Recent Clinical Trials of Pharmacologic Cardiovascular Interventions in Patients with Chronic Kidney Disease: An Update

As a consequence of both traditional and non-traditional risk factors, cardiovascular disease is over-represented, and the leading cause of mortality, among patients with Chronic Kidney Disease (CKD). Whilst recommendations for reducing cardiovascular risk in the general population exist, their applicability to the CKD population is questionable due to the exclusion of CKD patients from the majority of contemporary cardiovascular interventional studies. The aim of this review is to critically evaluate the literature regarding pharmacologic cardiovascular interventions in patients with CKD, with an emphasis on studies published since our 2008 review. Interventions discussed include erythropoiesis-stimulating agents (TREAT, U.S. Normal Hematocrit, CHOIR, CREATE, Palmer meta-analysis); statins (SHARP, AURORA, PPP, 4D, ALERT); Fibrates (VA-HIT); Folic Acid (ASFAST, US FOLIC acid trial, HOST); Antihypertensive Agents, Including Angiotensin-Converting Enzyme Inhibitors, angiotensin-receptor blockers, Beta-blockers and Combination therapy (Cice et al, FOSDIAL, Agarwal et al, ONTARGET); sevelamer (DCOR); Cinacalcet (ADVANCE, EVOLVE, Cunningham meta-analysis); Anti-oxidants (SPACE, HOPE, ATIC); Aspirin (HOT study re-analysis); vitamin D analogues (PRIMO); and multidisciplinary intervention (LANDMARK). Unfortunately, there remains a paucity of evidence in this area and a large number of methodologically poor quality studies with negative results. It is possible that these interventions do not have the same positive effect in CKD patients due to differences in the pathogenesis driving cardiovascular disease burden, such as altered bone metabolism and calcific vascular disease. Further well-designed studies with appropriately selected study populations and patient level outcomes are required. Until such time, physicians must consider on an individual patient basis the appropriateness of these interventions.