Recent clinical trials of pharmacologic cardiovascular interventions in patients with chronic kidney disease

Abstract

End stage kidney disease (ESKD) is associated with a 10- to 20-fold increased risk of cardiovascular mortality compared with age- and sex-matched controls without CKD. In spite of this marked increase in risk, the vast majority of cardiovascular intervention clinical trials to date have specifically excluded subjects with CKD. The aim of this paper is to critically review the recently published clinical trial evidence that cardiac outcomes in CKD patients are modified by cardiovascular risk factor interventions, including erythropoiesis stimulating agent therapy (US Normal Hematocrit, CHOIR and CREATE trials), statins (PPP, 4D and ALERT), fibrates (VA-HIT), folic acid (ASFAST, US folic acid trial, HOST), anti-oxidative stress therapy (SPACE, HOPE and ATIC), N-acetylcysteine, sevelamer (D-COR), cinacalcet (Cunningham meta-analysis), carvedilol, angiotensin converting enzyme inhibitor (FOSIDIAL), telmisartan, aspirin (HOT study re-analysis) and multidisciplinary multiple cardiovascular risk factor intervention clinics (LANDMARK). Although none of these studies could be considered conclusive, the negative trials to date should raise significant concerns about the heavy reliance of current clinical practice guidelines on extrapolation of findings from cardiovascular intervention trials in the general population. It may be that cardiovascular disease in dialysis populations is less amenable to intervention, either because of the advanced stage of CKD or because the pathogenesis of cardiovascular disease in CKD patients is different to that in the general population. Further large, well-conducted, multi-centre randomised controlled trials in this area are urgently required.