N Engl J Med 2016; :2519-2529December 29, 2016DOI: 10.1056/NEJMoa1611593
The cardiovascular safety of celecoxib, as compared with nonselective nonsteroidal antiinflammatory drugs (NSAIDs), remains uncertain.
Patients who required NSAIDs for osteoarthritis or rheumatoid arthritis and were at increased cardiovascular risk were randomly assigned to receive celecoxib, ibuprofen, or naproxen. The goal of the trial was to assess the noninferiority of celecoxib with regard to the primary composite outcome of cardiovascular death (including hemorrhagic death), nonfatal myocardial infarction, or nonfatal stroke. Noninferiority required a hazard ratio of 1.12 or lower, as well as an upper 97.5% confidence limit of 1.33 or lower in the intention-to-treat population and of 1.40 or lower in the on-treatment population. Gastrointestinal and renal outcomes were also adjudicated.
A total of 24,081 patients were randomly assigned to the celecoxib group (mean [±SD] daily dose, 209±37 mg), the naproxen group (852±103 mg), or the ibuprofen group (2045±246 mg) for a mean treatment duration of 20.3±16.0 months and a mean follow-up period of 34.1±13.4 months. During the trial, 68.8% of the patients stopped taking the study drug, and 27.4% of the patients discontinued follow-up. In the intention-to-treat analyses, a primary outcome event occurred in 188 patients in the celecoxib group (2.3%), 201 patients in the naproxen group (2.5%), and 218 patients in the ibuprofen group (2.7%) (hazard ratio for celecoxib vs. naproxen, 0.93; 95% confidence interval [CI], 0.76 to 1.13; hazard ratio for celecoxib vs. ibuprofen, 0.85; 95% CI, 0.70 to 1.04; P<0.001 for noninferiority in both comparisons). In the on-treatment analysis, a primary outcome event occurred in 134 patients in the celecoxib group (1.7%), 144 patients in the naproxen group (1.8%), and 155 patients in the ibuprofen group (1.9%) (hazard ratio for celecoxib vs. naproxen, 0.90; 95% CI, 0.71 to 1.15; hazard ratio for celecoxib vs. ibuprofen, 0.81; 95% CI, 0.65 to 1.02; P<0.001 for noninferiority in both comparisons). The risk of gastrointestinal events was significantly lower with celecoxib than with naproxen (P=0.01) or ibuprofen (P=0.002); the risk of renal events was significantly lower with celecoxib than with ibuprofen (P=0.004) but was not significantly lower with celecoxib than with naproxen (P=0.19).CONCLUSIONS
At moderate doses, celecoxib was found to be noninferior to ibuprofen or naproxen with regard to cardiovascular safety. (Funded by Pfizer; ClinicalTrials.gov number,
The non-steroidal inflammatory drugs (NSAIDs), are drugs widely used to treat many rheumatic diseases. Nevertheless, it exists in the population some caution to taking them, especially due to their side effects, such as gastric complications. But the question is if they are so harmful to the stomach as people believe. a) Is well established that exists a group of patients at risk if they take NSAIDs and these people must protect their stomach to avoid important side effects. In most of the patients, this protection is done with Omeprazole or similar drugs. But who are these persons at risk?
- People over 65 to 70 years old ·
- Those who have had a gastric ulcer previously or a hernia of hiatus, with reflux or colon diverticulitis
- Those who have had an ulcer complication, i.e. gastric perforation or a hemorrhagic process
- Those who, in addition, take cortisone or oral anticoagulants.
On the other hand, the rest of the population who does not have this history sing can take NSAIDs without Omeprazole, since the risk of a complication is low. However, in Spain it is practically impossible to find patients who take NSAIDs without gastric protection. Almost with complete certainty, this situation is specific to our country. While the protection of the stomach in other countries ranges between 40 to 60 % of the patients, in Spain almost 100% of this population receives gastro protection, which, is really absurd, and more taking into account that Omeprazole or derivatives are not a ‘candy’ But still is more: b) A group of persons prefers taking NSAIDs the day they have more pain as if it was freeing them of a complication of the stomach. I have the experience to have attended elderly people in the emergency room due to a massive hemorrhage of the stomach, after having taken a simple aspirin for headache… ¡ c) There are patients who say to you: I cannot take any painkiller drug because immediately I have a stomachache. This phrase that evidently I do not question, the majority of the times has nothing to do with a gastric injury produced by NSAIDs. Even more, between 30 to 40% of the digestive hemorrhages that appears after taking NSAIDs, they emerge without previous warning. In other words, in people who were taking them without noticing any gastrointestinal symptom On the other hand, many of the patients who have gastric symptoms with NSAIDs, if a gastroscopy is performed the doctor will not find any lesion
In conclusion: NSAIDs are extremely useful drugs for many rheumatic processes. They relieve pain and inflammation and improve the quality of life. For this reason, they might be prescribed even to patients who suffer a gastric problem if they are well protected. Omeprazole and other similar medicaments are extremely useful to avoid digestive complications in the population that we have defined above (paragraph a). Nonetheless, Omeprazole may produce some adverse reactions that sometimes can be important. Due to this, the widespread use of this drug should be avoided
Addendum: In this paragraph I have referred to NSAIDs for patients who had a rheumatic disease and needed to take these drugs long periods of time. In no case, I have referred to these clinical situations in which a person takes an NSAID for banal processes like a migraine, menstrual pain, or similar clinical situations.