Steven Nissen

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Steven E. Nissen (born 1948) is an American cardiologist, researcher and patient advocate. He was chairman of cardiovascular medicine at the Cleveland Clinic, in Cleveland, Ohio. [1]

Contents

Joining Cleveland Clinic in 1992, Nissen served as Vice-Chairman of the Department of Cardiology (1993–2002), Section Head of Clinical Cardiology (1992–2000), and Director of the Coronary Intensive Care Unit (1992–1997). Most recently, he served as Medical Director of the Cleveland Clinic Cardiovascular Coordinating Center (C5), an organization that directs multi-center clinical trials. Nissen still attends in the Cardiac Critical Care Unit periodically throughout the year. [1]

Education

Nissen graduated high school from the Webb School of California and pursued his undergraduate degree at the University of Michigan. He then went on to receive his medical degree from the University of Michigan School of Medicine in Ann Arbor. He completed his internal medicine internship and residency at the University of California, Davis in Sacramento, and thereafter completed his cardiology fellowship at the University of Kentucky Medical Center in Lexington. [1]

Imaging technology

He produced the first images in humans in 1990 and began using IVUS to document the ubiquitous prevalence of coronary artery disease. The technology has been the basis for his research during the last decade and Nissen is currently the principal investigator for several large IVUS atherosclerosis trials. [2]

Advocacy

Nissen has led a number of inquiries as to the scientific integrity of many medications currently on the market. Starting with linked COX-2 inhibitors, such as Vioxx (rofecoxib) in 2001, Nissen was one of the first physicians to link it to an increased risk of heart attacks and strokes. Three years later Merck pulled Vioxx from the market when additional studies confirmed that daily, long-term use of the drug could increase the risk of heart attacks and strokes. [3]

In 2005, Nissen re-analyzed the data related to the Bristol-Myers Squibb drug Pargluva (muraglitazar), an experimental type 2 diabetes drug. When an U.S. Food and Drug Administration (FDA) advisory panel charged with reviewing the clinical trial data approved the drug, he immediately began an in-depth analysis. [4]

In 2007, the meta-analysis by Nissen and his co-investigator Kathy Wolksi, published in the Journal of the American Medical Association online on October 20, found that the diabetes drug rosiglitazone (Avandia) produced by GlaxoSmithKline carried high cardiovascular risks,. [5] The FDA issued an alert on May 21, 2007, [6] leading to a warning by the Food and Drug Administration and a sales loss of about 75% for the drug. [7] The FDA was not made aware of the Nissen meta-analysis results until the day of its publication. In an editorial written in the Wall Street Journal, former FDA deputy commissioner Scott Gottlieb characterized the failure to inform FDA of the results in advance of publication as "upstage the FDA in an attempt to influence public debate". [8] [9] BioCentury editor Steve Edelson said that congressional staffers but not the FDA had been briefed on the study results in advance. [10] [11]

In November 2013, the FDA lifted its earlier restrictions on rosiglitazone after reviewing the results of the 2009 RECORD clinical trial (a six-year, open label randomized control trial), which failed to show heart infarct risks associated with the drug. [7] [8]

Research

In 2003, Nissen led a Journal of the American Medical Association study, producing evidence that five weekly infusions of ApoA-I Milano/phospholipids complex, a synthetic form of HDL, can possibly remove significant amounts of plaque from coronary arteries. The lipoprotein enhanced the ability of HDL cholesterol to usher fat out of the arteries and into the liver for excretion leading to the purchase of Esperion Therapeutics, the tiny company that had produced recombinant Apo-A1 Milano, by Pfizer for $1.3 billion. [12]

Also in 2005, Nissen published the results of the REVERSAL trial, a head-to-head comparison of the statins atorvastatin (Lipitor) and pravastatin (Pravachol). IVUS images showed that Lipitor had effectively halted the progression of plaque buildup, but coronary disease progressed considerably in those given Pravachol. The study suggested that treatments should aim to lower LDL cholesterol levels as much as possible. [13]

In 2006, Nissen and his co-investigators reported on The ASTEROID trial (A Study to Evaluate the Effect of Rosuvastatin On Intravascular Ultrasound-Derived Coronary Atheroma Burden). The study concluded that intensive use of statins resulting in a decreased LDL and increased HDL can reverse the build-up of plaque in coronary arteries, as measured by IVUS. [14]

Advisor

Conflict of Interest

There have been allegations about Nissen's potential conflicts of interest. [15]

Awards and recognitions

Publications

Related Research Articles

<span class="mw-page-title-main">Coronary artery disease</span> Reduction of blood flow to the heart

Coronary artery disease (CAD), also called coronary heart disease (CHD), ischemic heart disease (IHD), myocardial ischemia, or simply heart disease, involves the reduction of blood flow to the cardiac muscle due to build-up of atherosclerotic plaque in the arteries of the heart. It is the most common of the cardiovascular diseases. Types include stable angina, unstable angina, and myocardial infarction.

<span class="mw-page-title-main">Atherosclerosis</span> Inflammatory disease involving buildup of lesions in the walls of arteries

Atherosclerosis is a pattern of the disease arteriosclerosis, characterized by development of abnormalities called lesions in walls of arteries. This is a chronic inflammatory disease involving many different cell types, and driven by elevated levels of cholesterol in the blood. These lesions may lead to narrowing of the arterial walls due to buildup of atheromatous plaques. At onset there are usually no symptoms, but if they develop, symptoms generally begin around middle age. In severe cases, it can result in coronary artery disease, stroke, peripheral artery disease, or kidney disorders, depending on which body part(s) the affected arteries are located in the body.

<span class="mw-page-title-main">Statin</span> Class of drugs to lower cholesterol

Statins are a class of medications that reduce illness and mortality in people who are at high risk of cardiovascular disease. They are the most commonly prescribed cholesterol-lowering drugs.

<span class="mw-page-title-main">Hypercholesterolemia</span> High levels of cholesterol in the blood

Hypercholesterolemia, also called high cholesterol, is the presence of high levels of cholesterol in the blood. It is a form of hyperlipidemia, hyperlipoproteinemia, and dyslipidemia.

Dyslipidemia is a metabolic disorder characterized by abnormally high or low amounts of any or all lipids or lipoproteins in the blood. Dyslipidemia is a risk factor for the development of atherosclerotic cardiovascular diseases (ASCVD), which include coronary artery disease, cerebrovascular disease, and peripheral artery disease. Although dyslipidemia is a risk factor for ASCVD, abnormal levels don't mean that lipid lowering agents need to be started. Other factors, such as comorbid conditions and lifestyle in addition to dyslipidemia, is considered in a cardiovascular risk assessment. In developed countries, most dyslipidemias are hyperlipidemias; that is, an elevation of lipids in the blood. This is often due to diet and lifestyle. Prolonged elevation of insulin resistance can also lead to dyslipidemia. Likewise, increased levels of O-GlcNAc transferase (OGT) may cause dyslipidemia.

<span class="mw-page-title-main">Thiazolidinedione</span> Class of chemical compounds

The thiazolidinediones, abbreviated as TZD, also known as glitazones after the prototypical drug ciglitazone, are a class of heterocyclic compounds consisting of a five-membered C3NS ring. The term usually refers to a family of drugs used in the treatment of diabetes mellitus type 2 that were introduced in the late 1990s.

<span class="mw-page-title-main">Rosiglitazone</span> Chemical compound

Rosiglitazone is an antidiabetic drug in the thiazolidinedione class. It works as an insulin sensitizer, by binding to the PPAR in fat cells and making the cells more responsive to insulin. It is marketed by the pharmaceutical company GlaxoSmithKline (GSK) as a stand-alone drug or for use in combination with metformin or with glimepiride. First released in 1999, annual sales peaked at approximately $2.5-billion in 2006; however, following a meta-analysis in 2007 that linked the drug's use to an increased risk of heart attack, sales plummeted to just $9.5-million in 2012. The drug's patent expired in 2012.

<span class="mw-page-title-main">Atorvastatin</span> Cholesterol-lowering medication

Atorvastatin is a statin medication used to prevent cardiovascular disease in those at high risk and to treat abnormal lipid levels. For the prevention of cardiovascular disease, statins are a first-line treatment. It is taken by mouth.

<span class="mw-page-title-main">Atheroma</span> Accumulation of degenerative material in the inner layer of artery walls

An atheroma, or atheromatous plaque, is an abnormal accumulation of material in the inner layer of an arterial wall.

Intravascular ultrasound (IVUS) or intravascular echocardiography is a medical imaging methodology using a specially designed catheter with a miniaturized ultrasound probe attached to the distal end of the catheter. The proximal end of the catheter is attached to computerized ultrasound equipment. It allows the application of ultrasound technology, such as piezoelectric transducer or CMUT, to see from inside blood vessels out through the surrounding blood column, visualizing the endothelium of blood vessels.

<span class="mw-page-title-main">Ezetimibe</span> Medication used to treat high cholesterol

Ezetimibe is a medication used to treat high blood cholesterol and certain other lipid abnormalities. Generally it is used together with dietary changes and a statin. Alone, it is less preferred than a statin. It is taken by mouth. It is also available in the fixed combinations ezetimibe/simvastatin, ezetimibe/atorvastatin, ezetimibe/rosuvastatin, and ezetimibe/bempedoic acid.

<span class="mw-page-title-main">ApoA-I Milano</span>

Apolipoprotein A-I Milano is a naturally occurring mutated variant of the apolipoprotein A1 protein found in human HDL, the lipoprotein particle that carries cholesterol from tissues to the liver and is associated with protection against cardiovascular disease. ApoA-I Milano was first identified by Dr. Cesare Sirtori in Milan, who also demonstrated that its presence significantly reduced cardiovascular disease, even though it caused a reduction in HDL levels and an increase in triglyceride levels.

The lipid hypothesis is a medical theory postulating a link between blood cholesterol levels and the occurrence of cardiovascular disease. A summary from 1976 described it as: "measures used to lower the plasma lipids in patients with hyperlipidemia will lead to reductions in new events of coronary heart disease". It states, more concisely, that "decreasing blood cholesterol [...] significantly reduces coronary heart disease".

<span class="mw-page-title-main">Familial hypercholesterolemia</span> Genetic disorder characterized by high cholesterol levels

Familial hypercholesterolemia (FH) is a genetic disorder characterized by high cholesterol levels, specifically very high levels of low-density lipoprotein cholesterol, in the blood and early cardiovascular diseases. The most common mutations diminish the number of functional LDL receptors in the liver or produce abnormal LDL receptors that never go to the cell surface to function properly. Since the underlying body biochemistry is slightly different in individuals with FH, their high cholesterol levels are less responsive to the kinds of cholesterol control methods which are usually more effective in people without FH. Nevertheless, treatment is usually effective.

<span class="mw-page-title-main">Apolipoprotein AI</span> Protein used in lipid metabolism

Apolipoprotein AI(Apo-AI) is a protein that in humans is encoded by the APOA1 gene. As the major component of HDL particles, it has a specific role in lipid metabolism.

<span class="mw-page-title-main">PCSK9</span> Mammalian protein found in humans

Proprotein convertase subtilisin/kexin type 9 (PCSK9) is an enzyme encoded by the PCSK9 gene in humans on chromosome 1. It is the 9th member of the proprotein convertase family of proteins that activate other proteins. Similar genes (orthologs) are found across many species. As with many proteins, PCSK9 is inactive when first synthesized, because a section of peptide chains blocks their activity; proprotein convertases remove that section to activate the enzyme. The PCSK9 gene also contains one of 27 loci associated with increased risk of coronary artery disease.

<span class="mw-page-title-main">Muraglitazar</span> Chemical compound

Muraglitazar is a dual peroxisome proliferator-activated receptor agonist with affinity to PPARα and PPARγ.

<span class="mw-page-title-main">Apabetalone</span> Chemical compound

Apabetalone is an orally available small molecule created by Resverlogix Corp. that is being evaluated in clinical trials for the treatment of atherosclerosis and associated cardiovascular disease (CVD). In the phase II clinical trial ASSURE in patients with angiographic coronary disease and low high-density lipoprotein cholesterol (HDL-C) levels, apabetalone showed no greater increase in HDL-cholesterol (HDL-c) and apolipoprotein A-I (ApoA-I) levels or incremental regression of atherosclerosis than administration of placebo, while causing a statistically significant greater incidence of elevated liver enzymes. However, pooled analysis of the effect of apabetalone in three phase II clinical trials ASSERT, ASSURE, and SUSTAIN demonstrated increases in HDL-cholesterol (HDL-c) and apolipoprotein A-I (ApoA-I) levels, as well as decreases in the incidence of major adverse cardiac events (MACE). Reduction of MACE was more profound in patients with diabetes mellitus. In a short-term study in prediabetics, favorable changes in glucose metabolism were observed in patients receiving apabetalone. An international, multicenter phase III trial, “Effect of RVX000222 on Time to Major Adverse Cardiovascular Events in High-Risk Type 2 Diabetes Mellitus Subjects with Coronary Artery Disease” (BETonMACE) commenced in October 2015. The trial is designed to determine whether apabetalone in combination with statins can decrease cardiac events compared to treatment with statins alone.

Bempedoic acid, sold under the brand name Nexletol among others, is a medication for the treatment of hypercholesterolemia.

Dr. Robert S. Rosenson is a Professor of Medicine and also lending his services as the Director of cardio metabolic disorders at the Icahn School of Medicine at Mount Sinai.

References

  1. 1 2 3 4 5 6 Steven Nissen MD, physician profile , Cleveland Clinic, retrieved 2/2010
  2. ↑ Nissen SE, Gurley JC, Grines CL, Booth DC, McClure R, Berk M, Fischer C, DeMaria AN (1991). "Intravascular ultrasound assessment of lumen size and wall morphology in normal subjects and patients with coronary artery disease". Circulation. 84 (3): 1087–1099. doi: 10.1161/01.cir.84.3.1087 . PMID   1884441.
  3. ↑ Mukherjee D, Nissen SE, Topol EJ (2001). "Risk of cardiovascular events associated with selective COX-2 inhibitors". JAMA. 286 (8): 954–959. doi:10.1001/jama.286.8.954. PMID   11509060.
  4. ↑ Nissen SE, Wolski K, Topol EJ (2005). "Effect of muraglitazar on death and major adverse cardiovascular events in patients with type 2 diabetes mellitus". JAMA. 294 (20): 2581–6. doi:10.1001/jama.294.20.joc50147. PMID   16239637.
  5. ↑ Nissen SE, Wolski K (2007). "Effect of rosiglitazone on the risk of myocardial infarction and death from cardiovascular causes". N Engl J Med. 356 (24): 2457–71. doi: 10.1056/NEJMoa072761 . PMID   17517853.
  6. ↑ "FDA News Release: FDA Issues Safety Alert on Avandia". May 21, 2007. Retrieved February 17, 2010.
  7. ↑ Saul, Stephanie (July 22, 2007). "Drug Safety Critic Hurls Darts From the Inside". The New York Times. Retrieved February 17, 2010.
  8. ↑ Gottlieb, Scott (May 29, 2007). "Journalistic Malpractice - WSJ". Wall Street Journal.
  9. ↑ "Safety of Rosiglitazone Maleate (Avandia)". Food and Drug Administration .
  10. ↑ "Avandia and 9/11 - BioCentury.com".
  11. ↑ "- FDA'S ROLE IN THE EVALUATION OF AVANDIA'S SAFETY".
  12. ↑ Nissen SE, Tsunoda T, Tuzcu EM, Schoenhagen P, Cooper CJ, Yasin M, Eaton GM, Lauer MA, Sheldon WS, Grines CL, Halpern S, Crowe T, Blankenship JC, Kerensky R (2003). "Effect of recombinant ApoA-I Milano on coronary atherosclerosis in patients with acute coronary syndromes: a randomized controlled trial". JAMA. 290 (17): 2292–300. doi: 10.1001/jama.290.17.2292 . PMID   14600188.
  13. ↑ Nissen SE (2003). "Halting the progression of atherosclerosis with intensive lipid lowering: results from the Reversal of Atherosclerosis with Aggressive Lipid Lowering (REVERSAL) trial". Am J Med. 118 (Suppl 12A): 22–7. doi:10.1016/j.amjmed.2005.09.020. PMID   16356804.
  14. ↑ Nissen SE, Nicholls SJ, Sipahi I, Libby P, Raichlen JS, Ballantyne CM, Davignon J, Erbel R, Fruchart JC, Tardif JC, Schoenhagen P, Crowe T, Cain V, Wolski K, Goormastic M, Tuzcu EM; ASTEROID Investigators. (2006). "Effect of very high-intensity statin therapy on regression of coronary atherosclerosis: the ASTEROID trial". JAMA. 295 (13): 1556–65. doi:10.1001/jama.295.13.jpc60002. PMID   16533939.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  15. ↑ "Steven Nissen, Conflicts Of Interest, And The New Cholesterol Drugs". Forbes . June 12, 2015.
  16. ↑ Steven Nissen - The Time 100
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