Dual therapy with telmisartan and ramipril did not improve cardiovascular or renal outcomes over monotherapy in high-vascular risk patients with low glomerular filtration rate or albuminuria.
RCT
Yes
Does dual therapy with telmisartan and ramipril improve cardiovascular and renal outcomes compared to monotherapy in high-vascular risk patients with low glomerular filtration rate or albuminuria?
Dual therapy with an ACE inhibitor and ARB does not provide cardiovascular or renal benefits over monotherapy in high-vascular risk patients, even those with low eGFR or albuminuria.
Effect estimate: HR 2.35 (95% CI 1.33-4.15)
Absolute Event Rate: 0.37% vs 0.16%
p-value: p=0.01
BACKGROUND: In the Ongoing Telmisartan Alone and in Combination With Ramipril Global End Point Trial (ONTARGET), 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 (P = 0.01) 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). CONCLUSIONS: This post hoc analysis does not support dual therapy over monotherapy in high-vascular risk patients with low glomerular filtration rate or albuminuria. This observation is a post hoc comparison and should be interpreted appropriately. CLINICAL TRIAL REGISTRATION: URL: http://clinicaltrials.gov Identifier: NCT00153101.
Tobe et al. (Tue,) conducted a rct in High vascular risk with low glomerular filtration rate or elevated albuminuria. Telmisartan, ramipril, or both vs. Monotherapy or placebo was evaluated on Composite of chronic dialysis or doubling of creatinine in patients with normoalbuminuria (HR 2.35, 95% CI 1.33-4.15, p=0.01). Dual therapy with telmisartan and ramipril did not improve cardiovascular or renal outcomes over monotherapy in high-vascular risk patients with low glomerular filtration rate or albuminuria.