Highlights
The statement, published online in the February 26 Rapid Access issue of Circulation, recommends a new stepwise approach to the treatment of musculoskeletal pain in such patients, starting with nonpharmacologic treatments, such as physical therapy and exercise, weight loss to reduce stress on joints, and heat or cold therapy. If this does not provide enough pain relief, Acetaminophen, Aspirin (Salicylates), and even short-term use of narcotic analgesics are recommended as first-line drugs. Then, NSAIDs with the lowest COX-2 selectivity should be used next, and the more selective COX-2 inhibitors should be placed at the bottom of the list and used only as a last resort.
The statement says that all drugs should be used at the lowest dose necessary to control symptoms and prescribed for the shortest time possible.
The stepwise approach to pharmacologic therapy for musculoskeletal symptoms in patients with or at risk for cardiovascular disease includes the following drugs to be administered in this order:
- Acetaminophen, Tramadol, narcotic analgesics (short-term)
- Nonacetylated salicylates
- Non-COX-2 selective NSAIDs
- NSAIDs with some COX-2 activity
- COX-2 selective NSAIDs
Once the decision is made to prescribe a NSAID, the statement says that several additional points should be considered. These include:
- In patients at increased risk for thrombotic events, Aspirin (Low Dose) plus a proton-pump inhibitor could be added.
- COX inhibitors can lead to impaired renal perfusion, sodium retention, and increases in blood pressure, which may contribute to their adverse cardiovascular effects. Therefore, renal function and blood pressure should be monitored in subjects taking COX-2 inhibitors, and extra caution should be exerted when these drugs are given to subjects with preexisting hypertension, renal disease, and heart failure.
The statement says that more data are also needed on the cardiovascular safety of conventional NSAIDs. But until such data are available, the use of any COX inhibitor, including over-the-counter NSAIDs, for long periods should only be considered in consultation with a clinician.
- COX-2 inhibition can result in an increased risk for thrombosis due to increased activity of thromboxane A2 and reduced activity of prostacyclin. In addition, all NSAIDs can increase sodium and water retention, increasing the risk for exacerbations of hypertension and heart failure. Finally, COX-2 up-regulation may reduce myocardial ischemia and infarction during acute cardiac events, and inhibition of this isoenzyme can increase infarct size and lead to myocardial rupture.
- “Nonselective” NSAIDs also differ with regard to COX selectivity. Diclofenac has greater COX-2 selectivity than ibuprofen, which in turn has greater COX-2 selectivity compared with naproxen.
- Initial treatment of musculoskeletal pain should include nonpharmacologic therapy, including physical therapy, heat/cold, and orthotics. Acetaminophen and Aspirin (Salicylates) are probably the best initial choices for analgesia, although these agents should be used at the lowest possible dose for the shortest possible period.
- For patients who fail conservative therapy for musculoskeletal pain, NSAIDs may be chosen as a next step. Clinicians and patients should realize that the use of NSAIDs may slightly increase the risk for cardiovascular and cerebrovascular events. With this in mind, clinicians should try to use NSAIDs with lower selectivity for COX-2.
- Naproxen is probably the NSAID associated with the lowest risk for thrombosis. The Alzheimer’s Disease Anti-inflammatory Prevention Trial (ADAPT) questioned the safety of naproxen, but this trial had significant limitations.
- Patients with a history of gastrointestinal tract bleeding or who are at high risk for bleeding who require analgesia should be prescribed acetaminophen first. For these patients who require NSAID therapy, proton-pump inhibitors have been demonstrated to reduce the risk for recurrent gastrointestinal tract bleeding among patients receiving Aspirin (Low Dose) .
- Patients with active atherosclerotic processes are at increased risk for the thromboembolic complications of COX-2 inhibitors. Renal function and blood pressure should be monitored during treatment with COX-2 inhibitors.
- Ibuprofen , but not rofecoxib, Acetaminophen, or diclofenac, appears to reduce the physiologic efficacy of Aspirin (Salicylates) in preventing thrombosis. Current recommendations call for delaying Ibuprofen dosing until at least 30 minutes after taking Aspirin (Salicylates) or at least 8 hours prior to aspirin dosing.