October 9th, 2013
People Who Live Near Airports at Increased Risk for Cardiovascular Disease
Larry Husten, PHD
Most previous research on the health effects of noise has focused on road noise. Now two new observational studies published in BMJ extend the research to noise from airports and provide fresh evidence that people who live near airports are at increased risk for cardiovascular disease.
In the first paper, Anna Hansell and colleagues in the U.K. analyzed data from 3.6 million people living near Heathrow airport in London. People who lived in the noisiest areas had an elevated risk for stroke, coronary heart disease, and cardiovascular disease. The findings were diminished, but remained significant, after adjustments for ethnicity, social deprivation, smoking (estimated through lung cancer mortality), road traffic noise exposure, and air pollution. The researchers reported a dose-response relationship, in which the increased risk was greatest in the 2% of the population who experienced the highest levels of noise.
The authors acknowledged that they were unable to completely control for confounding or ecological bias and called for “further work to understand better the possible health effects of aircraft noise.”
In the second paper, Andrew Correia and colleagues analyzed data from more than 6 million people on Medicare who lived in zip codes around 89 North American airports. They found that people who lived in zip codes with the top 10% of noise exposure had a significant increase in the risk for hospital admission for cardiovascular disease (after adjusting for age; sex; race; zip code level socioeconomic status and demographics; zip code level air pollution; and roadway density). They calculated that for older people living near airports, 2.3% of hospitalizations for cardiovascular disease could be attributed to aircraft noise.
In an accompanying editorial Steven Stansfeld placed the new studies in the context of previous research looking at the effects of environmental noise on cardiovascular disease. Despite the inevitable limitations of observational studies, he writes that the studies “provide preliminary evidence that aircraft noise exposure is not just a cause of annoyance, sleep disturbance, and reduced quality of life but may also increase morbidity and mortality from cardiovascular disease.”
October 9th, 2013
Defining the “Appropriate Use” of Transthoracic Echo
Susan A Matulevicius, MD, MSCS
CardioExchange’s Harlan Krumholz interviews Susan Matulevicius about her study group’s analysis of the use of transthoracic echocardiography at a tertiary-care academic medical center. The article is published in JAMA Internal Medicine.
THE STUDY
Researchers retrospectively reviewed medical records from 535 consecutive transthoracic echocardiograms (TTEs). Two cardiologists, blinded to clinical impact, classified the TTEs according to appropriate use criteria (AUC) from 2011. Then the TTEs were assessed for clinical impact by 2 cardiologists who were blinded to AUC.
Of the TTEs, 31.8% resulted in an active change in care, 46.9% in continuation of current care, and 21.3% in no change in care. According to the 2011 AUC, 91.8% of TTEs were appropriate, 4.3% inappropriate, and 3.9% uncertain. The percentage of appropriate versus inappropriate TTEs that led to an active change in care did not differ significantly (32.2% vs. 21.7%, respectively; P=0.29).
THE INTERVIEW
Krumholz: In your study, 92% of the TTEs were appropriate but only 31.8% resulted in an active change in care. Isn’t that a number needed to change of roughly 3? That seems very good, so why does your conclusion characterize the 31.8% figure as low? In my 1994 study of changes in management as a result of an echocardiogram, the rate was much lower.
Matulevicius: To optimize the use of a diagnostic test in providing high-value care, we first need to understand its current use. The initial purpose of our study was simply to ask whether ordering providers are using the TTE’s results in any way. We did not assess whether the change in care that occurred could have occurred without the TTE. The 1 in 3 TTEs that leads to active change included many that altered care in nonmeaningful ways. Our online supplement shows data from our exploratory analysis: TTEs that led to active change were rated on a scale of 1 to 5 (where 1 was “misused” and 5 was “very useful”) by the consensus of two independent cardiologists. Only 19% (32/170) of all active-change TTEs were rated as a 4 or 5, which equates to only 6% (32/535) of all TTEs in our study being useful or very useful, similar to the rate of meaningful change in your 1994 study. For a diagnostic test that is used frequently, I would argue that even 1 in 3, especially when only a minority are being used in a valuable manner, is too low.
The harder part to evaluate (and which I did not address in the paper thoroughly) is the societal importance of the 47% of TTEs classified as “continuation of care.” Sometimes, reassuring patients or obtaining echocardiographic information that informs (even if it does not actively change) management is equally valuable. However, there is a spectrum of necessity of testing. For example, sometimes TTEs are performed when the pretest probability of an abnormality is low, given all the clinical and examination data. Similarly, it sometimes doesn’t matter what the TTE shows because nothing more can be done for the patient. Those are cases where the incremental value of TTE may not be high. However, at other times, when the pretest probability is intermediate from the physical exam and clinical data, a normal TTE that reassures the physician and the patient is of great value and, likely, of equal value to the TTE that was “very useful” in actively changing care. As a professional community, we must acknowledge the spectrum of value in testing and try to refrain from ordering a TTE just because it is part of the “protocol” for evaluating a given condition, if it provides very little necessary information for delivering high-value care to an individual patient.
Krumholz: How should we improve the use of echocardiography?
Matulevicius: Patient selection is a central aspect of quality in cardiac imaging or any diagnostic procedure. Imaging must be used in the proper patient subset at the optimal time, and we must be able to act on the results. Given limited resources and rising health care costs, additional research into the necessity of TTE is needed, requiring collaboration among hospitals, administrators, politicians, economists, the government, and patients. Previous attempts to reduce reimbursement for — and utilization of — TTE have been unsuccessful; TTE volume has continued to increase. Efforts to value physicians’ time in communicating the treatment plan and expectations of care to the patient may reduce use of diagnostic testing while enhancing patient-centered care. Medical school and post–medical school training about cost and value, as well as testing and professional society endorsement of programs like “Choosing Wisely,” may increase our stewardship of health resources. Incorporating necessity into the appropriateness framework may refine the use of TTE. In addition, quantifying the impact of TTE-based reassurance on patient-centered outcomes, and specifically examining whether alternate strategies that do not involve TTE provide a similar benefit to patients at a lower cost, may offer the greatest potential to decrease utilization while maintaining high-quality care.
Krumholz: In many academic centers, more volume brings more revenue, training material, and prestige. What is the incentive to reduce the volume?
Matulevicius: Doing more means more revenue and clinical volume not only in academic medical centers, but also in private practice offices and non-academic centers. And that goes for all diagnostic testing, not just TTE. In our current environment, it is difficult to incentivize reducing volumes. The key is to restructure the incentives. Among the countries in the Organization of Economic Cooperation and Development (OECD), the U.S. has among the lowest rates of doctor visits per capita (3.9, vs. 6.5 in the OECD overall) but one of the highest rates of MRI scans per 1000 population (91.2, vs. 46.6 in the OECD overall). If prestige came with providing high-value, efficient care — and if we were reimbursed equitably for definitive evaluation and management — we would probably be more willing to order fewer tests and provide more direct patient care.
We must remember that by 2021, national health expenditures are expected to grow to by nearly 5 trillion dollars. A person who retires at age 65 in 2030 will have to set aside 52% of his or her salary each and every year to cover the costs of retirement savings, health insurance, social security, and Medicare and Medicaid payroll taxes. This is 5 times more than a 65-year-old who retired in 1960 needed, and over 30% of those costs are directly related to health care (see the work by Sylvester Schieber).
Krumholz: You had a single site. How generalizable is your study?
Matulevicius: We did this study at a U.S. tertiary care academic medical center, limiting generalizability to other settings, especially non-U.S. or private practice settings. Adherence to AUC — as well as the clinical impact of TTE by region, practice, type, practice size, clinician experience, and payor mix — may differ in ways that our single-center study cannot capture.
Krumholz: How hard was this assessment to do? Can other sites repeat what you did?
Matulevicius: It takes a lot of time to go through each chart (and to convince three other people to do the same thing) and to ensure that all chart abstractors interpret the evaluation criteria similarly. Nevertheless, it is completely reproducible, especially in a system that has an electronic medical record. The one issue will be to ensure that the definition of continuation of care — “lack of escalation or de-escalation of current care, but direct communication provided to patients and/or documentation by providers in the chart about the TTE results” — is applicable in a given institution. Some institutions have automated methods for informing patients of test results, so this category would need to be refined at those institutions (otherwise, the “no change” TTEs would be included in the “continuation of care” category). The overall process, which could be applied not only to TTE but also to other diagnostic testing modalities, may inform how differences in payor mix, practice type, and clinician experience factor into use of diagnostic testing.
JOIN THE DISCUSSION
How do the findings from Dr. Matulevicius’s study affect your perspective on the appropriateness of TTE use at its current volume?
October 8th, 2013
Screen Kids for High Blood Pressure? USPSTF Says There’s Still Not Enough Evidence
Nicholas Downing, MD
In a reaffirmation of its 2003 guidance, the U.S. Preventive Services Task Force maintains that the evidence is insufficient to “assess the balance of benefits and harms” of screening for hypertension in asymptomatic children and adolescents to help lower their future risk for cardiovascular disease. The group’s statement is published in the Annals of Internal Medicine and
F. Bruder Stapleton, a pediatrician with NEJM Journal Watch, commented: “We know that childhood blood pressure tracks into adulthood and that hypertension is a proven cardiovascular risk factor in adults…. Determining the lifelong benefit of detecting and treating sustained childhood hypertension is likely never going to have evidence. Nevertheless, we should continue the inexpensive, safe practice of measuring blood pressure in children.”
Originally published in Physician’s First Watch
October 7th, 2013
Study Supports Loosening Guidelines for Surgery After Stent Implantation
Larry Husten, PHD
According to current guidelines, noncardiac surgery should be delayed for six weeks after bare-metal stent (BMS) implantation and for one year after drug-eluting stent (DES) implantation, though there is little good evidence to support these recommendations. Stent thrombosis caused by discontinuation of antiplatelet therapy in order to lower the risk of bleeding during surgery is the biggest concern. Now, a new study published in JAMA suggests that the guidelines may be over strict and that delays recommended after DES implantation are longer than warranted.
Mary T. Hawn and colleagues analyzed data from nearly 125,000 VA patients who received a stent between 2000 and 2010. Within this group more than 28,000 (22.5%) had a noncardiac operation within 2 years. Within 30 days, major adverse cardiac events (MACE) occurred in 1980 (4.7%) patients. The unadjusted MACE rate was 5.1% for patients who received a BMS and 4.3% in patients who received a DES (p<.001). Surgery within the first 6 months was associated with a higher risk of MACE. No significant effect was seen after 6 months. (The MACE rate was 11.6% in the first 6 weeks, 6.4% for 6 weeks to 6 months, 4.2% for 6-12 months, and 3.5% for the second year [p < .001].)
After adjusting for other factors, the most significant factors related to MACE were nonelective surgical admission, MI in the 6 months preceding surgery, and a high cardiac risk index. In a case-control analysis using 284 matched pairs, no relationship was observed between MACE and antiplatelet cessation.
The authors acknowledge the limitations of observational studies, and also point out that their study, which mostly contained elderly men, may not be fully applicable to women or younger patients. But, they write, their findings “suggest that underlying surgical and cardiac risk, rather than stent type, are the primary factors associated with perioperative MACE; that event rates stabilize by 6 months; and that APT (antiplatelet therapy) continuation does not substantially mitigate risk. Accordingly, the current focus of the guidelines on differential timing recommendations by stent type may warrant reconsideration, and greater concentration may need to be placed on assessing and optimizing cardiac risk.”
In an accompanying editorial, Emmanouil S. Brilakis and Subhash Banerjee write that the current recommendations for surgery after BMS implantation do not need to change, since the risk of stent thrombosis in patients undergoing surgery is very low after 6 weeks. For DES, however, they recommend that nonurgent operations be postponed until 6 months after the PCI procedure. They recommend that antiplatelet therapy should be continued if possible during the perioperative period to reduce the risk of stent thrombosis. For urgent surgeries in the first 6 months, they recommend that dual or at least single antiplatelet therapy be continued whenever possible. When this is not possible they recommend that a “bridging” strategy with short-acting agents be considered.
October 7th, 2013
Selections from Richard Lehman’s Literature Review: October 7th
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 3 Oct 2013 Vol 369
Saxagliptin and CV Outcomes in Patients with Type 2 Diabetes (pg. 1317): We definitely need better drugs to provide better outcomes in type 2 diabetes. But the pharmaceutical industry argues that so long as they can reduce HbA1c, their new products should be licensed for use on millions of people, and the hard outcomes can be collected later. And so it has been with dipeptidyl peptidase 4 (DPP-4) inhibitors saxagliptin and alogliptin. These drugs have been prescribed to hundreds of thousands of patients who were never told, “Actually, we have no idea what this stuff may do to you in the long term, but it will probably lower your blood sugar in the short term.” Well, now we know a bit more, because saxagliptin has been tested on 16 492 people with diabetes who are at high cardiovascular risk. In just over two years, it made no difference to their cardiovascular outcomes except admissions for heart failure, which were higher in the saxagliptin group. Moreover, the incidence of hypoglycaemia was higher than expected, in a group of drugs which is supposed to be relatively free of this risk. And the reduction in HbA1c was a measly 0.3%.
Alogliptin after ACS in Patients with Type 2 Diabetes (pg. 1327): At the same time, the rival agent alogliptin was undergoing a randomised double-blinded trial against placebo in diabetic patients who had recently had myocardial infarction. Good: the open-label methodology of the RECORD trial of rosiglitazone was not repeated here, even though the manufacturer had tight control over both the data collection and the write-up of this paper. A total of 5380 patients were followed up for 18 months and there was no difference in cardiovascular events. Nor was there an excess of pancreatic events in this and the previous trial, but it is too soon to relax vigilance: any increase in cancer would take much longer to show up.
The CV Safety of Diabetes Drugs — Insights from the Rosiglitazone Experience (pg. 1285): There is no ordinary editorial about these trials in the NEJM, but instead a Perspective at the beginning of the journal which is free for all to access, “The Cardiovascular Safety of Diabetes Drugs — Insights from the Rosiglitazone Experience.” Two of the three authors declare payments from NovoNordisk. They say that, “It is disappointing that neither intensive glycemic control nor the use of specific diabetes medications is associated with any suggestion of cardiovascular benefit. Thus the evidence does not support the use of glycated hemoglobin as a valid surrogate for assessing either the cardiovascular risks or the cardiovascular benefits of diabetes therapy.” Indeed; we’ve known that for five years. Nice to see the message is getting through. But earlier in the same piece they say that the new trials (and the RECORD trial!) show that the FDA is creating unnecessary work for itself and industry by insisting on trials to demonstrate cardiovascular safety before licensing drugs for diabetes. Pardon? The FDA “safety” margin indicates that diabetes drugs could be licensed if they show less than an 80% increase in CV events—is that too tight? For drugs that are meant to reduce CV risk in a high risk condition? Words fail me. What on earth are these drugs meant to achieve then? The answer comes in the saxagliptin paper: “Numerous studies, even those involving patients with advanced cardiovascular disease, have shown that improved glycemic control reduces microvascular complications.” But is this actually true? The evidence relating glycaemic control to real microvascular end-points, such as serious visual loss and end-stage renal failure, is very patchy, and involves numbers-needed-to-treat running into hundreds, with confidence intervals reaching infinity. The whole treat-the-sugar paradigm is wrong.
JAMA 2 Oct 2013 Vol 310
Menopausal HT and Health Outcomes During the Intervention and Extended Poststopping Phases of the Women’s Health Initiative Randomized Trials (pg. 1353): The Women’s Health Initiative is often cited as the prime example of a big randomised trial which demonstrated harm after the observational evidence had suggested benefit. Women randomised to receive conjugated equine oestrogens (CEE) had worse cardiovascular and cancer outcomes than those randomised to placebo. Red-faced doctors (myself included) had to eat our encouraging words and advise droves of patients to come off hormone replacement therapy. A lot of the ladies then had red faces as their flushes returned, and nobody was very happy. And half of them were not taking CEE anyway, but oestradiol-based preparations, which for all we know may have a quite different balance of harms and benefits. Here, free to the world, is a follow-up report from the WHI. “Menopausal hormone therapy has a complex pattern of risks and benefits. Findings from the intervention and extended postintervention follow-up of the 2 WHI hormone therapy trials do not support use of this therapy for chronic disease prevention, although it is appropriate for symptom management in some women.” Methinks they generalise too much. How about a rerun of WHI using different a different oestrogen? Or a risk/benefit chart so women can decide for themselves?
BMJ 5 Oct 2013 Vol 247
Effect of Smoking on Comparative Efficacy of Antiplatelet Agents: Clopidogrel was a massive earner for its manufacturer while its patent lasted, but like so many drugs which have cost health systems billions in long-term treatment, it may not actually do that much for most people who take it. A meta-analysis of nine trials in patients with established cardiovascular disease, the effect of clopidogrel was highly dependent on smoking status. Those who smoked showed a 25% reduction in a composite outcome of cardiovascular death, myocardial infarction or stroke, compared with a reduction of 8% in non-smokers. This may also apply to the newer agents ticagrelor and prasugrel, though with less certainty.
Association Between BMI and CV Disease Mortality in East Asians and South Asians: It has been said that the recommended limits of body mass index should be set lower for people of South Asian origin, because they store fat differently. But this study which pooled data from 20 prospective cohort studies was able to look at 3893 deaths in people from India and Bangladesh and was only able to identify a significant rise in cardiovascular deaths at a BMI level of 35 and above. This contrasts with people from further east (China, Taiwan, Singapore, Japan, and Korea) where the rise begins at a BMI of 25. In the “Far East” people really do seem to carry the “thrifty genotype.”
October 7th, 2013
A Novel Risk Score for Predicting MACE in Patients with Vasospastic Angina
Hiroaki Shimokawa, MD, PhD
CardioExchange Editor-in-Chief, Harlan Krumholz, interviewed Hiroaki Shimokawa about his research group’s Journal of the American College of Cardiology study, in which they developed a comprehensive clinical risk score for vasospastic angina (VSA) patients using a patient database of the multicenter registry study by the Japanese Coronary Spasm Association (JCSA).
The JCSA risk score includes 7 predictors of major adverse cardiac events (MACE), to which each is assigned an integer score: history of out-of-hospital cardiac arrest (4 points), smoking, angina at rest alone, organic coronary stenosis, multivessel spasm (2 points each), ST-segment elevation during angina, and beta-blocker use (1 point each). The 3 risk strata include low (score 0 to 2), intermediate (score 3 to 5) and high (score 6 or more). The incidences of MACE in the low-, intermediate-, and high-risk patients studied were 2.5%, 7.0%, and 13.0%, respectively (p < 0.001).
Krumholz: Is there any reason to believe that Japanese patients with spasm differ from patients elsewhere? What do you think about the generalizability of your findings?
Shimokawa: Many doctors used to think so, especially for the prevalence of the spasm. However, our ongoing international registry study, including Japan, Korea, U.K., Germany, Italy, and Australia, suggests that the differences in coronary spasm between Japanese (Asians) and Caucasian patients may not be so large. Indeed, the preliminary findings by Robert-Bosch-Hospital in Stuttgart, Germany, suggest that German patients have a similar prevalence of coronary spasm (VSA) as Japanese patients.
Krumholz: You identify predictors of adverse cardiac events. Beta-blocker treatment was an important predictor. Do you think that beta-blocker therapy was the cause? Should it be contraindicated in these patients?
Shimokawa: Our message is that beta-blockers could be dangerous for VSA when used as a monotherapy. However, we consider that beta-blockers can be used safely when combined with calcium channel blockers.
Krumholz: How do you suggest that clinicians use the information from this article? Do you have an app or website for ease of use? Are there other risk scores for patients with spasm?
Shimokawa: To the best of our knowledge, this is the first score for VSA in the world. I think that our findings with Japanese VSA patients could be applicable for Western patients with the disorder. The Japanese Circulation Society (JCS) guidelines for treating VSA are available for free on their website. We are currently revising the guidelines to include the novel risk score, and they will soon be published in Circulation Journal, the official journal of the JCS.
October 4th, 2013
A New Use for an Old Beta-Blocker?
Borja Ibanez, MD PhD
CardioExchange’s Harlan Krumholz interviews Borja Ibañez, lead investigator of the METOCARD-CNIC trial, which assessed the effect of intravenous beta-blocker use before reperfusion in patients undergoing primary PCI.
THE STUDY
Two hundred seventy patients with anterior STEMI and Killip class I or II undergoing PCI within 6 hours after symptom onset were randomized to receive intravenous metoprolol or not (control) before reperfusion. All patients without contraindications then received oral metoprolol within 24 hours.
Mean infarct size, according to MRI performed 5 to 7 days after STEMI in 220 patients, was significantly smaller in the intravenous metoprolol group than in the control group (25.6 vs. 32.0 g; P=0.012). Compared with controls, IV metoprolol recipients had a significantly higher post-PCI left ventricular ejection fraction (mean difference, 2.67%) and a nonsignificantly lower rate of the composite endpoint of death, malignant ventricular arrhythmia, cardiogenic shock, atrioventricular block, or reinfarction at 24 hours (7.1% vs. 12.3%; P=0.21).
THE INTERVIEW
Krumholz: What made you look to an older drug for a clinical trial? How did this trial get started?
Ibañez: The effect of beta-blockers on infarct size has been a matter of intense discussion with no clear answer. We started this program in 2006, when I was working at Mount Sinai Hospital in New York with Dr. Valentin Fuster and Dr. Juan Badimon. Using MRI, we showed that metoprolol could reduce infarct size and improve LVEF recovery in pigs. In a second study in the same pig model, we compared pre-reperfusion metoprolol versus oral post-reperfusion metoprolol (as clinical guidelines recommend) and observed that metoprolol reduced infarct size only when administered before reperfusion. We thought we generated enough evidence to merit a clinical trial in humans. Surprisingly, the effect of beta-blockers on infarct size had never been evaluated in the context of primary PCI. Given that this old, inexpensive drug is approved for STEMI, we believed that a trial like this one might have an impact in clinical practice.
Krumholz: Should a small, open-label study of infarct size, a surrogate outcome, be considered only as a rationale for a larger trial assessing outcomes, or should the findings be enough to change practice and guideline recommendations?
Ibañez: Ours was a PROBE trial rather than an open-label trial (all evaluations were done with blinding to treatment allocation). Given the clear effect of metoprolol on heart rate and blood pressure, double blinding would not eliminate this source of bias. The main endpoint is infarct size (a surrogate maker), but we must remember that intravenous metoprolol is allowed by clinical guidelines. We meticulously evaluated all side effects, and no excess was observed. All of these factors (infarct reduction, LVEF improvement, safety profile, and drug allowed by clinical guidelines) should be taken into consideration when revising the guidelines. Although a larger trial with hard endpoints is needed, the data from METOCARD-CNIC might be enough to reconsider the administration of pre-reperfusion metoprolol in patients with Killip I–II STEMI who present early (mainly due to the safety profile and potential benefit).
Krumholz: Will you now use intravenous beta-blockers as adjunctive therapy for selected patients with STEMI undergoing PCI?
Ibañez: I hope that soon we can embark on a large double-blind trial confirming these results with hard endpoints. I am convinced that this strategy will change outcomes for patients at a very low cost. While we await this trial, I will immediately start using intravenous metoprolol in patients with anterior Killip class I–II STEMI who undergo primary PCI. We know it is safe, reduces infarct size, and improves LVEF. This is too much to ignore for an already approved old drug. While we await data on mortality reduction, smaller infarcts are good news.
Krumholz: Some readers will remember the COMMIT trial. How do you see your study compared with the strategy and results of COMMIT?
Ibañez: Of course, COMMIT will be part of the discussion. Here are the main differences:
1. In COMMIT, all patients were revascularized by thrombolysis; in our trial, revascularization was by PCI.
2. In COMMIT, mean time from symptom onset to lytic initiation was 11 hours. This means that in half the population, even lytics would be questionable. After 11 hours of coronary occlusion, the amount of salvageable myocardium is negligible; therefore, the potential for infarct reduction is slim. In METOCARD-CNIC, all patients were revascularized within 6 hours, a much better time window for myocardial salvage.
3. COMMIT recruited patients with overt heart failure (Killip class III patients were included). This is a classical contraindication to IV beta-blockade, so the increase in shock was not surprising. In fact, in COMMIT’s subpopulation of Killip I–II patients, despite very late presentation, metoprolol was associated with a clear net benefit. Unfortunately, in the Killip III patients, metoprolol was unsurprisingly associated with a massive increase in shock. METOCARD-CNIC included only Killip I–II patients.
In summary, the COMMIT participants were not the kind of patients we treat every day, and the trial’s major effect on guidelines was, in my view, excessive. The lack of other available information was one major reason to conduct our trial. We still need the events trial, but I believe that the early-presenting population in our trial more closely represents daily practice. Thus, it might be prudent to consider pre-reperfusion metoprolol administration in Killip I–II STEMI patients. The strategy is safe and inexpensive.
JOIN THE DISCUSSION
What’s your view of using intravenous metoprolol in this clinical context, given the findings from the trial conducted by Dr. Ibañez and his colleagues?
October 3rd, 2013
Fellows: Want to Blog for CardioExchange at AHA.13?
Harlan M. Krumholz, MD, SM and John Ryan, MD
CardioExchange editors Harlan Krumholz and John Ryan are looking for fellows to blog for CardioExchange at the American Heart Association Annual Scientific Sessions from November 16th through the 20th in Dallas.
If you are interested in blogging, please contact us. We look forward to hearing from you!
October 3rd, 2013
ABI-Based Screening for PAD: Which Guidelines Are Right?
Rita F Redberg, MD, MSc and Mark A. Creager, MD
The United States Preventive Services Task Force (USPSTF) recently concluded that the existing evidence base is insufficient to weigh the benefits and harms of using the ankle–brachial index (ABI) to screen patients for peripheral artery disease (PAD) and assess their related risk for cardiovascular disease. Mark Creager and Rita Redberg offer differing analyses of this conclusion.
Creager: The new USPSTF recommendation on ABI screening for PAD contradicts the ACCF/AHA practice guidelines for PAD, which state that “the resting ABI should be used to establish the lower-extremity PAD diagnosis in patients with suspected lower-extremity PAD, defined as individuals with 1 or more of the following: exertional leg symptoms, nonhealing wounds, age 65 and older, or 50 years and older with a history of smoking or diabetes” (class I recommendation, level of evidence B).
PAD is a clinical manifestation of, not a risk factor for, atherosclerosis. It affects more than 7 million U.S. adults, including 15% to 20% of people age 65 or older, and is associated with more than a 2.5-fold risk for death from cardiovascular causes. PAD is also especially prevalent among patients with diabetes and among smokers. About half of patients with PAD do not have leg symptoms yet remain at high risk for adverse cardiovascular events. Patients with PAD often have a history of coronary or cerebrovascular disease, but even those who do not have such a history remain at increased risk for myocardial infarction and stroke.
Therefore, an important reason to detect PAD in an otherwise asymptomatic patient is to elicit findings of occult atherosclerosis and initiate risk factor–modifying therapies. Data from the National Health and Nutrition Examination Survey indicate that millions of patients with PAD, many of whom are asymptomatic and have no known coronary or cerebrovascular disease, are not taking a statin, an ACE inhibitor, or an antiplatelet drug.
The ABI is very easy to assess as part of a physical examination, using the same knowledge and skills required to assess blood pressure, except that a handheld Doppler device is used to measure ankle pressures. It is neither costly nor harmful. The ABI, calculated for each leg as the ratio of the systolic pressure at the ankle to that of the brachial artery, is considered abnormal if ≤0.90. Its diagnostic accuracy to detect PAD based on the area under the receiver-operating curve is 0.87–0.95. The ABI enables further characterization of risk beyond the Framingham risk score (FRS); 1 in 5 men and 1 in 3 women would have their FRS risk category reclassified by inclusion of the ABI.
By focusing rigidly on screening asymptomatic patients, the USPSTF limited its analysis and failed to consider important studies that reported outcomes of both symptomatic and asymptomatic PAD patients. The excluded studies have found that the risk for adverse cardiovascular events is high in asymptomatic patients with PAD, though likely less than in symptomatic patients. Similarly, the USPSTF excluded articles on the efficacy of treatment, such as statins or antiplatelet drugs, in reducing the risk for cardiovascular events, as the studies primarily included symptomatic PAD patients. I acknowledge that we lack large randomized trials of outcomes resulting from treatment of asymptomatic patients with PAD detected by ABI screening. Pending such trials, it is reasonable to infer — from studies showing a twofold increased risk for cardiovascular death in patients with asymptomatic PAD than in patients without PAD — that risk factor–modifying therapies known to be effective in symptomatic patients are likely to benefit asymptomatic PAD patients.
Given the evidence I have outlined, I concur with the ACCF/AHA PAD guidelines, which state that ABI screening should be performed in patients age 65 or older, and patients age 50 or older who have a history of smoking or diabetes.
Redberg: By definition, screening means looking for signs of subclinical disease in people who lack symptoms. The bar is high, and should remain so, before a screening test is used to justify an intervention in an asymptomatic patient. Generally, the rationale for an intervention is to help people either feel better or live longer. Given that asymptomatic people already feel perfectly well, we must offer something that helps them live longer if we are going to intervene. Any screening test should meet these criteria:
- It must be widely available and inexpensive.
- It must be safe.
- It should lead to therapy that can be guided only by use of that test.
- The therapy prompted by the test should yield better clinical outcomes.
The ABI meets the first two criteria, but it fails on the last two. We must counsel all patients in risk reduction: All smokers should be counseled to quit, and all patients should be encouraged to eat a heart-healthy diet and get regular physical activity. A patient’s ABI score would not change this advice. The USPSTF recommendations focus on screening and therefore require evidence of benefit, as they should. As the USPSTF notes, no data show improved outcomes after ABI screening.
It is hard to justify ABI screening without any evidence of clinical benefit. We clinicians (and our patients) are busy, so we should spend our time on what matters to patients, in terms of improving outcomes. Using that time to discuss, for example, the benefits of a heart-healthy diet and regular physical activity is much more productive than ABI screening would be in reducing patients’ risks for death, PAD, and CV disease. Clearly, we need to study whether ABI screening improves clinical outcomes before we proceed with using this test in clinical practice.
JOIN THE DISCUSSION
With which set of PAD guidelines are you more closely aligned: those from the USPSTF or those from the ACCF/AHA?
October 3rd, 2013
News From Our ‘Statin Civilization’: High-Dose Statins Found to Reduce Gum Disease Inflammation
Larry Husten, PHD
In addition to their well-known benefits in heart disease, high-dose statins appear to reduce gum inflammation caused by periodontal disease, a new report published in the Journal of the American College of Cardiology shows. The findings offer more evidence that heart disease and gum disease may be linked, and also help support the view that statins achieve at least some of their benefit not through their cholesterol-lowering effect but through separate inflammation-fighting mechanisms.
Researchers reported findings from 59 patients with cardiovascular disease or at high risk for cardiovascular disease who had evidence of arterial inflammation on a PET scan. The patients were randomized to a low (10 mg/day) or high (80 mg/day) dose of atorvastatin. After 12 weeks, there was a significant reduction in periodontal inflammation as measured by PET in patients on high-dose therapy. The effect was greatest in those who had active periodontal disease. There was evidence of a significant effect as early as 4 weeks. Furthermore, there was a strong correlation between reductions in periodontal inflammation and atherosclerosis, though the authors acknowledge that the precise nature of the association remains undefined.
They write that their findings raise the possibility that statins may reduce not only LDL cholesterol and arterial inflammation but may also reduce non-arterial inflammation in “inflamed tissues such as the periodontium.” This effect, they write, “may exert secondary benefits on the systemic arterial milieu,” ultimately helping to reduce inflammation in atherosclerotic vessels.
The investigators call for larger randomized studies to examine the effect of statins in patients with periodontal disease, and speculate that statins might be a useful adjunctive therapy in periodontal disease. “Furthermore,” they write, “the possible interrelationship between periodontitis, atherosclerosis and statins might prove to be of substantial importance, due to the high prevalence of both periodontal and atherosclerotic diseases along with the wide-spread use of statins.”
In an accompanying editorial, Michael Blaha and Seth Martin write that “now that we have become a statin civilization,” with as many as 200 million people worldwide taking the drugs, “perhaps it is time to figure out exactly how these drugs work.” They propose three non-mutually exclusive paradigms to potentially explain the beneficial effects of statins:
- Paradigm #1: “Lipoprotein Load Hypothesis”
- Paradigm #2: “Systemic Inflammatory Hypothesis”
- Paradigm #3 “Plaque Modulation Hypothesis”
The implications of their hypothesis go beyond a potential role for statins in periodontal disease:
“The question of who should be treated with statins over what time course is one of the most hotly debated in modern medicine. While statins certainly reduce atherogenic lipoproteins (Paradigm #1), the 2 reports from this intriguing FDG-PET feasibility study suggest that high-dose statins also reduce extra-arterial inflammation (Paradigm #2) and inflammation within atherosclerotic plaque (Paradigm #3).”
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