• People with heart failure.
• People with severe heart failure should not use NSAIDs.
• Those with moderate heart failure should not use coxibs.
• A standard NSAID may be used if necessary, but the individual should be closely monitored.
• Ibuprofen up to 1200 mg per day or naproxen up to 1000 mg per day are recommended as first-line options.
• People with ischaemic heart disease, cerebrovascular disease, or peripheral arterial disease.
• Coxibs are contraindicated.
• Ibuprofen up to 1200 mg per day or naproxen up to 1000 mg per day are recommended as first-line options.
• People with renal impairment (e.g. creatinine clearance less than about 20 mL/min).
• Ideally, avoid using NSAIDs.
• If an NSAID is used, the person should be closely monitored.
• People with risk factors for cardiovascular disease and all elderly people.
• Ibuprofen up to 1200 mg per day or naproxen up to 1000 mg per day are recommended as first-line options.
• People with hypertension
• Ideally, avoid using etoricoxib — etoricoxib may be associated with more frequent and severe effects on blood pressure than other coxibs and standard NSAIDs, particularly at high doses.
• Consider whether monitoring is needed.

The current summary of the evidence on thrombotic risk from the Medicines and Healthcare Products Regulatory Agency (MHRA) [CHM, 2006; MHRA, 2007; MHRA, 2009a] is that:

• The absolute risk of thrombotic risk for NSAIDs and coxibs is small.
• Coxibs (including celecoxib and etoricoxib) increase the risk for atherothrombosis by about 3 events per 1000 people per year (compared with placebo).
• Naproxen 1000 mg daily has a lower thrombotic risk than coxibs and, overall, epidemiological data do not suggest an increased risk of myocardial infarction.
• Ibuprofen may have a small thrombotic risk at high doses (e.g. 2400 mg daily), but at lower doses (e.g. 1200 mg daily or less), epidemiological data do not suggest an increased risk of myocardial infarction.
• Diclofenac 150 mg daily has a thrombotic risk profile similar to that of etoricoxib and possibly other coxibs.
• Other NSAIDs have less evidence on thrombotic risks, but they may all be associated with a small risk of thrombotic events.
• People with risk factors for cardiovascular events may be at higher risk of thrombotic adverse events, but some increased cardiovascular risk may apply to all NSAID users, including those at low estimated cardiovascular disease risk.
• Adverse effects may manifest early, and the risk may persist throughout treatment.
• However, the greatest concern relates to chronic use of high doses (especially for coxibs and diclofenac).

There is less evidence on the renal and renovascular risks (hypertension, heart failure) associated with coxibs and standard NSAIDs. The available evidence did not report absolute risk increases or numbers needed to harm.

• The MHRA continues to receive case reports of renal failure in NSAID users [MHRA, 2009b].
• One case-controlled study of standard NSAIDs found that they increase the risk of acute renal failure 3-fold; ibuprofen was associated with a lower risk than diclofenac in this study.
• Three systematic reviews found increased risks of hypertension and elevated blood pressure (particularly systolic blood pressure) with NSAIDs.
• The results are not entirely consistent among the studies.
• The risks for hypertension vary among drugs (indicating that this risk may not be a class effect); they may be greatest for etoricoxib, ibuprofen, and naproxen and least for celecoxib and diclofenac.
• The Commission on Human Medicines (formerly the Committee on Safety of Medicines) concluded that 'Etoricoxib, particularly at high doses, may be associated with more frequent and severe effects on blood pressure than other coxibs and standard NSAIDs' [CSM, 2005].
• One case-controlled study of standard NSAIDs found that they increase the risk of heart failure; indometacin carried the greatest risk.