Cardiac risks from NSAIDs: is naproxen safe?

The debate on the cardiac risks from NSAIDs has shifted. Quite a few years ago when Vioxx was yanked (yeah, remember Vioxx, the target of all the trial lawyer ads?) the word was that it was uniquely risky for cardiac events. In the ensuing years I followed the related literature closely and wrote many posts debunking that claim. And more here: [1] [2] [3]

In considering the multiple studies cited in those posts my take was that all the NSAIDs are dangerous, the older ones as much as the COX-2s. The common thread was that naproxen was the least harmful but still harmful.

So the other day I came across this post which points to a recent meta-analysis suggesting that naproxen is not associated with cardiovascular risk. From the meta-analysis:

The vascular risks of high-dose diclofenac, and possibly ibuprofen, are comparable to coxibs, whereas high-dose naproxen is associated with less vascular risk than other NSAIDs. Although NSAIDs increase vascular and gastrointestinal risks, the size of these risks can be predicted, which could help guide clinical decision making.

In terms of major vascular events the RR for naproxen was 0.93 (0.69-1.27).

The post comes just short of saying naproxen is safe and concludes:

If you can, avoid NSAIDs in patients with cardiac risk factors. Ibuprofen isn’t a safe alternative. If you need to give an NSAID for whatever reason, use naproxen and use short courses of therapy.

There are two pieces missing from the discussion:


Consider nonacetylated salicylates

That's what this patient information page from the American Heart Association suggests, but it is seldom discussed.
Cardiorenal risk may be more important than cardiovascular risk

As stated in the post, the absolute increase in cardiovascular risk from NSAIDs is low. The adverse cardiorenal effects of (non-salicylate) NSAIDs, though underdiscussed, are well documented. I don't know what the absolute cardiorenal risk is but I think it is much higher. In hospital medicine I see it week after week in patients with uncontrolled hypertension, heart failure exacerbations and AKI. Naproxen is NOT exempt form this. Note that in the meta-analysis cited above it was associated with nearly double the risk of heart failure. Heart failure due to NSAIDs is a cardiorenal phenomenon.