Cardiovascular Drugs and Therapy

, Volume 31, Issue 4, pp 445–458 | Cite as

Navigating the Future of Cardiovascular Drug Development—Leveraging Novel Approaches to Drive Innovation and Drug Discovery: Summary of Findings from the Novel Cardiovascular Therapeutics Conference

  • Thomas J. Povsic
  • Rob Scott
  • Kenneth W. Mahaffey
  • Robert Blaustein
  • Jay M. Edelberg
  • Martin P. Lefkowitz
  • Scott D. Solomon
  • Jonathan C. Fox
  • Kevin E. Healy
  • Aarif Y. Khakoo
  • Douglas W. Losordo
  • Fady I. Malik
  • Brett P. Monia
  • Rusty L. Montgomery
  • Jeffrey Riesmeyer
  • Gregory G. Schwartz
  • Steven L. Zelenkofske
  • Joseph C. Wu
  • Scott M. Wasserman
  • Matthew T. Roe



The need for novel approaches to cardiovascular drug development served as the impetus to convene an open meeting of experts from the pharmaceutical industry and academia to assess the challenges and develop solutions for drug discovery in cardiovascular disease.


The Novel Cardiovascular Therapeutics Summit first reviewed recent examples of ongoing or recently completed programs translating basic science observations to targeted drug development, highlighting successes (protein convertase sutilisin/kexin type 9 [PCSK9] and neprilysin inhibition) and targets still under evaluation (cholesteryl ester transfer protein [CETP] inhibition), with the hope of gleaning key lessons to successful drug development in the current era. Participants then reviewed the use of innovative approaches being explored to facilitate rapid and more cost-efficient evaluations of drug candidates in a short timeframe.


We summarize observations gleaned from this summit and offer insight into future cardiovascular drug development.


The rapid development in genetic and high-throughput drug evaluation technologies, coupled with new approaches to rapidly evaluate potential cardiovascular therapies with in vitro techniques, offer opportunities to identify new drug targets for cardiovascular disease, study new therapies with better efficiency and higher throughput in the preclinical setting, and more rapidly bring the most promising therapies to human testing. However, there must be a critical interface between industry and academia to guide the future of cardiovascular drug development. The shared interest among academic institutions and pharmaceutical companies in developing promising therapies to address unmet clinical needs for patients with cardiovascular disease underlies and guides innovation and discovery platforms that are significantly altering the landscape of cardiovascular drug development.


Cardiovascular drug development Innovation Drug discovery 


Compliance with Ethical Standards


No outside funding was provided for this work.

Conflict of Interest

Rob Scott was a former employee of Amgen Inc. and currently employee of AbbVie Pharmaceuticals. Robert Blaustein is an employee of Merck Research laboratories, Merck and Co. Jay Edelberg is an employee of Sanofi US. Martin P. Lefkowtiz is an employee of Novartis Pharmaceuticals. Jonathan C. fox was a former employee of Myokardia Inc. Aarif Y. Khakoo and Scott Wasserman are employees of Amgen Inc. Douglas W. Losordo is am employee of Caladrius Biosciences. Fady I. Malik is an employee of Cytokinetics Inc. Brett P. Monia is an employee Ionis Pharmaceuticals. Rusty Montgomery is an employee of mirage Therapeutics, Inc. Jeffery Riesmeyer is an employee of Eli Lilly, Inc. Steven L. Zelenkofske is an employee of AstraZeneca, Inc. Complete conflicts of interest statements for Drs. Roe and Povsic are available at Complete conflict of interest statements for Dr. Kenneth W. Mahaffey and Joseph C. Wu is available at Dr. Gregory G. Schwartz, through his institution, has received research support from Cerenis, The Medicines Company, Resverlogix, Roche, and Sanofi. Dr. Healy reports no conflicts of interest.

Ethical Approval

The manuscript does not describe new research involving human participants or animals and did not require separate ethical approval.

Informed Consent

The manuscript does not describe new research requiring informed consent.


  1. 1.
    Mozaffarian D, Benjamin EJ, Go AS, et al. Heart disease and stroke statistics—2015 update: a report from the American Heart Association. Circulation. 2015;131:e29–322.CrossRefPubMedGoogle Scholar
  2. 2.
    Braunwald E. The war against heart failure: the Lancet lecture. Lancet. 2015;385:812–24.CrossRefPubMedGoogle Scholar
  3. 3.
    Kaitin KI, DiMasi JA. Pharmaceutical innovation in the 21st century: new drug approvals in the first decade, 2000–2009. Clin Pharmacol Ther. 2011;89:183–8.CrossRefPubMedGoogle Scholar
  4. 4.
    Kaitin KI. Deconstructing the drug development process: the new face of innovation. Clin Pharmacol Ther. 2010;87:356–61.CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
  6. 6.
    Abifadel M, Varret M, Rabes J-P, et al. Mutations in PCSK9 cause autosomal dominant hypersholesterolemia. Nat Genet. 2003;34:154–6.CrossRefPubMedGoogle Scholar
  7. 7.
    Maxwell KN, Soccio RE, Duncan EM, Sehayek E, Breslow JL. Novel putative SREBP and LXR target genes identified by microarray analysis in liver of cholesterol-fed mice. J Lipid Res. 2003;44:2109–19.CrossRefPubMedGoogle Scholar
  8. 8.
    Benjannet S, Rhainds D, Essalmani R, et al. NARC-1/PCSK9 and its natural mutants: zymogen cleavage and effects on the low density lipoprotein (LDL) receptor and LDL cholesterol. J Biol Chem. 2004;279:48865–75.CrossRefPubMedGoogle Scholar
  9. 9.
    Rashid S, Curtis D, Garuti R, et al. Decreased plasma cholesterol and hypersentivity to statins in mice lacking PCSK9. Proc Natl Acad Sci U S A. 2005;102:5374–9.CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Cohen JC, Boerwinkle E, Mosley TH Jr, Hobbs HH. Sequence variations in PCSK9, low LDL, and protection against coronary heart disease. N Engl J Med. 2006;354:1264–72.CrossRefPubMedGoogle Scholar
  11. 11.
    Lambert G, Charlton F, Rye KA, Piper DE. Molecular basis of PCSK9 function. Atherosclerosis. 2009;203:1–7.CrossRefPubMedGoogle Scholar
  12. 12.
    Ference BA, Robinson JG, Brook RD, et al. Variation in PCSK9 and HMGCR and risk of cardiovascular disease and diabetes. N Engl J Med. 2016;375:2144–53.CrossRefPubMedGoogle Scholar
  13. 13.
    Myocardial Infarction Genetics Consortium Investigators. Inactivating mutations in NPC1L1 and protection from coronary heart disease. N Engl J Med. 2014;371:2072–82.CrossRefGoogle Scholar
  14. 14.
    TG and HDL Working Group of the Exome Sequencing Project. Loss-of-function mutations in APOC3, triglycerides, and coronary disease. N Engl J Med. 2014;371:22–31.CrossRefGoogle Scholar
  15. 15.
    Jørgensen AB, Frikke-Schmidt R, Nordestgaard BG, Tybjærg-Hansen A. Loss-of-function mutations in APOC3 and risk of ischemic valvular disease. N Engl J Med. 2014;371:32–41.CrossRefPubMedGoogle Scholar
  16. 16.
    Stitziel NO, Khera AV, Wang X, et al. ANGPTL3 deficiency and protection against coronary artery disase. J Am Coll Cardiol. 2017;69:2054–63.CrossRefPubMedGoogle Scholar
  17. 17.
    van Acker BA, Botma GJ, Zwinderman AH, et al. High HDL cholesterol does not protect against coronary artery disease when associated with combined cholesteryl ester transfer protein and hepatic lipase gene variants. Atherosclerosis. 2008;200:161–7.CrossRefPubMedGoogle Scholar
  18. 18.
    Boekholdt SM, Sacks FM, Jukema JW, et al. Cholesteryl ester transfer protein Taq1B variant, high-density lipoprotein cholesterol levels, cardiovascular risk, and efficiency of pravastatin treatment: individual patient meta-analysis of 13,677 subjects. Circulation. 2005;111:278–87.CrossRefPubMedGoogle Scholar
  19. 19.
    Voight BF, Peloso GM, Orho-Melander M, et al. Plasma HDL cholesterol and risk of myocardial infarction: a Mendelian randomisation study. Lancet. 2012;380:572–80.CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Giugliano RP, Sabatine MS. Are PCSK9 inhibitors the next breakthrough in the cardiovascular field? J Am Coll Cardiol. 2015;65:2638–51.CrossRefPubMedGoogle Scholar
  21. 21.
    Shan L, Pang L, SZhang R, Murgolo N, Lan H, Hedrick J. PCSK9 binds to multiple receptors and can be functionally inhibited by an EGF-A peptide. Biochem Biophys Res Commun. 2008;375:69–73.CrossRefPubMedGoogle Scholar
  22. 22.
    Ni YG, Condra JH, Orsatti L, et al. A proprotein convertase subtilisin-like/kexin type 9 (PCSK9) C-terminal domain antibody antigen-binding fragment inhibits PCSK9 internalization and restores low density lipoprotein uptake. J Biol Chem. 2010;285:12882–91.CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Graham MJ, Lemonidis KM, Whipple CP, et al. Antisense inhibition of proprotein convertase subtilisin/kexin type 9 reduces serum LDL in hyperlipidemic mice. J Lipid Res. 2007;48:763–7.CrossRefPubMedGoogle Scholar
  24. 24.
    Frank-Kamenetsky M, Grefhorst A, Anderson NN, et al. Therapeutic RNAi targeting PCSK9 acutely lowers plasma cholesterol in rodents and LDL cholesterol in nonhuman primates. Proc Natl Acad Sci U S A. 2008;105:11915–20.CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Catapano AL, Papadopoulos N. The safety of therapeutic monoclonal antibodies: implications for cardiovascular disease and targeting the PCSK9 pathway. Atherosclerosis. 2013;228:18–28.CrossRefPubMedGoogle Scholar
  26. 26.
    Schwartz GG, Bessac L, Berdan LG, et al. Effect of aliorcumab, a monoclonal antibody to PCSK9, on long-term cardiovascular outcomes following acute coronary syndromes: rationale and design of the ODYSSEY outcomes trial. Am Heart J. 2014;168:682–9.CrossRefPubMedGoogle Scholar
  27. 27.
    Sabatine MS, Giugliano RP, Keech AC, et al. Evolocumab and clinical outcomes in patients with cardiovascular disease. N Engl J Med. 2017;376:1713–22.CrossRefPubMedGoogle Scholar
  28. 28.
    Ridker PM, Amarenco P, Brunell R, et al. Evaluating bococizumab, a monoclonal antibody to PCSK9, on lipid levels and clinical events in broad patient groups with and without prior cardiovascular events: rationale and design of the studies of PCSK9 inhibition and the reduction of vascular events (SPIRE) lipid lowering and SPIRE cardiovascular outcomes trials. Am Heart J. 2016;178:135–44.CrossRefPubMedGoogle Scholar
  29. 29.
    Ridker PM, Revkin J, Amarenco P, et al. Cardiovascular efficacy and safety of bococizumab in high-risk patients. N Engl J Med. 2017.Google Scholar
  30. 30.
    Sabatine MS, Giugliano RP, Keech A, et al. Rationale and design of the further cardiovascular OUtcomes research with PCSK9 inhibition in subjects with elevated risk trial. Am Heart J. 2016;173:94–101.CrossRefPubMedGoogle Scholar
  31. 31.
    Ballantyne CM, Neutel J, Cropp A, et al. Results of dococizumab, a monoclonal antibody against proprotein convertase subtilisin/kexin type 9, from a randomized, placebo-controlled, dose-ranging study in statin-treated subjects with hypercholesterolemia. Am J Cardiol. 2015;115:1212–21.CrossRefPubMedGoogle Scholar
  32. 32.
    Pfizer Inc. Bococizumab SPIRE-2 cardiovascular outcome study fully enrolled. Accessed May 16, 2016.
  33. 33.
    Pfizer Inc. Pfizer discontinues global development of Bococizumab, its investigational PCSK9 inhibitor. detail/pfizer_discontinues_global_development_of_bococizumab_its_investigational_pcsk9_inhibitor. Accesses May 16, 2016.
  34. 34.
    Barter PJ, Kastelein JJP. Targeting cholesteryl ester transfer protein for the prevention and management of cardiovascular disease. J Am Coll Cardiol. 2006;47:492–9.CrossRefPubMedGoogle Scholar
  35. 35.
    Boden WE. High-density lipoprotein cholesterol as an independent risk factor in cardiovascular disease: assessing the data from framingham to the veterans affairs high-density lipoprotein intervention trial. Am J Cardiol. 2000;86:19–22.CrossRefGoogle Scholar
  36. 36.
    Parini P, Rudel LL. Is there a need for cholesteryl ester transfer protein inhibition? Arterioscler Thromb Vasc Biol. 2003;23:374–5.CrossRefPubMedGoogle Scholar
  37. 37.
    Barter PJ, Brewer HB Jr, Chapman MJ, Hennekens CH, Rader DJ, Tall AR. Cholesteryl ester transfer protein: a novel target for raising HDL and inhibiting atherosclerosis. Arterioscler Thromb Vasc Biol. 2003;23:160–7.CrossRefPubMedGoogle Scholar
  38. 38.
    Inazu A, Brown ML, Hesler CB, et al. Increased high-density lipoprotein levels caused by a common cholesteryl-ester transfer protein gene mutation. N Engl J Med. 1990;323:1234–8.CrossRefPubMedGoogle Scholar
  39. 39.
    Johannsen TH, Frikke-Schmidt R, Schou J, Nordestgaard BG, Tybjærg-Hansen A. Genetic inhibition of CETP, ischemic vascular disease and mortality, and possible adverse effects. J Am Coll Cardiol. 2012;60:2041–8.CrossRefPubMedGoogle Scholar
  40. 40.
    Ridker PM, Paré G, Parker AN, Zee RYL, Miletich JP, Chasman DI. Polymorphism in the CETP gene region, HDL cholesterol, and risk of future myocardial infarction: Genomewide analysis among 18 245 initially healthy women from the Women’s Genome Health Study. Circ Cardiovasc Genet. 2009;2:26–33.CrossRefPubMedPubMedCentralGoogle Scholar
  41. 41.
    Thompson A, Di Angelantonio E, Sarwar N, et al. Association of cholesteryl ester transfer protein genotypes with cetp mass and activity, lipid levels, and coronary risk. JAMA. 2008;299:2777–88.CrossRefPubMedGoogle Scholar
  42. 42.
    Rosenson RS, Koenig W. Mendelian randomization analyses for selection of therapeutic targets for cardiovascular disease prevention: a note of circumspection. Cardiovasc Drug Ther. 2016;30:65–74.CrossRefGoogle Scholar
  43. 43.
    Barter PJ, Caulfield M, Erikkson M, et al. Effects of torcetrapib in patients at high risk for coronary events. N Engl J Med. 2007;357:2109–22.CrossRefPubMedGoogle Scholar
  44. 44.
    Schwartz GG, Olsson AG, Abt M, et al. Effects of dalcetrapib in patients with a recent acute coronary syndrome. N Engl J Med. 2012;367:2089–99.CrossRefPubMedGoogle Scholar
  45. 45.
    Nicholls SJ, Brewer H, Kastelein JP, et al. Effects of the CETP inhibitor evacetrapib administered as monotherapy or in combination with statins on hdl and ldl cholesterol: a randomized controlled trial. JAMA. 2011;306:2099–109.CrossRefPubMedGoogle Scholar
  46. 46.
    Cannon CP, Shah S, Dansky HM, et al. Safety of anacetrapib in patients with or at high risk for coronary heart disease. N Engl J Med. 2010;363:2406–15.CrossRefPubMedGoogle Scholar
  47. 47.
    Hovingh GK, Kastelein JJP, van Deventer SJH, et al. Cholesterol ester transfer protein inhibition by TA-8995 in patients with mild dyslipidaemia (TULIP): a randomised, double-blind, placebo-controlled phase 2 trial. Lancet. 2015;386:452–60.CrossRefPubMedGoogle Scholar
  48. 48.
    Davidson MH, McKenney JM, Shear CL, Revkin JH. Efficacy and safety of torcetrapib, a novel cholesteryl ester transfer protein inhibitor, in individuals with below-average high-density lipoprotein cholesterol levels. J Am Coll Cardiol. 2006;48:1774–81.CrossRefPubMedGoogle Scholar
  49. 49.
    Nicholls SJ, Lincoff AM, Barter PJ, et al. Assessment of the clinical effects of cholesteryl ester transfer protein inhibition with evacetrapib in patients at high-risk for vascular outcomes: rationale and design of the ACCELERATE trial. Am Heart J. 2015;170:1061–9.CrossRefPubMedGoogle Scholar
  50. 50.
    Lincoff AM, Nicholls SJ, Riesmeyer JS, et al. Evacetrapib and cardiovascular outcomes in high-risk vascular disease. N Engl J Med. 2017;376:1933–42.CrossRefPubMedGoogle Scholar
  51. 51.
    Sacks FM, Pfeffer MA, Moye LA, et al. The effect of pravastatin on coronary events after myocardial infarction in patients with average cholesterol levels. N Engl J Med. 1996;335:1001–9.CrossRefPubMedGoogle Scholar
  52. 52.
    Nicholls SJ, Ruotolo G, Brewer HB, et al. Cholesterol efflux capacity and pre-beta-1 HDL concentrations are increased in dyslipidemic patients treated with evacetrapib. J Am Coll Cardiol. 2015;66:2201–10.CrossRefPubMedGoogle Scholar
  53. 53.
    Niesor EJ, Schwartz GG, Perez A, et al. Statin-induced decrease in ATP-binding cassette transporter A1 expression via microRNA33 induction may counteract cholesterol efflux to high-density lipoprotein. Cardiovasc Drug Ther. 2015;29:7–14.CrossRefGoogle Scholar
  54. 54.
    Pitts R, Gunzburger E, Ballantyne CM, et al. Treatment with dalcetrapib modifies the relationship between high-density lipoprotein cholesterol and c-reactive protein. J Am Coll Cardiol. 2016;68:2488–90.CrossRefPubMedGoogle Scholar
  55. 55.
    Oxford Uo. REVEAL: Randomized EValuation of the Effects of Anacetrapib Through Lipid-modification (REVEAL). Accessed September 28, 2016.
  56. 56.
    Gotto AM, Kher U, Chatterjee MS, et al. Lipids, safety parameters, and drug concentrations after an additional 2 years of treatment with anacetrapib in the DEFINE study. J Cardiovasc Pharmacol Ther. 2014;19:543–9.CrossRefPubMedGoogle Scholar
  57. 57.
    Ridker PM, Paynter NP, Danik JS, Glynn RJ. Interpretation of Mendelian randomization studies and the search for causal pathways in atherothrombosis: the need for caution. Metab Syndr Relat Disord. 2010;8:465–9.CrossRefPubMedGoogle Scholar
  58. 58.
    de Bold AJ, Borenstein HB, Veress AT, Sonnenberg H. A rapid and potent natriuretic response to intravenous injection of atrial myocardial extract in rats. Life Sci. 1981;28:89–94.CrossRefPubMedGoogle Scholar
  59. 59.
    Sonnenberg JL, Sakane Y, Jeng AY, et al. Identification of protease as the major atrial natriuretic factor degrading enzyme in the rat kidney. Peptides. 1988;9:173–80.CrossRefPubMedGoogle Scholar
  60. 60.
    von Lueder TG, Atar D, Krum H. Current role of neprilysin inhibitors in hypertension and heart failure. Pharmacol Ther. 2014;144:41–9.CrossRefGoogle Scholar
  61. 61.
    Rouleau JL, Pfeffer MA, Stewart DJ, et al. Comparison of vasopeptidase inhibitor, omapatrilat, and lisinopril on exercise tolerance and morbidity in patients with heart failure: IMPRESS randomised trial. Lancet. 2000;356:615–20.CrossRefPubMedGoogle Scholar
  62. 62.
    Packer M, Califf RM, Konstam M, et al. Comparison of omapatrilat and enalapril in patients with chronic heart failure: the Omapatrilat Versus Enalapril Randomized Trial of Utility in Reducing Events (OVERTURE). Circulation. 2002;106:920–6.CrossRefPubMedGoogle Scholar
  63. 63.
    Krum H, Tonkin A. Why do phase III trials of promising heart failure drugs often fail? The contribution of “regression to the truth”. J Card Fail. 2003;9:364–7.CrossRefPubMedGoogle Scholar
  64. 64.
    Massie BM. The dilemma of drug development for heart failure: when is the time to initiate large clinical trials? J Card Fail. 2003;9:347–9.CrossRefPubMedGoogle Scholar
  65. 65.
    Packer M. Current perspectives on the design of phase II trials of new drugs for the treatment of heart failure. Am Heart J. 2000;139:S202–6.CrossRefPubMedGoogle Scholar
  66. 66.
    Gu J, Noe A, Chandra P, et al. Pharmacokinetics and pharmacodynamics of LCZ696, a novel dual-acting angiotensin receptor-neprilysin inhibitor (ARNi). J Clin Pharmacol. 2010;50:401–14.CrossRefPubMedGoogle Scholar
  67. 67.
    McMurray JJ, Packer M, Desai AS, et al. Angiotensin-neprilysin inhibition versus enalapril in heart failure. N Engl J Med. 2014;371:993–1004.CrossRefPubMedGoogle Scholar
  68. 68.
    Nioi P, Sigurdsson A, Thorleifsson G, et al. Variant ASGR1 associated with a reduced risk of coronary artery disease. N Engl J Med. 2016;374:2131–41.CrossRefPubMedGoogle Scholar
  69. 69.
  70. 70.
    Green EM, Wakimoto H, Anderson RL, et al. A small-molecule inhibitor of sarcomere contractility suppresses hypertrophic cardiomyopathy in mice. Science. 2016;351:617–21.CrossRefPubMedPubMedCentralGoogle Scholar
  71. 71.
    van Rooij E, Purcell AL, Levin AA. Developing microRNA therapeutics. Circ Res. 2012;110:496–507.CrossRefPubMedGoogle Scholar
  72. 72.
    Montgomery RL, Hullinger TG, Semus HM, et al. Therapeutic inhibition of miR-208a improves cardiac function and survival during heart failure. Circulation. 2011;124:1537–47.CrossRefPubMedPubMedCentralGoogle Scholar
  73. 73.
    Jeevanantham V, Butler M, Saad A, Abdel-Latif A, Zuba-Surma EK, Dawn B. Adult bone marrow cell therapy improves survival and induces long-term improvement in cardiac parameters: a systematic review and meta-analysis. Circulation. 2012;126:551–68.CrossRefPubMedPubMedCentralGoogle Scholar
  74. 74.
    Zimmet H, Porapakkham P, Porapakkham P, et al. Short- and long-term outcomes of intracoronary and endogenously mobilized bone marrow stem cells in the treatment of ST-segment elevation myocardial infarction: a meta-analysis of randomized control trials. Eur J Heart Fail. 2012;14:91–105.CrossRefPubMedGoogle Scholar
  75. 75.
    Mathur A. BAMI. The effect of intracoronary reinfusion of bone marrow-derived mononuclear cells(BM-MNC) on all cause mortality in acute myocardial infarction (BAMI). 2015; Accessed March 24, 2016.
  76. 76.
    Povsic TJ, Junge C, Nada A, et al. A phase 3, randomized, double-blinded, active-controlled, unblinded standard of care study assessing the efficacy and safety of intramyocardial autologous CD34+ cell administration in patients with refractory angina: design of the RENEW study. Am Heart J. 2013;165:854–61.CrossRefPubMedGoogle Scholar
  77. 77.
    Ionis Pharmaceuticals Provides Update on IONIS-TTR Rx Program. 2016; Accessed October 23, 2016.
  78. 78.
    Takahashi K, Yamanaka S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell. 2006;126:663–76.CrossRefPubMedGoogle Scholar
  79. 79.
    Burridge PW, Keller G, Gold JD, Wu JC. Production of de novo cardiomyocytes: human pluripotent stem cell differentiation and direct reprogramming. Cell Stem Cell. 2012;10:16–28.CrossRefPubMedPubMedCentralGoogle Scholar
  80. 80.
    Lan F, Lee AS, Liang P, et al. Abnormal calcium handling properties underlie familial hypertrophic cardiomyopathy pathology in patient-specific induced pluripotent stem cells. Cell Stem Cell. 2013;12:101–13.CrossRefPubMedPubMedCentralGoogle Scholar
  81. 81.
    Sharma A, Marceau C, Hamaguchi R, et al. Human induced pluripotent stem cell-derived cardiomyocytes as an in vitro model for coxsackievirus B3-induced myocarditis and antiviral drug screening platform. Circ Res. 2014;115:556–66.CrossRefPubMedPubMedCentralGoogle Scholar
  82. 82.
    Liang P, Lan F, Lee AS, et al. Drug screening using a library of human induced pluripotent stem cell-derived cardiomyocytes reveals disease-specific patterns of cardiotoxicity. Circulation. 2013;127:1677–91.CrossRefPubMedGoogle Scholar
  83. 83.
    Matsa E, Ahrens JH, Wu JC. Human induced pluripotent stem cells as a platform for personalized and precision cardiovascular medicine. Physiol Rev. 2016;96:1093–126.CrossRefPubMedGoogle Scholar
  84. 84.
    Mathur A, Loskill P, Shao K, et al. Human iPSC-based cardiac microphysiological system for drug screening applications. Sci Rep. 2015;5:8883.CrossRefPubMedPubMedCentralGoogle Scholar
  85. 85.
    Mathur A, Ma Z, Loskill P, Jeeawoody S, Healy KE. In vitro cardiac tissue models: current status and future prospects. Adv Drug Deliv Rev. 2016;96:203–13.CrossRefPubMedGoogle Scholar
  86. 86.
    Malik FI, Hartman JJ, Elias KA, et al. Cardiac myosin activation: a potential therapeutic approach for systolic heart failure. Science. 2011;331:1439–43.CrossRefPubMedPubMedCentralGoogle Scholar
  87. 87.
    Teerlink JR, Felker GM, McMurray JJV, et al. Chronic oral study of myosin activation to increase contractility in heart failure (COSMIC-HF): a phase 2, pharmacokinetic, randomised, placebo-controlled trial. Lancet. 2016;388:2895–903.CrossRefPubMedGoogle Scholar
  88. 88.
    Nguyen PK, Rhee JW, Wu JC. Adult stem cell therapy and heart failure, 2000 to 2010: a systematic review. JAMA Cardiol. 2016;1:831–41.CrossRefPubMedPubMedCentralGoogle Scholar
  89. 89.
    Delewi R, Andriessen A, Tijssen JGP, Zijlstra F, Piek JJ, Hirsch A. Impact of intracoronary cell therapy on left ventricular function in the setting of acute myocardial infarction: a meta-analysis of randomised controlled clinical trials. Heart. 2013;99:225–32.CrossRefPubMedGoogle Scholar
  90. 90.
    Povsic TJ, Henry TD, Traverse JH, et al. Efficacy and safety of intramyocardial autologous CD34+ cell administration in patients with refractory angina. JACC Cardiovasc Intv. 2016;9:1576–85.CrossRefGoogle Scholar
  91. 91.
    Losordo DW, Henry TD, Davidson C, et al. Intramyocardial, autologous CD34+ cell therapy for refractory angina. Circ Res. 2011;109:428–36.CrossRefPubMedPubMedCentralGoogle Scholar
  92. 92.
    Patel AN, Henry TD, Quyyumi AA, et al. Ixmyelocel-T for patients with ischaemic heart failure: a prospective randomised double-blind trial. Lancet. 2016;387:2412–21.CrossRefPubMedGoogle Scholar
  93. 93.
    The purpose of this study is to evaluate the efficacy and safety of allogeneic mesenchymal precursor cells (CEP-41750) for the treatment of chronic heart failure. 2016; Accessed March 24, 2016.
  94. 94.
    Neofytou E, O’Brien CG, Couture LA, Wu JC. Hurdles to clinical translation of human induced pluripotent stem cells. J Clin Investig. 2015;125:2551–7.CrossRefPubMedPubMedCentralGoogle Scholar
  95. 95.
    Anderson ME, Goldhaber JI, Houser SR, Puceat M, Sussman MA. Embryonic stem cell-derived cardiac myocytes are not ready for human trials. Circ Res. 2014;115:335–8.CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2017

Authors and Affiliations

  • Thomas J. Povsic
    • 1
  • Rob Scott
    • 2
  • Kenneth W. Mahaffey
    • 3
  • Robert Blaustein
    • 4
  • Jay M. Edelberg
    • 5
  • Martin P. Lefkowitz
    • 6
  • Scott D. Solomon
    • 7
  • Jonathan C. Fox
    • 8
  • Kevin E. Healy
    • 9
  • Aarif Y. Khakoo
    • 10
  • Douglas W. Losordo
    • 11
  • Fady I. Malik
    • 12
  • Brett P. Monia
    • 13
  • Rusty L. Montgomery
    • 14
  • Jeffrey Riesmeyer
    • 15
  • Gregory G. Schwartz
    • 16
  • Steven L. Zelenkofske
    • 17
  • Joseph C. Wu
    • 18
  • Scott M. Wasserman
    • 10
  • Matthew T. Roe
    • 1
  1. 1.Duke Clinical Research InstituteDuke University School of MedicineDurhamUSA
  2. 2.AbbVie PharmaceuticalsChicagoUSA
  3. 3.Stanford Center for Clinical Research (SCCR)Stanford University School of MedicineStanfordUSA
  4. 4.Merck Research LaboratoriesMerck & Co., IncKenilworthUSA
  5. 5.Sanofi USBridgewaterUSA
  6. 6.Novartis PharmaceuticalsEast HanoverUSA
  7. 7.Harvard Medical SchoolBostonUSA
  8. 8.MyoKardia, IncSouth San FranciscoUSA
  9. 9.University of California, BerkeleyBerkeleyUSA
  10. 10.Amgen, IncThousand OaksUSA
  11. 11.Caladrius BiosciencesNew YorkUSA
  12. 12.Cytokinetics IncSouth San FranciscoUSA
  13. 13.Ionis PharmaceuticalsCarlsbadUSA
  14. 14.miRagen Therapeutics, IncBoulderUSA
  15. 15.Eli Lilly, IncIndianapolisUSA
  16. 16.University of Colorado School of MedicineDenverUSA
  17. 17.AstraZeneca IncAllentownUSA
  18. 18.Stanford Cardiovascular InstituteStanford University School of MedicineStanfordUSA

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