Table 2.
Problem and questions
| Problem | |
|---|---|
| Heart rate is a causative cofactor of several vital physiological phenomena: average cardiac output, arterial beat, average myocardial energy consumption. Some diseases or clinical events are mechanistically dependent of these phenomena. Thus, one can question whether modulation of heart rate can alter the course of these diseases. | |
| Leading hypothesis | |
| Funny channel (If) is highly expressed in the sino-atrial node, the atrio-ventricular node, and the Purkinje fibers of conduction tissue. Through its action on the ionic exchanges during the cardiac beat, it controls the rate of spontaneous activity of sinoatrial myocytes, hence the cardiac rate. Ivabradine is a drug that inhibits If activity. Thus it reduces heart rate with, as far as it was known at the time, little or no other activity. | |
| Questions | |
| Q1 | Can ivabradine, a heart rate moderator, prevent effort angina pectoris attack? |
| Q2 | If yes, is once a day better than b.i.d.? |
| Q3 | If yes, what is the dose-effect relation? |
| Q4 | What is the expected number of prevented attacks per day? |
| Q5 | Can heart rate reduction (with, e.g., ivabradine) prevent atherosclerotic plaque rupture? |
| Q6 | What would be the number of prevented plaque ruptures? |
| Q7 | What are the factors influencing the number of prevented plaque ruptures? |
| Q8 | How these factors modify the number of prevented plaque ruptures? |