Hypertension and hyperlipidaemia are major risk factors for the development of
atherosclerosis.
Calcium channel blockers (CCBs) have been used for decades and have established
antihypertensive effects.
Statins have been extensively used because of their potent
lipid lowering properties. Amongst other factors,
inflammation and oxidation are involved in enhanced progression of
atherosclerosis and new lesion development. Therefore, research has been initiated focusing on the
antioxidant and anti-inflammatory properties of CCBs and
statins, beyond their primary effect, in order to evaluate the possible additive effects of combined treatment of CCBs with
statins as antiatherosclerotic
therapy. Clinical studies (e.g., the International
Nifedipine Trial on Antiatherosclerotic
Therapy [INTACT]) have demonstrated that the antiatherosclerotic action of CCBs is limited to the attenuation of the first stage of atherosclerogenesis (fatty streak formation or new lesion growth). The lesions that pre-existed at the start of CCB
therapy did not demonstrate progression or regression on angiography. However, because the mechanisms of action of
lipid-lowering drugs and CCBs, and their role in preventing the progression of
atherosclerosis differ, it is conceivable to conclude that these two classes may have an additive or synergic effect, not only on new lesion formation but also on inhibiting the progression of established
coronary atherosclerosis. Indeed, this combined effect of
lipid-lowering
therapy and CCBs on human
coronary atherosclerosis has been reported in the Regression Growth Evaluation
Statin Study (REGRESS) trial. This beneficial effect of combining CCBs with
statins has now been replicated in transgenic atherosclerotic mice, where the combination of
amlodipine and
atorvastatin produced an additional 60% reduction of
atherosclerosis compared with that observed with the
statin alone.
Serum markers of
atherosclerosis and vascular integrity also improved most in the combination group. Synergistic effects of the combination of
atorvastatin and
amlodipine on acute
nitric oxide release/endothelial function, and additive effects of the combination of
amlodipine and
atorvastatin in the improvement of arterial compliance in hypertensive hyperlipidaemic patients has been demonstrated. Collectively, these studies support the clinical antiatherosclerotic advantages of combination of CCBs and
statins and in particular, of
atorvastatin with
amlodipine beyond their established antihyperlipidaemic and
antihypertensive modes of action.