scholarly journals Evaluating the Cardiovascular Safety of Nonsteroidal Anti-Inflammatory Drugs

Circulation ◽  
2017 ◽  
Vol 135 (21) ◽  
pp. 2062-2072 ◽  
Author(s):  
Elliott M. Antman
Keyword(s):  
Medical Condition ◽  
Controlled Trial ◽  
Analgesic Efficacy ◽  
Pharmaceutical Manufacturer ◽  
Safety Signal ◽  
Cardiovascular Safety ◽  
Planning Stage ◽  
General Medical Condition ◽  
Inflammatory Drugs ◽  
Anti Inflammatory

Some drugs used to treat noncardiovascular conditions may adversely impact the cardiovascular status of individuals both with and without known cardiovascular disease. When the US Food and Drug Administration judges the potential cardiovascular safety signal to be of sufficient concern, it may require the pharmaceutical manufacturer of the drug in question to conduct a postmarketing (phase 4) randomized controlled trial (RCT). Although historically many phase 4 RCTs focused on efficacy (using a superiority design), contemporary phase 4 RCTs often are focused on safety and use a noninferiority design. The choices made by investigators during the planning stage of a postmarketing phase 4 RCT dedicated to the evaluation of cardiovascular safety can influence the ability to compare the standard and test agents. Multiple factors reflecting the conduct of a phase 4 RCT for a general medical condition may influence interpretation of a cardiovascular safety signal. The higher the rates of failure to adhere to the protocol and dropout from the study, the greater the risk of bias. Trials evaluating the cardiovascular safety of nonsteroidal anti-inflammatory drugs (NSAIDs) when used for arthritis are difficult to conduct and even more challenging to interpret. Concerns include the comparison of drug regimens that do not provide comparable analgesic efficacy and problems with adherence to the protocol and retention in the study. On the basis of phase 4 RCTs of NSAIDs to date, it appears that a comparatively low dose of celecoxib administered to low-risk subjects is associated with approximately the same cardiovascular risk as NSAIDs with less cyclooxygenase-2 inhibitory activity, but at the cost of not controlling arthritic pain as effectively.

scholarly journals Rofecoxib-Induced Hepatotoxicity: A Forgotten Complication of the Coxibs

2006 ◽  
Vol 20 (5) ◽  
pp. 351-355 ◽  
Author(s):  
Brian Yan ◽  
Yvette Leung ◽  
Stefan J Urbanski ◽  
Robert P Myers
Keyword(s):  
Hepatic Injury ◽  
Hepatic Dysfunction ◽  
Cyclooxygenase 2 ◽  
Liver Histology ◽  
Cardiovascular Safety ◽  
Drug Induced ◽  
Severe Hepatotoxicity ◽  
Inflammatory Drugs ◽  
Anti Inflammatory

Rofecoxib is a member of the coxib family of nonsteroidal anti-inflammatory drugs that selectively inhibit cyclooxygenase-2. Although the coxibs are generally well-tolerated, rofecoxib was recently withdrawn from the market due to concerns regarding cardiovascular safety. Rare cases of hepatic injury attributable to the coxibs have been reported. In the present study, two additional cases of severe hepatotoxicity are described in patients with cholestatic symptoms and abnormal liver biochemistry, shortly following the initiation of rofecoxib for arthritic complaints. In both cases, liver histology was compatible with drug-induced hepatotoxicity, and rapid clinical and biochemical improvements were observed following rofecoxib discontinuation. With new coxibs and expanding indications on the horizon, physicians in all areas of practice must be aware of this disorder and consider it in any patient who develops hepatic dysfunction after taking a coxib.

scholarly journals Cardiovascular safety of non-steroidal anti-inflammatory drugs: network meta-analysis

BMJ ◽  
2011 ◽  
Vol 342 (jan11 1) ◽  
pp. c7086-c7086 ◽  
Author(s):  
S. Trelle ◽  
S. Reichenbach ◽  
S. Wandel ◽  
P. Hildebrand ◽  
B. Tschannen ◽  
...  
Keyword(s):  
Meta Analysis ◽  
Cardiovascular Safety ◽  
Inflammatory Drugs ◽  
Anti Inflammatory

Designing a clinical trial of non-steroidal anti-inflammatory drugs for cancer pain: a survey of UK palliative care physicians

2020 ◽  
pp. bmjspcare-2020-002792
Author(s):  
Andrew J Page ◽  
Matthew R Mulvey ◽  
Michael I Bennett
Keyword(s):  
Palliative Care ◽  
Cancer Pain ◽  
Palliative Medicine ◽  
Bone Pain ◽  
Controlled Trial ◽  
Perceived Efficacy ◽  
Inflammatory Drugs ◽  
Cox 2 ◽  
Anti Inflammatory ◽  
Cox 2 Inhibitors

ObjectivesInsufficient quality evidence exists to support or refute the use of non-steroidal anti-inflammatory drugs (NSAIDs) in the management of cancer pain. We aimed to determine the most clinically pragmatic design of a future randominsed controlled trial (RCT), based on how NSAIDs are currently used and perceived efficacy.MethodsAn online survey was distributed to members of the Association for Palliative Medicine of Great Britain and Ireland examining NSAID use, indications and perceived efficacy, as well as duration of respondents’ experience in palliative medicine.Results23% of 968 members responded. A placebo-controlled trial of NSAIDs as a strong opioid adjunct in cancer-related bone pain was considered the most clinically pragmatic design. Concerning current practice, oral administration was the preferential route (79.4%), dosed regularly (79.5%). Selective cyclooxygenase-2 (COX-2) inhibitors and non-selective COX-2 inhibitors were considered similarly effective by 45% in cancer pain; ibuprofen being the first line oral NSAID of choice (42.6%). Treatment efficacy is generally determined within 1 week (94.3%). On a Likert scale, most physicians consider NSAIDs improve cancer pain either ‘sometimes’ (57.7%) or ‘often’ (40%). Years of specialist palliative care experience did not affect perception of efficacy (p=0.353).ConclusionsA randomised controlled trial of NSAIDs as opioid adjuncts for cancer-related bone pain would be the most pragmatic design supported by palliative care clinicians to benefit clinical practice.

Sign in / Sign up

Export Citation Format

Share Document