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Milton Packer

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Milton Packer (b. ca 1951) is an American cardiologist who is known for his clinical research concerning heart failure.

Early life and education

Milton Packer was born in the US to holocaust survivors who were saved from the Vilna ghetto by Karl Plagge. He grew up in Philadelphia, where his father worked as a tailor. He was politically active in the 1960s.[1]

He earned his undergraduate degree at Pennsylvania State University in 1971 and his medical degree from Jefferson Medical College in Philadelphia in 1973[2] when he was 22 years old.[1] He did his residency at Albert Einstein College of Medicine in New York City where Edmund Sonnenblick was working, and a fellowship in cardiology at Mount Sinai School of Medicine in New York, where Richard Gorlin was conducting research.[1]

He entered the field of cardiology in an era of revolution in that field, with the introduction of interventional cardiology and echocardiography doctors could measure what was happening with their patients' hearts in a way that had never been possible; much of the innovation was happening in New York City.[1]

Academic career

In 1979 he was made an assistant professor at Mount Sinai, was promoted to associate professor in 1983, and was made a professor in 1988. In 1992 he moved to Columbia University and was made the Dickinson Richards Professor of Medicine.[2] Columbia has recruited him with an invitation to build a clinical and research program in heart failure and he in turn recruited faculty who had a strong interest in both; members of the group could come up with a hypothesis about heart failure while treating a patient and that doctor or another member would begin exploring it in research the same day.[1]

In 2004 he moved to University of Texas Southwestern Medical Center as a trailing spouse.[1] He was offered a named professorship and the opportunity to set up a center within the college focused on teaching clinical research and supporting career development for doctors who wanted to pursue a career in clinical research. The center also brought biostaticians, who had been in the public health department, together with physicians from many branches of medicine, with the goal of spreading the appreciation for rigorous statistical design of clinical research. and making statistical expertise more widely available in the college.[3] Packer also won UT Southwest an NIH Clinical and Translational Science Award in 2007 to support these efforts.[4]

In 2015 he joined the Baylor University Medical Center at Dallas with an appointment of Distinguished Scholar.[5]

Research

Along with practicing cardiology, he spent the first part of his career doing small clinical research studies trying to better understand the pathology of heart failure.[3]

In 1992 he published a paper on a neurohormonal hypothesis to explain heart failure that synthesized ideas that were percolating at the time; the paper made him known as the father of that idea.[1][6]

In 1986 he joined the Cardiac and Renal Drugs Advisory Committee at the FDA,[2] an event that he said was life-changing.[3]

"The pivotal event for me was my appointment as a member of the cardiorenal advisory committee for the Food and Drug Administration. The Food and Drug Administration is the country's most valuable resource for clinical data, clinical research design, and clinical research analysis. The people who are there receive voluminous amounts of data about drugs in development and drugs already on the market and are challenged with how to find the "truth" in the data and how to translate that truth into decisions about public health. This is an unbelievably hard job and a terribly important responsibility. If the FDA makes a mistake, there is a potential for an enormous amount of suffering; if they do the right thing, there is a real opportunity for an enormous number of lives to be saved and the quality of lives to be improved. They have, within their community, developed clinical trial methodology to an unbelievably high standard, the highest standard in the world."[3]

After this he started getting involved running large multi-center clinical trials for heart failure drugs, several of which were landmark studies in the care of heart failure.[3]

He was principal investigator on the REFLECT trial for flosequinan which ran from 1987-1989 and the following PROFILE trial from 1991-1994. He was PI on a study of amlodipine that ran from 1987-1989 and the following PRAISE trial from 1992-1995 and PRAISE 2 from 1996-1999; the PROMISE trial for milrinone 1988-1990; the ATLAS trial for lisinopril from 1993-1997; the PRECISE trial for carvedilol from 1993-1995 and the following COPERNICUS trial from 1997-2002; the ENABLE trial (1999-2001) and REACH-1 trial (1997-2003) for bosentan; the OVERTURE trial (1999-2002) for omapatrilat; REVIVE I and II (2001-2006) for levosimendan; and the TRUE-AHF trial of ularitide that started in 2013. He also chaired the steering committee for the RADIANCE trial from 1989-1992 which studied the use of digoxin in people who were also treated with ACE inhibitors and chaired the steering committee for the RENEWAL trial (1999-2002) for etanercept.[2] He was also the co-PI of the PARADIGM-HF trial that led to the approval of valsartan/sacubitril.[7][8]

The PROFILE trial had negative results; it was terminated early in 1993 due to increased mortality in the drug arm of the trial. Packer was the lead author of the conference abstract in which topline results were presented. The abstract promised that data and analysis would be forthcoming in a future paper; as of 2001 no such paper had been published.[9] Similarly, the REACH-1 trial had negative results and was terminated early, and the preliminary results were presented at a conference by Packer, with no full publication following as of 2001, leaving the field without insight into why the drug caused harm at the dosage given in that trial.[9] Results of both trials were published in 2017, with an explanation about the delay.[10][11]

The success of the PARADIGM-HF trial was a great satisfaction for him, as it validated the neurohormonal hypothesis; an earlier effort with omapatrilat had failed due to side effects caused by the drug candidate.[1]

He was a founding member and former President of Heart Failure Society of America.[2] His research on the treatment of heart failure led to him being awarded the Lewis Katz lifetime achievement award in cardiovascular research.[12][1]

References

  1. ^ a b c d e f g h i Nicholls, Mark (1 June 2016). "CardioPulse Articles: Pioneers in cardiovascular medicine -- Milton Packer MD". European Heart Journal. 37 (21): 1633–41. doi:10.1093/eurheartj/ehw169. PMID 27252477.
  2. ^ a b c d e "Milton Packer CV" (PDF). FDA Cardiovascular and Renal Drugs Advisory Committee. Retrieved 6 August 2017.
  3. ^ a b c d e Packer, M (November 2004). "Milton Packer, MD, Director, Center for Biostatistics and Clinical Science at UT Southwestern". Journal of Investigative Medicine. 52 (7): 421–4. doi:10.1136/jim-52-07-01. PMID 15651258.
  4. ^ "Press release: UT Southwestern earns $34M NIH grant to foster patient-oriented research". UT Southwestern via EurekAlert!. September 18, 2007.
  5. ^ "Press release: Cardiologist Milton Packer, M.D., Joins Baylor University Medical Center at Dallas". Baylor Scott & White Health. December 3, 2015.
  6. ^ Packer, M (July 1992). "The neurohormonal hypothesis: a theory to explain the mechanism of disease progression in heart failure". Journal of the American College of Cardiology. 20 (1): 248–54. doi:10.1016/0735-1097(92)90167-L. PMID 1351488.
  7. ^ Husten, Larry (March 31, 2014). "Novartis Trial Was Stopped Early Because Of A Significant Drop In Cardiovascular Mortality". Forbes.
  8. ^ McMurray, JJ; Packer, M; Desai, AS; Gong, J; Lefkowitz, MP; Rizkala, AR; Rouleau, JL; Shi, VC; Solomon, SD; Swedberg, K; Zile, MR; PARADIGM-HF Investigators and, Committees. (11 September 2014). "Angiotensin-neprilysin inhibition versus enalapril in heart failure". The New England Journal of Medicine. 371 (11): 993–1004. doi:10.1056/NEJMoa1409077. hdl:10993/27659. PMID 25176015.
  9. ^ a b van Veldhuisen, DJ; Poole-Wilson, PA (August 2001). "The underreporting of results and possible mechanisms of 'negative' drug trials in patients with chronic heart failure". International Journal of Cardiology. 80 (1): 19–27. doi:10.1016/S0167-5273(01)00447-8. PMID 11532543.
  10. ^ Packer, M; Pitt, B; Rouleau, JL; Swedberg, K; DeMets, DL; Fisher, L (June 2017). "Long-Term Effects of Flosequinan on the Morbidity and Mortality of Patients With Severe Chronic Heart Failure: Primary Results of the PROFILE Trial After 24 Years". JACC: Heart Failure. 5 (6): 399–407. doi:10.1016/j.jchf.2017.03.003. PMID 28501522.
  11. ^ Packer, M; McMurray, JJV; Krum, H; Kiowski, W; Massie, BM; Caspi, A; Pratt, CM; Petrie, MC; DeMets, D; Kobrin, I; Roux, S; Swedberg, K; ENABLE Investigators and, Committees. (May 2017). "Long-Term Effect of Endothelin Receptor Antagonism With Bosentan on the Morbidity and Mortality of Patients With Severe Chronic Heart Failure: Primary Results of the ENABLE Trials". JACC: Heart Failure. 5 (5): 317–326. doi:10.1016/j.jchf.2017.02.021. PMID 28449795.
  12. ^ "Profile: Dr. Milton Packer". Baylor Scott & White Health. Retrieved 6 August 2017.
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