In the long struggle against heart disease — still the world's leading cause of death — medicine suffered a quiet but significant defeat this week. Novartis's experimental drug pelacarsen, which had drawn genuine hope from cardiologists for its novel mechanism of action, failed to meet its primary endpoints in a large, rigorous clinical trial. The result is a reminder that the distance between a promising idea and a proven therapy is rarely as short as early science suggests, and that progress in medicine is measured not only in breakthroughs but in the honest reckoning with what does not work