January 21st, 2014
A Clinical Decision-Making Toolkit from Europe
Héctor Bueno, MD, PhD
The Acute Cardiovascular Care Association (ACCA), one of the six scientific associations of the European Society of Cardiology, has designed a toolkit for non-experts and experts in training who care for patients with acute cardiovascular conditions. The ACCA Clinical Decision-Making Toolkit, available in PDF format on the ESC’s website, includes algorithms, tables, and other guidance that, according to the preface, “are based either on the latest clinical practice guidelines or the clinical experience of a number of European experts in each field when guidelines are not available.” CardioExchange’s Harlan Krumholz interviewed the toolkit’s editor, Héctor Bueno, about this new instrument.
Krumholz: You embarked on an ambitious project. Why did you do it?
Bueno: Managing patients with acute cardiovascular diseases has become increasingly complex during the past several years. Several of these syndromes, some life-threatening, require immediate diagnosis and treatment. The best acute care relies not only on specialists but on systems that involve many non-cardiologists. Critical decisions often must be made quickly by professionals with different backgrounds and levels of expertise in environments with limited resources. This poses a significant clinical challenge.
We realized that there was not a unified guide to help clinicians making the right decision rapidly for patients with different cardiovascular problems. We designed the toolkit to help guide the clinical decision making of non-experts who are involved in the initial management of patients with acute CV conditions. Our aim is to help improve the quality of acute cardiovascular care. As our preface describes, our work will be worthwhile if it saves even only one life or improves one outcome.
Krumholz: This is an ESC initiative. Tell us about your working group and about how this effort was funded.
Bueno: ACCA is the latest of the ESC’s scientific groups. Its mission is “to improve the quality of care and outcomes of patients with acute cardiovascular diseases.” We have established a multidisciplinary community of professionals who are involved in acute cardiovascular care, and we are building a platform for disseminating pertinent knowledge (learning & science) and skills (training & certification). ACCA has reached more than 4100 members in its first year and is currently the third largest association in the ESC. The Toolkit was funded by unrestricted grants to ACCA from AstraZeneca and Novartis, to develop an ambitious multidisciplinary educational program. Those companies did not participate at all in the selection of topics, authors, or (of course) content.
Krumholz: What is the most important message from your product?
Bueno: The toolkit is an instrument to help providers make initial decisions correctly when managing patients who present with the most common CV symptoms or acute CV syndromes. It is based on guideline recommendations or, when there is not enough evidence to guide decisions, on the clinical experience of experts in different fields. The quality of acute cardiovascular care can be improved, and we need tools and interventions to achieve that goal. The toolkit is just one of the instruments that the ACCA has developed for quality improvement.
Krumholz: How do you hope that the toolkit will be used? What is happening so far?
Bueno: We decided to design the toolkit, on the one hand, as a comprehensive resource and, on the other hand, as a simple instrument that is easy to use in environments where initial acute cardiovascular care is typically provided. That is why the toolkit is constituted mostly of algorithms and tables. We would like it to be used in ambulances, emergency departments, CCUs, ICUs, and so on. For instance, the Emergency Systems in Madrid (SAMUR) adopted it immediately and asked for a copy for each of its physicians who work in medical ambulances. We would like all professionals in these settings to have access to the toolkit (and soon the ACCA Toolkit App, which is currently under development). We also believe that the toolkit can be extremely useful as a teaching resource for trainees and students.
Review the ACCA’s Clinical Decision-Making ToolKit, and share your thoughts about it here on CardioExchange.
January 21st, 2014
Anatomical Burden in CAD Predicts Outcome Better Than Ischemic Burden
In stable coronary artery disease (CAD), anatomical burden (the degree of occlusion found on angiography) and left-ventricular ejection fraction seem better predictors of outcome than either ischemic burden (as measured during stress CT) or initial treatment with medical therapy alone or added PCI.
In a substudy of the COURAGE trial, 621 patients underwent both anatomical and ischemic studies. Half received optimal medical therapy initially, and half received medical therapy plus PCI.
During a mean 5 years’ follow-up, the composite outcome (death, MI, or non-ST-segment elevation acute coronary syndrome) was better predicted by anatomic burden and ejection fraction than by ischemic burden. However none of the measures — alone or in combination — identified a group that would have benefited from early PCI.
Writing in the Journal of the American College of Cardiology: Cardiovascular Interventions, an editorialist speculates that greater anatomical burden may signal the presence of more plaques that could cause later events, whereas established ischemic burden would not be as predictive. He also points out that the ongoing ISCHEMIA study may further clarify the best approach in these patients.
Adapted from Physician’s First Watch
January 20th, 2014
Selections from Richard Lehman’s Literature Review: January 20th
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.
JAMA 15 Jan 2014 Vol 311
Calcium Density of Coronary Artery Plaque and Risk of Incident CV Events (pg. 271): My take on coronary calcium scoring is simple: if you are worried enough to think about it, just swallow a statin every night and take more exercise. But like the medieval theologians who supposedly argued about how many angels could fit on the end of a pin, the coronary artery calcium scorers have taken to arguing about how thick the calcium needs to be. Bizarrely, the thinner the calcium, the more dangerous it seems to be. You can read the full paper for nothing. But you’d be better off going for a walk and eating an orange.
Prevalence of Vascular Complications Among Patients With Glucokinase Mutations and Prolonged, Mild Hyperglycemia (pg. 279): This British study looks at a set of individuals who are genetically programmed to run at a higher “normal” level of blood glucose than the rest of us, because they carry heterozygous, inactivating glucokinase (GCK) mutations. They run at a mean HbA1c of 6.9% and provide an interesting insight into the long-term significance of high sugar in isolation: “Despite a median duration of 48.6 years of hyperglycemia, patients with a GCK mutation had low prevalence of microvascular and macrovascular complications.” By contrast, a cohort of similar age who had developed type 2 diabetes of youth had a horrific rate of macrovascular and microvascular complications. There is so much more to “type 2 diabetes” than sugar.
BMJ 18 Jan 2014 Vol 347
Dietary Fiber Intake and Risk of CV Disease: You have to be very old to remember the fibre needle. It was used to play shellac discs revolving at 78rpm on machines which produced sound by mechanical amplification. I am reminded of them by this systematic review of dietary fibre intake and cardiovascular disease. As far as I am concerned, this is just another case of medieval theologians counting angels on the head of a fibre needle. In the real world, we eat food, not fibre. Things that we know are good for the heart, like fresh fruit and vegetables, happen to contain a lot of cellulose. This counts as insoluble fibre—or is it soluble?—who cares. If you want the theology, turn to an editorial which worries about people not eating enough brown rice. If you want a life, go for a walk and eat an orange. Play some 78s. Drink wine. Eat fish. Dig the garden, using plenty of fibre as compost, because this is the best way for fibre to help your heart.
January 20th, 2014
FDA Grants Earlier Than Expected Approval for Medtronic’s CoreValve
Larry Husten, PHD
The FDA today approved Medtronic’s CoreValve transcatheter aortic valve replacement (TAVR) system for patients with severe aortic stenosis who are unable to undergo conventional open-heart surgery. The approval came several months ahead of expectations and without an FDA advisory panel meeting.
The approval was based largely on results from the Extreme Risk Study of the CoreValve U.S. Pivotal Trial. As previously reported, the rate of death or major stroke at one year was 25.5%, which was 40.7% lower than the prespecified performance goal of 43% (p<0.0001) based on historical standards. All-cause mortality was 7.9% at 30 days and 24% at 1 year. Cardiovascular mortality was 7.9% and 17.9%. The rate of major stroke was 2.4% at 30 days and 4.1% at 1 year.
“The low rates of stroke and valve leakage with the CoreValve System — two of the most concerning complications of valve replacement because they increase the risk of death and have a dramatic impact on quality of life — set a new standard for transcatheter valves,” said Jeffrey J. Popma, co-principal investigator of the trial, in a press release.
Medtronic said the FDA had approved the entire CoreValve platform, including 23mm, 26mm, 29mm, and 31mm sizes.
CoreValve will now compete in the U.S. marketplace with the Edwards Sapien device. Edwards anticipates approval this year of its next generation device, the Sapien XT. Edwards and Medtronic are locked in a bitter and wide-ranging dispute over patents. Earlier this week in the latest round of the fight, a federal jury awarded Edwards $394 million from Medtronic.
January 17th, 2014
FDA Panel Once Again Rejects ACS Indication for Rivaroxaban
Larry Husten, PHD
The FDA’s Cardiovascular and Renal Drugs Advisory Committee has once again turned down the supplemental new drug application for an acute coronary syndrome (ACS) indication for Johnson & Johnson’s Xarelto (rivaroxaban). The nearly unanimous vote (10-0, with 1 abstention) was in line with a highly negative review from FDA staff members.
Although originally the subject of high praise when it first came out, the pivotal ATLAS ACS 2-TIMI 51 trial has been bedeviled by criticism since the FDA drew attention to the unusually large amount of missing trial data. Previous discussions of the trial at the FDA brought the word “missingness” into common usage in the medical community. Although Johnson & Johnson made efforts to supply some of the missing data this time around, ultimately the panel members agreed with the most recent assessment from the FDA reviewers that the large amount of still-missing data made it impossible to reach firm conclusions about the relative safety and efficacy of the drug in the setting of ACS.
Panel member Linda Fried, from the University of Pittsburgh, gave voice to a view adopted by many of the committee members. ATLAS, she said, was probably “an overall positive study” but, because of the large amount of missing data and the absence of a confirmatory study, was “not robust enough” to support the ACS indication. Speaking on behalf of the sponsor, cardiologists C. Michael Gibson and Marvin Konstam tried to persuade the panel to accept their multiple positive analyses of the trial. But panel members, including outspoken critics like Steve Nissen and Sanjay Kaul, left little doubt throughout the day’s meeting that they were unlikely to vote in favor of the new indication.
January 16th, 2014
FDA Advisory Panel Votes in Favor of Approval for Merck’s Vorapaxar
Larry Husten, PHD
The FDA’s Cardiovascular and Renal Drugs Advisory Committee voted 10-1 in favor of approval for vorapaxar, Merck’s novel thrombin receptor antagonist. The “roller coaster ride” cliché might have been invented for this drug, which was the subject of tremendous early hopes followed by major disappointments and, finally, a subsequent revival.
The committee voted in favor of the drug for use as an adjunct therapy for the reduction of atherothrombotic events in patients with a history of myocardial infarction (MI). Panel chairperson Philip Sager said that “this drug addresses a real unmet medical need and can make a real difference for patients.”
The University of Colorado’s Mori Krantz provided the one negative vote, though in his comments he indicated that he was not entirely opposed to approval. He characterized his vote as a “formal dissent” and said that he wanted to get on the record his concerns about the large number of patients who would need to be treated with vorapaxar to prevent a single event and his fear that the bleeding complications observed in the study might be amplified in the real world.
Sanjay Kaul said that Merck “convincingly demonstrated that the benefit exceeded the risk in the selected patient cohort. Like all development programs, it has its fair share of warts, but there is an unmet need in this population where we have no safe and effective therapies available. Hopefully, if approved, it will be used in scenarios that optimize its benefit-risk profile.”
The panel spent much of the day wrestling with the complex questions raised by the drug’s troubled history, in which one large trial, TRACER, was stopped early due to high rates of serious bleeding and the other trial, the TRA2P trial, was redesigned in midstream. Ultimately, the panel believed that TRA2P had been able to show that vorapaxar was effective in a post-MI population in which patients with a history of stroke were excluded.
January 16th, 2014
Co-Chairs of JNC8 Hypertension Guidelines Address a Challenging Case
Justin Sadhu, MD, Paul James and Suzanne Oparil, MD
Washington University in St. Louis cardiology fellow Justin Sadhu presents a challenging case to the co-chairs of the JNC8 hypertension guidelines: Paul James, Professor and Chair of the Department of Family Medicine at the University of Iowa, and Suzanne Oparil, Professor of Medicine and director of the vascular biology and hypertensive program at the University of Alabama at Birmingham’s School of Medicine.
Sadhu: My patient is a 76-year-old black male who presents to the cardiology clinic for routine follow-up. His medical history includes hypertension, coronary artery disease (CAD) with prior stenting several years ago for anginal symptoms but no history of myocardial infarction (MI), and stage II chronic kidney disease (CKD) without proteinuria (estimated GFR 68 mL/min/1.73 m2 by the CKD-EPI equation). His current medications include aspirin (81 mg), atorvastatin (20 mg), hydrochlorothiazide (25 mg), lisinopril (40 mg), and metoprolol succinate (25 mg), all taken once daily.
The patient reports overall good quality of life without any angina or dyspnea and denies any adverse symptoms related to medications. Specifically, he denies any orthostatic lightheadedness. He remains reasonably active with housework and social activities, although he does not exercise regularly.
On exam, heart rate is 67 and blood pressure (BP) is 108/62. Body-mass index (BMI) is 24 kg/m2.
How would you proceed with further management of this patient? Would you consider discontinuing any of his antihypertensive medications?
James and Oparil: This case is important because it is similar to what many clinicians see frequently. It also highlights some of the important elements of the new 2014 Hypertension Guidelines.
Our comments are intended to address the clinical problem of hypertension, though it is difficult to separate BP elevation from other cardiovascular risk factors.
Set Goal BP
First we must address the characteristics of the patient that are decision points in assessing and recommending BP goals and then address the appropriate choices of medications.
To set goals for BP, we must know a patient’s age and whether he has diabetes or chronic kidney disease. The patient, at age 76, is older than age 60. The case report identifies a history of CKD without proteinuria, apparently based on the estimated GFR of 68 ml/min/1.73 m2. There is no reported history of diabetes, so the question before us is: Does this gentleman actually have CKD? Much of the discussion about his care will hinge on how we answer this question.
The clinical challenge is that the estimating equations for GFR were not validated in individuals over age 70 and we do know that an age-related decline in the estimated GFR is to be expected. Our recommendation is to individualize therapy and we do not have evidence to guide us here. If this gentleman had proteinuria, that would confirm the presence of CKD. Given his age, we would not label this patient with the diagnosis of CKD and would attribute this laboratory value to age-related decline.
Based on strong evidence in support of Recommendation 1 in our guideline, and his age being over 60, we would set a goal BP target of less than 150/90. If we were more convinced of CKD, the goal would be less than 140/90. Since his BP is 108/62, this does not appear to be a clinically significant distinction.
Is he “overtreated”? What medications should he be taking?
The patient’s BP today is 108/62. We would recommend that his BP be measured again after standing for one minute, as he may not remember if he has orthostatic symptoms at home. If there is any evidence that he is orthostatic, we would discontinue the metoprolol and reduce the dosage of the lisinopril.
There is not an evidence-based answer to the question about whether BP can be too low in a patient who is taking antihypertensive medications if he/she is asymptomatic, though many of us have a concern about a J curve at systolic BP < 120 mm Hg.
Other reasons to adjust his medications would be to improve adherence, reduce the costs of his therapy, and reduce the potential for adverse effects or drug-drug interactions. The benefit of lowering BP with medications to any goal below 150/90 mm Hg in this age group remains unproven. It would be important to assess the patient’s perception of the burden of his medication regimen and compare this to the potential benefits of drug treatment and make a shared decision about therapy moving forward.
Rationale:
The patient is on three medications that could be considered anti-hypertensives. He is on a diuretic (hydrochlorothiazide 25 mg daily), an angiotensin converting enzyme (ACE) inhibitor (lisinopril 40 mg daily) and a beta blocker (metoprolol 25 mg daily). His race is reported as black and, thus, based on Recommendation 7 of our guideline, we would recommend a diuretic or calcium channel blocker as initial therapy. He is on a diuretic at a dosage that has been demonstrated to improve health outcomes (see Table 4 of the guidelines). He is not on a calcium channel blocker — this would be a consideration if his BP were not controlled.
One rationale for the ACE inhibitor is if the clinician believed that the patient does in fact have CKD — treatment with an ACE inhibitor or angiotensin II receptor blocker has been shown to improve kidney outcomes in this patient group. However, based on the discussion above, the evidence is not strong that this gentleman does have CKD and this would be an area where his medication regimen could be simplified by reducing the dosage or eliminating the medication if his BP remains well controlled. One argument for leaving this medication without change is that he is doing well without any perceived harms. However, if concerns about polypharmacy, adherence, or adverse effects were to present, this would be an opportunity to reduce his medication burden. We also emphasize that we do not see a history of previous MI or heart failure (HF) and this strengthens our resolve to suggest that an ACE inhibitor is not required to achieve the goals for treatment of hypertension.
The patient is also on a beta blocker (metoprolol 25 mg daily). Beta blockers are a proven treatment for hypertension but did not rise to the level of the other four classes recommended for the initial treatment of hypertension in the 2014 Guidelines (Recommendation 6). This gentleman does have a history of CAD, but no documented MI or systolic HF — both indications for use of a beta blocker to improve patient outcomes. He is status post-stent placement and it is unclear if this medication was added to achieve goals of treatment for CAD or for hypertension. In the absence of MI or HF, the evidence is less convincing for the benefit of adding beta blockers to the regimen. Our first recommendation would be to stop the metoprolol given that the systolic BP is less than 120 mm Hg. We found no evidence to suggest that a lower BP goal should be recommended for those with CAD than for the general population.
We should emphasize continued vigilance with life-style interventions. His BMI is acceptable, but maintaining physical activity would be important. He should continue his daily aspirin and statin therapy given his CAD.
January 16th, 2014
Are All Carotid Stenting Systems Equal?
Jay Giri, MD, MPH and Robert W. Yeh, MD MSc MBA
CardioExchange’s Harlan Krumholz interviews Jay Giri and Robert W. Yeh about their research group’s analysis of patient-registry data on embolic protection devices that are commonly used in carotid artery stenting. The study is published in JACC: Cardiovascular Interventions.
THE STUDY
Researchers used the NCDR’s CARE registry to analyze data from 12,135 consecutive carotid stent procedures performed from January 2007 through March 2012. Stents were used in conjunction with their corresponding FDA-approved embolic protection device (EPD) in 78% of cases. The rate of in-hospital death or stroke was nonsignificantly higher with the Precise/Angioguard system (2.5%) than with the Xact/Emboshield system (1.9%) or the Acculink/Accunet system (1.8%); the differences remained nonsignificant in adjusted analyses. These three devices were used in 73% of all procedures.
THE INTERVIEW
Krumholz: How much weight do you put on comparative effectiveness research that is derived from registry data?
Giri: Registries provide a valuable resource for comparative effectiveness research, particularly regarding questions that require large patient volumes to answer and that are unlikely to be addressed in randomized clinical trials. In those circumstances, registries (despite biases inherent in observational analyses) may provide the only available evidence and have the advantage of not being limited to highly selected centers and patient populations. Therefore, their conclusions may be more generalizable to everyday practice. Finally, registries can serve an important exploratory role in providing information for power estimates and patient enrollment numbers for RCTs.
Yeh: Observational comparisons of devices and therapies from large registries complement RCTs in several ways: (1) They yield data on the safety and effectiveness of new treatments in diverse populations, including groups traditionally underrepresented in RCTs; (2) they provide adequate sample sizes to detect small signals that RCTs are not powered to study; and (3) they can address comparisons that are important to physicians and patients but are less likely to be funded by industry or federal agencies.
Of course, registry analyses are susceptible to confounding if they do not try to identify and account for the various factors that may influence physicians’ selection of a particular treatment. I believe that the weight one places on any particular observational comparison from registry data should depend on the following factors: What is the nature of the comparison? Do prognostic patient characteristics strongly influence treatment selection in the given clinical setting? Does the registry collect data on those factors? Do the methods adequately address the lack of randomization? Thus, the validity of registry data must be judged on a case-by-case or a study-by-study basis. With respect to our study, the selection of carotid stenting systems is probably governed more by institutional contracts and by physician training and comfort than by prognostically important, unmeasured patient characteristics. We believe that this allows for a robust observational comparison of carotid stenting systems.
Krumholz: Should we be doing head-to-head trials of the different EPD devices?
Giri: Given that the devices were associated with quite small differences, I do not think a randomized trial comparing them would be a good use of limited resources for clinical investigation. Besides, given the in-hospital event rates we found, a head-to-head trial of the compared devices is very unlikely to occur, as it would take well over 10,000 patients. With the current reimbursement situation for carotid stenting, device makers have waning interest in even continuing their own postmarketing registries, let alone supporting a much more expensive RCT that runs the risk of reflecting poorly on their device.
Yeh: Traditional post-approval randomized comparisons of these devices that do not have substantive mechanistic differences don’t seem to be a good use of resources, particularly in the field of carotid artery disease, where the role of carotid stenting is still not well defined. There is much promise in doing more pragmatically designed randomized comparisons that can leverage existing registries to compare devices cost-effectively, similar to what the TASTE trial did for aspiration thrombectomy in STEMI patients. On the pre-approval side, there is also an important question regarding whether “me too” devices that effectively do the same thing as existing devices must demonstrate more than “substantial equivalence” or “noninferiority” to gain FDA approval.
Krumholz: Are in-hospital outcomes sufficient to conclude that the devices are similar?
Giri: In this case, on the question of procedural safety, I would say yes. Our primary endpoint was procedure-related adverse events (stroke/death) associated with use of the different devices. We used in-hospital outcomes as the primary endpoint to avoid the selection bias associated with our 30-day data, which were available in only about three quarters of patients. Nevertheless, the proportions of adverse events between devices were nearly identical with the available 30-day data, further supporting the conclusions from our primary analysis. Notably, we focused on the procedural safety of carotid stenting but not procedural efficacy (i.e., primary or secondary stroke prevention over several years), which would have to be evaluated with long-term follow-up. We cannot comment on whether one carotid stent type is associated with greater efficacy than another with respect to long-term stroke prevention, given the data contained within the NCDR CARE registry.
Yeh: For EPDs, whose purpose is to prevent procedural complications and which are removed before the procedure is complete, in-hospital outcomes seem to be adequate. Data out to 30 days definitely provide even more reassurance. Efficacy and safety of the stent component of these systems would benefit from longer-term follow-up data. We have discussed the possibility of linking the CARE registry with long-term administrative claims data, as has been done for the NCDR CathPCI registry, but we have yet to do that. Such a linkage could help provide longer-term comparative data on these devices.
Krumholz: What are the implications of your findings for clinical practice?
Giri: Operators do not mix and match carotid stents and EPDs very often. This is a very different device-usage pattern from what we see in other coronary and peripheral interventions, where operators use their judgment to select equipment tailored to given anatomic situations. This practice may be driven, in a large proportion of cases, by the current carotid-stenting reimbursement requirements for industry-sponsored post-marketing surveillance study participation.
In addition, the three most commonly used carotid stenting systems are associated with a similar procedural safety profile, so operators should feel confident in using the devices they feel most comfortable with for a given clinical situation. A tremendous amount of time and energy has been spent theorizing about various technical considerations of carotid stents and EPDs that might make one superior to another. The current study effectively argues that continued focus on these technical issues is unlikely to significantly improve stroke rates around the time of carotid stenting. Nevertheless, we should still search for novel ways to prevent stroke in this population.
Yeh: Operators often choose among different devices that are intended to achieve the same goal. In interventional cardiology, we’ve seen substantial variation in the use of devices, more often governed by physicians’ preferences rather than by patient characteristics. In the case of carotid stenting systems, our registry data seem to provide reassurance that operators can continue to use their preferred devices according to their comfort level and experience, without adversely affecting patient outcomes.
How do the comments from Dr. Giri and Dr. Yeh affect your view of the carotid stenting systems that are commonly used to treat carotid artery stenosis?
January 14th, 2014
All Lots of Liptruzet In U.S. Recalled Over Packaging Defect
Larry Husten, PHD
Merck said today that it was recalling all lots of Liptruzet, its combination of the cholesterol-lowering drugs ezetimibe and atorvastatin, in the U.S. The company said the recall was due to a packaging defect that could potentially allow air and moisture to affect the quality of the drug, although “the likelihood of the packaging defects decreasing the effectiveness of Liptruzet on a patient’s lipid profile or negatively impacting the safety of the product is remote.” To date, there have been no adverse events or product complaints reported to the company.
Merck is recalling the drug from U.S. wholesalers but is not asking patients or pharmacies to return their stock. The company said that patients may continue taking the pills already in their possession.
Today’s action will deplete the current supply of the drug in the U.S., the company said, noting that it will resupply the drug “as soon as possible.”
January 13th, 2014
Minority Report: Five Guideline Authors Reject Change in Systolic Blood Pressure Goal
Larry Husten, PHD
It didn’t seem possible, but the guideline situation just got even more confusing. Last December, after years of delay and other twists and turns, the Eighth Joint National Committee (JNC 8) hypertension guideline was published in JAMA. The previous guideline recommended that all adults have a target systolic blood pressure below 140 mm Hg. In the new guideline, the target remained the same for adults under 60 years of age but for people over the age of 60 the new guideline set a more conservative, easier-to-achieve target of 150 mm Hg or lower.
Now, however, five of the seventeen JNC 8 authors have written a commentary, published in Annals of Internal Medicine, disagreeing with this change. They say they are in agreement with the other major recommendations of JNC 8 but that they reject the new target, arguing that the evidence does not support the change, and predict that the change may well lead to harmful consequences.
The JAMA article was “was not the place to discuss a dissenting view” of the recommendation, said the first author of the Annals dissent, Jackson T. Wright, Jr, in an interview. The Annals article provides a forum for the minority position and outlines the key areas of disagreement.
The Annals authors write that the evidence to support changing the target “was insufficient and inconsistent with the evidence supporting the panel’s recommendations.” They argue that the new target could reverse gains in blood pressure treatment achieved in recent decades. Currently 82% of people with hypertension are receiving treatment, and the median systolic blood pressure of people being treated is 136 mm Hg. “If we go to the higher blood pressure target that would mean potentially backing off on therapy in over half of the patients who are already below 140,” Wright said.
Furthermore, the median blood pressure for the population not currently being treated is 152 mm Hg. According to Wright, this means that about half of this group would not receive treatment with the new target.
A central argument is that the revised goal could reverse the gains in public health of recent years. Both coronary heart disease and stroke mortality “have been decreasing as the blood pressure has been declining and has been decreasing at twice the rate in those over the age 60 as those under age 60,” said Wright.
They note that other guideline groups have stayed with the 140 mm Hg goal. In addition, since people over age 60 are much more likely to die of cardiovascular disease, “this means we would be backing off on patients at highest risk,” said Wright.
Finally, the authors write that although there are two trials that support the lower target in patients over 60, “We failed to identify any evidence of the risk benefit of treating to a systolic blood pressure of less than 140 in those under age 60, and yet we still we recommended a target of less than 140 in that population,” said Wright. He said the Annals authors were particularly concerned about reducing treatment in the high-risk subpopulations of people over 60, including African Americans, patients with established cardiovascular disease, and patients with multiple cardiovascular risk factors.
Response to Confusion
In their rejection of the lower target, the Annals authors appear to have gathered some key support. The American College of Cardiology and the American Heart Association, which have assumed responsibility for developing and publishing cardiovascular guidelines, said in a statement that they continue to “recognize the most recent hypertension guidelines, published in 2004 by the Joint National Committee (JNC 7), as the national standard.” In other words, they are ignoring the JAMA JNC 8 publication and tacitly endorsing the old targets. The ACC and the AHA said they had “begun the process of developing” a new hypertension guideline and anticipate that they will publish it in 2015 “for clinicians to follow as the national standard for hypertension prevention and treatment.”
It appears unlikely that any consensus will emerge before then. Some observers think that the confusion may turn out to be beneficial. Harlan Krumholz made the following comment:
This turn of events is quite surprising and adds to the uncertainty around treatment. It may be that we are seeing the beginning of the end of monolithic treatment goal recommendations as the uncertainty should highlight the importance of personalizing treatment according to patient preferences.”
Sanjay Kaul thinks the difference in opinion “reflects the uncertainty in the evidence”:
When the same evidence is viewed differently by different individuals, it only reflects the uncertainty in the evidence. In my opinion JAMA should have published this minority report. Nonetheless, I am glad that the dissenting opinion is getting the proper attention it deserves. I tend to agree with the authors of this minority report that the quality and the quantity of evidence is not persuasive enough to formally change BP treatment thresholds, even if one can arguably disagree with them. Recommending different treatment thresholds is only going to end up confusing practicing clinicians, making them more skeptical of guideline recommendations and ultimately detracting from the Institute of Medicine’s stated goal of developing trustworthy guidelines.”
NEJM Journal Watch — Recent Cardiology Articles- New Recommendations for Lipid Management in Patients with Acute Coronary Syndromes
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