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Objective To analyse the available evidence on cardiovascular safety of non-steroidal anti-inflammatory drugs.Design Network meta-analysis.Data sources Bibliographic databases, conference proceedings, study registers, the Food and Drug Administration website, reference lists of relevant articles, and reports citing relevant articles through the Science Citation Index (last update July 2009). Manufacturers of celecoxib and lumiracoxib provided additional data.Study selection All large scale randomised controlled trials comparing any non-steroidal anti-inflammatory drug with other non-steroidal anti-inflammatory drugs or placebo. Two investigators independently assessed eligibility.Data extraction The primary outcome was myocardial infarction. Secondary outcomes included stroke, death from cardiovascular disease, and death from any cause. Two investigators independently extracted data.Data synthesis 31 trials in 116 429 patients with more than 115 000 patient years of follow-up were included. Patients were allocated to naproxen, ibuprofen, diclofenac, celecoxib, etoricoxib, rofecoxib, lumiracoxib, or placebo. Compared with placebo, rofecoxib was associated with the highest risk of myocardial infarction (rate ratio 2.12, 95% credibility interval 1.26 to 3.56), followed by lumiracoxib (2.00, 0.71 to 6.21). Ibuprofen was associated with the highest risk of stroke (3.36, 1.00 to 11.6), followed by diclofenac (2.86, 1.09 to 8.36). Etoricoxib (4.07, 1.23 to 15.7) and diclofenac (3.98, 1.48 to 12.7) were associated with the highest risk of cardiovascular death.Conclusions Although uncertainty remains, little evidence exists to suggest that any of the investigated drugs are safe in cardiovascular terms. Naproxen seemed least harmful. Cardiovascular risk needs to be taken into account when prescribing any non-steroidal anti-inflammatory drug.

Summary This systematic review examines the incidence of Immune Reconstitution Disease (IRD) in HIV-1 infected patients starting antiretroviral combination therapy (ART). We analysed 13103 patients from 54 cohort studies; 1685 patients developed IRD. Pooled incidences with 95% credibility intervals (CrI) were calculated using Bayesian methods. In patients with previously diagnosed AIDS-defining conditions the incidence was 37.7% (95% CrI 26.6–49.4%) for CMV retinitis, 19.5% (6.7–44.8%) for cryptococcal meningitis, 15.7% (9.7–24.5%) for tuberculosis, 16.7% (2.3–50.7%) for progressive multifocal leukencephalopathy and 6.4% (1.2–24.7%) for Kaposi’s sarcoma. The incidence of any type of IRD, based on studies of unselected patients starting ART, was 16.1% (11.1–22.9%). Lethality was 4.5% (2.1–8.6%) for any type of IRD, 3.2% (0.7–9.2%) for tuberculosis and 20.8% (5.0–52.7%) for cryptococcal meningitis. Meta-regression analyses showed that the incidence is largely determined by the CD4 cell count at the start of ART, with a high risk in patients starting below 50 cells/μl. Many of the IRD events might therefore be prevented with earlier initiation of ART.