EXPERT ANALYSIS FROM RWCS 2016
MAUI, HAWAII (FRONTLINE MEDICAL NEWS) – One of the major happenings in the field of osteoarthritis in the past year was a disturbing report of dramatically increased risk of acute MI for at least 6 months after total knee replacement, panelists agreed at the 2016 Rheumatology Winter Clinical Symposium.
“What they found borders on frightening,” according to Dr. Martin J. Bergman of Drexel University, Philadelphia, and chief of rheumatology at Taylor Hospital in Ridley Park, Pa.
Dr. Bergman and copanelist Dr. Orrin M. Troum of the University of Southern California in Los Angeles highlighted key developments in osteoarthritis during the past year, including two major studies on total knee replacement, the Food and Drug Administration’s updated stronger warning on the cardiac and stroke risks of NSAIDs, a randomized trial which effectively takes hydroxychloroquine (Plaquenil) off the treatment menu for hand osteoarthritis, and a reassuring report on the safety of repeated intra-articular corticosteroid injections in patients with synovitic knee osteoarthritis.
Acute MI risk after total knee replacement
British investigators utilizing the U.K. National Health Service database retrospectively identified 13,849 patients who underwent total knee replacement (TKR) and an equal number of nonsurgical controls propensity-matched for cardiovascular risk factors. These two very large groups were followed for 5 years.
During the first month after TKR, the acute MI risk was 8.75-fold greater than in the matched controls. The elevated risk gradually declined thereafter, but it remained significantly higher than in controls until 1 year after surgery. At 3 months post surgery the TKR group was at fourfold increased risk of MI, compared with controls, and at 6 months their risk was still nearly double that of controls ( Arthritis Rheumatol. 2015 Oct;67[10]:2771-9 ).
The British investigators also found a prolonged postsurgical elevated risk of MI in a large group of patients who underwent total hip replacement, although the magnitude of the increased risk, compared with matched controls, wasn’t as large as that seen after TKR.
Dr. Troum commented that the increased risk of MI during the first year after TKR identified in this study is something physicians now need to bring up in the risk/benefit discussion with patients considering TKR.
“Also, this study underscores that it may behoove us to make sure that these presurgical patients are really well worked up by a cardiologist or their primary care physician to mitigate that coronary risk as much as possible,” he added.
Another key finding in the U.K. study was that unlike the acute MI risk, the risk of venous thromboembolism following TKR remained elevated throughout the full 5 years of follow-up.
“Once you’ve had that surgery, you are at increased risk for venous thromboembolism. I think that’s something we have to keep in mind when a patient comes in with a history of total knee replacement and a complaint of calf pain or swelling – at that point, you have to think about deep venous thrombosis,” Dr. Bergman said.
TKR – Why wait?
In a Danish trial of 100 knee osteoarthritis patients deemed eligible for TKR, participants were randomized to prompt TKR followed by a 3-month regimen of exercise, dietary weight loss, physical therapy, and pain medication or to the nonsurgical regimen alone. At 12 months of follow-up, the prompt TKR group showed significantly greater improvement in a standardized score encompassing pain, symptoms, quality of life, and activities of daily living, even though one-quarter of patients in the nonsurgical treatment group bailed and underwent TKR before 12 months was up ( N Engl J Med. 2015 Oct 22;373[17]:1597-606 ).
“My conclusion is that once you’ve determined that a patient needs and wants a total knee replacement, the patient should probably get it. Delaying – trying other modalities in an effort to lose weight and improve function – is really not going to buy you much in the way of time,” Dr. Bergman observed.
Hydroxychloroquine for hand osteoarthritis
At the 2015 European League Against Rheumatism ( EULAR ) meeting in Rome, Dutch investigators presented a randomized, double-blind trial in which 196 patients with symptomatic hand osteoarthritis received 6 months of hydroxychloroquine at 400 mg/day or placebo. Unlike in mild rheumatoid arthritis or lupus, hydroxychloroquine had no beneficial effect on hand osteoarthritis pain, disability, or quality of life measures.
“Plaquenil [Hydroxychloroquine] is not a good choice for patients with osteoarthritis of the hand. I think it’s a dead therapy,” Dr. Troum declared.
FDA expands warning on NSAIDs’ cardiovascular risk
On July 9, 2015, the FDA announced updated labels for NSAIDs. The new warning states that MI and stroke risk can increase as early as in the first week of NSAID use and appear to be dose- and duration-related. The agency also warned that patients who take an NSAID after a first MI are more likely to die within 1 year.
“This really brought a lot of folks to my office,” Dr. Troum recalled.
“Absolutely, this was big stuff,” Dr. Bergman agreed. “This became a nightmare for many of us because all of a sudden patients were scared to death about taking their NSAIDs.”
Intra-articular corticosteroids for knee osteoarthritis don’t accelerate cartilage deterioration
At last fall’s American College of Rheumatology meeting in San Francisco, Jeffrey B. Driban, Ph.D., of Tufts Medical Center, Boston, presented a double-blind, randomized trial of intra-articular injections of triamcinolone hexacetonide 40 mg versus saline quarterly for 2 years in 140 patients with symptomatic knee osteoarthritis with ultrasound evidence of synovitis. Participants underwent annual evaluation of periarticular bone and cartilage changes via MRI and dual-energy x-ray absorptiometry.
After 2 years, there was no difference between the two groups in terms of pain scores, walk time, or other functional measures. The injections – eight in total over 2 years – were safe, with new-onset hypertension and hyperglycemia rates of 3% in this obese population. And most important of all, there were no major differences between the two groups in terms of quantitative or semiquantitative structural endpoints; in other words, the injections didn’t increase the rate of structural disease progression. The intra-articular steroid group showed a modestly greater rate of loss of cartilage thickness, which the investigators deemed of uncertain clinical significance.
“The structural changes were minimal,” Dr. Troum noted. “This is only a 2-year study, but I can say that I now feel more comfortable giving these injections in patients who for whatever reason can’t get surgery.”
Dr. Bergman said that many orthopedic surgeons talk up the potential risk that intra-articular steroid injections will accelerate cartilage damage. They place an arbitrary limit on the number of injections a patient can receive.
“I think this study really helps us push back and say, ‘No, I think you’re fine in getting this procedure,’” the rheumatologist commented.
Dr. Bergman and Dr. Troum reported having no financial conflicts regarding their presentation.
