Drug discovery for heart failure: a new era or the end of the pipeline?

Heart failure is a progressive disorder initiated by myocardial injury (typically myocardial infarction), which is subsequently perpetuated by the deleterious effects of a wide range of secondary myocardial, neurohormonal and vascular changes.Heart failure affects 6–10% of those aged over 65 years, and on average is associated with a 4-year survival rate of 50%.An extensive body of evidence based on clinical research demonstrated that β-adrenoceptor blockade and renin–angiotensin system inhibition improved survival, and slowed progression of heart failure.Despite extensive cellular, molecular biological and biochemical studies in heart failure there have recently been a number of disappointing clinical trial failures in the attempt to find new targets for therapy in heart failure.As a consequence of these failures, the rate of development of new compounds for heart failure treatment seems to have significantly slowed. Instead, a greater emphasis has been put on the development of devices, including pacemakers and implantable defibrillators.In this review, we provide an insight into current and emerging targets for drug development. We also highlight the emerging role of pharmacogenomics in optimizing the utilization of current drug therapy.As heart failure is typically a disease of older individuals, other disease processes, such as diabetes, anaemia and renal failure, might co-exist. Tailoring of current and new therapies to address these issues could also be of importance.