June 30th, 2014
Selections from Richard Lehman’s Literature Review: June 30th
Richard Lehman, BM, BCh, MRCGP
CardioExchange is pleased to reprint this selection 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.
NEJM 26 Jun 2014 Vol 370
AF in Patients with Cryptogenic Stroke (pg. 2478): Cryptogenic is a good word. It’s up there with “idiopathic” and “pleiotropic” and “diathesis” for covering gross ignorance with a smattering of Greek. “Cryptogenic” sounds as if it was first used to describe the odd symptoms that Superman experienced when exposed to kryptonite. However, its first use was recorded 30 years before the caped crusader first appeared in the skies above Metropolis in 1938. “Cryptogenic stroke” is a fairly recent term, covering 20-40% of incident stroke, and it challenges researchers to hunt around the garden looking for kryptonite hidden under stones. A patent foramen ovale! Ah yes, but it may be an innocent bystander. Atrial fibrillation (AF) then! Possibly, according to the EMBRACE study, but still unlikely to account for most unexplained ischaemic strokes. The Canadian researchers monitored 572 patients who had had an unexplained ischaemic stroke or transient ischaemic attack, half of them using standard 24 hour ECG, and half with a 30 day event monitor. Their mean age was 72, and the detection rate for AF was 3.2% versus 16.1% in the two groups.
Cryptogenic Stroke and Underlying Atrial Fibrillation (pg. 2478): In another study—a multinational trial funded by Medtronic—the longer the investigators looked for AF after an unexplained ischaemic stroke, the more they detected. Their cohort was considerably younger, with a mean age of 61.5. Here the comparison was between 24 hour ECGs done at one, six, and 12 months and continuous monitoring for a whole year using an implantable event detector. There was a cumulative difference through the year, at the end of which the detection rate was 2% versus 12.4%. These data lead the editorialist to conclude: “The results of two studies published in this issue of the NEJM indicate that prolonged monitoring of heart rhythm should now become part of the standard care of patients with cryptogenic stroke.”
JAMA 25 Jun 2014 Vol 311
Decline in Estimated Glomerular Filtration Rate and Subsequent Risk of End-Stage Renal Disease and Mortality (pg. 2518): “Chronic kidney disease (CKD) is a worldwide public health problem, with increasing prevalence, poor outcomes, and high treatment costs.” I don’t know if I believe a word of this. To me, the kidneys are complex appendages of the cardiovascular system, and most “CKD” is just an expression of cardiovascular disease. Its increasing prevalence is because people are living longer, and ditto its high costs. As the circulation fails, or diabetes gets into its final phase, people show a steep decline in glomerular filtration rate (GFR); this is not good news for these individuals, but it is hardly a public health problem. The more they are tinkered with, the higher their treatment costs become. Nobody likes to tell them how futile most of this treatment is, and how little renal physicians know about what works. I am sometimes called cynical for saying things like this, but am I missing something? This entirely nephrocentric paper paints a picture of gloom, based on the prognostic characteristics of a swiftly falling estimated GFR. We are indeed all doomed; but in my experience of generalist practice, to die of primary renal failure is actually quite rare.
JAMA Intern Med Jun 2014
Long-term Survival in Patients Undergoing Percutaneous Interventions With or Without Intracoronary Pressure Wire Guidance or Intracoronary Ultrasonographic Imaging (OL): A London registry lists 41 688 patients who had percutaneous coronary intervention (PCI) in NHS hospitals between 2004 and 2011. During this time, clever cardiologists in our centres of teaching and excellence increasingly adopted sophisticated techniques such as intracoronary ultrasound and intracoronary pressure wire measurement of fractional flow reserve. This long term survival study shows that they made no difference to outcomes compared with old fashioned angiography guided PCI. This paper does not bear the “Less is More” label, but it could.
Lancet 28 Jun 2014 Vol 383
Efficacy and Safety of Colchicine for Treatment of Multiple Recurrences of Pericarditis (pg. 2232): Forgive me if you have heard this before: colchicine is a good treatment for acute pericarditis and for preventing recurrences. Colchicums abound on the hills of Northern Italy, where this study was conducted. Don’t eat any part of them or you might die an unpleasant death. However, if you are an adult weighing more than 70kg and happen to have pericarditis, you may take 0.5mg twice daily for six months and this will halve your chance of having recurrences.
The BMJ 28 Jun 2014 Vol 348
Higher Potency Statins and the Risk of New Diabetes: The news that statins can “cause diabetes” broke about two years ago. This new Canadian study looks at several large primary care databases and discovers that: “In the first two years of regular statin use, we observed a significant increase in the risk of new onset diabetes with higher potency statins compared with lower potency agents (rate ratio 1.15, 95% confidence interval 1.05 to 1.26). The risk increase seemed to be highest in the first four months of use (rate ratio 1.26, 1.07 to 1.47).” So statins cause small elevations in blood glucose that correlate with their potency, i.e. their degree of LDL-C lowering. The usual reason to take a statin is not to lower LDL-C but to lower cardiovascular risk, and we do not really know whether risk lowering is directly linked with “potency”. We have only one individual patient data meta-analysis to go by, and its data are not available to researchers outside the Oxford Clinical Trials Support Unit. As for the “diabetes” bit, it should not matter to any individual whether they are classed as lying slightly below or slightly above the arbitrary definition line. What matters is the long term risk of harm associated with that particular level of blood sugar and their likelihood of benefit from treatment. And playing those odds, they would be better off staying on their statin, whichever it may be. But the choice is always a personal one.
June 26th, 2014
To Screen or Not for AF: Is That the Question?
Physician's First Watch, CardioExchange Staff
Up to one third of ischemic strokes are of uncertain etiology or “cryptogenic,” meaning that there is no overt explanation such as severe carotid stenosis, intracranial stenosis, or documented atrial fibrillation (AF). For some of these patients, intermittent AF may be present and could explain the ischemic stroke. This issue has been addressed by two recent studies published in the New England Journal of Medicine.
In the EMBRACE study, researchers randomized 572 patients aged 55 or older with cryptogenic stroke to either 30-day electrocardiogram (ECG) monitoring with a portable event monitor or to a standard 24-hour ECG recording. The primary outcome was newly detected AF lasting 30 seconds or more within 90 days of study entry. This endpoint was detected in 16.1% of the prolonged monitoring group, compared with 3.2% in the control group (P<0.001). By 90 days, significantly more patients in the prolonged monitoring group than in the control group were placed on anticoagulants (19% vs. 11%).
In the CRYSTAL AF study, investigators randomized 441 patients aged 40 or older with cryptogenic stroke to receive an insertable cardiac monitor (ICM) or undergo conventional follow-up. AF lasting more than 30 seconds was detected in 8.9% of the ICM patients versus 1.4% of the control group by 6 months (the primary endpoint; P<0.001). At 12 months, the rates were 12.4% vs. 2.0% (P<0.001). The median time from randomization to the first detection of AF was 84 days with ICM and 53 days with conventional follow-up.
Comment: Atrial fibrillation is the leading cause of cardioembolic stroke and is associated with severe strokes and high mortality. Therefore, identifying its presence in patients with stroke or transient ischemic attack is important. At face value, screening for AF in patients with strokes of uncertain cause would seem sensible.
In these two studies, brief episodes of AF were fairly common, in the range of 12% to 16% over a period of 1 to 12 months after the stroke event. The number needed to screen ranged from 8 to 10. However, some relevant uncertainties remain. Is a brief episode of asymptomatic AF, especially if detected months after the stroke, causally related to the stroke? How long must an AF episode last to be clinically significant, and when should it trigger initiation of anticoagulant therapy? Which stroke patients would benefit the most from AF screening? Screening for AF in patients with cryptogenic stroke likely should increase, but these questions must be addressed to determine how often we should screen for and treat AF in such cases.
–Seemant Chaturvedi, MD
Dr. Chaturvedi is Professor of Neurology at Wayne State University School of Medicine and Director of the Wayne State/Detroit Medical Center Comprehensive Stroke Program.
Reprinted from NEJM Journal Watch Neurology
June 25th, 2014
FDA Completes Safety Review of Olmesartan
Larry Husten, PHD
The FDA announced on Tuesday that it had completed its safety review of the antihypertensive drug olmesartan (sold as Benicar and other names). The investigation was initiated in 2010 when results from the ROADMAP trial showed that patients with type 2 diabetes taking olmesartan had an increased risk for cardiovascular death.
Now the FDA says that it “has found no clear evidence of increased cardiovascular risks associated” with olmesartan in diabetic patients. The FDA said that it would not change the recommendations for the use of olmesartan but it will include new data about the drug in its label.
June 24th, 2014
In Emerging China, STEMI Admissions Skyrocket But Treatment Lags
Larry Husten, PHD
Accompanying all the other changes in China over the past decade, admission to the hospital for ST-segment elevation MI (STEMI) has soared, according to a paper published in the Lancet. Although the study finds that there have been some genuine improvements in treatment, the Chinese healthcare system still has a long way to go to improve the outcome of STEMI patients.
The study, which is the first of its kind to assess heart attack treatment across China, offers details about what its authors, a group of prominent Chinese and U.S. researchers, call China’s “period of epidemiological transition.” They analyzed data from nearly 14,000 STEMI patients at 162 hospitals across China. From 2001 to 2011, they observed a highly significant 4-fold increase in admissions for STEMI, from 3.7 to 15.8 per 100,000 people. This was accompanied by significant increases in smoking, hypertension, diabetes, and dyslipidemia.
There were some improvements in treatment, but overall the findings suggest important gaps. There were significant improvements in the use of some drug therapies, including aspirin and clopidogrel, but no significant improvement in other important drugs, including beta-blockers and ACE inhibitors. Although there was a significant increase in the percentage of patients who received primary percutaneous coronary intervention, from 10% to 28%, there was no change in the overall percentage of STEMI patients who underwent reperfusion (45%). There were no significant improvements in mortality rates or other measures of outcome over the study decade.
In a Lancet press release. the study’s corresponding author, Lixin Jiang, said:
The growing needs for inpatient STEMI care will create pressure for Chinese hospitals to increase capacity, adequately train health-care professionals, develop infrastructure, and improve care. The striking increases in hospital admissions for STEMI noted in our study show that important improvements in capacity have been made; however, national STEMI mortality suggests that further growth will be necessary to ensure adequate access for patients with the disorder in China. Furthermore, our study underlines that access to care does not ensure the delivery of the highest-quality care; suggesting that in addition to improvements in capacity, hospitals in China must simultaneously strive to improve care.
One of the U.S. authors, Harlan Krumholz (editor-in-chief of CardioExchange), provided the following comment:
This first-ever national report of heart attack care in China reveals a quadrupling of hospitalizations for STEMI and clear targets for quality improvement. What is truly remarkable is the Chinese government funded the study and committed to allow it to proceed independently and did not have a role in the science or the publication. There is a realization at high levels that for health care to improve there must be an honest and transparent assessment of current and past performance as a prelude to future initiatives. I am hopeful that this approach will strengthen and grow. This is the first step.
June 24th, 2014
FDA Recalls Another Batch of Generic Metoprolol
Larry Husten, PHD
The FDA has recalled more than 13,000 bottles of metoprolol succinate extended-release tablets manufactured by Dr. Reddy’s Laboratories. In addition, the agency recently recalled another lot of generic metoprolol from a different company, Wockhardt. Both recalls were for medicines manufactured at facilities in India. There have been multiple reports in recent years of problems with generic drugs made in India.
The recalls were categorized as Class II, which the FDA says “may cause temporary or medically reversible adverse health consequences or where the probability of serious adverse health consequences is remote.”
A story in the New York Times details the long-simmering and growing concerns of Cleveland Clinic cardiologist Harry Lever over generic metoprolol. Lever reported his concerns to the FDA and attempted to get Congress involved, but he could not prove the generics were at fault. “’You see enough people and you get a feel, but it’s anecdotes. It’s not science’,” Lever told the Times. Now, he “is feeling a sort of sad vindication,” the Times reports.
June 23rd, 2014
Unethical Health Screening: When Unnecessary Tests Do More Harm Than Good
Ethan J Weiss, M.D.
The policy group Public Citizen is urging 20 hospitals in eight states to sever their relationships with HealthFair Health Screening because they believe the company’s heavily promoted, community-wide cardiovascular health screening programs are unethical and are more likely to do harm than good. ACC president Patrick O’Gara released a statement saying that, “The questions raised about screening have some merit.” CardioExchange asked Ethan Weiss, an Associate Professor at the UCSF School of Medicine, to share his thoughts on this issue. Further details are included in CardioExchange’s news coverage.
Conceptually, people (including many doctors) believe that we should do everything we can to discover occult disease like heart disease. The assumption is that if we look hard enough, we can find disease and intervene to change the outcome in a positive way. People may ask, “What’s the harm?” However, for cardiology at least, there is no evidence to support this assumption outside of screening for hypertension, lipid abnormalities, and diabetes. This situation is worsened when options such as executive physicals are offered, which harden the perception that there must be some health benefit, but you just need money to access it. Again, sadly, this is not supported by evidence.
There can be serious consequences to false-positive results. Usually the harm is limited to unnecessary anxiety caused by false-positive tests, but there are also costs (many of these tests are not reimbursed) and the rare cases where false positives result in more tests that lead to complications and very serious medical consequences.
I once had a symptomatic patient with well-managed risk factors who insisted on having a nuclear stress test annually. It had been something started by a colleague of mine who had seen him before me — a very senior and respected doctor — and it was hard for me as a young doctor to overcome the perception that I did not know what I was talking about.
I kept doing the stress tests for a few years, but all the while I tried to convince him it was a mistake. I finally resorted to telling him that I was concerned about all the radiation he was getting. He continued to insist on the tests because he believed (firmly) that this was helping him and could not harm him.
One summer, I got an urgent call from him from the U.S./Canada border where he was being detained — he had set off the Geiger counter crossing the border a few days after his stress test. He was shaken. I reassured him and convinced the border patrol that he was not a terrorist. The next time he came to see me, he agreed to stop having stress tests and has not had one since.
I do believe that we can and will eventually improve our prediction tools. Right now blood pressure, lipids, and diabetes are the only validated — and thus, recommended — things to screen. This does not mean that we shouldn’t talk about other factors such as weight, body composition, nutrition, and exercise with our patients. The truth is that the evidence base for these factors is pretty flimsy too, but we make the assumption that it can’t hurt, and I try to inform patients where we have strong evidence and where we do not.
The bottom line for me is to be honest with patients about what prediction and prevention tools we have and what the evidence base is for each of them. Going forward, we need to work on more robust and careful studies from which we can learn how to better identify at-risk individuals and also validate whether the new tools do what they should. Finally, we should work to show that the information we learn from these tools can help improve clinical outcomes.
June 23rd, 2014
Selections from Richard Lehman’s Literature Review: June 23rd
Richard Lehman, BM, BCh, MRCGP
CardioExchange is pleased to reprint this selection 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.
NEJM 19 Jun 2014 Vol 370
Antidepressant Use in Pregnancy and the Risk of Cardiac Defects (pg. 2397): The serotonin reuptake inhibitors have been one of pharma’s greatest success stories of the last quarter century. Easy to start and hard to stop, they can be tried for almost anything that makes people feel down, and at almost any age. As a result, a large number of women become pregnant while taking an SRI. Within the Medicaid system alone, 64 389 women (6.8%) used antidepressants during the first trimester between the years 2000 and 2007. What happened to their babies? It seems that they have no significant added risk of cardiovascular abnormalities. If there are other harms, we don’t yet know.
JAMA 18 Jun 2014 Vol 311
Thrombolysis for PE and Risk of All-Cause Mortality, Major Bleeding, and Intracranial Hemorrhage (pg. 2414): Geoffrey Rose said that “There is no disease that you either have or don’t have—except perhaps sudden death or rabies. All other diseases you either have a little or a lot of.” This is true of pulmonary embolism, as I keep pointing out. It is demonstrated by this meta-analysis of “Thrombolysis for Pulmonary Embolism and Risk of All-Cause Mortality, Major Bleeding, and Intracranial Haemorrhage.” “Among patients with pulmonary embolism, including those who were hemodynamically stable with right ventricular dysfunction, thrombolytic therapy was associated with lower rates of all-cause mortality and increased risks of major bleeding and ICH. However, findings may not apply to patients with pulmonary embolism who are hemodynamically stable without right ventricular dysfunction.”
The BMJ 21 Jun 2014 Vol 348
Effect of Screening and Lifestyle Counselling on Incidence of Ischemic Heart Disease in General Population: Here is a truly important study that needs to be mulled over. In a Danish group of 6000 people at high risk of cardiovascular disease, “After five years of counselling a significant effect on lifestyle was seen, with a substantial reduction in the prevalence of smoking, improved dietary habits, sustained physical activity (among men), and a decrease in binge drinking. Furthermore, a significant improvement in self reported mental health and sustained self reported physical health occurred. These findings indicate that counselling promotes beneficial changes at the individual level for at least a limited period of time.” But this intervention had no effect on ischaemic heart disease, stroke, or mortality at the population level after 10 years. The individuals benefited, but the “population” did not. Does this negate the value of the intervention? I think not, but then I am not a public health physician.
June 23rd, 2014
FDA: Risk for Venous Thromboembolism with All Testosterone Products
Kristin J. Kelley, CardioExchange Staff
The FDA is requiring an expanded label change to all approved testosterone products to warn of the increased risk for venous thromboembolism. Labels currently address the risk for clots associated with polycythemia caused by testosterone treatment.
The action follows reports of blood clots in testosterone users unrelated to polycythemia. The agency says the warning is not related to an ongoing investigation announced in January about possible cardiovascular risks associated with testosterone treatment.
June 23rd, 2014
Mobile Cardiovascular Screening Programs Come Under Fire
Larry Husten, PHD
The consumer group Public Citizen has urged 20 hospitals to sever their involvement in a mobile cardiovascular screening program. The HealthFair Cardiovascular Screening Packages are unethical, mislead consumers, and do more harm than good, according to Public Citizen.
In a statement, the president of the American College of Cardiology, Patrick O’Gara, said that “the questions raised about screening have some merit…. we do not recommend broad and untargeted screening.”
The program, says Public Citizen, “peddles inexpensive cardiovascular disease screening packages to people living near the hospitals and institutions without identifying who has relevant risk factors that would make each of the screening tests medically appropriate. HealthFair’s basic cardiovascular screening packages include six tests that, among other things, take pictures of the heart, measure its electrical activity and look for blockages in arteries.”
“The promotions rely on fearmongering and erroneously suggest that for most adults in the general population, these screening tests are useful in the prevention of several potentially life-threatening cardiovascular illnesses – including heart attacks, strokes and ruptured abdominal aortic aneurysms – and make them sound like an appealing bargain,” according to Public Citizen. Among the harms cited by Public Citizen are false-positive results or the discovery of inconsequential abnormalities. “Both circumstances can lead to additional unnecessary and risky tests and treatments that will harm some people, cause unfounded anxiety, and cost patients and insurance companies.”
Here is O’Gara’s response to Public Citizen:
The questions raised by Public Citizen about mass screenings have some merit. Medical screenings can be hugely beneficial to patients, but they are also costly and can contribute to some of [the] issues of false positives and overdiagnosis outlined in the letters. To that end, both the ACC and the American Heart Association have joint guidelines that offer recommendations to guide physicians in making decisions with individual patients about their risk for heart attack and stroke. Other than assessing blood pressure and serum cholesterol, being attentive to diabetes and promoting a healthy weight with regular exercise, we do not recommend broad and untargeted screening.
From the patient perspective, decisions about the need for additional testing should be based on each patient’s circumstances. The College was one of the first associations to participate in the Choosing Wisely campaign, which encourages physicians and patients to discuss the costs and benefits of often overused tests and procedures. In addition, the College’s CardioSmart initiative is focused on educating patients and caregivers about cardiovascular disease, treatments and prevention.
Note: Comments on this news story are closed, but please join the discussion about this topic over at Ethan Weiss’ post, where he discusses the consequences of unethical and unnecessary cardiovascular screening.
June 23rd, 2014
If You Snus, You Lose: Study Shows Benefits of Quitting Smokeless Tobacco
Larry Husten, PHD
The adverse effects of smoking are well known and documented. The effect of smokeless tobacco is less clear. Now a study from Sweden, published in Circulation, offers evidence that quitting smokeless tobacco after MI is about as beneficial as quitting smoking. The results do not support the common view that smokeless tobacco is a safe alternative to smoking.
In their main analysis, the investigators analyzed the risk for death in Swedish MI patients, 675 of whom had quit using snus (the Swedish form of oral snuff) after MI and 1799 of whom continued to use snus. After 2.1 years of follow-up, the mortality rate was reduced in half among those who quit relative to those who continued using snus, from 18.7 to 9.7 per 1000 person-years. After adjustment for other risk factors, the hazard ratio for quitters was 0.57, similar to the 0.54 HR seen in a separate analysis among those who quit smoking after MI compared with those who continued to smoke.
“We didn’t expect to see such a strong association among those people who stopped using (smokeless tobacco),” said lead author Gabriel Arefalk, in an AHA press release. “After a heart attack, no doubt smoking cessation reduces the risk of death approximately one third and is really a cornerstone of cardiac rehabilitation worldwide. For smokeless tobacco, we did not know.”
NEJM Journal Watch — Recent Cardiology Articles- Major and Intracranial Hemorrhage Risk with Direct Oral Anticoagulants vs. Aspirin
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