Background

In Europe, 5% of hospital admissions in adults are due to Heart Failure – a larger proportion caused by myocardial infarction. Overall, Heart Failure consumes ~2% of the total health care resources. Despite significant progress in the treatment of HF with systolic dysfunction, event rate, mainly driven by CV death and hospitalisation is still unacceptably high. Actually, it is even more concerning that there is no established evidence based therapy in HF with preserved ejection fraction. Ageing of the EU population will make incidence and prevalence of HF rise inexorably, unless effective preventive therapy is applied.

 Research has provided proof-of-principle that the development of HF can be delayed or prevented and that HF can be treated once it appears. The disease is mutable in contrast to many other diseases in older people where treatments have not been able to prolong healthy or indeed total life span. The aim is now to improve on existing treatment.

So far antihypertensive therapy has had some success in preventing HF, as well as aggressive management of acute myocardial infarction. Current therapy is oriented to act on the "external aggressors". Therapy is applied indiscriminately in all patients at risk and/or with overt HF. And no therapy targeting pathophysiological mechanisms in HF such as fibrosis, inflammation or myocyte growth, is available for clinical use. The FIBROTARGETS Consortium believes that there is room for a new paradigm where therapy may be better targeted toward more specific mechanistic phenotypes. Indeed, new strategies are emerging focused on acting on the "intrinsic responses".

At last, beyond the impact on MIF, nearly 45% of all deaths in the developed world can be attributed to some type of chronic fibroproliferative disease. Therefore, the demand for anti-fibrotic drugs that are both safe and effective is of added-value and will likely continue to increase in the coming years.

FIBROTARGETS is based on the hypothesis that the intervention on novel fibrosis-related targets involved in the processes of fibroblast differentiation to myofibroblasts, on the collagen synthesis over degradation balance and/or on collagen maturation may allow for interstitial repair, thus providing a new strategy for the prevention and treatment of MIF, a key mechanism of cardiac remodelling involved in both the transition to HF and in the progression of HF.
The global output of our research would be to prevent new onset Heart Failure with therapies directed at targets that are involved in the transition to Heart Failure, such as MIF. Delaying the onset or preventing the progression of Heart Failure will increase quality- (QALY) and or disability- (DALY) adjusted life-years for millions of older Europeans.