Risk of acute myocardial infarction with real‐world <scp>NSAID</scp>s depends on dose and timing of exposure

Bally, Michèle; Beauchamp, Marie-Ève; Abrahamowicz, Michał; Nadeau, Lucie; Brophy, James M.

doi:10.1002/pds.4358

Cited by 34 publications

(34 citation statements)

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“…We have reported a nested case-control analysis of NSAID and MI risk, based on the same dataset. That study [ 14 ] aimed to characterize the temporal association between time‐varying NSAID exposure and acute MI and provided evidence for the dose relationship, precise timing of risk onset, and the existence of a cumulative effect. This nested case-control dataset was also included in our previously published patient-level meta-analysis of population-based studies [ 15 ] therefore these works share some methodological aspects.…”

Section: Methodsmentioning

confidence: 99%

“…We [ 14 , 15 ]identified risk factors for the outcome and potential confounders based on substantive knowledge and literature search. [ 25 – 28 ] Using a simplified causal graph[ 29 ] we mapped relationships between variables,[ 30 ] including time-dependent confounders that are mediating intermediates on the causal pathway between NSAID exposures and acute MI,[ 31 ] then confirmed the final set of confounders (Figure A in S1 File ).…”

Section: Methodsmentioning

confidence: 99%

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Studying additive interaction in a healthcare database: Case study of NSAIDs, cardiovascular profiles, and acute myocardial infarction

2018

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PurposeThere are clinical trial data on risk of acute myocardial infarction (MI) with nonsteroidal anti-inflammatory drugs (NSAIDs) in patients at increased cardiovascular (CV) risk requiring chronic daily treatment. This study investigated whether risks of acute MI with real-world prescription NSAIDs, such as low-dose or intermittent use, vary according to an individual’s CV profile.MethodsNested case-control analyses were carried out on an administrative health cohort from Quebec, Canada by randomly selecting 10 controls per case matched on age ± 1 year, sex, and month and year of cohort entry. We measured the additive joint effects on acute MI of current NSAID use and presence of hypertension, coronary heart disease (CHD), history of previous MI, or concomitant use of cardioprotective aspirin. The endpoint was the relative excess risk due to interaction (RERI). To verify the robustness of interaction findings, we performed sensitivity analyses with varying specifications of NSAID exposure-related variables.ResultsThe cohort consisted of 233 816 elderly individuals, including 21 256 acute MI cases. For hypertension, CHD, and previous MI, we identified additive interactions on MI risk with some but not all NSAIDs, which also depended on the definition of NSAID exposure. Hypertension was sub-additive with naproxen but not with the other NSAIDs. Celecoxib and CHD were sub-additive in the primary analysis only (modelling NSAID dose on index date or up to 7 days before–best-fitting base model) whereas celecoxib and rofecoxib were super-additive with a history of previous MI in the secondary analysis only (modelling NSAID use on index date). For cardioprotective aspirin we found no evidence for an additive interaction with any of the NSAIDs.ConclusionsAlternative specifications of NSAID exposure concurred in finding that concomitant use of cardioprotective aspirin does not attenuate the risks of acute MI with NSAIDs. However we were unable to demonstrate consistent interactions between an individual’s cardiovascular comorbidities and NSAID-associated acute MI. Our study highlights challenges of studying additive interactions in a healthcare database and underscores the need for sensitivity analyses.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Studying additive interaction in a healthcare database: Case study of NSAIDs, cardiovascular profiles, and acute myocardial infarction

2018

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“…The risks also vary across different analgesics; for example, the increased mortality risk appears to be much higher with diclofenac compared with aspirin or paracetamol . Even though the absolute risk is still very low in healthy individuals, these risks are greater with larger doses and/or with chronic use of these pharmacological interventions …”

Section: Safety and Ethical Considerationsmentioning

confidence: 99%

“…66 Even though the absolute risk is still very low in healthy individuals, these risks are greater with larger doses and/or with chronic use of these pharmacological interventions. 70…”

Section: Considerationsmentioning

confidence: 99%

Analgesic and anti‐inflammatory drugs in sports: Implications for exercise performance and training adaptations

Lundberg

Howatson

2018

Scandinavian Med Sci Sports

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Over-the-counter analgesics, such as anti-inflammatory drugs (NSAIDs) and paracetamol, are widely consumed by athletes worldwide to increase pain tolerance, or dampen pain and reduce inflammation from injuries. Given that these drugs also can modulate tissue protein turnover, it is important to scrutinize the implications of acute and chronic use of these drugs in relation to exercise performance and the development of long-term training adaptations. In this review, we aim to provide an overview of the studies investigating the effects of analgesic drugs on exercise performance and training adaptations relevant for athletic development. There is emerging evidence that paracetamol might acutely improve important endurance parameters as well as aspects of neuromuscular performance, possibly through increased pain tolerance. Both NSAIDs and paracetamol have been demonstrated to inhibit cyclooxygenase (COX) activity, which might explain the reduced anabolic response to acute exercise bouts. Consistent with this, NSAIDs have been reported to interfere with muscle hypertrophy and strength gains in response to chronic resistance training in young individuals. Although it remains to be established whether any of these observations also translate into detriments in sport-specific performance or reduced training adaptations in elite athletes, the extensive use of these drugs certainly raises practical, ethical, and important safety concerns that need to be addressed. Overall, we encourage greater awareness among athletes, coaches, and support staff on the potential adverse effects of these drugs. A risk-benefit analysis and professional guidance are strongly advised before the athlete considers analgesic medicine for training or competition.

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“…NSAIDS are widely used both as a self-administered over the counter therapy and from prescription to manage pain and in ammation resulting from osteoarthritis (OA). However, there are signi cant adverse effects associated with chronic use, including gastrointestinal [8] (GI) and cardiovascular complications including myocardial infarction [9][10][11].…”

Section: Introductionmentioning

confidence: 99%

Pulsed Shortwave Therapy in Cervical Osteoarthritis: An NSAID- Controlled, Randomized Clinical Trial

Mohameed¹,

Koneru

Staelin

et al. 2020

Preprint

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Objective Assess treatment superiority of Pulsed Shortwave Therapy (PSWT) against COX-2 NSAID therapy, in reducing disability and pain due to cervical osteoarthritis.Design 200chronic pain suffers (average pain duration about 2 years)diagnosed with cervical osteoarthritis by radiological imaging were randomized into one of two treatmentarms: COX-2 NSAID treatment: Etoricoxib 60mg/day for 4 weeks; or, PSWT treatmentworn 24 hours/day for 4 weeks. The primary outcome measure was the 4-week score on the Neck Disability Index (NDI): a 10-question assessment on a 50-point scale. Secondary outcome measures included pain(at rest and during activity)measured on a Visual Analog Scale (VAS)of0-100 mm, dose count of rescue pain medication (paracetamol)use and a treatment satisfaction rating. These 4-week scores were compared across the two arms to assess superiority.Results After 4 weeks of treatment,subjects in both study arms reported significantly lower (p<0.0001) 4-week measures (11.24-NSAID;9.34-PSWT; 0-50 points),VASrest (30.08-NSAID;22.76-PSWT; 0-100 mm) and VASactivity (36.40-NSAID; 27.42-PSWT; 0-100 mm).The absolute reduction from baseline in NDI was significantly greater in the PSWT arm than NSAID arm(by 3.66 points; 95% CI 2.3 to 5.02; p<0.0001). Similarly, the reductions from baseline inVASrest and VASactivitywere significantly greater in the PSWT arm than NSAID arm(by 10.89 mm;95% CI 6.90 to 14.87; p<0.0001 and 12.05 mm;95% CI 7.76 to 16.33; p<0.0001 respectively).The PSWT arm used 50% less rescue pain medication. Eleven adverse effects were reported in the NSAID arm and zero in the PSWT arm.Conclusion Both NSAID and PSWT treatments resulted in clinically meaningful increases in quality of life(NDI) and decreases in pain (VAS) associated with cervicalosteoarthritis. However, the PSWT armshowed superior improvements in all outcome measures when compared to the NSAID armwith no adverse effects.

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Risk of acute myocardial infarction with real‐world NSAIDs depends on dose and timing of exposure

Cited by 34 publications

References 67 publications

Studying additive interaction in a healthcare database: Case study of NSAIDs, cardiovascular profiles, and acute myocardial infarction

Studying additive interaction in a healthcare database: Case study of NSAIDs, cardiovascular profiles, and acute myocardial infarction

Analgesic and anti‐inflammatory drugs in sports: Implications for exercise performance and training adaptations

Pulsed Shortwave Therapy in Cervical Osteoarthritis: An NSAID- Controlled, Randomized Clinical Trial

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