, and other biases. A random-effects meta-analysis to examine patients with acute LBP (N = 1,108 adults) was performed, along with a subsequent sensitivity analysis.
RESULTS
Five studies in patients with LBP were included in the qualitative synthesis. Four of these studies in acute LBP were included in the first meta-analysis. A sensitivity test based on risk of bias (three moderate- to high-quality studies) found that the combination therapy of diclofenac plus TPC was associated with a significant reduction in the duration of treatment (around 50%) compared with diclofenac monotherapy (odds ratio = 2.23, 95% confidence interval = 1.59 to 3.13, P < 0.00001). We found no differences in the safety profile and patient satisfaction.
CONCLUSIONS
This meta-analysis demonstrated that combination therapy of diclofenac with TPC might have an analgesic superiority compared with diclofenac monotherapy in acute LBP. However, there is not enough evidence to recommend this therapy in other types of pain due to the scarcity of high-quality studies.
Topics: Anti-Inflammatory Agents, Non-Steroidal; Diclofenac; Drug Therapy, Combination; Humans; Low Back Pain; Pain Measurement; Pyridoxine; Thiamine; Vitamin B 12; Vitamin B Complex
PubMed: 31529101
DOI: 10.1093/pm/pnz216 -
Drugs & Aging Apr 2019We aimed to assess the safety of topical non-steroidal anti-inflammatory drugs (NSAIDs) in the management of osteoarthritis (OA) in a systematic review and meta-analysis... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
We aimed to assess the safety of topical non-steroidal anti-inflammatory drugs (NSAIDs) in the management of osteoarthritis (OA) in a systematic review and meta-analysis of randomized, placebo-controlled trials.
METHODS
A comprehensive literature search was undertaken in the MEDLINE, Cochrane Central Register of Controlled Trials (CENTRAL), and Scopus electronic databases. Randomized, double-blind, placebo-controlled, parallel-group trials that assessed adverse events (AEs) with topical NSAIDs in patients with OA were eligible for inclusion. Authors and/or study sponsors were contacted to obtain the full report of AEs. The primary outcomes were overall severe and serious AEs, as well as the following MedDRA System Organ Class (SOC)-related AEs: gastrointestinal, vascular, cardiac, nervous system, skin and subcutaneous tissue, musculoskeletal and connective tissue.
RESULTS
The search strategy identified 1209 records, from which 25 papers were included in the qualitative synthesis and 19 were included in the meta-analysis, after exclusions. Overall, more total AEs (odds ratio [OR] 1.16, 95% confidence interval [CI] 1.04-1.29; I = 0.0%) and more withdrawals due to AEs (OR 1.49, 95% CI 1.15-1.92; I = 0.0%) were observed with topical NSAIDs compared with placebo. The same results were achieved with topical diclofenac, largely driven by an increase in skin and subcutaneous tissue disorders (OR 1.73, 95% CI 0.96-3.10), although the difference was not statistically significant compared with placebo. No significant difference in the odds for gastrointestinal disorders was observed between topical NSAIDs and placebo (OR 0.96, 95% CI 0.73-1.27).
CONCLUSIONS
Topical NSAIDs may be considered safe in the management of OA, especially with regard to low gastrointestinal toxicity. The use of topical NSAIDs in OA should be considered, taking into account their risk: benefit profile in comparison with other anti-OA treatments.
Topics: Administration, Cutaneous; Anti-Inflammatory Agents, Non-Steroidal; Diclofenac; Drug-Related Side Effects and Adverse Reactions; Humans; Osteoarthritis; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 31073923
DOI: 10.1007/s40266-019-00661-0 -
Endoscopy International Open Apr 2019Endoscopic retrograde cholangiopancreatography (ERCP) is the primary therapeutic procedure for treatment of diseases that affect the biliary tree and pancreatic... (Review)
Review
Endoscopic retrograde cholangiopancreatography (ERCP) is the primary therapeutic procedure for treatment of diseases that affect the biliary tree and pancreatic duct. While the therapeutic success rate of ERCP is high, the procedure can cause complications, such as acute pancreatitis (PEP), bleeding, and perforation. This meta-analysis aimed to assess the efficacy of nonsteroidal anti-inflammatory drugs (NSAIDs) in preventing PEP following (ERCP). We searched databases, such as MEDLINE, Embase, and Cochrane Central Library. Only randomized controlled trials (RCTs) that compared the efficacy of NSAIDs and placebo for the prevention of PEP were included. Outcomes assessed included incidence of PEP, severity of pancreatitis, route of administration, and type of NSAIDs. Twenty-one RCTs were considered eligible with a total of 6854 patients analyzed. Overall, 3427 patients used NSAIDs before ERCP and 3427 did not use the drugs (control group). In the end, 250 cases of acute pancreatitis post-ERCP were diagnosed in the NSAIDs group and 407 cases in the placebo group. Risk for PEP was lower in the NSAID group (risk difference (RD): -0.05; 95 % confidence interval (CI): -0.07 to - 0.03; number need to treat (NNT), 20; < 0.05). Use of NSAIDs effectively prevented mild pancreatitis compared with use of placebo (2.5 % vs. 4.1 %; 95 % CI, -0.05 to - 0.01; NNT, 33; < 0.05), but the information on moderate and severe PEP could not be completely elucidated. Only rectal administration reduced incidence of PEP (6.8 % vs. 13 %; 95 % CI, -0.10 to - 0.04; NNT, 20; < 0.05). Furthermore, only diclofenac or indomethacin use was effective in preventing PEP. Rectal administration of diclofenac and indomethacin significantly reduced risk of developing mild PEP. Further RCTs are needed to compare efficacy between NSAID administration pathways in prevention of PEP after ERCP.
PubMed: 30957004
DOI: 10.1055/a-0862-0215 -
Frontiers in Pharmacology 2019Currently, although non-steroidal anti-inflammatory drugs (NSAIDs) were recommended for acute renal colic in the 2018 European Association of Urology guidelines, there...
Increasing Nonsteroidal Anti-inflammatory Drugs and Reducing Opioids or Paracetamol in the Management of Acute Renal Colic: Based on Three-Stage Study Design of Network Meta-Analysis of Randomized Controlled Trials.
Currently, although non-steroidal anti-inflammatory drugs (NSAIDs) were recommended for acute renal colic in the 2018 European Association of Urology guidelines, there are no specific NSAIDs and no specific routes of administration in this guideline. The clinical practice of advocating intravenous opioids as the initial analgesia is still common out of the fear of adverse events from NSAIDs. To comprehensively assess the efficacy and safety of NSAIDs, opioids, paracetamol, and combination therapy for acute renal colic. Ovid MEDLINE, Ovid EMbase, the Cochrane Library, Clinical Trials Registry Platform for Clinicaltrials.gov, and WHO International Clinical Trials Registry Platform were searched through February 2, 2018. Two reviewers selected all randomized controlled trails (RCTs) regarding NSAIDs, opioids, paracetamol, combination therapy, and placebo were identified for analysis. We designed a three-stage strategy based on classification and pharmacological mechanisms in the first stage, routes of administration in the second stage, and specific drug branches with different routes in the third stage using network meta-analysis. The pain variance at 30 min was seen as the primary outcome. 65 RCTs with 8633 participants were involved. Comparing different classification and pharmacological mechanisms, combination therapy with more adverse events was more efficient than NSAIDs for the primary outcomes. Opioids gave rise to more nonspecific adverse events and vomiting events. NSAIDs were superior to opioids, paracetamol, and combination therapy after a full consideration of all outcomes. Comparing different routes of administration, NSAIDs with IV or IM route ranked first from efficacy and safety perspective. Comparing different specific drug branches with different routes, ibuprofen via IV route, ketorolac via IV route and diclofenac via IM route were superior for the management of acute renal colic. The results from diclofenac using IM route were more than those from ibuprofen used with IV route and ketorolac with IV route. In patients with adequate renal function, diclofenac via the IM route is recommended for patients without risks of cardiovascular events. Ibuprofen and ketorolac with IV route potentially superior to diclofenac via IM route remain to be investigated. Combination therapy is an alternative choice for uncontrolled pain after the use of NSAIDs.
PubMed: 30853910
DOI: 10.3389/fphar.2019.00096 -
The Cochrane Database of Systematic... Jan 2019Laparoscopy is a common procedure used to diagnose and treat various gynaecological conditions. Shoulder-tip pain (STP) as a result of the laparoscopy occurs in up to... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Laparoscopy is a common procedure used to diagnose and treat various gynaecological conditions. Shoulder-tip pain (STP) as a result of the laparoscopy occurs in up to 80% of women, with potential for significant morbidity, delayed discharge and readmission. Interventions at the time of gynaecological laparoscopy have been developed in an attempt to reduce the incidence and severity of STP.
OBJECTIVES
To determine the effectiveness and safety of methods for reducing the incidence and severity of shoulder-tip pain (STP) following gynaecological laparoscopy.
SEARCH METHODS
We searched the following databases: Cochrane Gynaecology and Fertility (CGF) Specialised Register, the Cochrane Central Register of Studies Online (CRSO), MEDLINE, Embase, PsycINFO and CINAHL from inception to 8 August 2018. We also searched the reference lists of relevant articles and registers of ongoing trials.
SELECTION CRITERIA
Randomised controlled trials (RCTs) of interventions used during or immediately after gynaecological laparoscopy to reduce the incidence or severity of STP.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures expected by Cochrane. Primary outcomes: incidence or severity of STP and adverse events of the interventions; secondary outcomes: analgesia usage, delay in discharge, readmission rates, quality-of-life scores and healthcare costs.
MAIN RESULTS
We included 32 studies (3284 women). Laparoscopic procedures in these studies varied from diagnostic procedures to complex operations. The quality of the evidence ranged from very low to moderate. The main limitations were risk of bias, imprecision and inconsistency.Specific technique versus "standard" technique for releasing the pneumoperitoneumUse of a specific technique of releasing the pneumoperitoneum (pulmonary recruitment manoeuvre, extended assisted ventilation or actively aspirating intra-abdominal gas) reduced the severity of STP at 24 hours (standardised mean difference (SMD) -0.66, 95% confidence interval (CI) -0.82 to -0.50; 5 RCTs; 670 participants; I = 0%, low-quality evidence) and reduced analgesia usage (SMD -0.53, 95% CI -0.70 to -0.35; 4 RCTs; 570 participants; I = 91%, low-quality evidence). There appeared to be little or no difference in the incidence of STP at 24 hours (odds ratio (OR) 0.87, 95% CI 0.41 to 1.82; 1 RCT; 118 participants; low-quality evidence).No adverse events occurred in the only study assessing this outcome.Fluid instillation versus no fluid instillationFluid instillation is probably associated with a reduction in STP incidence (OR 0.38, 95% CI 0.22 to 0.66; 2 RCTs; 220 participants; I = 0%, moderate-quality evidence) and severity (mean difference (MD) (0 to 10 visual analogue scale (VAS) scale) -2.27, 95% CI -3.06 to -1.48; 2 RCTs; 220 participants; I = 29%, moderate-quality evidence) at 24 hours, and may reduce analgesia usage (MD -12.02, 95% CI -23.97 to -0.06; 2 RCTs; 205 participants, low-quality evidence).No study measured adverse events.Intraperitoneal drain versus no intraperitoneal drainUsing an intraperitoneal drain may reduce the incidence of STP at 24 hours (OR 0.30, 95% CI 0.20 to 0.46; 3 RCTs; 417 participants; I = 90%, low-quality evidence) and may reduce analgesia use within 48 hours post-operatively (SMD -1.84, 95% CI -2.14 to -1.54; 2 RCTs; 253 participants; I = 90%). We are uncertain whether it reduces the severity of STP at 24 hours, as the evidence was very low quality (MD (0 to 10 VAS scale) -1.85, 95% CI -2.15 to -1.55; 3 RCTs; 320 participants; I = 70%).No study measured adverse events.Subdiaphragmatic intraperitoneal local anaesthetic versus control (no fluid instillation, normal saline or Ringer's lactate)There is probably little or no difference between the groups in incidence of STP (OR 0.72, 95% CI 0.42 to 1.23; 4 RCTs; 336 participants; I = 0%; moderate-quality evidence) and there may be no difference in STP severity (MD -1.13, 95% CI -2.52 to 0.26; 1 RCT; 50 participants; low-quality evidence), both measured at 24 hours. However, the intervention may reduce post-operative analgesia use (SMD-0.57, 95% CI -0.94 to -0.21; 2 RCTs; 129 participants; I = 51%, low-quality evidence).No adverse events occurred in any study.Local anaesthetic into peritoneal cavity (not subdiaphragmatic) versus normal salineLocal anaesthetic into the peritoneal cavity may reduce the incidence of STP at 4 to 8 hours post-operatively (OR 0.23, 95% CI 0.06 to 0.93; 2 RCTs; 157 participants; I = 56%; low-quality evidence). Our other outcomes of interest were not assessed.Warmed, or warmed and humidified CO versus unwarmed and unhumidified COThere may be no difference between these interventions in incidence of STP at 24 to 48 hours (OR 0.81 95% CI 0.45 to 1.49; 2 RCTs; 194 participants; I = 12%; low-quality evidence) or in analgesia usage within 48 hours (MD -4.97 mg morphine, 95% CI -11.25 to 1.31; 1 RCT; 95 participants; low-quality evidence); there is probably little or no difference in STP severity at 24 hours (MD (0 to 10 VAS scale) 0.11, 95% CI -0.75 to 0.97; 2 RCTs; 157 participants; I = 50%; moderate-quality evidence).No study measured adverse events.Gasless laparoscopy versus CO insufflationGasless laparoscopy may be associated with increased severity of STP within 72 hours post-operatively when compared with standard treatment (MD 3.8 (0 to 30 VAS scale), 95% CI 0.76 to 6.84; 1 RCT; 54 participants, low-quality evidence), and there may be no difference in the risk of adverse events (OR 2.56, 95% CI 0.25 to 26.28; 1 RCT; 54 participants; low-quality evidence).No study measured the incidence of STP.
AUTHORS' CONCLUSIONS
There is low to moderate-quality evidence that the following interventions are associated with a reduction in the incidence or severity, or both, of STP, or a reduction in analgesia requirements for women undergoing gynaecological laparoscopy: a specific technique for releasing the pneumoperitoneum; intraperitoneal fluid instillation; an intraperitoneal drain; and local anaesthetic applied to the peritoneal cavity (not subdiaphragmatic).There is low to moderate-quality evidence that subdiaphragmatic intraperitoneal local anaesthetic and warmed and humidified insufflating gas may not make a difference to the incidence or severity of STP.There is low-quality evidence that gasless laparoscopy may increase the severity of STP, compared with standard treatment.Few studies reported data on adverse events. Some potentially useful interventions have not been studied by RCTs of gynaecological laparoscopy.
Topics: Acetaminophen; Analgesics; Anti-Inflammatory Agents, Non-Steroidal; Carbon Dioxide; Diclofenac; Drainage; Female; Gynecologic Surgical Procedures; Gynecological Examination; Humans; Incidence; Insufflation; Laparoscopy; Meperidine; Pain Measurement; Pain, Procedural; Pirinitramide; Pneumoperitoneum; Randomized Controlled Trials as Topic; Shoulder Pain
PubMed: 30699235
DOI: 10.1002/14651858.CD011101.pub2 -
Journal of Orthopaedic Surgery (Hong... 2018Current guidelines on the management of hip and knee osteoarthritis (OA) do not compare safety of treatment modalities. We therefore systematically reviewed 20 studies... (Meta-Analysis)
Meta-Analysis
Current guidelines on the management of hip and knee osteoarthritis (OA) do not compare safety of treatment modalities. We therefore systematically reviewed 20 studies investigating mortality and serious complications of both medical and surgical treatments for hip and knee OA using PubMed, Scopus, Web of Knowledge and Google Scholar. Mortality was the highest for naproxen (hazard ratio (HR) = 3 (1.9, 4.6)) and lowest for total hip replacement (relative risk (RR) = 0.7 (0.7, 0.7)). Highest gastrointestinal complications were reported for diclofenac (odds ratio (OR) = 4.77 (3.94, 5.76)) and lowest for total knee replacement (HR = 0.6 (0.49, 0.75)). Ibuprofen had the highest renal complications (OR = 2.32 (1.45, 3.71)), whereas celecoxib had the highest cardiovascular risk (OR = 2.26 (1, 5.1)) and lowest was for tramadol (RR = 1.1 (0.87, 1.4)). Results show that medical management of hip and knee OA, particularly with non-steroidal anti-inflammatory drugs, may carry higher mortality compared to surgery. Careful consideration should be given to medical management taking into account known co-morbidities.
Topics: Anti-Inflammatory Agents, Non-Steroidal; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Disease Management; Humans; Osteoarthritis, Hip; Osteoarthritis, Knee
PubMed: 30415598
DOI: 10.1177/2309499018808669 -
The Cochrane Database of Systematic... Aug 2018Postoperative administration of non-steroidal anti-inflammatory drugs (NSAIDs) reduces patient opioid requirements and, in turn, reduces the incidence and severity of... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Postoperative administration of non-steroidal anti-inflammatory drugs (NSAIDs) reduces patient opioid requirements and, in turn, reduces the incidence and severity of opioid-induced adverse events (AEs).
OBJECTIVES
To assess the analgesic efficacy and adverse effects of single-dose intravenous diclofenac, compared with placebo or an active comparator, for moderate to severe postoperative pain in adults.
SEARCH METHODS
We searched the following databases without language restrictions: the Cochrane Central Register of Controlled Trials (Cochrane Register of Studies Online), MEDLINE, and Embase on 22 May 2018. We checked clinical trials registers and reference lists of retrieved articles for additional studies.
SELECTION CRITERIA
We included randomized trials that compared a single postoperative dose of intravenous diclofenac with placebo or another active treatment, for treating acute postoperative pain in adults following any surgery.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures expected by Cochrane. Two review authors independently considered trials for review inclusion, assessed risk of bias, and extracted data.Our primary outcome was the number of participants in each arm achieving at least 50% pain relief over a four- and six-hour period.Our secondary outcomes were time to, and number of participants using rescue medication; withdrawals due to lack of efficacy, AEs, and for any cause; and number of participants experiencing any AE, serious AEs (SAEs), and NSAID-related AEs. We performed a post hoc analysis of opioid-related AEs, to enable indirect comparisons with other analyses of postoperative analgesics.For subgroup analysis, we planned to analyze different doses and formulations of parenteral diclofenac separately.We assessed the overall quality of the evidence for each outcome using GRADE and created two 'Summary of findings' tables.
MAIN RESULTS
We included eight studies, involving 1756 participants undergoing various surgeries (dental, mixed minor, abdominal, and orthopedic), with 20 to 175 participants receiving intravenous diclofenac in each study. Mean study population ages ranged from 24.5 years to 54.5 years. Intravenous diclofenac doses varied among and within studies, ranging from 3.75 mg to 75 mg. Five studies assessed newer formulations of parenteral diclofenac that could be administered as an undiluted intravenous bolus. Most studies had an unclear risk of bias for several domains and a high risk of bias due to small sample size. The overall quality of evidence for each outcome was generally low for reasons including unclear risk of bias in studies, imprecision, and low event numbers.Primary outcomeThree studies (277 participants) produced a number needed to treat for an additional beneficial outcome (NNTB) for at least 50% of maximum pain relief versus placebo of 2.4 (95% confidence interval (CI) 1.9 to 3.1) over four hours (low-quality evidence). Four studies (436 participants) produced an NNTB of 3.8 versus placebo (95% CI 2.9 to 5.9) over six hours (low-quality evidence). No studies provided data for the comparison of intravenous diclofenac with another NSAID over four hours. At six hours there was no difference between intravenous diclofenac and another NSAID (low-quality evidence).Secondary outcomesFor secondary efficacy outcomes, intravenous diclofenac was generally superior to placebo and similar to other NSAIDs.For time to rescue medication, comparison of intravenous diclofenac versus placebo demonstrated a median of 226 minutes for diclofenac versus 80 minutes for placebo (5 studies, 542 participants, low-quality evidence). There were insufficient data for pooled analysis for comparisons of diclofenac with another NSAID (very low-quality evidence).For the number of participants using rescue medication, two studies (235 participants) compared diclofenac with placebo. The number needed to treat to prevent one additional harmful event (NNTp) (here, the need for rescue medication) compared with placebo was 3.0 (2.2 to 4.5, low-quality evidence). The comparison of diclofenac with another NSAID included only one study (98 participants). The NNTp was 4.5 (2.5 to 33) for ketorolac versus diclofenac (very low-quality evidence).The numbers of participants withdrawing were generally low and inconsistently reported (very low-quality evidence). Participant withdrawals were: 6% (8/140) diclofenac versus 5% (7/128) placebo, and 9% (8/87) diclofenac versus 7% (6/82) another NSAID for lack of efficacy; 2% (4/211) diclofenac versus 0% (0/198) placebo, and 3% (4/138) diclofenac versus 2% (2/129) another NSAID due to AEs; and 11% (21/191) diclofenac versus 17% (30/179) placebo, and 18% (21/118) diclofenac versus 15% (17/111) another NSAID for any cause.Overall adverse event rates were similar between intravenous diclofenac and placebo (71% in both groups, 2 studies, 296 participants) and between intravenous diclofenac and another NSAID (55% and 58%, respectively, 2 studies, 265 participants) (low-quality evidence for both comparisons). Serious and specific AEs were rare, preventing meta-analysis.There were sufficient data for a dose-effect analysis for our primary outcome for only one alternative dose, 18.75 mg. Analysis of the highest dose employed in each study demonstrated a relative benefit compared with placebo of 1.9 (1.4 to 2.4), whereas for the group receiving 18.75 mg, the relative benefit versus placebo was 1.6 (1.2 to 2.1, 2 studies). Compared to another NSAID, the high-dose analysis demonstrated a relative benefit of 0.9 (0.8 to 1.1), for the group receiving 18.75 mg, the relative benefit was 0.78 (0.65 to 0.93). For direct comparison of high dose versus 18.75 mg, the proportion of participants with at least 50% pain relief was 66% (90/137) for the high-dose arm versus 57% (77/135) in the low-dose arm. There were insufficient data for subgroup meta-analysis of different diclofenac formulations.
AUTHORS' CONCLUSIONS
The amount and quality of evidence for the use of intravenous diclofenac as a treatment for postoperative pain is low. The available evidence indicates that postoperative intravenous diclofenac administration offers good pain relief for the majority of patients, but further research may impact this estimate. Adverse events appear to occur at a similar rate to other NSAIDs. Insufficient information is available to assess whether intravenous diclofenac has a different rate of bleeding, renal dysfunction, or cardiovascular events versus other NSAIDs. There was insufficient information to evaluate the efficacy and safety of newer versus traditional formulations of intravenous diclofenac. There was a lack of studies in major and cardiovascular surgeries and in elderly populations, which may be at increased risk for adverse events.
Topics: Acute Pain; Adult; Analgesics, Opioid; Anti-Inflammatory Agents, Non-Steroidal; Diclofenac; Humans; Injections, Intravenous; Pain, Postoperative; Placebos; Randomized Controlled Trials as Topic
PubMed: 30153336
DOI: 10.1002/14651858.CD012498.pub2 -
Journal of Pharmacy & Pharmaceutical... 2018Concomitant use of some non-Aspirin nonsteroidal anti-inflammatory drugs (NANSAIDs) reduces the extent of platelet aggregation of Aspirin (acetylsalicylic acid). This is... (Meta-Analysis)
Meta-Analysis
PURPOSE
Concomitant use of some non-Aspirin nonsteroidal anti-inflammatory drugs (NANSAIDs) reduces the extent of platelet aggregation of Aspirin (acetylsalicylic acid). This is while many observational studies and clinical trials suggest that Aspirin reduces cardiovascular (CV) risk attributed to the use of NANSAIDs. Thus, the therapeutic outcome of the interaction needs to be assessed.
METHODS
We searched various databases up to October 2017 for molecular interaction studies between the drugs and long-term clinical outcomes based on randomized clinical trials and epidemiological observations that reported the effect estimates of CV risks (OR, RR or HR; 95% CI) of the interacting drugs alone or in combinations. Comparisons were made between outcomes after Aspirin alone, NANSAIDs alone and Aspirin with naproxen, ibuprofen, celecoxib, meloxicam, diclofenac or rofecoxib.
RESULTS
In total, 32 eligible studies (20 molecular interactions studies and 12 observational trials) were found. Conflicting in vitro/in vivo/ex vivo platelet aggregation data were found for ibuprofen, naproxen and celecoxib. Nevertheless, for naproxen, the interaction at the aggregation level did not amount to a loss of cardioprotective effects of Aspirin. Similarly, for ibuprofen, the results overwhelmingly suggest no negative clinical CV outcomes following the combination therapy. Meloxicam and rofecoxib neither interacted with Aspirin at the level of platelet aggregation nor altered clinical outcomes. The clinical outcomes data for celecoxib and diclofenac are in conflict.
CONCLUSION
Aspirin appears to maintain its cardioprotective effect in the presence of naproxen, ibuprofen, meloxicam and rofecoxib. The limited available data suggest that the effect of interaction at the platelet aggregation level may dissipate shortly, or the reduced platelet aggregation yielded by the interaction may be sufficient for cardioprotection; i.e., no need for near complete aggregation. In addition, cardioprotective effect of Aspirin, despite reduced platelet aggregation caused by NANSAIDs, may be through its involvement in other mechanisms such as the renin-angiotensin system and/or metabolism of arachidonic acid to biologically active compounds mediated by cytochrome P450. This article is open to POST-PUBLICATION REVIEW. Registered readers (see "For Readers") may comment by clicking on ABSTRACT on the issue's contents page.
Topics: Anti-Inflammatory Agents, Non-Steroidal; Aspirin; Cardiovascular Diseases; Humans; Platelet Aggregation; Treatment Outcome
PubMed: 29891025
DOI: 10.18433/jpps29854 -
The Cochrane Database of Systematic... Apr 2018Ureteral colic is a common reason for patients to seek medical care. Alpha-blockers are commonly used to improve stone passage through so-called medical expulsive... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Ureteral colic is a common reason for patients to seek medical care. Alpha-blockers are commonly used to improve stone passage through so-called medical expulsive therapy (MET), but their effectiveness remains controversial. This is an update of a 2014 Cochrane review; since that time, several large randomised controlled trials (RCTs) have been reported, making this update relevant.
OBJECTIVES
To assess effects of alpha-blockers compared with standard therapy for ureteral stones 1 cm or smaller confirmed by imaging in adult patients presenting with symptoms of ureteral stone disease.
SEARCH METHODS
On 18 November 2017, we searched CENTRAL, MEDLINE Ovid, and Embase. We also searched ClinicalTrials.gov and the WHO Portal/ICTRP to identify all published/unpublished and ongoing trials. We checked all references of included and review articles and conference proceedings for articles relevant to this review. We sent letters to investigators to request information about unpublished or incomplete studies.
SELECTION CRITERIA
We included RCTs of ureteral stone passage in adult patients that compared alpha-blockers versus standard therapy.
DATA COLLECTION AND ANALYSIS
Two review authors screened studies for inclusion and extracted data using standard methodological procedures. We performed meta-analysis using a random-effects model. Primary outcomes were stone clearance and major adverse events; secondary outcomes were stone expulsion time, number of pain episodes, use of diclofenac, hospitalisation, and surgical intervention. We assessed the quality of evidence on a per-outcome basis using the GRADE approach.
MAIN RESULTS
We included 67 studies with 10,509 participants overall. Of these, 15 studies with 5787 participants used a placebo.Stone clearance: Based on the overall analysis, treatment with an alpha-blocker may result in a large increase in stone clearance (risk ratio (RR) 1.45, 95% confidence interval (CI) 1.36 to 1.55; low-quality evidence). A subset of higher-quality, placebo-controlled trials suggest that the likely effect is probably smaller (RR 1.16, 95% CI 1.07 to 1.25; moderate-quality evidence), corresponding to 116 more (95% CI 51 more to 182 more) stone clearances per 1000 participants.Major adverse events: Based on the overall analysis, treatment with an alpha-blocker may have little effect on major adverse events (RR 1.25, 95% CI 0.80 to 1.96; low-quality evidence). A subset of higher-quality, placebo-controlled trials suggest that alpha-blockers likely increase the risk of major adverse events slightly (RR 2.09, 95% CI 1.13 to 3.86), corresponding to 29 more (95% CI 3 more to 75 more) major adverse events per 1000 participants.Patients treated with alpha-blockers may experience shorter stone expulsion times (mean difference (MD) -3.40 days, 95% CI -4.17 to -2.63; low-quality evidence), may use less diclofenac (MD -82.41, 95% CI -122.51 to -42.31; low-quality evidence), and likely require fewer hospitalisations (RR 0.51, 95% CI 0.34 to 0.77; moderate-quality evidence), corresponding to 69 fewer hospitalisations (95% CI 93 fewer to 32 fewer) per 1000 participants. Meanwhile, the need for surgical intervention appears similar (RR 0.74, 95% CI 0.53 to 1.02; low-quality evidence), corresponding to 28 fewer surgical interventions (95% CI 51 fewer to 2 more) per 1000 participants.A predefined subgroup analysis (test for subgroup differences; P = 0.002) suggests that effects of alpha-blockers may vary with stone size, with RR of 1.06 (95% CI 0.98 to 1.15; P = 0.16; I² = 62%) for stones 5 mm or smaller versus 1.45 (95% CI 1.22 to 1.72; P < 0.0001; I² = 59%) for stones larger than 5 mm. We found no evidence suggesting possible subgroup effects based on stone location or alpha-blocker type.
AUTHORS' CONCLUSIONS
For patients with ureteral stones, alpha-blockers likely increase stone clearance but probably also slightly increase the risk of major adverse events. Subgroup analyses suggest that alpha-blockers may be less effective for smaller (5 mm or smaller) than for larger stones (greater than 5 mm).
Topics: Adrenergic alpha-Antagonists; Adult; Analgesics; Diclofenac; Hospitalization; Humans; Randomized Controlled Trials as Topic; Time Factors; Ureteral Calculi
PubMed: 29620795
DOI: 10.1002/14651858.CD008509.pub3 -
International Journal of Hepatology 2018Nonsteroidal anti-inflammatory drugs (NSAIDs) are the most widely used medication in several countries, including Thailand. NSAIDs have been associated with hepatic side... (Review)
Review
BACKGROUND
Nonsteroidal anti-inflammatory drugs (NSAIDs) are the most widely used medication in several countries, including Thailand. NSAIDs have been associated with hepatic side effects; however, the frequency of these side effects is uncertain.
AIM OF THE REVIEW
To systematically review published literature on randomized, controlled trials that assessed the risk of clinically significant hepatotoxicity associated with NSAIDs.
METHODS
Searches of bibliographic databases EMBASE, PubMed, and the Cochrane Library were conducted up to July 30, 2016, to identify randomized controlled trials of ibuprofen, naproxen, diclofenac, piroxicam, meloxicam, mefenamic acid, indomethacin, celecoxib, and etoricoxib in adults with any disease that provide information on hepatotoxicity outcomes.
RESULTS
Among the 698 studies, 18 studies met the selection criteria. However, only 8 studies regarding three NSAIDs (celecoxib, etoricoxib, and diclofenac) demonstrated clinically significant hepatotoxic evidence based on hepatotoxicity justification criteria. Of all the hepatotoxicity events found from the above-mentioned three NSAIDs, diclofenac had the highest proportion, which ranged from 0.015 to 4.3 (×10), followed by celecoxib, which ranged from 0.13 to 0.38 (×10), and etoricoxib, which ranged from 0.005 to 0.930 (×10).
CONCLUSION
Diclofenac had higher rates of hepatotoxic evidence compared to other NSAIDs. Hepatotoxic evidence is mostly demonstrated as aminotransferase elevation, while liver-related hospitalization or discontinuation was very low.
PubMed: 29568654
DOI: 10.1155/2018/5253623