Reconsidering the Treatment of Patients with Coronary Artery Disease

Abstract

Treatment of hypertensive patients with coronary artery disease is still a debated issue. In particular, relatively few controlled clinical trials have prospectively assessed the impact of specific drug classes on adverse outcomes in patients with coronary artery disease and, moreover, it is not clear if a more aggressive therapeutic approach aimed to reduce blood pressure values well below 140/90mm Hg might achieve an adjunctive beneficial effect.

There is a general consensus that hypertensive patients with coronary artery disease should receive treatment with an ACE inhibitor. This consensus is based on the results of the HOPE (Heart Outcomes Prevention Evaluation) and EUROPA (EUropean trial on Reduction Of cardiac events with Perindopril in stable coronary Artery disease) studies (testing ramipril and perindopril, respectively) and does not take into account that these trials compared an active treatment with placebo, which basically produced a further decrease in blood pressure values, thereby making it difficult to establish whether the beneficial outcome was related to a specific effect of drugs or to the blood pressure reduction. These positive results were not confirmed by the PEACE (Prevention of Events with Angiotensin Converting Enzyme inhibition) study, which demonstrated that adding trandolapril to the treatment of patients with stable coronary artery disease did not produce a further beneficial effect compared with placebo, therefore demonstrating that the addition of an ACE inhibitor in patients with coronary artery disease does not universally produce a beneficial effect.

More recently, two clinical trials have clearly demonstrated that dihydropyridine calcium channel blockers can determine a beneficial outcome in high-risk patients with coronary artery disease. The ACTION (A Coronary disease Trial Investigating Outcome with Nifedipine GITS) trial demonstrated that long-acting nifedipine was effective in reducing cardiovascular events in patients with stable symptomatic angina and in patients with high blood pressure values, whereas in normotensive patients there was no difference from placebo. The CAMELOT (Comparison of Amlodipine vs Enalapril to Limit Occurrence of Thrombosis) trial demonstrated that amlodipine produced a statistical 31% reduction in cardiovascular events, while enalapril, despite a blood pressure reduction similar to that achieved with the calcium channel blocker, produced a 15.3% reduction in cardiovascular events, which was not statistically significant. It is worth noting that the effect of amlodipine was still evident in patients with blood pressure values within the normal range.

At least part of the beneficial effect of calcium channel blockers on coronary events can be related to the well documented effect of this class of drugs in preventing atherosclerosis. It is well documented that calcium channel blockers can improve endothelial function by an antioxidant effect and several clinical trials have demonstrated that these drugs can inhibit the progression of atherosclerotic plaque. In CAMELOT, this beneficial effect was confirmed in a sub-study indicating that amlodipine, but not enalapril or placebo, was able to completely block the progression of coronary atherosclerosis, as assessed by intravascular ultrasound.

In conclusion, the CAMELOT study supports the possibility that blood pressure reduction to values much lower than those indicated by current guidelines might achieve a further beneficial effect in patients with coronary artery disease.