Circadian variation of ischaemic events in patients with chronic stable angina: pathophysiological and therapeutical considerations.

A large body of evidence has conclusively shown that the majority of ischaemic events that occur in patients with chronic stable angina (CSA) and severe coronary artery disease are not precipitated by a sudden increase in MVO2 exceeding the possibility of increase in coronary blood flow. Although the observation suggests that these events are caused by transient impairment of regional myocardial perfusion, common practice as well as controlled clinical trials indicate that betablockers are extremely effective in this condition. This apparent contradiction is partly explained by the observation that, in these patients, episodes of ischaemia predominate in the day time (from 7 am to 11 pm), when heart rate and blood pressure are tonically increased, due to the presence of high sympathetic tone. This suggests that transient ischaemic events probably occur when phasic reductions in coronary blood flow are superimposed on high resting levels of myocardial metabolic demand. By lowering heart rate, blood pressure and contractility, betablockers reduce cardiac requirements and decrease the likelihood for transient reductions in regional myocardial perfusion to reach the critical ischaemic threshold. We studied 20 patients with CSA, severe coronary disease and frequent daily episodes of myocardial ischaemia. They all received three different treatment schedules with atenolol 100 mg (od), diltiazem 120 mg (tds) and atenolol 100 mg (od) + nifedipine 20 mg SR (tds) and underwent serial recordings of the ambulatory ECG. Although both monotherapies significantly reduced the frequency and duration of cardiac ischaemic events atenolol was significantly more effective than diltiazem. Predictably, the betablocker calcium antagonist combination afforded the best therapeutic response.