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Objective: Now that long-term survival after successful renal transplantation is no longer limited by excessive cardiovascular risk, the primary care physician should consider that infection and malignancy are leading noncardiovascular causes of death even in the recipient with diabetes., Methods: We accessed the National Institutes of Health-sponsored Folic Acid for Vascular Outcome Reduction in Transplantation (FAVORIT) study population (4010 renal transplant recipients with elevated homocysteine levels) studied to determine whether folate and B12 supplementation would reduce cardiovascular end points. This trial had a null result. Patients were classified as being nondiabetic or having type 1 or type 2 diabetes., Results: We report an excess (cardiovascular and noncardiovascular) 6-year mortality risk associated with the presence of diabetes mellitus. Two thirds of fatal events in our renal transplant recipients were centrally adjudicated as noncardiovascular. The incidence of noncardiovascular death was 70% higher in the diabetic patient cohort than in the nondiabetic cohort., Conclusions: These results demonstrate that infection (but not malignancy) risks are far higher in diabetic than nondiabetic immunosuppressed individuals (although noncardiovascular death rate in nondiabetic individuals also exceeded cardiovascular deaths) and may play a larger role in the excess mortality populations than previously thought. Given that follow-up in this study was 4 to 10 years after allograft surgery, there was a lesser degree of acute rejection requiring high-dose immunosuppression than in the initial postallograft years. This unique perspective allows transplant recipients to return to primary physicians when taking low doses of immunosuppressive agents and provides focus for follow-up care., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Observational studies and randomized trials have reported increased cardiovascular risk associated with cyclooxygenase-2 inhibitors. Prior placebo-controlled randomized studies had limited ability to assess the relationship of either celecoxib dose or pretreatment cardiovascular status to risk associated with celecoxib. Our aim was to assess the cardiovascular risk associated with celecoxib in 3 dose regimens and to assess the relationship between baseline cardiovascular risk and effect of celecoxib on cardiovascular events., Methods and Results: We performed a patient-level pooled analysis of adjudicated data from 7950 patients in 6 placebo-controlled trials comparing celecoxib with placebo for conditions other than arthritis with a planned follow-up of at least 3 years. Patients were administered celecoxib in 3 dose regimens: 400 mg QD, 200 mg BID, or 400 mg BID. From the pooled data, we calculated a hazard ratio for all dose regimens combined and individual hazard ratios for each dose regimen and examined whether celecoxib-related risk was associated with baseline cardiovascular risk. The primary end point was the combination of cardiovascular death, myocardial infarction, stroke, heart failure, or thromboembolic event. With 16,070 patient-years of follow-up, the hazard ratio for the composite end point combining the tested doses was 1.6 (95% CI, 1.1 to 2.3). The risk, which increased with dose regimen (P=0.0005), was lowest for the 400-mg-QD dose (hazard ratio, 1.1; 95% CI, 0.6 to 2.0), intermediate for the 200-mg-BID dose (hazard ratio, 1.8; 95% CI, 1.1 to 3.1), and highest for the 400-mg-BID dose (hazard ratio, 3.1; 95% CI, 1.5 to 6.1). Patients at highest baseline risk demonstrated disproportionately greater risk of celecoxib-related adverse events (P for interaction=0.034)., Conclusions: We observed evidence of differential cardiovascular risk as a function of celecoxib dose regimen and baseline cardiovascular risk. By further clarifying the extent of celecoxib-related cardiovascular risk, these findings may help guide treatment decisions for patients who derive clinical benefit from selective cyclooxygenase-2 inhibition.