By Dr. Geoffrey Modest
And so the wonder drug spironolactone seems to have another possible indication: knee effusions from osteoarthritis (see Elsaman AM. J Rheumatol 2016; 43: 1114).
Details:
- 200 patients with unilateral knee effusion related to osteoarthritis (OA) based on clinical exam, ultrasound and synovial fluid analysis
- Mean age 51, 40% male, weight 84 kg, mean duration of effusion 16.5 days, mean thickness of fluid by ultrasound was 7.6 mm thick
- Randomized to 2 weeks of: spironolactone 25 mg daily; ibuprofen 400 mg three times/d; cold compresses twice a day, for 10 minutes each time; or placebo
- Assessment: effusion considered if >4mm fluid; complete improvement if <4mm, partial improvement if a decrease but still >4mm
Results:
- At 2 weeks after treatment
- Spironolactone group: 66% had complete improvement/20% partial/14% no improvement; mean fluid thickness 3.7 mm
- Ibuprofen group: 24% had complete improvement/12% partial/64% no improvement; mean fluid thickness 6.3 mm
- Cold compress group: 28% had complete improvement/14% partial/58% no improvement; mean fluid thickness 5.9 mm
- Placebo group: 6% had complete improvement/10% partial/84% no improvement; mean fluid thickness 7.3 mm
- At 4 weeks after treatment
- Spironolactone group:mean fluid thickness 2.4 mm; 79% no recurrence of effusion/21% recurrence
- Ibuprofen group: mean fluid thickness 5.1 mm; 44% no recurrence of effusion/56% recurrence
- Cold compress group: mean fluid thickness 5.0 mm; 38% no recurrence of effusion/62% recurrence
- Placebo group: mean fluid thickness 6.9 mm; 13% no recurrence of effusion/88% recurrence
- VAS (visual analog scale of pain, from 0-10):
- Spironolactone group:at 2 weeks, decreased from 5.42 to 2.66, then at 4 weeks to 1.06
- Ibuprofen group: at 2 weeks, decreased from 4.64 to 3.70, then at 4 weeks to 2.44
- Cold compress group: at 2 weeks, decreased from 5.16 to 4.00, then at 4 weeks to 2.53
- Placebo group: at 2 weeks, decreased from 5.14 to 4.50, then at 4 weeks to 4.00
- Adverse effects of spironolactone: 8% had lowering of blood pressure, but not below normal; 6% had “disturbances in their sodium and potassium levels”, not otherwise elucidated.
Commentary:
- About 45% of patients with painful knee OA have an effusion, increasing to 79% during activity in a European study; another study found effusion in 55%
- In this study, NSAIDs were no better than placebo, though cold compresses were better than placebo
- Spironolactone was chosen because of its effect on other effusions (e.g. ascites, pleural effusion). Also, it does seem to have anti-inflammatory properties (aldosterone being pro-inflammatory). Other studies have found that spironolactone can improve muscle function in functionally-impaired elderly.
- Pretty striking response to spironolactone after only 2 weeks of therapy, with lack of recurrence at 4 weeks and impressive continued decrease in effusion size. The VAS pain scale tracked with the effusion resolution, and continued to improve after therapy ended in all groups.
- One pretty significant problem with the study was that those on spironolactone were hospitalized for the first 3 days, to check the blood pressure every six hours. Not only is this questionably necessary, but it might well distort/increase the “placebo effect” of the intervention.
- Another very recent article, a proof-of-concept study, found the opposite conclusion in elderly Scottish patients (see McMurdo MET. Arthritis Care & Research 2016; 68:716). Briefly:
- 86 community-dwelling elderly patients (all >70 yo, with mean age of 77, 62% women) with symptomatic knee OA pain and radiologic OA, were randomized to spironolactone 25 mg vs placebo for 12 weeks
- Result: no difference in pain, stiffness or physical function scores on WOMAC (Western Ontario and McMaster Universities Osteroarthritis Index)
- I’m not exactly sure why these outcomes are so different. But though both dealt with patients with symptomatic OA, they are very different studies. The latter was older patients, no comment on whether effusion was present or not, 50% were on opiates, 66% on nonopioid preparations, and 18% were on neuropathic drugs (amitriptyline, pregabalin, gabapentin). The study above, however, was pretty much the opposite (younger patients with short-term knee effusions and not on other meds, though they did not comment explicitly on how often patients took any other meds during the 2-week study or in the month after the study)
- So, given the increasing indications and use of spironolactone over the past decade or more (resistant hypertension, hyperaldosteronism, heart failure, hirsutism, ….) and that we in primary care in general are pretty comfortable using it and monitoring for safety, its short-term use in patients with symptomatic OA is appealing. I think it is overall less toxic than many of the other meds we use (esp NSAIDs), so it might be reasonable to consider. Larger and confirmatory studies would be helpful prior to a stronger recommendation. My go-to therapy in most patients with symptomatic and functionally-impairing painful knee OA is still steroid knee injections for OA (really rapid response and ability to get back to their activities; a local therapy, which works almost all of the time, with minimal systemic effects).
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