Combinations of inhibitors of the renin-angiotensin system with calcium channel blockers for the treatment of hypertension: focus on perindopril/amlodipine.

BACKGROUND: Combination antihypertensive therapy with an inhibitor of the renin-angiotensin system (RAS) and a calcium channel blocker (CCB) is a rational approach to achieve blood pressure (BP) goals in patients with hypertension, and may provide additional cardiovascular protection compared to other strategies in special populations. This article reviews the rationale for, and evidence supporting, the use of newer fixed-dose combinations of RAS inhibitors and CCBs, with particular emphasis on perindopril/amlodipine. METHODS: A literature search was performed in Medline and EMBASE databases to identify articles published up to May 2010 describing the impact of combination treatment with angiotensin receptor blocker (ARB)/CCB or angiotensin-converting enzyme (ACE) inhibitor/CCB based antihypertensive strategies on BP or clinical outcomes. FINDINGS: A substantial body of evidence supports the BP-lowering efficacy of RAS inhibitor/CCB combination therapy in patients with hypertension. RAS inhibitors and CCBs represent two different and complementary mechanisms of actions; their use in combination is associated with effective BP lowering with favourable tolerability and fewer adverse metabolic effects than some other combination therapies. Currently, intervention studies demonstrating the impact of ARB/CCB combinations on cardiovascular mortality and morbidity are lacking. However, evidence from large outcome trials supports the use of ACE inhibitor/CCB combinations for reducing the risk of cardiovascular and renal events, particularly in high-risk patients. There is also evidence that the benefits of ACE inhibitor/CCB combinations may extend beyond those solely associated with brachial BP lowering, by an additional impact on central BP haemodynamics. CONCLUSIONS: RAS inhibitor/CCB combination therapy is an effective antihypertensive therapy. Strong evidence supports the antihypertensive efficacy of ACE inhibitor/CCB combinations with cardioprotective and renoprotective properties. In particular, evidence suggests that fixed-dose perindopril/amlodipine effectively decreases BP and currently is the only RAS inhibitor/CCB combination proven to decrease all-cause and cardiovascular mortality as well as major cardiovascular events, and thus is a valuable option for the management of hypertension, especially in high-risk patients.