Combination therapy in the extended cardiovascular continuum: a focus on perindopril and amlodipine.

The progression of cardiovascular disease could be regarded as following atherosclerosis-related and age-related pathways. The starting points for these pathways are different--risk factors or aortic ageing--but they conclude in the same way: end-stage heart disease. Together these interlinked pathways form the extended cardiovascular continuum. Renin-angiotensin-aldosterone system (RAAS) inhibitors have been shown to interrupt or slow the progression of cardiovascular disease along one pathway, the cardiovascular atherosclerotic continuum. Cardiovascular protection with RAAS inhibitors varies; different RAAS inhibitors offer different levels of protection. Similarly, calcium channel blockers (CCBs) also have clearly shown protective effect of cardiovascular system, especially as it regards cerebrovascular disease risk. The AngloScandinavian Cardiac Outcomes Trial (ASCOT) showed that a combination of the angiotensin-converting enzyme (ACE) inhibitor perindopril and CCB amlodipine offered better cardiovascular protection in at-risk hypertensive patients than beta-blocker and thiazide. By attenuating the deleterious effects of cardiovascular disease at multiple stages of the extended cardiovascular continuum on top of lowering blood pressure (BP), perindopril and amlodipine could interrupt and slow the progression of cardiovascular disease. These antihypertensive agents have complementary vascular effects that enhance cardiovascular protection and reduce side-effects. Evidence from ASCOT shows that antihypertensive and vascular effects of amlodipine with and without perindopril have translated into real-life clinical benefits. A strategy using ACE inhibitors and CCBs, such as perindopril and amlodipine, to target multiple stages in both pathways of cardiovascular disease could effectively reduce cardiovascular risk and lower BP.