Aspirin, NSAID, Coxib and PPI

Clinical bottom line

Using aspirin, NSAIDs, coxibs and PPIs for treating daily pain and protecting against vascular and gastrointestinal events is a tricky business. But help is at hand from some thoughtful and intelligent use of evidence.

References

C Baigent, C Patrono. Selective cyclooxygenase 2 inhibitors, aspirin, and cardiovascular disease. Arthritis & Rheumatism 2003 48: 12-20.

RH Hunt et al. Recommendations for the appropriate use of anti-inflammatory drugs in the era of the coxibs: defining the role of gastroprotective agents. Canadian Journal of Gastroenterology 2002 16: 231-240.

Problem

The problem is that people with arthritis who need NSAIDs or coxibs for their everyday pain are usually older, and may also have cardiovascular risk factors that may require prophylactic low dose aspirin to minimise the possibility of heart attack or stroke.

Complicating factors include:

Some NSAIDs (and certainly ibuprofen) can interfere with the action of aspirin, and block it, but some coxibs may not.
Some NSAIDs (possibly only naproxen, and definitely not coxibs) may themselves have a cardioprotective effect.
Both NSAIDs and aspirin can harm the digestive tract and cause ulceration and bleeding.
Aspirin may, in addition, diminish the safety of coxibs with regard to the lower rates of ulceration and bleeding associated with coxibs.
Some patients may have independent risk factors (age, steroid use, prior complications) that predispose them to a higher rate of gastrointestinal problems in the future, especially with aspirin and NSAIDs, and possibly coxibs.

Baigent & Patrono review the available information and suggest a strategy for analgesic or anti-inflammatory treatment and cardiovascular prevention in patients with inflammatory disease and different levels of risk for vascular events and gastrointestinal complications (Figure 1).

Figure 1: Suggested strategy

In this strategy they suggest low risk (less than 0.2% per year) is found in individuals aged below 50 years, and risks above 0.5% a year in those aged 80 years or more. A vascular event is defined as fatal or nonfatal heart attack or stroke.

In patients with lower risk of gastrointestinal complications, the strategy may be influenced by whether aspirin is coadministered. Conventional NSAIDs may interfere with aspirin's antithrombotic efficacy, making a coxib the rational choice with aspirin. Always, to minimise gastrointestinal toxicity, the lowest effective dose of NSAID or coxib should be used, as well as the lowest effective dose of aspirin, which they advise as 75-100 mg daily).

Hunt and colleagues address the appropriate use of gastroprotective agents in people who need to take an NSAID or coxib. Their recommendations are shown in Table 1.

Table 1: Recommendations for individuals needing gastroprotective therapy

Risk level	Profile	Recommended treatment
New patient
High risk	Previous upper GI bleeding	Coxib plus GPA
	Age 75 or more
	Concomitant steroid or anticoagulant
	Two or more other risk factors
Intermediate risk	One risk factor	Coxib alone
	No upper GI bleeding
	Age 60-75 years
Low risk	No risk factors	NSAID or coxib alone, discuss with patient
Previously treated patient
Previous ulcer disease		Coxib, eradication of H pylori if present
Prior complication		Coxib plus GPA, eradication of H pylori if present
Dyspepsia	Mild or intermittent	H2A or PPI
	Moderate or nonresponding	PPI
Current therapy of NSAID plus GPA		Re-evaluate as for new patient

Comment

Both of these papers spend time reviewing the evidence, and each has to be read. This is becoming a complicated business, but gradually less so. Better treatment of pain, and prophylaxis against vascular and gastrointestinal events all seem to be possible with as little thought.