Medical Reversals
Practices that have been found, through randomized controlled trials, to be no better than a prior or lesser standard of care. [Herrera-Perez et al., 2019; Prasad et al., 2013; Prasad et al., 2011]
146 MEDICAL REVERSALS IN NEJM | 2001-2010
Through an analysis of randomized controlled trials published in the NEJM between 2001 and 2010, Vinay Prasad and Adam Cifu identified 146 medical reversalsPractices that have been found, through randomized controlle… More. “These are not occasions when a newer, better therapy was announced, and they are not negative studies of potential innovations; they are reversals—each study provided evidence that overturned a practice that was already in use, suggesting that what had come before that practice was better.”
| # | Study | Publication date | Summary |
|---|---|---|---|
| 1 | Vaccinations and the risk of relapse in multiple sclerosis | 02/01/2001 | Long-standing concerns about vaccinations preceding the onset or relapse of multiple sclerosis led to clinicians’ reluctance to give vaccinations to these patients. This study proved no increased risk of relapse in the two-month period immediately following tetanus, hepatitis B, or influenza vaccination. |
| 2 | Hepatitis B vaccination and the risk of multiple sclerosis | 02/01/2001 | On a topic related to the previous study, this study disproved the relationship between vaccination and the development of multiple sclerosis. |
| 3 | Lack of effect of induction of hypothermia after acute brain injury | 02/22/2001 | This study found that the practice of cooling patients after brain injury, which had been done for decades, is not beneficial. |
| 4 | Initial plasma HIV-1 RNA levels and progression to AIDS in women and men | 03/08/2001 | This study contradicted a common decision-making practice concerning when to start medications for HIV in women. |
| 5 | The teratogenicity of anticonvulsant drugs | 04/12/2001 | Two medical textbooks and one review article have doubted that anticonvulsants taken during pregnancy are more teratogenic than epilepsy itself. This large study found the opposite: anticonvulsants during pregnancy increase the risk of fetal malformation. |
| 6 | Effect of early or delayed insertion of tympanostomy tubes for persistent otitis media on developmental outcomes at the age of three years | 04/19/2001 | Guidelines recommended insertion of ear tubes in a child with an ear infection of greater than three months’ duration because of concerns that associated conductive hearing loss might lead to poor developmental outcomes. This study did not find any benefit in early tube placement. |
| 7 | The effect of chelation therapy with succimer on neuropsychological development in children exposed to lead | 05/10/2001 | This study looked at an accepted therapy for children with moderately elevated blood lead levels and found no benefit. |
| 8 | Long-term effects of indomethacin prophylaxis in extremely-low-birthweight infants | 06/28/2001 | This study showed that a preventive therapy, commonly used in infants with extremely low birth weights, did not improve survival without neurosensory impairment at 18 months. |
| 9 | Two controlled trials of antibiotic treatment in patients with persistent symptoms and a history of Lyme disease | 07/12/2001 | These studies showed no benefit of a controversial but often-utilized treatment: a prolonged course of antibiotics for patients with persistent symptoms of Lyme disease. |
| 10 | Three months versus one year of oral anticoagulant therapy for idiopathic deep venous thrombosis | 07/19/2001 | When treating blood clots in the legs, longer therapy is often considered better. This trial showed that a prolonged course of therapy delayed but did not reduce the risk for a recurrent clot. |
| 11 | Failure of metronidazole to prevent preterm delivery among pregnant women with asymptomatic Trichomonas vaginalis infection | 08/16/2001 | Pregnant women are often screened for an asymptomatic vaginal infection (which is treated if found), in the hopes of decreasing the risk of preterm birth. This trial showed that this practice actually increases the risk of preterm birth. |
| 12 | Effect of prone positioning on the survival of patients with acute respiratory failure | 08/23/2001 | This study overturned a practice of positioning ICU patients prone while they are on a ventilator. |
| 13 | Medical treatment for neurocysticercosis characterized by giant subarachnoid cysts | 09/20/2001 | This trial showed that surgical therapy for a parasitic brain infection may not be as widely necessary as was the accepted practice. |
| 14 | Naltrexone in the treatment of alcohol dependence | 12/13/2001 | In this multicenter, double-blind, placebo-controlled study, a commonly used therapy for alcohol dependence was shown to be ineffective. |
| 15 | Comparison of two diets for the prevention of recurrent stones in idiopathic hypercalciuria | 01/10/2002 | This trial showed that a lowcalcium diet, commonly recommended for kidney stones, actually increased the risk of stones. |
| 16 | Frequency of uterine contractions and the risk of spontaneous preterm delivery | 01/24/2002 | This study added to evidence that monitoring for frequent contractions (commonly done on labor and delivery wards) is not helpful in decreasing the rate of preterm delivery. |
| 17 | Screening of infants and mortality due to neuroblastoma | 04/04/2002 | Studies 17 and 18 overturned a screening test, adopted in Japan, for a childhood cancer. |
| 18 | Neuroblastoma screening at one year of age | 04/04/2002 | See study 17. |
| 19 | Immediate repair compared with surveillance of small abdominal aortic aneurysms | 05/09/2002 | This trial raised doubts about a common threshold for when abdominal aortic aneurysms should be repaired. |
| 20 | Intranasal mupirocin to prevent postoperative Staphylococcus aureus infections | 06/13/2002 | This randomized controlled trial overturned a common practice of eradicating nasal colonization with Staphylococcus aureus before surgery. |
| 21 | A controlled trial of arthroscopic surgery for osteoarthritis of the knee | 07/11/2002 | As discussed in chapter 3, this study found that arthroscopic surgery for osteoarthritis of the knee is ineffective. |
| 22 | Twenty-five-year followup of a randomized trial comparing radical mastectomy, total mastectomy, and total mastectomy followed by irradiation | 08/22/2002 | In a follow-up of an older reversal, this trial failed to show benefit for a more aggressive surgery, which dominated medicine in the 20th century. |
| 23 | Sex-based differences in the effect of digoxin for the treatment of heart failure | 10/31/2002 | Contradicting recommendations by the American College of Cardiology, the European Society of Cardiology, and the Heart Failure Society of America, this analysis found that digitalis increases the rate of death among women. |
| 24 | Antimicrobial treatment in diabetic women with asymptomatic bacteriuria | 11/14/2002 | Some groups recommended screening and treating women with diabetes for the asymptomatic presence of bacteria in urine specimens. This randomized trial found that this practice does not reduce complications or delay the onset of symptomatic infection. |
| 25 | A comparison of rate control and rhythm control in patients with atrial fibrillation | 12/05/2002 | Studies 25 and 26 were landmark studies showing that a lesser intervention for atrial fibrillation, a common arrhythmia, was as effective as a more aggressive approach. |
| 26 | A comparison of rate control and rhythm control in patients with recurrent persistent atrial fibrillation | 12/05/2002 | See study 25. |
| 27 | A randomized, controlled trial of the use of pulmonary- artery catheters in high-risk surgical patients | 01/02/2003 | This trial added to data questioning the use of a common monitoring device, the pulmonary artery catheter, in elderly, high-risk patients. |
| 28 | Imaging studies after a first febrile urinary tract infection in young children | 01/16/2003 | This study suggested that at least part of our evaluation of young children with urinary-tract infections is unnecessary. |
| 29 | Serum retinol levels and the risk of fracture | 01/23/2003 | This suggests that some nations’ practice of vitamin A supplementation and food fortification ought to be reevaluated, since high levels of vitamin A are associated with fractures. |
| 30 | Factors associated with progression of carcinoid heart disease | 03/13/2003 | This trial showed that an intervention for a rare tumor was associated with significant harm. |
| 31 | Effects of estrogen plus progestin on health-related quality of life | 05/08/2003 | On the topic that is probably the best-known example of reversal, this Women’s Health Initiative study found that the use of estrogen plus progestin did not improve women’s quality of life. There was no significant effect on health, vitality, mental health, depressive symptoms, or sexual satisfaction in women receiving the hormones as compared to placebo. This study is discussed in chapter 9. |
| 32 | Involved-field radiotherapy for advanced Hodgkin’s lymphoma | 06/12/2003 | This study suggested an important change in the treatment of advanced Hodgkin’s lymphoma. |
| 33 | Conventional adjuvant chemotherapy with or without high-dose chemotherapy and autologous stem-cell transplantation in high-risk breast cancer | 07/03/2003 | In a rapidly changing field, this study showed that a commonly used, more aggressive intervention reduced risk of relapse of breast cancer but did not improve mortality. |
| 34 | A multicenter, randomized, double-blind, controlled trial of nebulized epinephrine in infants with acute bronchiolitis | 07/03/2003 | This trial compared nebulized epinephrine with placebo in 194 infants with bronchiolitis and showed that there was no significant difference in length of hospitalization, a more meaningful end point than those used in previous trials that supported this therapy. |
| 35 | Evaluation of impermeable covers for bedding in patients with allergic rhinitis | 07/17/2003 | The encasement of bedding with impermeable covers has been recommended for the treatment of allergic rhinitis. Although this study showed that this intervention reduced allergen emission from mattresses, it had no effect on clinical outcomes. |
| 36 | Control of exposure to mite allergen and allergen-impermeable bed covers for adults with asthma | 07/17/2003 | Similar to study 35, this doubleblind, randomized, placebocontrolled trial of more than 1,100 patients found no benefit on any clinical or physiological outcome for this practice. |
| 37 | Estrogen plus progestin and the risk of coronary heart disease | 08/07/2003 | Following study 31, studies 37 and 38 furthered the evidence that estrogen-replacement therapy is ineffective. |
| 38 | Hormone therapy and the progression of coronaryartery atherosclerosis in postmenopausal women | 08/07/2003 | See study 37. |
| 39 | Outcomes at school age after postnatal dexamethasone therapy for lung disease of prematurity | 03/25/2004 | This study raised serious concerns about one of the standard therapies for premature newborns. |
| 40 | C-reactive protein and other circulating markers of inflammation in the prediction of coronary heart disease | 04/01/2004 | Measuring C-reactive protein (CRP) to evaluate for the risk of coronary atherosclerosis had been supported by numerous guidelines. This study showed that CRP was only a moderate predictor of the risk of coronary-artery disease and added only marginally to the predictive value of established risk factors. The authors called for guidelines to be reviewed on the basis of their findings. |
| 41 | The influence of resection and aneuploidy on mortality in oral leukoplakia | 04/01/2004 | This article suggested a reversal in the treatment of a precancerous lesion, but the article was retracted when suspicions arose that the data contained in the paper were falsified. |
| 42 | A comparison of highdose and standard-dose epinephrine in children with cardiac arrest | 04/22/2004 | This study overturned recommendations from the American Heart Association for pediatric advanced life support. |
| 43 | Open mesh versus laparoscopic mesh repair of inguinal hernia | 04/29/2004 | This study argued that the older, open method for repairing hernias is superior to the newer, laparoscopic approach. |
| 44 | Folate therapy and in-stent restenosis after coronary stenting | 06/24/2004 | This study suggested that folate therapy (actually folic acid, vitamin B6, and vitamin B12) is ineffective in preventing the failure of stenting procedures for coronaryartery disease. |
| 45 | Methylprednisolone, valacyclovir, or the combination for vestibular neuritis | 07/22/2004 | It was common practice to prescribe an antiviral medication and steroid for vestibular neuritis until this study showed that only the steroid, and not the antiviral medication, improved recovery. |
| 46 | Lumpectomy plus tamoxifen with or without irradiation in women 70 years of age or older with early breast cancer | 09/02/2004 | This study suggested that withholding radiation therapy for a group of older women with breast cancer does not worsen their outcomes. |
| 47 | Fresh whole blood versus reconstituted blood for pump priming in heart surgery in infants | 10/14/2004 | This study suggested that a novel and physiologically sensible transfusion strategy was not better than the former standard in infants undergoing cardio-pulmonary bypass surgery. |
| 48 | Angiotensin converting– enzyme inhibition in stable coronary-artery disease | 11/11/2004 | This is a controversial reversal in which a former standard (use of ACE-inhibitor medications in patients with vascular disease) was overturned. The failure of these medications to work in this study might be less a reversal and more the result of improvements in the care of these patients. |
| 49 | Secondary surgical cytoreduction for advanced ovarian carcinoma | 12/09/2004 | This study strongly suggested that less aggressive surgical care in a subset of patients with ovarian cancer is as effective as recently adopted, more aggressive care. |
| 50 | Coronary-artery revascularization before elective major vascular surgery | 12/30/2004 | This randomized, multicenter VA trial revealed that a common intervention, coronary-artery revascularization in patients with stable disease who are scheduled to undergo elective vascular surgery, did not offer any benefit. |
| 51 | Mild intraoperative hypothermia during surgery for intracranial aneurysm | 01/13/2005 | Hypothermia was found to be helpful as a neurosurgical adjunct in 1955. At the time of this publication, the technique was being used in nearly 50 percent of aneurysm surgeries. This large randomized study showed no improvement in neurological outcomes with hypothermia and an increase in bacterial infections. |
| 52 | Clopidogrel versus aspirin and esomeprazole to prevent recurrent ulcer bleeding | 01/20/2005 | For patients who have had gastrointestinal bleeding while on aspirin, guidelines recommended either the use of clopidogrel or the addition of a proton pump inhibitor to aspirin as equivalent strategies. This study showed that aspirin plus the proton pump inhibitor esomeprazole was far superior to clopidogrel in preventing future ulcer bleeding. |
| 53 | The risk of cesarean delivery with neuraxial analgesia given early versus late in labor | 02/17/2005 | The American College of Obstetrics and Gynecology recommended that epidural anesthesia be delayed until cervical dilation had reached at least 4 centimeters. This study showed that early and late epidural anesthesia are equivalent strategies. |
| 54 | UK controlled trial of intrapleural streptokinase for pleural infection | 03/03/2005 | Although guidelines suggested that intrapleural fibrinolytics helped the drainage of infected pleural effusions (fluid collections around the lungs) and reduced the need for surgical drainage, this study found no benefit in the important end points. |
| 55 | Cardiovascular events associated with rofecoxib in a colorectal adenoma chemoprevention trial | 03/17/2005 | This study, and studies 56 and 57, have been widely reported on. All three suggest that selective COX-2 inhibitors, widely prescribed pain medications that include Celebrex and Vioxx, might increase the risk of cardiovascular events. |
| 56 | Cardiovascular risk associated with celecoxib in a clinical trial for colorectal adenoma prevention | 03/17/2005 | See study 55. |
| 57 | Complications of the COX-2 inhibitors parecoxib and valdecoxib after cardiac surgery | 03/17/2005 | See study 55. |
| 58 | Comparison of warfarin and aspirin for symptomatic intracranial arterial stenosis | 03/31/2005 | Some doctors use the anticoagulant warfarin in the treatment of intracranial arterial stenosis. This study showed that warfarin therapy was associated with higher rates of adverse events and no benefit compared to aspirin. |
| 59 | Long-term outcomes of coronary-artery bypass grafting versus stent implantation | 05/26/2005 | Patients with narrowing of multiple coronary arteries have traditionally been treated with coronary-artery bypass surgery. Recently, percutaneous coronary intervention (PCI, or stenting) has been increasingly used to treat these patients. This observational study found that bypass surgery is still superior to PCI. |
| 60 | Hydroxyurea compared with anagrelide in highrisk essential thrombocythemia | 07/07/2005 | Anagrelide was a new drug that was gaining use for patients with essential thrombocythemia5abnormally high blood platelets. This trial showed that the traditional therapy, hydroxyurea plus aspirin, is superior. |
| 61 | Inhaled nitric oxide for premature infants with severe respiratory failure | 07/07/2005 | This large, multicenter, randomized trial showed that the use of inhaled nitric oxide was ineffective in infants weighing less than 1,500 grams at birth. This treatment was previously supported by a singlecenter study. |
| 62 | An evaluation of echinacea angustifolia in experimental rhinovirus infections | 07/28/2005 | As discussed in chapter 6, this study showed that echinacea provides no benefit in symptom duration or severity with rhinovirus infection (the common cold). |
| 63 | Developmental outcomes after early or delayed insertion of tympanostomy tubes | 08/11/2005 | Similar to study 6, this study showed no difference in development between prompt and delayed placement of ear tubes. |
| 64 | Amnioinfusion for the prevention of the meconium aspiration syndrome | 09/01/2005 | This trial contradicted a metaanalysis by finding that infusion of saline into the amniotic cavity of high-risk pregnant women had no benefit for preventing meconium aspiration syndrome (or other major maternal or neonatal disorders). |
| 65 | Early invasive versus selectively invasive management for acute coronary syndromes | 09/15/2005 | In a rapidly changing field, this study suggested that a common, more invasive strategy for patients with unstable coronary disease might not be superior. |
| 66 | Long-term vasodilator therapy in patients with severe aortic regurgitation | 09/29/2005 | Although guidelines suggested the use of the drug nifedipine for asymptomatic patients with severe aortic regurgitation (a heart-valve disease), this study found no benefit of the treatment in reducing or delaying the need for valvereplacement surgery. |
| 67 | Continuous positive airway pressure for central sleep apnea and heart failure | 11/10/2005 | This study was a controversial reversal, in that although the study showed numerous benefits for the use of continuous positive airway pressure (CPAP) for treating central sleep apnea in patients with heart failure, it showed neither a mortality benefit nor a quality-of-life benefit. |
| 68 | A trial of contraceptive methods in women with systemic lupus erythematosus | 12/15/2005 | Oral contraceptives are often withheld from patients with lupus for fear that they might worsen the disease. Studies 68 and 69 showed that the use of oral contraceptives does not increase the incidence of lupus flares. |
| 69 | Combined oral contraceptives in women with systemic lupus erythematosus | 12/15/2005 | See study 68. |
| 70 | The risk associated with aprotinin in cardiac surgery | 01/26/2006 | This trial showed that a drug used for patients having surgery for myocardial infarction was associated with increased risk of renal failure, myocardial infarction or heart failure, and stroke. |
| 71 | Clozapine alone versus clozapine and risperidone with refractory schizophrenia | 02/02/2006 | Often patients with schizophrenia are given multiple drugs to control symptoms. This study showed that the combination of two commonly used drugs was no better than one. |
| 72 | Saw palmetto for benign prostatic hyperplasia | 02/09/2006 | Although saw palmetto is used by more than 2 million men in the United States for the symptoms of prostate enlargement, this study showed no benefit in multiple outcomes. |
| 73 | Calcium plus vitamin D supplementation and the risk of fractures | 02/16/2006 | As discussed in chapter 6, this study suggested the commonly used calcium with vitamin D supplementation does not reduce hip fracture and increases the risk of kidney stones. |
| 74 | Glucosamine, chondroitin sulfate, and the two in combination for painful knee osteoarthritis | 02/23/2006 | Also discussed in chapter 6, this study showed that glucosamine and chondroitin sulfate, alone or in combination, did not reduce pain in patients with osteoarthritis of the knee. |
| 75 | Efficacy and safety of corticosteroids for persistent acute respiratory distress syndrome | 04/20/2006 | This study overturned the practice of using steroids to treat patients with acute respiratory distress syndrome, a common complication of critically ill patients. |
| 76 | Pulmonary-artery versus central venous catheter to guide treatment of acute lung injury | 05/25/2006 | Similar to study 27, this study called into question the utility of the pulmonary artery catheter. |
| 77 | A controlled trial of homocysteine lowering and cognitive performance | 06/29/2006 | Because observational studies suggested that people with low levels of plasma homocysteine retain better cognitive function, some clinicians have prescribed the vitamins folate, B12, and B6. This double-blind, placebo-controlled, randomized clinical trial showed that this intervention is not beneficial. |
| 78 | Effectiveness of atypical antipsychotic drugs in patients with Alzheimer’s disease | 10/12/2006 | This important study demonstrated the high incidence of adverse effects caused by medications commonly used to treat psychosis, aggression, and agitation in patients with Alzheimer’s disease. |