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August 2010 Vol. 16 No.8 From the publishers of The New England Journal of Medicine CA RDI OLOGY More Bad News for Rosiglitazone Mounting evidence of adverse cardiovascular effects continues to erode justification for its use. For more than 10 years, thiazolidinediones (TZDs) have been prescribed for diabetes therapy in the U.S. on the sole basis of evidence that they improve glycemic control. An association of TZDs with heart failure is relatively well-established; however, recent data have implicated rosiglitazone in other adverse cardiovascular events as well. Two new studies further address the risks of rosiglitazone. In an observational cohort study, 227,571 Medicare patients (median age, 74.4) began therapy with either rosiglitazone or pioglitazone between July 2006 and June 2009. During a median follow-up of 105 days, rosiglitazone recipients were significantly more likely than pioglitazone recipients to experience adverse events including stroke (hazard ratio, 1.27); heart failure (HR, 1.25); death from any cause (HR, 1.14); and a composite of acute myocardial infarction (AMI), stroke, heart failure, and death (HR, 1.18). The risk for AMI alone did not differ between the two groups. For the composite endpoint, the estimated overall number needed to harm was 60 patients treated for 1 year. In an extension of a well-known 2007 meta-analysis of clinical trials of rosiglitazone (JW Cardiol Jul 2007, p. 53, and N Engl J Med 2007; 356:2457), researchers examined 56 trials involving 35,531 patients randomized to receive rosiglitazone or a control therapy for more than 24 weeks. Treatments used in the control groups included placebo, usual care, and nonTZD antidiabetic therapies. Compared with controls, patients in the rosiglitazone groups had a significantly higher risk for MI (odds ratio, 1.28) but not for cardiovascular mortality. Separate analyses that either included or excluded studies with no adverse cardiovascular events yielded similar results. COMMENT cardiovascular events. The different rosiglitazone-associated adverse outcomes in the studies may be explained by differences in study designs, patient populations, comparison groups, lengths of follow-up, and methods of outcomes ascertainment. Although observational studies are prone to confounding, and meta-analyses have their own limitations, these findings will increase pressure on the FDA to reconsider whether rosiglitazone should remain on the market, bearing in mind the availability of pioglitazone, which appears to be a safer alternative. In my view, there is no good reason to use rosiglitazone in diabetic patients. — Frederick A. Masoudi, MD, MSPH Graham DJ et al. Risk of acute myocardial infarction, stroke, heart failure, and death in elderly Medicare patients treated with rosiglitazone or pioglitazone. JAMA 2010 Jun 28; [e-pub ahead of print]. (http://dx.doi.org/10.1001/jama.2010.920) Juurlink DN. Rosiglitazone and the case for safety over certainty. JAMA 2010 Jun 28; [e-pub ahead of print]. (http://dx.doi.org/10.1001/jama.2010.954) Nissen SE and Wolski K. Rosiglitazone revisited: An updated meta-analysis of risk for myocardial infarction and cardiovascular mortality. Arch Intern Med 2010 Jun 28; [e-pub ahead of print]. (http:// dx.doi.org/10.1001/archinternmed.2010.207) These studies add to growing evidence that, despite lowering glucose levels, rosiglitazone causes important adverse CONTENTS SUMMARY & COMMENT More Bad News for Rosiglitazone ........................... 61 Angiotensin-Receptor Blockers and Cancer: An Inconvenient Truth? ........................................... 61 Unintended Effects of Statin Drugs.......................... 62 Poor Self-Reported Oral Hygiene and Excess Cardiovascular Risk ........................... 63 Thromboembolic Events in Men with Prostate Cancer ............................................... 63 Do Busy Hospitals Mean Better Care for Medical Patients? .............................................. 63 Routine Echocardiography Before Vascular Surgery? .................................................... 64 Transcatheter Valve-in-Valve Implantation — A New Option for Failed Bioprostheses .............. 64 Do Statins Slow Progression of Rheumatic Mitral Stenosis?............................... 65 Dogma Challenged — β-Blockers for Patients with Cocaine-Associated Chest Pain? ................ 65 Typical Angina vs. Atypical Chest Pain ................... 65 How Does the San Francisco Syncope Rule Perform in Canada? ....................... 66 Rapid Treatment and Discharge of Patients with Recent-Onset Atrial Fibrillation or Flutter ...................................... 66 Are Zotarolimus-Eluting Stents Really Noninferior to Everolimus-Eluting Stents? .......... 66 Using Clopidogrel with a Proton-Pump Inhibitor ......................................... 67 The Importance of Being Timely............................... 67 Cardiac Arrest Data — by Neighborhood READERS’ POLL Angiotensin-Receptor Blockers and Cancer: An Inconvenient Truth? A meta-analysis fuels uncertainty about safety, highlighting an imperative need for more data. ...... 68 Which Conference Would You Attend? .................. 65 In 2003, the Candesartan in Heart failure Assessment of Reduction in Mortality and Morbidity (CHARM) investigators reported a small but significant elevation in the rate of cancer deaths in patients treated with candesartan versus placebo. Now, U.S. investigators have conducted a metaanalysis of randomized controlled trials of JOURNAL WATCH (AND ITS DESIGN) IS A REGISTERED TRADEMARK OF THE MASSACHUSETTS MEDICAL SOCIETY. AN EDITORIALLY INDEPENDENT LITERATURE-SURVEILLANCE NEWSLETTER SUMMARIZING ARTICLES FROM MAJOR MEDICAL JOURNALS. ©2010 MASSACHUSETTS MEDICAL SOCIETY. ALL RIGHTS RESERVED. DISCLOSURE INFORMATION ABOUT OUR AUTHORS CAN BE FOUND AT http://cardiology.jwatch.org/misc/board_disclosures.dtl 62 EDITOR-IN-CHIEF Harlan M. Krumholz, MD, SM, Harold H. Hines, Jr., Professor of Medicine, Section of Cardiovascular Medicine, Yale University School of Medicine, New Haven EXECUTIVE EDITOR Kristin L. Odmark Massachusetts Medical Society DEPUTY EDITOR Howard C. Herrmann, MD, Professor of Medicine, Director, Interventional Cardiology and Cardiac Catheterization Laboratories, University of Pennsylvania Medical Center, Philadelphia ASSOCIATE EDITORS JoAnne M. Foody, MD, Director, Cardiovascular Wellness Center, Brigham and Women’s Hospital, Boston Joel M. Gore, MD, Edward Budnitz Professor of Cardiovascular Medicine, University of Massachusetts, Worcester Mark S. Link, MD, Associate Professor of Medicine, New England Medical Center and Tufts University School of Medicine, Boston Frederick A. Masoudi, MD, MSPH, Division of Cardiology, Denver Health Medical Center and Associate Professor of Medicine, University of Colorado at Denver Beat J. Meyer, MD, Associate Professor of Cardiology, University of Bern; Chief, Division of Cardiology, Lindenhofspital, Bern, Switzerland CONTRIBUTING EDITORS William T. Abraham, MD, Professor of Medicine, Chief, Division of Cardiovascular Medicine, The Ohio State University Heart Center, Columbus Hugh Calkins, MD, Professor of Medicine and Director of Electrophysiology, The Johns Hopkins Hospital, Baltimore FOUNDING EDITOR Kim A. Eagle, MD, Albion Walter Hewlett Professor of Internal Medicine and Chief of Clinical Cardiology, Division of Cardiology, University of Michigan Medical Center, Ann Arbor MASSACHUSETTS MEDICAL SOCIETY Christopher R. Lynch, Vice President for Publishing; Alberta L. Fitzpatrick, Publisher Betty Barrer, Christine Sadlowski, Sharon S. Salinger, Staff Editors; Kara O’Halloran, Copy Editor; Misty Horten, Layout; Matthew O’Rourke, Director, Editorial and Product Development; Robert Dall, Editorial Director; Art Wilschek, Christine Miller, Lew Wetzel, Advertising Sales; William Paige, Publishing Services; Bette Clancy, Customer Service Published 12 times a year. Subscription rates per year: $119 (U.S.), C$166.67 (Canada), US$165 (Intl); Residents/Students/Nurses/PAs: $69 (U.S.), C$96.19 (Canada), US$80 (Intl); Institutions: $219 (U.S.), C$256.19 (Canada), US$230 (Intl); individual print only: $89 (U.S.). Prices do not include GST, HST, or VAT. In Canada remit to: Massachusetts Medical Society C/O #B9162, P.O. Box 9100, Postal Station F, Toronto, Ontario, M4Y 3A5. All others remit to: Journal Watch Cardiology, P.O. Box 9085, Waltham, MA 02454-9085 or call 1-800-843-6356. E-mail inquiries or comments via the Contact Us page at JWatch.org. Information on our conflict-of-interest policy can be found at JWatch.org/misc/conflict.dtl CARDIOLOGY Vol. 16 No. 8 angiotensin-receptor blockers (ARBs) to learn more about their effect on cancer. Telmisartan was the ARB used in most of the studies. Of the five trials that included data on new cancer occurrence, the overall cancer rate was higher in the ARB groups than in the control groups (7.2% vs. 6.0%; relative risk, 1.08; 95% confidence interval, 1.01–1.15). When the analysis was restricted to the three trials in which cancer was a prespecified endpoint, the excess risk associated with ARBs persisted (RR, 1.11; 95% CI, 1.04– 1.18). In the one study in which patients received concomitant angiotensinconverting–enzyme (ACE) inhibitor treatment, ARBs were associated with a 13% increase in risk for incident cancer (95% CI, 1.03–1.24). The number needed to harm was estimated to be 143 with 4 years of treatment. COMMENT Unintended Effects of Statin Drugs Kidney failure and cataracts were associated significantly with statin use. Statins lower risk for adverse cardiovascular events, especially in high-risk patients. In this large prospective U.K. cohort study, investigators sought to quantify unintended effects of these widely used drugs. Of the more than 2 million study participants (age range, 30–84), about 225,000 were new statin users: 160,000 were prescribed simvastatin, 50,000 received atorvastatin, and ≈15,000 received pravastatin, rosuvastatin, or fluvastatin. Statin use was associated significantly with lower risk for esophageal cancer and higher risks for liver dysfunction (alanine transaminase levels ≥3× upper limit of normal), myopathy (clinical diagnosis or creatinine kinase level ≥4× upper limit of normal), acute kidney failure, and cataracts; liver dysfunction and acute kidney failure were dose-dependent. Adverse effects for individual statins were similar, except for liver dysfunction, in which risk was highest for fluvastatin. All excess risks persisted during treatment and returned to normal after drug cessation. Statin use was not associated with risk for osteoporotic fracture, venous thromboembolism, dementia, Parkinson disease, rheumatoid arthritis, or cancers (stomach, lung, breast, colon, kidney, and prostate cancers or melanoma). COMMENT Nearly 7 years after the CHARM study raised questions about ARB-associated cancer risk, this analysis of the available evidence only heightens the concern. Unfortunately, we are no closer to understanding whether this is truly a problem than we were in 2003. Is the risk real? Is it restricted to certain drugs, is it a class effect of ARBs, or does it involve all drugs that affect the renin-angiotensin system? No similar elevation in cancer risk has yet been associated with ACE inhibitors, although more data on this drug class is also needed. The current results point to the importance of thorough and timely collection of safety data on drugs — and the necessity of analyzing all relevant data, published and unpublished. Clinicians and patients need more information to accurately weigh the benefits and risks of using ARBs. — Harlan M. Krumholz, MD, SM Sipahi I et al. Angiotensin-receptor blockade and risk of cancer: Meta-analysis of randomized controlled trials. Lancet Oncol 2010 Jul 1; 11:627. Nissen SE. Angiotensin-receptor blockers and cancer: Urgent regulatory review needed. Lancet Oncol 2010 Jul 1; 11:605. Most clinicians are familiar with statinassociated liver dysfunction and myopathy. The results of this study suggest that clinicians should be familiar with and monitor for two more possible statinassociated adverse effects: acute kidney failure and cataracts. In addition, with the exception of esophageal cancer risk, the results are consistent with those of a prior meta-analysis, in which researchers found no association between statin use and cancer risk (JAMA 2006; 295:74). — Paul S. Mueller, MD, MPH, FACP, Journal Watch General Medicine Hippisley-Cox J and Coupland C. Unintended effects of statins in men and women in England and Wales: Population based cohort study using the QResearch database. BMJ 2010 May 20; 340:c2197. August 2010 JWatch.org 63 Poor Self-Reported Oral Hygiene and Excess Cardiovascular Risk People who never or rarely brushed their teeth had 70% higher risk for adverse cardiovascular events. Thromboembolic Events in Men with Prostate Cancer Data confirm elevated risk for thromboembolism among prostate cancer patients, particularly those who receive androgendeprivation therapy. Poor oral hygiene is the most important cause of periodontal disease, and selfreported oral hygiene can predict clinically important periodontal disease. Prior research findings suggest that periodontal disease is associated with excess risk for cardiovascular (CV) disease. In this Scottish population-based survey, investigators determined whether a simple self-reported measure of oral hygiene — frequency of tooth brushing — as a proxy of periodontal disease was associated with risk for adverse CV events (e.g., myocardial infarction, stroke, coronary artery bypass surgery). Among the nearly 12,000 survey respondents (average age, 50), 555 adverse CV events (170 fatal) occurred during an average 8.1 years of follow-up. After adjustments for multiple confounders, participants who reported poor oral hygiene (never or rarely brushed teeth) had a significant 70% higher risk for adverse CV events than did those who reported good oral hygiene (brushed teeth twice a day). Likewise, participants who reported poor oral hygiene had significantly higher blood levels of C-reactive protein and fibrinogen. COMMENT higher level of suspicion for evaluating early symptoms of possible thromboembolism in patients with prostate cancer, especially given the increasing numbers of men (i.e., those with early-stage disease) who receive ADT. — Robert Dreicer, MD, MS, FACP, Journal Watch Oncology and Hematology Van Hemelrijck M et al. Risk of thromboembolic diseases in men with prostate cancer: Results from the population-based PCBaSe Sweden. Lancet Oncol 2010 May; 11:450. Patients with cancer (especially epithelial malignancies such as prostate cancer) are at excess risk for thromboembolic events. Risk among patients with prostate cancer might be further elevated by androgendeprivation therapy (ADT), which has been linked to risk for deep venous thrombosis (DVT) and pulmonary embolism (PE). Given more widespread use of ADT for nonmetastatic prostate cancer (as well as traditional use for metastatic disease) and longer treatment durations, evaluating thromboembolic risks has become even more important. Using data from the National Prostate Cancer Register of Sweden (from 1997 through 2007), investigators assessed risk for thromboembolic events among 76,600 prostate cancer patients. Seventeen percent of patients had metastatic disease (or prostate-specific antigen >100 ng/mL). Among the entire cohort, 40% received ADT as primary therapy, 35% received curative treatment, and 25% underwent surveillance. Of those who received ADT, most received a gonadotropin-releasing hormone (GnRH) agonist (alone or in combination with an antiandrogen) or underwent orchiectomy. During the 11-year period, 1881 men (2.5%) experienced thromboembolic events: DVT in 767, PE in 873, and arterial embolism in 241. Standard incidence ratios for observed-to-expected events were significantly elevated for both DVT and PE, regardless of whether patients received ADT, curative treatment, or surveillance. The highest risk was for DVT among ADT recipients (SIR, 2.48; 95% CI, 2.25–2.73). Risk for arterial embolism was not raised in any group. Among those who received ADT, risk for thromboembolism was higher in men younger than 75 and in those with metastatic disease. COMMENT Do Busy Hospitals Mean Better Care for Medical Patients? Patients admitted to high-volume hospitals for specific conditions are less likely to die, but a threshold volume exists. Previous studies on surgical and medical procedures have shown that higher hospital volumes for specific procedures translate to lower mortality. Whether this observation holds true for acute medical illnesses is less clear. Investigators examined Medicare data for patients who were hospitalized from 2004 through 2006 with diagnoses of acute myocardial infarction, pneumonia, or heart failure. Using the number of annual admissions for these conditions, hospitals were classified as large-, medium- or small-volume for each condition. The investigators analyzed the association between all-cause 30-day mortality and hospital volume for each condition and calculated the volume threshold, above which mortality for each condition no longer improved significantly. Higher hospital volume was associated with lower 30-day mortality for patients hospitalized for all three conditions: acute myocardial infarction (odds ratio, 0.89), heart failure (OR, 0.91), and pneumonia (OR, 0.95). The volume effect was greatest in small-volume hospitals and Self-reported poor oral hygiene — never or rare tooth brushing — is associated with elevated risk for CV events and higher blood levels of inflammatory markers. Whether improving oral hygiene mitigates this risk is unclear. Nevertheless, regardless of the association between oral hygiene and CV risk, clinicians can reasonably encourage patients to practice good oral hygiene for good oral health. — Paul S. Mueller, MD, MPH, FACP, Journal Watch General Medicine de Oliveira C et al. Toothbrushing, inflammation, and risk of cardiovascular disease: Results from Scottish Health Survey. BMJ 2010 May 27; 340:c2451. JOURNAL WATCH ONLINE Is computed tomography safe? Listen to an interview with a radiologist who has written on the subject. Although these findings do not break new ground, they confirm excess risk for thromboembolic events in men with prostate cancer, particularly those who receive ADT. These findings should prompt a JWatch.org/online 64 CARDIOLOGY Vol. 16 No. 8 was least in large-volume hospitals. Investigators also determined annual volume thresholds above which 100 additional patients were no longer associated significantly with lower odds of death: 610 for patients with acute myocardial infarction, 500 for patients with heart failure, and 210 for patients with pneumonia. In a subgroup analysis of teaching hospitals, these thresholds were significantly lower: 260, 148, and 37, respectively. COMMENT noncardiac surgery (Circulation 1999; 100:1043). But, what about asymptomatic left ventricular (LV) dysfunction? Dutch researchers performed routine preoperative echocardiography in 1005 consecutive patients who were scheduled for elective vascular surgery (carotid, abdominal aorta, or lower extremity). Half the patients had normal LV function, 21% had asymptomatic isolated diastolic dysfunction, 19% had asymptomatic systolic dysfunction (ejection fraction <50%, with or without diastolic dysfunction), and 10% had symptomatic heart failure. In multivariate analysis adjusted for other standard perioperative risk factors, asymptomatic LV dysfunction independently predicted elevated risk for cardiovascular events within 30 days after open vascular surgery (odds ratios, 2.3 for systolic and 1.8 for diastolic dysfunction). For patients who underwent endovascular procedures, asymptomatic systolic dysfunction and diastolic dysfunction also were associated with doubled risk for cardiovascular events, but these differences did not reach statistical significance, possibly because event rates were much lower after endovascular procedures. COMMENT Flu W-J et al. Prognostic implications of asymptomatic left ventricular dysfunction in patients undergoing vascular surgery. Anesthesiology 2010 Jun; 112:1316. Groban L and Kitzman DW. Diastolic function: A barometer for cardiovascular risk? Anesthesiology 2010 Jun; 112:1303. Transcatheter Valve-in-Valve Implantation — A New Option for Failed Bioprostheses Promising results from a small case series could be good news for patients with no or few alternatives. This study demonstrates that patients with acute myocardial infarction, heart failure, or pneumonia might have lower risk for death if they receive care at hospitals that handle higher volumes of such patients. This finding could be due to standardized care protocols or diseasespecific management programs that have been implemented at these centers. How policymakers might use these data to increase volume at smaller hospitals is less clear. Although regionalization for elective surgical procedures might be practical, regionalization of care for acute medical conditions would not be feasible. — Grace C. Huang, MD, Journal Watch Hospital Medicine Ross JS et al. Hospital volume and 30-day mortality for three common medical conditions. N Engl J Med 2010 Mar 25; 362:1110. Reoperation for structural failure of bioprosthetic heart valves carries considerable surgical risk. In this report, investigators describe the results of transcatheter heart valve implantation in 24 patients with degenerating bioprostheses. The failing valves were aortic in 10 patients, mitral in 7, pulmonary in 6, and tricuspid in 1. All patients were ineligible for repeat surgery or at high risk for complications because of ≥2 prior thoracotomies, complex congenital heart disease, severe double-valve disease, or other comorbidities. Mean predicted 30-day mortality according to the Society of Thoracic Surgeons risk score was 11% in patients with failing aortic valves and 15% in patients with failing mitral valves. All patients received balloon-expandable SAPIEN or SAPIEN XT transcatheter valves. After a percutaneous approach in the first patient failed, all aortic valves were successfully implanted via transapical access. Similarly, six of seven mitral valves were successfully implanted transapically after transseptal and open transatrial attempts in the first patient both failed. The pulmonary valves were implanted percutaneously after stenting of the failing bioprosthesis. At 30 days, one patient had died, and one had had a stroke. No embolizations or structural failures occurred during a median follow-up of 135 days. COMMENT Routine Echocardiography Before Vascular Surgery? Echocardiography can predict complications, but whether it improves perioperative outcomes is unclear. In most predictive models, history of symptomatic heart failure is an independent risk factor for complications after Visit Journal Watch Online! View content in 13 primary and specialty care areas; sign up for free daily, weekly, or monthly e-mail alerts; take convenient online CME exams — all at Journal Watch Online. Visit JWatch.org today and get the most out of Journal Watch. On the basis of these results, the authors recommend routine preoperative echocardiography for asymptomatic patients undergoing open vascular surgery; editorialists go even further, recommending echocardiography for asymptomatic patients undergoing any high-risk noncardiac surgery. However, this analysis does not tell us how often adding echocardiography to standard risk indexes would reclassify patients among low-, intermediate-, and high-risk categories. Until we have better data on the incremental contribution of echocardiography to risk stratification — and until we identify evidence-based interventions that improve perioperative outcomes in patients with asymptomatic LV dysfunction — we do not recommend routine preoperative echocardiography for asymptomatic patients. — Allan S. Brett, MD, Journal Watch General Medicine; and Harlan M. Krumholz, MD, SM This small series demonstrates the feasibility of transcatheter valve-in-valve implantation in selected high-risk patients with failing surgically implanted bioprosthetic valves. Long-term data are needed to determine whether this procedure is a reasonable alternative to repeat surgery in patients at lower surgical risk. — Howard C. Herrmann, MD August 2010 Webb JG et al. Transcatheter valve-in-valve implantation for failed bioprosthetic heart valves. Circulation 2010 Apr 27; 121:1848. Carabello BA. Percutaneous therapy for valvular heart disease: A huge advance and a huge challenge to do it right. Circulation 2010 Apr 27; 121:1798. JWatch.org 65 Dogma Challenged — β-Blockers for Patients with Cocaine-Associated Chest Pain? β -blockers seem to be safe in the short term, with potential long-term benefit as well. offering β -blockers to more patients with favorable risk-benefit ratios after counseling them about the potential negative interactions between cocaine and β -blockers. — Aaron J. Calderon, MD, FACP, Journal Watch Hospital Medicine Rangel C et al. β -blockers for chest pain associated with recent cocaine use. Arch Intern Med 2010 May 24; 170:874. Do Statins Slow Progression of Rheumatic Mitral Stenosis? Findings from a retrospective study suggest that they do. The pleiotropic anti-inflammatory properties of statins are believed to bring about the slowing in progression of calcific aortic stenosis seen in some previous studies (but not in all; see JW Cardiol Aug 2005, p. 67, and N Engl J Med 2005; 352:2389). In this observational study, investigators examined the effect of statin therapy on the progression of rheumatic mitral stenosis (MS). The study population consisted of 315 patients with rheumatic MS (mean age, 61 years; 71% women), of whom 35 (11%) were taking statins, and 280 (89%) were not. Baseline echocardiographic characteristics, including mitral valve area (MVA) and degree of mitral regurgitation, were similar in both groups. After a mean follow-up of 6.1 years, the annualized decrease in mean MVA was significantly smaller in statin-treated patients than in non–statin-treated patients (0.027 vs. 0.067 cm2; P=0.005). In a multivariable analysis, statin treatment independently predicted slower MS progression. COMMENT Despite the proven survival benefit of β -blockers in patients with myocardial infarction, traditional teaching and current guidelines dictate that they are contraindicated in patients with cocaineassociated chest pain (JW Cardiol Jun 2008, p. 49, and Circulation 2008; 117:1897). β -blockers might exacerbate the toxic cardiovascular effects of cocaine, such as coronary vasospasm and hypertension, secondary to “unopposed” α stimulation. However, evidence supporting this hypothesis is not robust. Researchers performed a retrospective study to assess the safety of β -blockers in 311 consecutive patients in San Francisco who were admitted for chest pain and tested positive for cocaine by urine drug screens. (Those with pulmonary etiologies of chest pain were excluded.) Patients who received β -blockers in the emergency department (46%) were significantly more likely to receive “cardioprotective” medications, such as nitroglycerin, angiotensin-converting–enzyme inhibitors or angiotensin-receptor blockers, aspirin, or statins than patients who did not receive β -blockers. Only patients who received β -blockers exhibited systolic blood pressure decreases (median, –8 mm Hg). Short-term hospitalization outcomes revealed no differences in electrocardiographic changes, myocardial infarction rates, ventricular tachycardia/fibrillation, or death between the two groups. β -blocker recipients were significantly less likely to die from cardiovascular causes during a median follow-up of 2.7 years. COMMENT Typical Angina vs. Atypical Chest Pain In patients presenting to an emergency department, presence and type of symptoms did not predict inducible myocardial ischemia. Patients with acute coronary syndromes (ACS) present with a wide variety of symptoms. Investigators at a single center in New York City conducted a retrospective study involving 2525 patients with no previous history of myocardial infarction or coronary revascularization who were evaluated for ACS in an emergency department–based chest pain unit. Typical angina was defined as “the presence of substernal chest pain or discomfort that was provoked by exertion or emotional stress and was relieved by rest and/or nitroglycerin.” All patients underwent provocative stress testing after serial biomarkers were obtained. Presenting symptoms did not vary significantly by sex, age, or history of diabetes. Ischemia was induced by stress testing in 14% of 231 patients with typical angina, 11% of 2140 patients with atypical chest pain, and 16% of 153 patients with This is the first study to examine the effect of statin therapy on progression of rheumatic MS. Given the high prevalence of rheumatic disease in many parts of the world, even the small decrease in disease progression that was demonstrated in this study could have important public health implications. These findings support the need for a randomized trial of statin therapy for the prevention of valvular stenosis in patients with rheumatic heart disease. — Howard C. Herrmann, MD Antonini-Canterin F et al. Effect of hydroxymethylglutaryl coenzyme-A reductase inhibitors on the long-term progression of rheumatic mitral valve disease. Circulation 2010 May 18; 121:2130. READERS’ POLL If you could attend only one national or international cardiology meeting in the next 12 months, which would it be? ▶ European Society of Cardiology ▶ Transcatheter Cardiovascular Therapeutics ▶ American Heart Association ▶ American College of Cardiology ▶ Society for Cardiovascular Angiography and Interventions ▶ Other Vote online at http://bit.ly/91DUXo This study suggests that β -blockers are safe for patients who are hospitalized for cocaine-related chest pain, although definitive conclusions cannot be drawn because significantly more patients who received β -blockers also received cardioprotective medications. The long-term benefit is difficult to determine because recidivism rates and other treatments were not reported. Nonetheless, these results are encouraging. Armed with this information, clinicians might consider 66 CARDIOLOGY Vol. 16 No. 8 no chest pain at presentation. Thus, patients with typical angina were not significantly more likely than those with no or atypical chest pain to have inducible myocardial ischemia. COMMENT In this study, patients presenting with typical angina symptoms were no more likely than those with no or atypical symptoms to have inducible myocardial ischemia. Although data on the presence and type of chest pain were recorded before stress testing, they were collected hours after presentation, and we cannot infer if or how they affected decisions about testing and patient disposition. How to clinically identify patients with noncardiac symptoms before stress testing remains an important and considerable challenge. — Joel M. Gore, MD Hermann LK et al. Comparison of frequency of inducible myocardial ischemia in patients presenting to emergency department with typical versus atypical or nonanginal chest pain. Am J Cardiol 2010 Jun 1; 105:1561. syncope during an 18-month period. Serious outcomes were defined as death, myocardial infarction, arrhythmia, pulmonary embolism, stroke, subarachnoid hemorrhage, significant bleeding, any procedural intervention to treat a related cause of syncope, any condition causing or likely to cause a return emergency visit, and hospitalization for a related event. Overall, 9.7% of patients had serious outcomes within 30 days. The rule had a sensitivity of 90% for predicting these outcomes. COMMENT cessful in 92% and 100% of the remaining 243 patients with fibrillation and 20 with flutter, respectively. Overall, 97% of patients were discharged home, and 93% of discharged patients were in sinus rhythm. Median ED stay was 4.9 hours. Adverse events (including transient hypotension and bradycardia) occurred in 7.6% of patients, and 8.6% of patients relapsed within 7 days; no cases of torsades de pointes or stroke were reported and no deaths occurred. COMMENT The results of this study are consistent with those from other validation studies. The San Francisco Syncope Rule will likely need to be improved and then validated before it is adopted in practice. Until then, clinical judgment should continue to guide treatment and disposition. — Richard D. Zane, MD, FAAEM, Journal Watch Emergency Medicine Thiruganasambandamoorthy V et al. External validation of the San Francisco Syncope Rule in the Canadian setting. Ann Emerg Med 2010 May; 55:464. Primary ED cardioversion (by IV or oral antidysrhythmic agent [JW Cardiol Feb 2005, p. 15, and N Engl J Med 2004; 351:2384] or synchronized electrical cardioversion) is a reasonable option for patients with uncomplicated atrial fibrillation or atrial flutter. — Kristi L. Koenig, MD, FACEP, Journal Watch Emergency Medicine Stiell IG et al. Association of the Ottawa Aggressive Protocol with rapid discharge of emergency department patients with recent-onset atrial fibrillation or flutter. CJEM 2010 May; 12:181. How Does the San Francisco Syncope Rule Perform in Canada? The rule had a sensitivity of 90% for predicting serious outcomes at 30 days. Rapid Treatment and Discharge of Patients with Recent-Onset Atrial Fibrillation or Flutter Rapid cardioversion and discharge home is safe for emergency department patients who present within 48 hours of onset of atrial fibrillation or flutter. Are Zotarolimus-Eluting Stents Really Noninferior to Everolimus-Eluting Stents? Only time will tell. Patients with syncope often are admitted to the hospital despite negative emergency department (ED) evaluations. The San Francisco Syncope Rule was developed to identify syncope patients who are at sufficiently low risk for serious outcomes to be safely discharged home after ED evaluation. The rule classifies patients as high risk if they have histories of congestive heart failure, hematocrit <30%, abnormal electrocardiogram, shortness of breath, or triage systolic blood pressure <90 mm Hg. The rule was initially reported to have 96% and 98% sensitivity for predicting serious outcomes at 7 days and 30 days, respectively, but has not performed as well in subsequent validation studies in the U.S. and Australia, where sensitivities ranged from 74% to 90% (Ann Emerg Med 2008; 52:151, and CJEM 2007; 9:157). To evaluate performance of the rule in Canada, researchers retrospectively applied the rule to 505 patients who presented to a single tertiary care hospital with Researchers evaluated the efficacy and safety of a protocol for rapid emergency department (ED) cardioversion and discharge of patients with recent-onset (<48 hours) atrial fibrillation or atrial flutter in a retrospective observational study of 660 consecutive patients (95% with atrial fibrillation, 5% with atrial flutter) at a single ED in Canada from 2000 to 2005. The protocol involved ED pharmacologic cardioversion with intravenous (IV) procainamide (1 g during 60 minutes) and, if needed, electrical cardioversion, followed by discharge home within 1 hour after cardioversion. Sixty percent of patients with atrial fibrillation and 28% of those with atrial flutter converted to sinus rhythm with IV procainamide. Electrical cardioversion (not attempted in 32 patients) was suc- Second-generation drug-eluting stents (DES) are staking their claims to superiority over established DES, but in the recent SORT OUT III trial (JW Cardiol Apr 2010, p. 33, and Lancet 2010; 375:1090), a first-generation sirolimus-eluting stent outperformed the novel zotarolimuseluting stent (ZES). Now, European investigators have compared the ZES with the second-generation everolimus-eluting stent (EES) in an all-comers, multicenter, open-label, randomized, noninferiority, manufacturer-funded trial in patients undergoing percutaneous coronary intervention (PCI). Of the 2292 participants (mean age, 64; 77% men), 66% had at least one off-label criterion for stent placement. The incidence of the composite endpoint — cardiac death, myocardial infarction (MI), and clinically indicated targetvessel revascularization at 12 months — was 8.2% in the ZES group and 8.3% in the EES group (95% confidence interval, August 2010 JWatch.org 67 –2.4% to 2.2%; P<0.001 for noninferiority). However, the rate of stent thrombosis was 2.3% in the ZES group and 1.5% in the EES group (95% CI, –0.3 to 1.9; P=0.17 for noninferiority). In follow-up angiography at 13 months (performed in a randomly selected 20% of participants), rates of binary in-stent restenosis were similar in the ZES and EES groups (4.2% and 3.8%, respectively; 95% CI, –3.5% to 4.4%; P=0.04 for noninferiority), but instent late lumen loss was 0.27 mm and 0.19 mm, respectively (P=0.08). COMMENT patients by baseline cardiovascular risk. During 1 year of follow-up, combinedtherapy recipients were more likely than clopidogrel-alone recipients to be rehospitalized for MI or coronary stent procedures (27.6 vs. 14.3 events per 100 person-years) or to be rehospitalized for MI (9.7 vs. 4.1 events per 100 person-years). COMMENT Thrombolysis in MI (TIMI) risk scores were significantly associated with increased 30-day mortality. Fibrinolysis was untimely (>30 minutes after presentation) in 54% of recipients, and PPCI was untimely (>90 minutes after presentation) in 68% of recipients. In patients who received untimely treatment, all-cause mortality was significantly higher than in those whose treatment was timely, at both 30 days and 1 year; these associations remained largely unchanged after multivariate adjustment. In both PPCI and fibrinolysis recipients, the 1-year rate of readmission for heart failure was significantly lower with timely than with untimely treatment; however, rates of readmission for acute MI did not differ significantly by timeliness of treatment. COMMENT In this randomized cohort with minimal exclusion criteria, the rates of clinical endpoints in the ZES group were low and similar to those in the EES group. However, the slightly higher rates of stent thrombosis and greater in-stent late lumen loss with the ZES are cause for concern. Given the all-cause mortality findings from SORT OUT III, longer-term follow-up of the ZES is needed to definitively establish that it is noninferior to the EES. — Beat J. Meyer, MD Serruys PW et al. Comparison of zotarolimuseluting and everolimus-eluting coronary stents. N Engl J Med 2010 Jul 8; 363: 138. Once again, PPIs have been shown to lower the efficacy of clopidogrel. Of note, a few studies have suggested that pantoprazole inhibits CYP2C19 less than other PPIs do and that it does not impair clopidogrel efficacy. In this study, pantoprazole had adverse effects that were similar to those of other PPIs. Discouraging use of PPIs in conjunction with clopidogrel seems prudent. — Jamaluddin Moloo, MD, MPH, Journal Watch General Medicine Stockl KM et al. Risk of rehospitalization for patients using clopidogrel with a proton pump inhibitor. Arch Intern Med 2010 Apr 26; 170:704. The Importance of Being Timely In a population-based cohort with STsegment-elevation myocardial infarction, time to reperfusion had a stronger effect than method of reperfusion on outcomes. Using Clopidogrel with a Proton-Pump Inhibitor Risks for rehospitalization for myocardial infarction or stent placement were higher with combined therapy. Studies have suggested that clopidogrel’s efficacy is weakened if it is used in combination with a proton-pump inhibitor (PPI), given that the drugs compete for CYP2C19 activity. However, earlier retrospective studies might not have fully accounted for the likelihood that patients who receive PPIs are at higher baseline risk for cardiovascular events than are those who do not. In this retrospective cohort study, based on U.S. claims data, researchers assessed risks for rehospitalization for myocardial infarction (MI) or stent placement among 2066 patients (mean age, 69) who were discharged from hospitals after MI or coronary stent placement; half the patients received clopidogrel alone, and half received it in combination with a PPI. Propensity scores were used to match Clinical trial and registry data show that rapid coronary reperfusion improves outcomes in patients with ST-segmentelevation myocardial infarction (STEMI). To assess the importance of timely treatment in a broader population, investigators evaluated STEMI care from October 2006 through March 2007 at 80 hospitals where >95% of patients with acute MI in Quebec, Canada, are treated. Of 2356 STEMI patients, 61.1% received primary percutaneous coronary intervention (PPCI), 16.6% received fibrinolysis, and 22.2% received neither intervention. At 30 days, mortality was 6.1% in fibrinolytic recipients and 5.2% in PPCI recipients. At 1 year, mortality was 7.4% in fibrinolytic recipients and 7.9% in PPCI recipients, and the rates of combined death or readmission for acute MI or heart failure were 13.5% and 13.6%, respectively. In patients who received no acute reperfusion treatment, 30-day and 1-year death rates were 18% and 29%, respectively. Both female sex and higher These findings confirm that reperfusion treatment delays are associated with substantial increases in mortality. All programs at the hospital, community, and national levels should be aimed at treating STEMI patients as rapidly as possible. According to this study, not only is watchful waiting unacceptable, but timely fibrinolysis might be more effective than delayed PPCI in some situations. — Joel M. Gore, MD Lambert L et al. Association between timeliness of reperfusion therapy and clinical outcomes in ST-elevation myocardial infarction. JAMA 2010 Jun 2; 303:2148. Save time and stay informed with a FREE daily e-mail alert. • Relevant information and practical intelligence you can use • Brief reviews of the medical news that affects your practice • Gleaned from government agencies, journals, and other key sources • Delivered to your e-mail box each weekday by 7:30 a.m. ET Visit JWatch.org to sign up FREE JW ONLINE CME JOURNAL WATCH SUBSCRIBERS HAVE 10 FREE CREDITS! This is one of four questions in a recent Journal Watch Online CME exam. from “Cardiac Arrest Data — by Neighborhood” (below) In a study of out-of-hospital cardiac arrest in different neighborhoods in a single urban county, the reliability-adjusted rates of bystander cardiopulmonary resuscitation ranged from: A. 0% to 100% B. 4% to 21% C. 10% to 57% D. 25% to 49% Category: Cardiovascular Diseases Exam Title: Initial Management of Cardiac Arrest and Myocardial Infarction Posted Date: Jul 27 2010 View this exam and others at http://cme.jwatch.org User name and password are required. CME FACULTY Kelly Anne Spratt, DO, FACC, Section Editor, Cardiology No part of this newsletter may be reproduced or otherwise incorporated into any information retrieval system without the written permission of the Massachusetts Medical Society. Printed in the USA. ISSN 1521-5822. Massachusetts Medical Society 860 Winter Street Waltham, MA 02451-1413 JWatch.org 68 CARDIOLOGY Vol. 16 No. 8 Cardiac Arrest Data — by Neighborhood Sectors of an urban county in Georgia varied widely in their incidence of out-ofhospital cardiac arrest and their frequency of bystander cardiopulmonary resuscitation. Survival rates after out-of-hospital cardiac arrest remain stubbornly stable in the U.S. We know that rates of cardiac arrest incidence and of bystander cardiopulmonary resuscitation (CPR) vary widely by region and by city, but what about by neighborhood? To find out, investigators analyzed registry data from Fulton County, Georgia, to identify rates of cardiac arrest and bystander CPR in 161 neighborhoods from October 2005 through November 2008. A total of 1108 cardiac arrests were eligible for analysis. The average adjusted incidence was 0.64 cardiac arrests per 1000 persons, but it ranged from 0.04 to 2.11 per 1000 persons across the 161 neighborhoods. Bystander CPR was administered in 279 cardiac arrests (25%). Across the neighborhoods, the raw percentage of cardiac-arrest patients who received bystander CPR ranged from 0% to 100%; adjustment for reliability narrowed that range to 10% to 57%. Cardiac-arrest incidence did not correlate well with the frequency of bystander CPR. Notably, of the 41 patients who survived to hospital discharge, 20 (49%) had received bystander CPR. COMMENT The Journal Watch Series Journal Watch AIDS Clinical Care Journal Watch Cardiology Journal Watch Dermatology Journal Watch Emergency Medicine Journal Watch Gastroenterology Journal Watch General Medicine Journal Watch Hospital Medicine Journal Watch Infectious Diseases Journal Watch Neurology Journal Watch Oncology and Hematology Journal Watch Pediatrics and Adolescent Medicine Journal Watch Psychiatry Journal Watch Women’s Health FOR MORE INFORMATION From the United States and Canada: call (800) 8436356, fax (781) 893-0413, or see JWatch.org From all other locations: call (49) 30 312 3883, fax (49) 30 313 2032 (Germany) call +1 781 893 3800 x5515, fax +1 781 893 0413 (U.S.) These data from a single, urban county suggest that neighborhoods vary markedly in their incidence of cardiac arrest and in their frequency of bystander CPR. CPR training initiatives should target areas with high rates of cardiac arrest. — Joel M. Gore, MD Sasson C et al. for the CARES Study Group. Small area variations in out-of-hospital cardiac arrest: Does the neighborhood matter? Ann Intern Med 2010 Jul 6; 153:19.