Beta-Blockers Decrease Opioid Rx in Comorbid OA, HTN

The anti-nociceptive effect of beta-adrenergic blockade is associated with decreased joint pain and reduced opioid requirements in patients with symptomatic large joint osteoarthritis (OA) and hypertension (HTN).¹ The results of the observational study, recently reported in Arthritis Care & Research, suggest that patients with chronic joint pain related to symptomatic OA with comorbid HTN may benefit from beta-blocker pharmacotherapy.

Study participants were identified through the Genetics of Osteoarthritis and Lifestyle (GOAL) case–control study from 2002 to 2006. Based in the UK, the study was initially designed to identify the genetic associations with OA and modifications secondary to lifestyle and environmental factors.

Patients eligible for inclusion in the study had symptomatic radiographic knee OA (defined by tibiofemoral or patellofemoral compartment Kellgren Lawrence grade ≥2) or radiographic hip OA (defined as Croft grade ≥3), regardless of history of joint replacement, as well as a history of physician-diagnosed hypertension and at least 1 current prescribed antihypertensive.

All study participants had weight-bearing tibiofemoral and 30 degree flexion knee radiographs and pelvic radiographs performed.  Levels of hip or knee pain were quantified by measuring  Western Ontario and McMaster Universities Arthritis (WOMAC) score.

A thorough medication history was taken, wherein antihypertensive therapy was classified as either alpha-adrenergic blockers, beta-adrenergic blockers, angiotensin-converting enzyme inhibitors, angiotensin II receptor antagonists, calcium channel blockers, or diuretics.  Prescription analgesics were classified as either opioids, nonsteroidal anti-inflammatory drugs (NSAIDs), or other prescription analgesic drugs.

Researchers found that beta-blocker use was associated with reductions in reported joint pain after adjustments were made for age, gender, and body mass index (odds ratio [OR] joint pain = 0.70, 95% confidence interval [CI], 0.51-0.91). This association remained significant even after adjusting for a prior medical history of knee OA, hip OA, arthroplasty, anxiety, or depression (adjusted OR= 0.68 ; 95% CI, 0.51-0.91).

A similar association was also found when examining the use of adrenergic blockers in general (OR= 0.70; 95% CI, 0.52-0.93).  Further, the duration of beta-blockade appeared to further reduce the risk of joint pain (OR per 1 year increase in beta-blocker use = 0.96 (95% CI, 0.930 -0.99; P <.004).

A prior history of arthroplasty with residual symptomatic joints at non-surgically treated sites did not change the association between beta-blocker use and decreased risk for joint pain. Further adjustment for number of antihypertensives did not change the association.

Notably, a lower rate of prescription analgesics was noted in patients who used prescription beta-blockers (OR= 0.74; 95% CI, 0.56-0.97). This relationship was not seen with other classes of antihypertensives.

Log transformation of WOMAC pain scores in linear regressions to adjust for potential confounders further confirmed the association between improved WOMAC pain scores with beta-adrenergic blockade in both men and women, regardless of history of arthroplasty at other sites.

Summary and Clinical Applicability

Beta-adrenergic receptor blockade in adult patients with comorbid OA and HTN was associated with decreased WOMAC scores and reduced rates of opioid prescriptions, suggesting that the anti-nociceptive properties of beta blockers may be a modifying factor for choice of antihypertensives. Currently, the eighth report of the Joint National Committee states that beta-blockers should not be the preferred initial class of antihypertensives chosen for routine cases, unless other indications like angina or heart failure co-occur. ²

“If confirmed in randomized controlled trials, the data presented here could suggest that in people with chronic joint pain β-blockers may be considered as part of their anti-hypertensive regimen,” the authors concluded.

Limitations and Disclosures

• Cross-sectional, observational study design did not allow for the establishment of causality or for control of external potential confounders
• Selection bias stemming from the inclusion of patients from a hospital-based cohort (with high percentages of those who had undergone arthroplasty) cannot be excluded
• Adverse effects associated with beta-blocker use was not examined in this study

Disclosures: The GOAL cohort collection was partly funded by AstraZeneca. Dr Maciwicz is an employee of AstraZeneca. 

References

1. Valdes AM, Abhishek A, Muir K, Zhang W, Maciewicz RA, Doherty M. Beta-blocker use associates with lower prevalence of joint pain and lower opioid requirement in people with osteoarthritis. Arthritis Care Res (Hoboken). 2016 Oct 13.  doi: 10.1002/acr.23091  [Epub ahead of print]
2. James PA, Oparil S, Carter BL, et al. 2015 evidence-based guideline for the management of high blood pressure in adults: reports from the panel members appointed to the Eighth Joint National Committee (JNC 8). .JAMA. 2014 Feb 5;311(5):507-20.

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