However, it is different from the VAL-HEFT and CHARM studies, which also examined the combination of an ACE inhibitor with an ARB {2,3}. The latter two trials showed an added benefit from the combination therapy, but they examined different patient populations (congestive heart failure) and their design did not stress an increase in the dose of ACE inhibitor to a maximum, which could account for the differences in their results. Questions also remain about the benefits of ACE inhibitor-ARB combination therapy in patients with established chronic kidney disease, given the benefits described in earlier (albeit much smaller) clinical trials and about the role of novel renin-inhibitor aliskiren. References: {1} Anderson et al., Am Heart J 2008, 155:706-711 [PMID:18371480]; {2} Krum et al., Eur J Heart Fail 2004, 6:937-945 [PMID:15556056]; {3} Pfeffer et al., Lancet 2003, 362:759-766 [PMID:13678868]. Trial registration: NCT00153101.

This study concludes that the angiotensin-receptor blocker (ARB) telmisartan was equivalent to the ACE inhibitor ramipril in preventing cardiovascular events in high-risk patients with vascular disease or diabetes mellitus. The combination of telmisartan and ramipril offered no advantage over maximally dosed ramipril and was associated with higher risk of adverse events. The authors examined the non-inferiority of therapy with telmisartan compared to maximally dosed ramipril and to combination therapy of telmisartan plus ramipril in high-risk patients with established cardiovascular disease or diabetes mellitus with end-organ damage (but normal serum creatinine). The Ongoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial (ONTARGET) study was a randomized, controlled, double-blind trial. There was no difference in the three groups in incidence of primary outcome. Patients in the telmisartan group had a lower incidence of cough and angioedema, but a higher incidence of hypotension compared to patients on ramipril. The incidence of syncope was identical in these two groups. Patients in the combination arm had a higher incidence of hypotension, syncope and renal dysfunction compared to patients in the ramipril arm. Another interesting finding was the fact that ACE inhibitor-ARB combination therapy did not result in better outcomes compared to ramipril therapy alone, in spite of better blood pressure (BP) control seen in patients treated with the combination regimen (2.4/1.4mmHg lower BP in the combination arm). One potential explanation for this is the higher incidence of adverse effects such as hypotension and renal complications seen with combination therapy, which might have offset the benefits of better blood pressure reduction. The conclusion here, regarding combination therapy with ACE inhibitors plus ARBs, is similar to the VALIANT trial which examined the combination of full dose captopril plus valsartan {1}.