dual therapy did not reduce cardiovascular or renal outcomes compared with either angiotensin-converting enzyme inhibitors or angiotensin receptor blockers alone. Previous controlled trials with angiotensin-converting enzyme inhibitors or angiotensin receptor blockers have demonstrated greater cardiovascular and renal benefit in people with renal risk. We hypothesized that dual therapy would be more effective than monotherapy in patients with low glomerular filtration rate and elevated albuminuria. Methods and Results-Post hoc analysis was performed of renal subgroups of dual therapy versus monotherapy for the ONTARGET study and angiotensin receptor blocker versus placebo for the Telmisartan Randomized Assessment Study in ACE Intolerant Subjects With Cardiovascular Disease (TRANSCEND). The studies featured hazard ratios by subgroups and Cox regression models with factors for treatment, subgroup, and interactions. The main cardiovascular outcome was the composite of cardiovascular death, myocardial infarction, stroke, or hospitalization for heart failure, and the main renal outcome was the composite of chronic dialysis or doubling of creatinine. In ONTARGET, there was no cardiovascular or renal benefit from dual over monotherapy in any subgroup, even with low glomerular filtration rate and/or elevated albuminuria. In TRANSCEND, in the comparison of angiotensin receptor blocker with placebo, there was a significant interaction for the main renal outcome (Pϭ0.01) in the direction of harm for patients with normoalbuminuria (0.37 versus 0.16 events per 100 patient-years; hazard ratio, 2.35; confidence interval, 1.33 to 4.15) but a trend to benefit with microalbuminuria (0.52 versus 0.89 events per 100 patient-years; hazard ratio, 0.60; confidence interval, 0.25 to 1.46) and macroalbuminuria (1.57 versus 2.60 events per 100 patient-years; hazard ratio, 0.71; confidence interval, 0.21 to 2.44). Key Words: albuminuria Ⅲ cardiovascular outcomes Ⅲ dialysis Ⅲ mortality Ⅲ renal insufficiency C hronic kidney disease is associated with accelerated cardiovascular disease. 1 For example, in post-myocardial infarction patients with estimated glomerular filtration rate (eGFR) Ͻ60 but Ͼ45 mL/min per 1.73 m 2 , total mortality was 25% higher 2 than with an eGFR Ͼ60 mL/min per 1.73 m 2 , and after an acute coronary artery syndrome, a fall in GFR also was associated with worse cardiovascular outcomes. 3 Blockade of the renin-angiotensin-aldosterone system (RAAS) is associated with less renal progression 4 and therefore potentially with better cardiovascular outcomes. Indeed, RAAS blockade with an angiotensin-converting enzyme (ACE) inhibitor or an angiotensin receptor blocker (ARB) in patients with cardiovascular risk and a low eGFR significantly lowered the risk for cardiovascular mortality. 5,6 More intense inhibition of the RAAS with an ACE inhibitor and an ARB ("dual therapy") reduced albuminuria to a greater extent than either drug alone, but major cardiovascular or renal end points were not examined. 7
Conclusions-This
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