Most hypertensive patients have multiple risk factors that put them at high risk of developing cardiovascular disease (CVD). These patients can be identified in routine clinical practice as having several of the following risk factors: older age, male sex, smoking, obesity, hypertension, diabetes, dyslipidemia, known vascular disease (myocardial infarction, revascularisation, stroke, transient ischaemic attack, peripheral vascular disease), left ventricular hypertrophy, heart failure and/or adverse family history. Defining the treatment algorithm for high risk patients is an area of continuing clinical research.

Large-scale clinical studies in high risk patients have shown that using angiotensin-converting enzyme (ACE) inhibitors to target the renin-angiotensin system (RAS) results in a considerable cardiovascular risk reduction. However there is uncertainty about the role of angiotensin-II receptor blockers (ARBs), which also target the RAS, when used alone or in combination with these ACE inhibitors.

The ONTARGET^® trial aims to explore new therapeutic options for preventing CV events in high risk patients by investigating double blockade of the RAS.

It was designed to investigate the efficacy of the ARB telmisartan as monotherapy and in combination with the ACE inhibitor ramipril at reducing CV mortality and morbidity in high risk patients. The rationale behind the double blockade is that telmisartan's strong and selective AT1 blockade should overcome the negative consequences of ACE escape encountered with ramipril monotherapy and ensure that any excess angiotensin II acts to stimulate the AT2 receptors, which appear to be associated with more beneficial effects in stroke patients. In addition, the use of ramipril will bring about increased plasma levels of bradykinin, which may result in further tissue protection as a result of vasodilatation.

Ramipril is being used in the ONTARGET^® trial as it has been the gold standard ACE inhibitor since the HOPE (Heart Outcomes Prevention Evaluation) study, while the unique pharmacologic profile of telmisartan makes it an ideal candidate for combination therapy with an ACE inhibitor. Telmisartan is highly specific for the AT1 receptor and stands out among ARBs for its long duration of action and half-life (~24 hours). The sustained blood pressure control of telmisartan during the last few hours before dosing means it remains effective during the crucial early morning hours when there is a frequency of cardiovascular events.