Preclinical and Clinical Effects of RAS Inhibition with a Focus on Telmisartan

Blockade of the renin-angiotensin system with angiotensin II receptor blockers (ARBs) provides blood pressure (BP)-independent effects throughout the cardiovascular (CV) continuum. In the landmark ongoing telmisartan alone and in combination with ramipril global endpoint trial (ONTARGET), telmisartan reduced CV events in patients at high CV risk, similar to the angiotensin-converting enzyme inhibitor, ramipril. This reduction in CV events is a consequence of non-BP effects on disease pathophysiology which have been demonstrated in preclinical and clinical studies. For example, telmisartan significantly reduces markers of inflammation, such as interleukin-6 and C-reactive protein, and improves markers of vascular function, such as pulse wave velocity. Both these are associated with target organ damage. Telmisartan also has numerous potentially beneficial metabolic effects in preclinical studies. Telmisartan reduces markers of renal disease and its progression, left ventricular hypertrophy, and the risk of primary or secondary atrial fibrillation. Many of these effects are shared with other RAS inhibitors. However, several studies indicate differential effects between telmisartan and other ARBs. These differences probably reflect telmisartan’s distinct pharmacologic profile, including the longest plasma half-life, high receptor-binding affinity, and highest lipophilicity of the class. These differences suggest that the results of ONTARGET do not necessarily extrapolate to other ARBs.