July 2nd, 2013
Hundreds of Questions About the Integrity of Stem-Cell Research Group
Larry Husten, PHD
Serious questions have been raised about the integrity and validity of research conducted by a well-established German stem-cell research group. An article in the International Journal of Cardiology exhaustively details a multitude of discrepancies and contradictions in papers from the group. Further, the revelation of such widespread misconduct may lead to broader, disturbing questions about the reliability of scientific publications and the ability of the clinical research system to police itself.
In their article titled “Autologous Bone Marrow-Derived Stem Cell Therapy in Heart Disease: Discrepancies and Contradictions,” Darrel Francis and colleagues scrutinize 48 papers from the research group Bodo-Eckehard Strauer. According to Francis et al., the 48 papers from Strauer’s group contained reports on only 5 actual clinical studies, or “families” of reports, and duplicate or overlapping reports were common. The Francis article details more than 200 errors in the papers, including contradictory descriptions of the design, protocol, and results of the trials. Francis and colleagues write:
“Readers cannot always tell whether a study is randomised versus not, open-controlled or blinded placebo-controlled, or lacking a control group. There were conflicts in recruitment dates, criteria, sample sizes, million-fold differences in cell counts, sex reclassification, fractional numbers of patients and conflation of competitors’ studies with authors’ own.
Contradictory results were also common. These included arithmetical miscalculations, statistical errors, suppression of significant changes, exaggerated description of own findings, possible silent patient deletions, fractional numbers of coronary arteries, identical results with contradictory sample sizes, contradictory results with identical sample sizes, misrepresented survival graphs and a patient with a negative NYHA class.”
Strauer: Attracting Controversy
In 2009, Strauer retired from his position as the head of cardiology at Düsseldorf University Hospital. He has remained active in research at Rostock University. In December 2012, the German newspaper Süddeutsche Zeitung reported that fraud allegations against Strauer were being investigated by Düsseldorf University Hospital. The news seems not to have been reported outside Germany, and no further details have been revealed to date.
Bodo-Eckehard Strauer
Strauer has been the subject of previous controversies. In 2010, he presented the results of the STAR trial at a Hot Line session during the annual meeting of the European Society of Cardiology. However, all the data had been published a month earlier in the the European Journal of Heart Failure. When the fact of the publication became public during the meeting, the ESC leadership rebuked Strauer and said that it would not accept his abstracts for two years.
In 2007, several prominent stem-cell researchers were sharply critical of Strauer for hyping the results of a single case to a German newspaper and calling it a “global innovation.” Andreas Zeiher, a stem-cell researcher who was also the head of cardiology at the University of Frankfurt, told the Scientist that “Science is not [done by] reporting a single case… What Strauer has done is to give a patient report, not a scientific study.”
When contacted by CardioExchange about the new allegations, Zeiher said he agreed with the major findings of Francis’s International Journal of Cardiology paper. “It is indeed more than scary and disappointing to learn that the extent of ‘imperfectness’ in reporting clinical data by the group of Strauer is so enormous. This will be another major blow against an emerging field (cell-based therapies), which did raise tremendous expectations, but appears to be crippled by irresponsible ‘clinical scientists,’ who appear to be focused exclusively on their own agenda.”
Other stem-cell researchers, cardiologists, and clinical trial researchers had similar thoughts about the glaring deficiencies of the Strauer papers cited by Francis et al., although several said they were unable to fully judge the nature and extent of the misconduct.
In an accompanying editorial, Peter Wilmshurst, a cardiologist who has been involved in several previous scientific controversies, writes:
“The analysis by Francis et al. suggests that there have been numerous publications of the same sets of data from Strauer’s group. Moreover what initially appear to be duplicate publications provide contradictory descriptions of experimental designs and of results. At the same time there are implausible agreements between data in populations of different sizes as well as statistical and arithmetic impossibilities in other datasets. I can see no logical option but to suspend belief in any of the data reported in these publications until an appropriate investigation has been performed.”
Some of the details cited by Francis et al. appear to be trivial, but some of the errors are startling. Francis et al. cite one example of a figure that appears unchanged in 2 separate publications. The two figures, reprinted below, showing the change in ejection fraction over time in the treatment and control groups, are from 2 separate publications about 2 different clinical trials with different numbers of enrolled patients. The first figure is reprinted from a chapter about the BEST-Heart study by Strauer and 2 colleagues in a book edited by Strauer and 2 colleagues (one of whom was also a coauthor of the chapter). The second figure is from the European Journal of Heart Failure publication of the STAR-heart study. Click to enlarge each figure.
Francis et al. also report that there were “many more patients being treated than bone marrow aspirations actually being processed.” In other words, the number of patients reported to have been treated with stem cells in the trials was greater than the number of stem cell preparations. In addition, they report:
Extraordinarily unlikely occurrences were reported. In one case two samples of very different sizes and different means had identical standard deviations.
And:
Kaplan–Meier plots proved an unexpected quagmire. Some failed to start at time 0, whilst others failed to show the vertical steps at event times, and some did not have horizontal plateaus between events… Presumably through incorrect software use, curves sometimes looked almost manually-sketched … Authors did not always realise that Kaplan–Meier analysis and survival regression are contrary approaches.
The Watchdog
The lead author of the new report is Darrel Francis, an academic research cardiologist at the National Heart and Lung Institute in London. His own research is far removed from the stem-cell arena. He became interested in the field when one of his patients travelled to Germany for stem-cell treatment from Strauer’s group. When the STAR trial was published, he “noticed that the numbers didn’t add up.” When he failed to receive an adequate answer to his questions from Strauer or from the journal, he began a more systematic examination of papers from the group. He was shocked by the findings.
Darrel Francis
The Francis paper in International Journal of Cardiology has itself been criticized by academics and clinical researchers who have seen it. For one, Francis overstates the prominence of Strauer and the impact of his work. Although the paper describes Strauer’s group as the “foremost group in this field,” other researchers in the field strongly disagree with this opinion. Strauer appears to have been an active researcher with many publications, but he is not considered a thought leader or a highly influential figure.
Another more serious critique of the Francis paper is that it fails to sort out minor or trivial errors from major flaws that raise the possibility of serious scientific misconduct or fraud. The overwhelming amount of detail contained in the paper makes it difficult to assess the situation without an enormous commitment of time and energy. But the experts who spoke to CardioExchange agreed that there were enough instances of serious flaws to warrant concern.
Beyond Strauer: Journals and the Scientific Community
A second major issue raised by Francis et al. is the unwillingness of journal editors to investigate articles they have published. In the online supplement to their article, Francis et al. reprint their correspondence with the editors of the Journal of the American College of Cardiology and the European Journal of Heart Failure (published by the European Society of Cardiology). The editors dismiss the issues raised by Francis et al., although they do not provide a substantive response to the issues. Zeieher was equally critical of journal editors for being “unwilling to take the necessary steps to ensure scientific validity of their own publications, even if confronted with obvious discrepancies in some of the papers published.”
Francis et al. also point out that although publications from Strauer’s group have been frequently cited, and also included in meta-analyses, the authors have failed to uncover many of the glaring errors in the papers.
July 1st, 2013
Selections from Richard Lehman’s Literature Review: July 1st
Richard Lehman, BM, BCh, MRCGP
CardioExchange is pleased to reprint selections from Dr. Richard Lehman’s weekly journal review blog at BMJ.com. Selected summaries are relevant to our audience, but we encourage members to engage with the entire blog.
JAMA 26 June 2013 Vol 309
Personalized Medicine vs. Guideline-Based Medicine (pg. 2559): Another Viewpoint piece has the tempting title “Personalised Medicine vs Guideline-Based Medicine” and discusses the uses and abuses of subgroup analysis. I think we may need more of this, once statistical science has developed sufficiently to meet the challenge of massive individual patient data sharing. This piece dwells on the counter-intuitive findings of trials of implantable cardioverter-defibrillators: they have no mortality benefit in the months of highest risk after myocardial infarction, but only show benefit much later on—perhaps as much as two years later.
JAMA Intern Med 24 June 2013 Vol 173
Aggressive Fluid and Sodium Restriction in Acute Decompensated HF (pg. 1058): Emergency rooms are dangerous places for people with heart failure. In some cases (I know from an unpublished study) the doctor is likely to put up a litre of saline and give you inhaled beta stimulants and corticosteroids before doing anything else: in many other places, your fluid intake will be restricted while you are rendered thirsty, hypovolaemic, and hypotensive with loop diuretics, and then given inotropes to bring you round and/or kill you. To try to bring some science (and humanity) into this situation, patients admitted with acute decompensated systolic HF in this trial were randomized to fluid and sodium restriction or none. “Aggressive fluid and sodium restriction has no effect on weight loss or clinical stability at three days and is associated with a significant increase in perceived thirst. We conclude that sodium and water restriction in patients admitted for ADHF are unnecessary.”
Yield of Routine Provocative Cardiac Testing Among Patients in an Emergency Department–Based Chest Pain Unit (pg. 1128): Coming to hospital with non-cardiac chest pain is also extremely perilous, especially in the USA. Guidelines there mandate that you are offered an appointment with a cardiologist within three days, irrespective of the likelihood of your chest pain being cardiac. The cardiologist will then order a treadmill test, just to be on the safe side (and to earn money); and as you will know from reading Sackett et al, the false positive yield of stress tests depends on the pre-test probability, which in some of these patients will be close to zero. False positive treadmill means angiography (another nice little earner) and maybe the detection of some atheroma, sitting quietly and doing nothing. In goes the stent: the patient is grateful: she thinks her life may have been saved, and she has a label of ischaemic heart disease so every future chest twinge gets similar attention. Or, as this study observes, “In an emergency department–based chest pain unit, routine provocative cardiac testing generated a small therapeutic yield, new diagnoses of coronary artery disease were uncommon, and false-positive results were common.” But as my example demonstrates, this is only the half of it: detecting atheroma in the coronary arteries is not the same as establishing it as the cause of the chest pain. Why don’t people get this? Here is the distinguished Pat Crosskerry writing in the first article of this week’s New England Journal: “When a patient undergoes analytic assessment for chest pain in a cardiac clinic that culminates in angiography, the conclusion is invariably correct.” Oh boy.
July 1st, 2013
New Anticoagulant Found Safe and Effective in Acute Venous Thromboembolism
Larry Husten, PHD
In a large clinical trial the new oral anticoagulant apixaban (Eliquis, Pfizer and Bristol-Myers Squibb) was at least as effective as standard therapy and caused fewer bleeding complications in patients with acute venous thromboembolism (VTE). The results of the AMPLIFY (Apixaban for the Initial Management of Pulmonary Embolism and Deep-Vein Thrombosis as First-Line Therapy) trial are being presented today at the annual meeting of the International Society on Thrombosis and Haemostasis in Amsterdam and are being published in the New England Journal of Medicine. (The embargo on the trial was lifted early by the Journal after being broken by Reuters.)
The AMPLIFY investigators randomized 5,395 patients with acute VTE to either conventional therapy with enoxaparin and warfarin or apixaban (10 mg twice daily for a week, followed by 5 mg twice daily for 6 months). The rate of recurrent symptomatic VTE or death related to VTE, the primary efficacy outcome, was 2.3% in the apixaban group versus 2.7% in the control group (relative risk 0.84, CI 0.60-1.18). This result met the prespecified criteria for noninferiority. In addition, apixaban was associated with significant reductions in the rate of major bleeding (0.6% versus 1.8%, RR 0.31, CI 0.17-0.55, p<0.001 for superiority) and the rate of major bleeding plus clinically significant nonmajor bleeding (4.3% versus 9.7%, RR 0.44, CI 0.36-0.55, p<0.001).
The results were consistent across a broad range of subgroups and were similar in patients who had pulmonary embolism and in patients who had deep vein thrombosis. The results were similar even when apixaban was compared only with those centers where warfarin was used most skillfully.
The study results “add to the evidence that the new oral anticoagulants are simple alternatives to conventional therapy for patients with acute venous thromboembolism,” the authors wrote.
Results from a related previous trial, AMPLIFY-EXT, showed that after patients completed a standard anticoagulation regimen, recurrent VTE could be safely prevented with an extended course of apixaban.
In an accompanying editorial, Mary Cushman discusses the role of apixaban and other new oral anticoagulants in the treatment of VTE. She reminds physicians that there is still an important role for Vitamin K antagonists and that they will not “disappear from practice.” She lists six “key components” in the selection of a new anticoagulant in VTE patients: patient preference, patient selection, drug interactions, compliance, follow-up, and monitoring. Currently, rivaroxaban (Xarelto, Johnson & Johnson) is the only new oral anticoagulant with an FDA indication for acute VTE.
June 28th, 2013
More Bad News for HDL Therapies: ASSURE Trial Misses Primary Endpoint
Larry Husten, PHD
The string of bad news for HDL-related therapies continues. Resverlogix yesterday announced that the ASSURE clinical trial had failed to meet its primary endpoint. RVX-208, the drug being studied in the trial, is a novel small molecule that increases production of Apolipoprotein A-I (ApoA-1), which raises HDL levels and is thought to enhance reverse cholesterol transport.
ASSURE was a phase 2b multicenter, double-blind, randomized, parallel group, placebo-controlled trial studying RVX-208 in 324 patients with coronary artery disease and low HDL levels. The company said the trial “did not meet its primary endpoint of a -0.6% change in percent atheroma volume as determined by intravascular ultrasound (IVUS). The RVX-208 treated group had -0.4% plaque regression (p=0.08).” The company reported that the trial did meet “the secondary endpoints of regression of total (coronary) atheroma volume (TAV) and increases in Apolipoprotein A-I (ApoA-I) and HDL cholesterol.” The company said that results in the placebo arm of the study were stronger than expected.
Full results of the trial are expected to be presented later this year. Earlier this month the company said the results may be presented at the European Society of Cardiology meeting in Amsterdam at the end of the summer.
ASSURE was run by the Cleveland Clinic. Steve Nissen is the chairman of the trial and Stephen Nicholls is the principal investigator.
In recent years the once-highly promising area of HDL-raising therapies has experienced a series of disappointments. Large trials with niacin (AIM-HIGH and HPS2-THRIVE) and CETP inhibitors (Pfizer’s anacetrapib and Roche’s dalcetrapib) have failed spectacularly. Some critics maintain that although the drugs in these trials raised HDL levels, they did not enhance the functional aspect of HDL. RVX-208 was intended to do just that. One remaining question about ASSURE is whether a 26-week study with an IVUS endpoint was actually capable of measuring the potential clinical benefits of the drug. IVUS has never been validated as a surrogate endpoint.
June 28th, 2013
FDA Turns Back New Indication for Rivaroxaban to Prevent Stent Thrombosis in ACS Patients
Larry Husten, PHD
Johnson & Johnson said today that it had received a complete response letter from the FDA for the supplemental new drug application (sNDA) for rivaroxaban (Xarelto) for the prevention of stent thrombosis in patients with acute coronary syndromes (ACS). Earlier this year the FDA turned down for the second time the sNDA for the general use of rivaroxaban to treat ACS patients.
Both sNDAs were based on the pivotal ATLAS ACS 2-TIMI 51 trial. Initially the trial was widely praised, leading to expectations that rivaroxaban would be the first anticoagulant to receive an ACS-related indication. But the enthusiasm evaporated when FDA reviewers raised concerns about the trial and when the FDA’s Cardiovascular and Renal Drugs Advisory Committee voted against the ACS indication. (Diverging from their U.S. colleagues, European regulators granted the general ACS indication for rivaroxaban in May.)
“We remain confident in the results of the ATLAS ACS 2 TIMI 51 trial and are in ongoing discussions with the FDA regarding this sNDA,” said a company official.
Rivaroxaban is currently approved to reduce the risk of blood clots following knee and hip replacement surgery, for stroke prevention in people with nonvalvular atrial fibrillation, and for the treatment of and to prevent the recurrence of pulmonary embolism and deep vein thrombosis.
June 27th, 2013
Novel Heart Failure Drug from Novartis Gains ‘Breakthrough Therapy’ Designation from FDA
Larry Husten, PHD
Serelaxin, the novel therapy under development for the treatment of acute heart failure, has received a “breakthrough therapy” designation from the FDA, according to Novartis, the company developing the drug. The designation, the FDA explains, “is intended to expedite the development and review of drugs for serious or life-threatening conditions” and requires “preliminary clinical evidence that demonstrates the drug may have substantial improvement on at least one clinically significant endpoint over available therapy.” In addition to getting a speedier review process, the sponsor of a drug with the designation receives “more intensive FDA guidance” on the development program.
Serelaxin, also known as RLX030, could become the first significant new treatment for acute decompensated heart failure patients in a generation. The FDA action was based on promising results from the RELAX-AHF trial, which was presented at the American Heart Association meeting last November and published simultaneously in the Lancet. Patients who received serelaxin in the trial had a significant reduction in relief from dyspnea, one of the primary endpoints of the trial. But what really attracted the interest of the experts was the surprising finding of a small but statistically significant difference in mortality at six months in favor of serelaxin. The trial investigators acknowledged that the findings of a six-month survival benefit “for a drug given for 48 h with a moderate number of death events (107 total) raises the question of whether this benefit is due to chance and whether another, confirmatory trial should be done.” At the time, heart failure expert Milton Packer said that “if the mortality effect is true then this trial changes the way we do things.” But, he emphasized, ”the real question is whether the mortality difference seen in this trial is true and replicable.”
Serelaxin is a recombinant form of the naturally occurring human hormone relaxin-2, which has been found to help women adjust to the cardiovascular changes that occur during pregnancy.
June 26th, 2013
Some Patients with Minor Stroke or TIA May Benefit from Early Clopidogrel and Aspirin
Larry Husten, PHD
Some people with minor ischemic stroke or transient ischemic attack (TIA) may benefit from dual antiplatelet therapy with aspirin and clopidogrel, according to a large new study from China published in the New England Journal of Medicine.
In the immediate period following a TIA or minor stroke, people are at high risk for having a major stroke. Aspirin is known to cause a modest reduction in recurrent events. More potent antiplatelet agents like clopidogrel may also be beneficial, but they have not been well studied in the early phase and may increase the risk for bleeding complications, including the conversion of an ischemic stroke into a worse hemorrhagic stroke.
Investigators in the CHANCE (Clopidogrel in High-Risk Patients with Acute Nondisabling Cerebrovascular Events) trial randomized 5170 patients within 24 hours of a minor ischemic stroke or high-risk TIA to 3 months of treatment with either clopidogrel and aspirin or placebo and aspirin. At 90 days, the rate of stroke was 8.2% in the combination group versus 11.7% in the aspirin-alone group (hazard ratio 0.68, CI 0.57-0.81, p<0.001). There were also significant reductions in the rates of fatal or disabling stroke and ischemic stroke.
There was no difference in moderate or severe hemorrhage, which occurred in 0.3% of patients in each group. Bleeding complications of any type occurred in 2.3% of the combination group versus 1.6% of the aspirin group (HR 1.41, CI 0.95-2.10, p=0.09). The investigators calculated that 29 patients would need to be treated to prevent one stroke in the 3-month period.
The authors speculate that their results were achieved because they “targeted a population at particularly high risk for recurrent ischemia and at low risk for hemorrhage.” Earlier trials had included patients with more severe strokes and had not studied patients in the very early period studied in CHANCE. The investigators note that most of the benefit occurred in the first few days.
In an accompanying editorial, Graeme Hankey praises the study but cautions that its results are not widely applicable, since more than 41,000 patients were screened to obtain the study population of 5200 patients. Because of this, he writes, the results “cannot be generalized to most patients; the study excluded patients with major ischemic stroke, who are at risk for hemorrhagic transformation, and patients with TIA due to isolated sensory, visual, or vertiginous syndromes, who are at low risk for recurrence.”
In addition, accoridng to Hankey, “the results may not apply to non-Chinese patients with different forms of underlying arterial disease (e.g., a higher prevalence of extracranial large-artery atherosclerosis) and different prevalences of genetic polymorphisms of liver cytochrome P-450 (CYP) isozymes, which metabolize clopidogrel to its active metabolites.”
June 25th, 2013
What Will We Count in 30 Years?
Robert L Rosenthal, MD and James De Lemos, MD
From the perspective of today, cardiology 30 years ago was full of wrong ideas and practices. What will cardiology today look like in 30 years? In a paper published in the American Journal of Cardiology entitled “What We Counted,” Robert Rosenthal remembers practices that were once considered dogma but were later proven to be either incorrect or even harmful. He then speculates about which current practices will be judged in the future to have been misguided. James de Lemos interviewed Dr. Rosenthal for Cardioexchange.
de Lemos: Dr. Rosenthal, I thoroughly enjoyed reading your paper in the Am J Cardiol. I think it provides a great temporal context for “modern” cardiology. What prompted you to write this piece?
Rosenthal: I have always been interested in hearing how life was “back in the day”, stories told at first by my elderly relatives and recently by my patients, especially those who served in World War II. As a medical student, I was able to sit down with some great medical legends like H. Houston Merritt and Franz Ingelfinger, who enjoyed being asked what it was like for them to practice medicine when they were young. So I wanted to pick out some stories that I would tell if I was asked.
de Lemos: You seem to focus on history. What practical information can a young cardiologist learn from studying past practices in that field?
Rosenthal: No matter what field, cardiology or otherwise, I think you are at a disadvantage if you can’t place yourself in the context of time and appreciate what was understood and undertaken 20, 30, 40 years before you. As a specific example, all we had in our day were M-mode echos. Now, we don’t even perform or teach M-mode echo at our hospital. It is regarded as obsolete. But M-mode provides a more precise measuring and timing tool than current techniques. It will become a lost art like phonocardiography, which is a shame because both provide distinctive insights. Most current cardiology fellows would not even know what a phonocardiogram was.
de Lemos: When you look at contemporary cardiology, what are the current practices that you think we will look back on as useless or even dangerous?
Rosenthal: Of course, we don’t know now what will be looked on years hence as harmful or we wouldn’t be doing them, but I think we can be pretty certain that some of the things we do fall into that category. I did give examples in my article of practices that I think may become obsolete. I think we are seeing some of that evolve pretty rapidly in the field of lipids and so maybe 20 years from now people will be astonished to hear that doctors around the year 2000 actually focused on measuring and trying to raise the HDL. There are certainly a lot of fashions that come and go: coronary spasm and silent myocardial ischemia were very fashionable topics for a while, but now you don’t hear them spoken of much. Today’s fashions may be fractional flow reserve or diastolic dysfunction.
To our readers: Which of today’s practices or paradigms do you think will be looked upon in the future as folly?
June 24th, 2013
Large NIH Trial Finds No Cardiovascular Benefits for Weight Loss and Exercise in Type 2 Diabetics
Larry Husten, PHD
A large NIH-sponsored trial has found that an intensive lifestyle intervention was no better than standard care in reducing cardiovascular events in people with type 2 diabetes. The results of the Look AHEAD trial were presented today at the American Diabetes Association meeting and published simultaneously in the New England Journal of Medicine.
A total of 5,145 people with type 2 diabetes were randomized to either an intensive lifestyle intervention, focusing on weight loss through a low-calorie diet and increased exercise, or conventional diabetes care. Trial investigators had planned to run the study for as long as 13.5 years, in the hope of finding a significant difference in the rate of major cardiovascular events (death from cardiovascular causes, nonfatal MI, nonfatal stroke, or hospitalization for angina). However, after 9.6 years of followup the data and safety monitoring board performed an analysis and recommended that the trial be stopped for futility.
Major cardiovascular events occurred in 418 people in the control group versus 403 people in the intervention group (hazard ratio 0.95, CI 0.83-1.09, p=0.51). There were no significant differences in any of the individual components of the composite endpoint or any of the secondary outcomes. The results were consistent across the prespecified subgroups.
The trial did demonstrate the feasibility of long-term, modest weight reduction. People in the intervention group had lost 8.6% of their weight at 1 year, compared with 0.7% in the control group. At the end of the trial the difference had narrowed considerably, though there was still a statistically significant advantage for the intervention group (6% versus 3.5%). A similar pattern occurred with physical fitness, waist circumference, and glycated hemoglobin, with a large difference at 1 year in favor of the intervention group and a much smaller but still significant difference at the end of the trial. However, there were no significant differences at any time in LDL levels.
One ray of hope was that people in the intervention group were less likely to be treated with insulin during the first year of the trial and were more likely to have a partial remission of diabetes during the initial 4 years of the trial. In addition, as the trial investigators had previously reported, during the early years of the trial people in the intervention group had reductions in urinary incontinence, sleep apnea, and depression, and improvements in quality of life, physical functioning, and mobility.
The authors speculated that a larger weight loss in the intervention group might have produced better results, but observed that “the weight loss achieved in the intervention group is representative of the best that has been achieved with current lifestyle approaches.” They noted that the control group may have benefited from the increased use of statins, thereby lessening differences between the groups. They also speculated that the results might have been different with an alternative intervention, such as the Mediterranean diet.
In an accompanying editorial, Hertzel Gerstein takes an upbeat view of the trial, stating that physicians can tell their patients “that changes in activity and diet safely reduce weight, reduce the need for and cost of medications, reduce the rate of sleep apnea, improve well-being, and (in some cases) achieve a diabetes remission.” About the cardiovascular effects of intensive lifestyle interventions, physicians can “reassure their patients that intensive lifestyle interventions are unlikely to cause harm… and may provide a modest benefit. However,” he concludes, “even with no clear evidence of cardiovascular benefit, the Look AHEAD investigators have shown that attention to activity and diet can safely reduce the burden of diabetes and have reaffirmed the importance of lifestyle approaches as one of the foundations of modern diabetes care.”
June 24th, 2013
Selections from Richard Lehman’s Literature Review: June 24th
Richard Lehman, BM, BCh, MRCGP
CardioExchange is pleased to reprint selections from Dr. Richard Lehman’s weekly journal review blog at BMJ.com. Selected summaries are relevant to our audience, but we encourage members to engage with the entire blog.
JAMA 19 June 2013 Vol 309
Time to Treatment with Intravenous tPA and Outcome from Acute Ischemic Stroke (pg. 2480): Here is an outcome analysis of thrombolysis for stroke which leads the authors to call for even greater effort to ensure that stroke patients get intravenous tissue-type plasminogen activator (tPA) as quickly as possible. That’s one way of looking at it. The odds ratios are pitifully small and the cost implications are huge.
General Health Checks in Adults for Reducing Morbidity and Mortality from Disease (pg. 2489): The indefatigable Peter Gøtzsche is ever one for taking the battle to the enemy. Here he and two colleagues present the findings of their Cochrane review of regular health checks. Until recently this would have been the equivalent of launching a paintball attack on the Statue of Liberty. “There were no statistically significant favourable or harmful associations of general health checks with these outcomes [cardiovascular disease, cancer]. There was no association with hospital admission rates, disability, worry, additional physician visits, or absence from work.” Americans, this is one health cost you can cut right away.
NEJM 20 June 2013 Vol 309
Rapid BP Lowering in Patients with Acute Intracerebral Hemorrhage (pg. 2355): Here’s what you might call a tick-off trial: one that disposes of an intervention in one good randomized go. Does intensive blood pressure lowering in acute haemorrhagic stroke improve outcomes? Take 2839 patients and compare: there is no significant difference in outcomes between the normally treated and intensively treated groups.
BMJ 22 June 2013 Vol 346
Telemonitoring-Based Service Redesign for the Management of Uncontrolled Hypertension: Just what is telemedicine for? Is it trying to improve communication with patients, or avoid communication with patients? And what is the most important goal in hypertension research? Is it to put more people on more treatment with a number-needed-to-treat of 500, or to identify the 499 who will never benefit from their treatment? I am only an aged GP asking simple questions: I don’t know the answers. I’m glad to see the modest reporting of this trial of telemonitoring in the management of uncontrolled hypertension: “Supported self monitoring by telemonitoring is an effective method for achieving clinically important reductions in blood pressure in patients with uncontrolled hypertension in primary care settings. However, it was associated with increase in use of National Health Service resources. Further research is required to determine if the reduction in blood pressure is maintained in the longer term and if the intervention is cost effective.” And then, perhaps, some hard end-points? No, no, that would take much too long.
NEJM Journal Watch — Recent Cardiology Articles- Does Use of Drug-Coated Devices Improve Outcomes in Chronic Limb-Threatening Ischemia?
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- Beta-Blocker Use After Takotsubo Syndrome
- CTA-Guided Care in Stable Angina: Long-Term Results