BACKGROUND: Heart Failure continues to be a leading cause of mortality and morbidity worldwide. The dismal prognosis of patients in acute heart failure (AHF) can be altered only by exploring novel drug molecules. Although the treatment for chronic heart failure (CHF) has seen remarkable progress, there is still a need to develop molecules that could improve the long-term survival outcomes. PURPOSE: To review the drug targets for acute and chronic heart failure and the molecules acting on these targets. METHODS: The article discusses on the mechanism of how the potential drug targets can be modulated to alter the pathophysiological processes in heart failure. Current evidence on molecules acting on these targets has also been described from published literature using the PubMed and Clinical Trials.gov databases. RESULTS: Some of the molecules that are currently being explored for AHF includeomecamtiv mecarbil which activates cardiac myosin ATPase, istaroxime an ionotropicagent that activates SERCA2a pump activity, ularitide and carperitide which are ANP(atrial natriuretic peptide) analogues and recombinant relaxin. Some of the targets forCHF include stabilization of ryanodine receptors, renin inhibition, neprilysin inhibition, neuregulins and SERCA2a gene therapy. CONCLUSION: Clinical trials in heart failure must be designed to minimize the risk of "drug failures." Nevertheless, it is hoped that in the days to come, drugs with superior efficacy and safety will eventually be produced from the surge of molecules that are in the pipeline.
BACKGROUND:Heart Failure continues to be a leading cause of mortality and morbidity worldwide. The dismal prognosis of patients in acute heart failure (AHF) can be altered only by exploring novel drug molecules. Although the treatment for chronic heart failure (CHF) has seen remarkable progress, there is still a need to develop molecules that could improve the long-term survival outcomes. PURPOSE: To review the drug targets for acute and chronic heart failure and the molecules acting on these targets. METHODS: The article discusses on the mechanism of how the potential drug targets can be modulated to alter the pathophysiological processes in heart failure. Current evidence on molecules acting on these targets has also been described from published literature using the PubMed and Clinical Trials.gov databases. RESULTS: Some of the molecules that are currently being explored for AHF includeomecamtiv mecarbil which activates cardiac myosin ATPase, istaroxime an ionotropicagent that activates SERCA2a pump activity, ularitide and carperitide which are ANP(atrial natriuretic peptide) analogues and recombinant relaxin. Some of the targets forCHF include stabilization of ryanodine receptors, renin inhibition, neprilysin inhibition, neuregulins and SERCA2a gene therapy. CONCLUSION: Clinical trials in heart failure must be designed to minimize the risk of "drug failures." Nevertheless, it is hoped that in the days to come, drugs with superior efficacy and safety will eventually be produced from the surge of molecules that are in the pipeline.
Authors: Jasper W L Hartog; Suzan Willemsen; Dirk J van Veldhuisen; Jan L Posma; Leen M van Wijk; Yoran M Hummel; Hans L Hillege; Adriaan A Voors Journal: Eur J Heart Fail Date: 2011-06-13 Impact factor: 15.534
Authors: John R Teerlink; Cyril P Clarke; Khalil G Saikali; Jacqueline H Lee; Michael M Chen; Rafael D Escandon; Lyndsey Elliott; Rachel Bee; Mohammad Reza Habibzadeh; Jonathan H Goldman; Nelson B Schiller; Fady I Malik; Andrew A Wolff Journal: Lancet Date: 2011-08-20 Impact factor: 79.321
Authors: Markku S Nieminen; Dirk Brutsaert; Kenneth Dickstein; Helmut Drexler; Ferenc Follath; Veli-Pekka Harjola; Matthias Hochadel; Michel Komajda; Johan Lassus; Jose Luis Lopez-Sendon; Piotr Ponikowski; Luigi Tavazzi Journal: Eur Heart J Date: 2006-09-25 Impact factor: 29.983
Authors: Krisztina Zsebo; Alex Yaroshinsky; Jeffrey J Rudy; Kim Wagner; Barry Greenberg; Mariell Jessup; Roger J Hajjar Journal: Circ Res Date: 2013-09-24 Impact factor: 17.367
Authors: John J V McMurray; Milton Packer; Akshay S Desai; Jim Gong; Martin P Lefkowitz; Adel R Rizkala; Jean Rouleau; Victor C Shi; Scott D Solomon; Karl Swedberg; Michael R Zile Journal: Eur J Heart Fail Date: 2013-04-05 Impact factor: 15.534