Top Medical Stories of 2008 Challenged 'Lower Is Better' Mantra

By Peggy Peck

27 dec 2008--When it comes to LDLs and glycosylated hemoglobin, the philosophy of lower is better was dealt evidence-based blows this year with a series of surprising findings. In this year-end review, the editors of present their picks of the medical news events in 2008 that influenced clinical practice or triggered ongoing discussion among clinicians. Among them was a handful of studies that reassessed interpretation of surrogate endpoints such as HbA1c and LDL cholesterol that emerged as a theme. Take the potent lipid-lowering action of the combination of ezetimibe and simvastatin, marketed as Vytorin. It was reported in January that it brought levels down by 50% or more. But that, it turned out, did not slow or regress the progression of atherosclerosis. The disappointing bottom-line effect of the dramatic drops in lipids, as revealed in the ENHANCE trial, was supposed to come from findings that had been expected in March 2007 at the American College of Cardiology and then in November 2007 at the American Heart Association, but the data failed to materialize at either venue. By last January the rumor mill was abuzz, and the word was that that ENHANCE would provide proof that ezetimibe/simvastatin did not slow atherosclerosis as measured by plaque volume in the carotid arteries. And on Jan. 14 the naysayers were proven correct when Merck/Schering-Plough released the ENHANCE findings in a press release. (See: ENHANCE Finds No Slowing of Plaque Burden With Ezetimibe/Simvastatin (Vytorin)) That was just the beginning for events focused on this once blockbuster drug. Before the year was out, ENHANCE would be the subject of a controversial session at the ACC meeting, an FDA review, and a congressional investigation. (See: ACC: ENHANCE Data on Ezetimibe/Simvastatin (Vytorin) Reveal Wavy Bottom Line) The other shoe dropped in July when the SEAS investigators reported -- again at a press conference -- that the ezetimibe/simvastatin combination reversed aortic stenosis, but use of the drug appeared to be associated with an increase in cancer mortality. The cancer link, they said, appeared to be explained by the play of chance. (See: ESC: SEAS Data Fail to Quiet Ezetimibe/Simvastatin Controversy) But lipids aren't everything, and at the start of the year it still seemed logical to argue that if well controlled, low blood glucose levels were good. That being so, aggressive control with a glycosylated hemoglobin target of less than 6% would be even better. So it seemed. That presumption, it turned out, was not only wrong, but also dangerously so. On Feb. 6, the National Heart, Lung, and Blood Institute shocked both diabetologists and cardiologists with the news that it was pulling the plug on intensive-glucose-lowering arm of the ACCORD (Action to Control Cardiovascular Risk in Diabetes) trial because that strategy was associated with excess mortality. At a press conference, Elizabeth G. Nabel, M.D., director of the NHLBI, said there were 257 deaths in the intensive-treatment group and 203 in the standard-treatment group, an excess of 54 deaths, or three per 1,000 participants each year, since the 10,251-patient trial was started in 2001. (See: Deaths Force NHLBI to Drop Intensive Glucose-Lowering Strategy in Type 2 Diabetes) The FDA had more than its share of headaches this year -- and most of them started on foreign shores. Late last year and continuing well into this year, the FDA began receiving reports that led to a massive recall of heparin that linked to serious and sometimes fatal allergic reactions. Months of sleuthing, finally identified the contaminant as chemically altered chondroitin-sulfate added to the crude heparin manufactured in plants in China. (See: Chemically Altered Chondroitin-Sulfate Found in Recalled Heparin) The FDA had barely caught its breath when the CDC began receiving reports of a salmonella outbreak. The source, initially, was believed to be tomatoes, and the FDA blocked shipments from a number of tomato farms -- most of which were in south central Florida. But the "DNA fingerprint" identified Salmonella saintpaul in water from an irrigation system at a farm in Nuevo Leon, Mexico, and serrano peppers grown there. And by that time, almost 400 salmonella cases were reported to the CDC. (See: More Salmonella Cases Reported as Trail of Infected Tomatoes Goes Cold FDA Finds Salmonella Saintpaul in Water and Peppers at Mexican Farm) On top of those import woes, the FDA had to deal with reports of melamine contamination in coffee and tea drinks imported from China and shut down import of generic drugs from two plants located in India. (See: Chinese Melamine Contamination Triggers U.S. Recall of Instant Coffee and Tea Products FDA Blocks Imports of 30 Generics from Two Plants in India) Meanwhile, the mounting toll of traumatic head injury and post traumatic stress disorder was a major medical story this year. (See: APA: PTSD May Be Major Combat Scar of Iraq Vets IOM Cites Poor Preparedness for Brain Injuries of Iraq and Afghanistan Vets ) One is never too old for blood pressure control, as was demonstrated in the 3,800-patient Hypertension in the Very Elderly Trial (HYVET), which found that even at age 80 blood pressure-lowering treatments were beneficial. (See: ACC: Octogenarians and Older Derive Benefits from Hypertension Therapy) And it might be that one is never too healthy for a statin -- or maybe not. The results of the 17,800-participant JUPITER trial suggest that patients ages 60 or older who had elevated C-reactive protein but no real evidence of atherosclerosis reduced cardiovascular events -- including deaths due to heart attacks and stroke -- compared with controls. But cardiologists attending the American Heart Association meeting where the data were released said it was still too early to add statins to the water. (See: AHA: JUPITER Results Point to Role of Statins for 'Apparently Healthy' Patients ) And rounding out the year, there were a pair of reports dealing with unusual and unique therapies -- the first U.S. face transplantation and an unexpected side effect of a bone marrow transplant for acute myeloid leukemia. The face transplant took occurred at the Cleveland Clinic, which has been sitting on an IRB approval for the procedure for more than four years. The ideal patient and a suitable donor finally showed up several weeks ago. The clinic team went public with the news at a press conference December 16. (See: First U.S. Face Transplant Reported at Cleveland Clinic) The news of a potential cure for HIV first surfaced last February at the Conference on Retroviruses and Opportunistic Infections, but it wasn't until last month when Gero Hütter, M.D., and colleagues at the Charité-Medical University in Berlin, discussed the results at a press conference that the story really gained traction. It's now been more than eight months and the 42-year-old American man, who received the bone marrow transplant to treat acute myeloid leukemia, is still free of HIV virus.