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Use of NSAIDs in
Athletic Medicine
George Phillips, MD
Sports Medicine Rounds
October 28, 2004
Cases
l
Case #1 – A 16-year-old competitive female gymnast with persistent
back pain has no neurologic symptoms and improves (modestly) with rest.
However, she needs to add new skills for competition and college
audition tapes. Ibuprofen and naproxen were not helpful. A trial of
celecoxib was instituted, but did not provide major relief. Valdecoxib
has proven to provide some additional relief.
Cases
l Case #2 – A 17-year-old male multi-sport athlete presents in
follow-up from the ED 5 days s/p a “high ankle sprain”. His exam is
consistent with a grade II ATFL sprain, probable medial sided bone
contusion, and no evidence of mortise disruption. The ED physician gave
morphine acutely, with an out-patient Rx for Percocet, and advised
against the use of NSAIDs due to possible interference with healing.
Reasons for Using NSAIDs
l Anti-inflammatory
l Pain relief
l Promotes range of motion
l Speeds return to participation
Concerns for Using NSAIDs
l Anti-inflammatory ® Interferes with healing
l Pain relief ® Blocks natural limiter of activity
l Side effects
Common NSAIDs
l Non-selective
l
Ibuprofen
l
Naproxen
l
Toradol (ketorolac)
l
COX –2 Selective
l
Celebrex (celecoxib)
l
Vioxx (rofecoxib)
l
Bextra (valdecoxib)
Side
Effect Profile of Non-selective NSAIDs
l Ibuprofen
– Gastrointestinal (4-16%)
– Dizziness (3-9%)
– Tinnitus (1-3%) and hearing loss – often reversible
– Hepatitis, GI bleeding, kidney failure, bone marrow failure,
anaphylaxis, hypertension, heart failure all less than 1%
Side Effect Profile of COX-2 Inhibitors
l Bextra (valdecoxib)
– Gastrointestinal (7-8%)
– Abnormal liver function tests (8%, ~ to placebo)
– Hypertension (2-3%, ~ to naproxen)
– Back pain (2%, ~ to non-selective NSAIDs)
– Chest pain, heart failure, bone marrow failure all <2%
– Heart attack, blood clot < 0.1%
Clinical Questions for NSAID Use
l Do NSAIDs affect tissue healing?
– Beneficial or detrimental
l Are NSAIDs better for pain relief?
l Do NSAIDs improve clinical outcomes following sport-related injury?
l Should the use of NSAIDs be tempered by their side effect profiles?
– Do we use NSAIDs too often?
Use of NSAIDs in Muscle Injury
l Almekinders and Gilbert, AJSM 1986
– Piroxicam preserved tensile strength, but may have delayed muscle
regeneration (qualitative).
l Thorsson, AJSM 1998
– Naproxen had no effect on healing of macroscopic muscle injury.
l Both studies are animal models.
Use of NSAIDs in Muscle Injury
l
Mishra et al, JBJS 1995
– In chronic, eccentric loading injury, flurbiprofen had initial
protective effect followed by delayed functional and structural recovery
(animal model).
l
Dudley et al, Clin J Sp Med 1997
– In DOMS, naproxen improved recovery after eccentric exercise (human
model).
Use of NSAIDs in Ligament Injuries
l Dahners, AJSM 1988
– In an animal model of MCL injury, piroxicam increased strength at
14 days post-injury, but not at 21 days, nor in non-injured ligaments.
l Moorman CT , AJSM 1999
– Animal model of transected MCL with primary repair.
– No significant difference between ibuprofen and placebo in average
failure load at 14 or 28 days.
Use of NSAIDs in Ligament Injuries
l Slatyer et al, AJSM 1997 – Kapooka Ankle Sprain Study
– In army recruits with ankle sprain, piroxicam was superior to
placebo for pain relief and faster return to activity.
– Nausea was significantly increased with piroxicam (6.8% vs. 0.3%).
– “some evidence of local abnormalities such as instability and
reduced range of movement”
Use of NSAIDs in Ligament Injuries
l Ekman et al, Am J Orthop 2002
– Celecoxib versus ibuprofen versus placebo
– Only significant differences in pain and activity were between
celecoxib and placebo.
l
Petrella et al, Clin J Sport Med 2004
– Celecoxib versus naproxen
– No differences in pain and activity between the two.
– GI side effects were 14% versus 21% respectively.
Use of NSAIDs in Tendon Injuries
l What type of tendon injury is it?
– Tendonitis
– Tendinosis
– Tendinopathy
– (Do we even know how to spell these words?)
l Some believe that a poor inflammatory response results in tendon
degeneration.
Use of NSAIDs in Tendon Injuries
l
Astrom M, Acta Orthop Scand 1992
– 70 adults with Achilles tendinopathy were randomized to piroxicam
versus placebo.
– With respect to pain, tenderness, swelling, ankle joint movement,
and strength, no differences were seen between treatment groups.
Use of NSAIDs in Tendon Injuries
l Almekinders LC, Med Sci Sports Exerc 1998
– Between 1966-1998, only 9 prospective, placebo- controlled trials
of tendonitis treatment with anti-inflammatories.
–
Pain relief was shown in 5 out of 9, but healing of the tendon was
not studied.
Use of NSAIDs in Bone Injury
l
Van Staa et al, Bone 2000
– Retrospective study from the UK of 716,004 patients, divided into
regular NSAID users, incidental NSAID users, and control patients.
– Regular NSAID use was associated with a 47% increase in
non-vertebral fractures versus placebo.
– No differences between actual NSAIDs used (all non-selective COX
inhibitors).
Use of NSAIDs in Bone Injury
l NSAIDs inhibit production of inflammatory prostaglandins, including
PGE-2, which has a proven role in bone healing.
l In patients with stress fractures, keeping activity below the pain
threshold is critical to successful management. The analgesic effect of
NSAIDs may interfere by masking pain.
Clinical Questions for NSAID Use
l Do NSAIDs affect tissue healing?
– Beneficial or detrimental
l Are NSAIDs better for pain relief?
l Do NSAIDs improve clinical outcomes following sport-related injury?
l Should the use of NSAIDs be tempered by their side effect profiles?
– Do we use NSAIDs too often?
Quality of Pain Relief with NSAIDs
l Aghababian RV, Clin Ther 1986
– Diflunisal versus acetaminophen with codeine in 40 patients with
grade II ankle sprain.
– Excellent or very good pain relief in 89% of patients with
diflunisal versus 43% with T#3.
– No reported adverse effects with NSAID, versus 29% adverse effect
rate with T#3.
Quality of Pain Relief with NSAIDs
l Bradley et al, NEJM 1991.
– For osteoarthritis of the knee, daily doses of 4000 mg
acetaminophen, 1200 mg ibuprofen, and 2400 mg ibuprofen were equally
effective.
– Suggests ceiling effect of pain relief properties of NSAIDs, versus
dose-dependent inhibition of prostaglandins (increased GI side effects,
etc.).
Quality of Pain Relief with NSAIDs
l Annals of Rheumatic Diseases, August 2004
– Meta-analysis of acetaminophen versus NSAIDs showed NSAIDs were
better at pain relief, but with significantly increased side effects.
– A separate clinical trial showed superior pain relief of celecoxib
versus acetaminophen, with no significant difference in reported side
effects.
Quality of Pain Relief with NSAIDs
l For low back pain, Cochrane Review shows no evidence that NSAIDs
are more effective than acetaminophen (Harwoood MI, J Fam Prac 2002).
l In patients presenting to an ED with acute pain, celecoxib 200 mg/
400 mg and ibuprofen 600 mg were equally effective (Salo et al, Acad
Emerg Med 2003).
Quality of Pain Relief with NSAIDs
l In outpatient orthopedic surgery patients, celecoxib provided
superior pain relief compared with T#3, including longer pain relief and
less use of “rescue medication”.
l The rate of adverse events in celecoxib patients was 43%, versus
89% in T#3 users (Gimbel JS, Clin Ther 2001).
Clinical Questions for NSAID Use
l Do NSAIDs affect tissue healing?
– Beneficial or detrimental
l Are NSAIDs better for pain relief?
l Do NSAIDs improve clinical outcomes following sport-related injury?
l Should the use of NSAIDs be tempered by their side effect profiles?
– Do we use NSAIDs too often?
NSAIDs and Clinical Outcomes
l NSAIDs work on pain, but pain can be useful, and the side effects
may not justify the results.
l NSAIDs may benefit minor muscle injury, but they may interfere in
the healing process of more severe injury.
l Evidence for the benefit of NSAIDs in ligament and tendon injury is
equivocal at best.
l NSAIDs may be detrimental in the treatment of stress fractures.
Clinical Questions for NSAID Use
l Do NSAIDs affect tissue healing?
– Beneficial or detrimental
l Are NSAIDs better for pain relief?
l Do NSAIDs improve clinical outcomes following sport-related injury?
l Should the use of NSAIDs be tempered by their side effect profiles?
– Do we use NSAIDs too often?
Rofecoxib: 5/21/99 – 9/30/04
l Original study looked at GI side effects in patients with
rheumatoid arthritis (Bombardier et al, NEJM 2000). This data was not
submitted for review until 1 year after FDA approval.
l The original study did not adequately account for possible
cardiovascular side effects.
Rofecoxib: 5/21/99 – 9/30/04
l Vioxx Gastrointestinal Outcomes Research (VIGOR) – rofecoxib versus
naproxen.
l Serious GI events were cut in half, from 4% to 2%.
l Incidence of heart attack increased 500%, but this was argued to be
due to the small total number of heart attacks and a possible protective
effect of naproxen.
Rofecoxib: 5/21/99 – 9/30/04
l Adenomatous Polyp Prevention on Vioxx (APPROVe) study was stopped
early.
l The study showed an 84% increase in the incidence of heart attack
in rofecoxib users, and a 390% increase in serious blood clots.
l Theory: PGI-2 blocks platelet clumping and protects blood
vessels. It was thought to come from COX-1, but new studies show it is
COX-2 mediated.
Rofecoxib: 5/21/99 – 9/30/04
l In the APPROVe study, there were an extra 16 heart attacks or
stroke for every 1000 patients.
l The average number of rofecoxib prescriptions in the U.S. is 10
million per month.
l Therefore, as many as 160,000 persons could be at risk of heart
attack or stroke due to rofecoxib use.
What about Celecoxib?
l In the Celecoxib Long Term Arthritis Safety Study (CLASS), no
increase in cardiovascular risk was seen in the first six months.
l However, after the full 12 months, celecoxib did not have good GI
protective results, except in patients not also on aspirin.
l There also appears to be a trend for increased cardiovascular risk,
although the study was not designed to detect this risk.
Use of NSAIDs by Student Athletes
l In a study of 604 Indiana high school football players, 75% had
used NSAIDs in the previous 3 months for sport-related reasons.
l Of the users, 20% took NSAIDs daily.
l (Phillips GC, AAP Grand Rounds 2002)
Reasons for NSAID Use in HS Athletes
Use of NSAIDs in Athletic Medicine
l The primary benefit of NSAIDs is in pain relief, which may be
either beneficial (early motion) or detrimental (stress fracture
management).
l No clear evidence suggests NSAIDs are uniquely beneficial in
recovery from sports injury, although there may be some benefit in minor
muscle injury.
Use of NSAIDs in Athletic Medicine
l The improvement in side effect profile of COX-2 inhibitors versus
non-selective NSAIDs may be tenuous, especially when the cardiovascular
risk factors are considered.
l Athletes self-medicate with NSAIDs on a regular basis, without
supervision, and at doses of their own choosing with motivators of
performance enhancement and pain prevention.
Cases
l Case #1 – The family history is not suggestive of increased risk of
MI or stroke. Tylenol is added for pain relief, and valdecoxib is
primarily being used only as needed.
l Case #2 – The Kapooka study results are explained, and the patient
is advised to use either acetaminophen or ibuprofen only if needed. The
patient has not required pain medication in > 48 hours. |
