{"id":627,"date":"2015-03-05T11:00:39","date_gmt":"2015-03-05T11:00:39","guid":{"rendered":"http:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/?p=627"},"modified":"2017-08-21T11:53:22","modified_gmt":"2017-08-21T11:53:22","slug":"primary-care-corner-with-geoffrey-modest-md-nsaids-post-mi","status":"publish","type":"post","link":"https:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/2015\/03\/05\/primary-care-corner-with-geoffrey-modest-md-nsaids-post-mi\/","title":{"rendered":"Primary Care Corner with Geoffrey Modest MD: NSAIDs post-MI???"},"content":{"rendered":"

By: Dr. Geoffrey Modest<\/strong><\/p>\n

A retrospective\u00a0Danish study evaluated\u00a0patients post-MI to see if taking NSAIDs influenced subsequent\u00a0mortality, using their nationwide administrative registries. In Denmark, NSAIDs require prescriptions,\u00a0except for the lowest dose ibuprofen. (see\u00a0JAMA. 2015;313(8):805-814<\/strong>)\u200b. Guidelines in Denmark advise that all patients with MI have dual antithrombotic\u00a0therapy (aspirin and clopidogrel) for up\u00a0to 12 months, then single agent thereafter, and\u00a0discourage the use of NSAIDs. Details:<\/p>\n

–61,971 patients (mean age 67.7, 63% men) were analyzed during a median followup of 3.5 years. 2% were\u00a0not on antithrombotics, 19.7% on only one agent, 64.9% on aspirin plus clopidogrel, and 5% either on oral anticoagulant (OAC)\u00a0alone or with one other\u00a0agent, and 8.5% on triple therapy (aspirin, clopidogrel, and OAC). also 78.1% on b-blockers, 49.8% ACE-I\/ARB, 75.1% statins, 24.3% PPIs<\/p>\n

–34% filled at least 1 NSAID prescription: 23.1% ibuprofen, 9.9% diclofenac, 1.7% naproxen, 2% coxibs<\/p>\n

–total number of deaths in the followup period was\u00a018,105 (29.2%). \u00a0a total of 5288 (799 fatal)\u00a0bleeding events occurred (8.5%) as well as 18,568 cardiovascular events (30.0%)<\/p>\n

–crude incidence rates were (as events per 100 person-years):<\/p>\n

–bleeding:\u00a04.2 for those taking NSAIDs and 2.2 if not. Risk even higher when NSAIDs were added to double or triple antihrombotic regimens<\/p>\n

–cardiovascular events:\u00a011.2 for those taking NSAIDs and 8.3\u00a0if not\u200b.<\/p>\n

–multivariate analysis:\u00a0adjusting for age; gender; comorbidities of peripheral or cerebral vascular disease, renal failure, COPD, previous bleeding; or concommitant med therapy (b-blockers, statins, ACE-I\/ARB, glucose lowering drugs, diuretics, PPIs)<\/p>\n

–increased bleeding with\u00a0NSAIDs, HR=2.02 (1.81-2.26) –, ie twice the risk<\/p>\n

\u200b–increased cardiovascular\u00a0risk, HR=1.40 (1.30-1.49) \u00a0— ie, 40% increase<\/p>\n

–these increases were evident with NSAID use, independent of antithrombotic treatment, types of NSAIDs or duration of use
\n–for overall bleeding risk, highest for celecoxib (crude rate 9.1\/100 person-yrs), then diclofenac (6.1),\u00a0rofecoxib (4.6). Naproxen (3.3) and ibuprofen (3.1) were better than average. And no NSAI was 2.2<\/p>\n

–for overall cardiovascular risk, highest for celecoxib (crude rate 25.9\/100 person-yrs), then diclofenac (12.0), ibuprofen (10.0), and naproxen (7.4). And no NSAID was 8.3.<\/p>\n

A few comments:<\/p>\n

–Part of the issue may be that taking NSAIDs may decrease the antiplatelet\u00a0efficacy of aspirin. For example, a study found that taking aspirin prior to NSAIDs did not block the cyclooxygenase-1 activity of aspirin (as measured by serum thromboxane B levels), BUT taking a single dose of\u00a0ibuprofen 2 hours before aspirin did block\u00a0the inhibition of thromboxane B and inhibition of platelet aggregation\u00a0by aspirin. This was not found with acetaminophen or diclofenac\u00a0(see\u00a0N Engl J Med. 2001;345:1809<\/strong>).<\/p>\n

–Several studies have looked at the different NSAIDs and cardiovascular outcomes, generally finding that naproxen is the safest. A recent network meta-analysis\u00a0(see\u00a0BMJ.2011;342:c7086<\/strong>) of 31 trials and >115,000 patient-years of followup\u00a0found that ibuprofen had the highest risk of stroke, followed by diclofenac (which has somewhat better GI tolerability and is used\u00a0a\u00a0lot in Europe,\u00a0has mixed anti-COX1 and anti-COX-2 effects, though it has\u00a0stronger anti-COX-2 than most other nonselective NSAIDs,\u00a0similar\u00a0to celecoxib). Diclofenac is also associated with high risk of cardiovascular death. and, their conclusion: “Naproxen seemed least harmful”.<\/p>\n

So, this study adds to several other observational studies finding adverse cardiovascular effects by the use of NSAIDs (with the possible exception of naproxen). But, as well as the known GI adverse effects, NSAIDs in general are associated with increases in blood pressure, heart failure, atrial fibrillation (in a couple of studies), stroke, MI, and cardiovascular death (these outcomes are noted both in patients with and without known cardiovascular disease). I personally think NSAIDs\u00a0are way overused, especially in the elderly, and should be used sparingly, at the lowest dose and shortest duration possible, and that we should consider using acetaminophen, topical preparations or local injections when possible to treat pain. and, if NSAIDs are necessary, I think the data are pretty consistently better for naproxen.<\/p>\n","protected":false},"excerpt":{"rendered":"

NSAIDs post-MI??? […]<\/p>\n

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