Background The combined thickness of the intima and media of the carotid artery is associated with the prevalence of cardiovascular disease. We studied the associations between the thickness of the carotid-artery intima and media and the incidence of new myocardial infarction or stroke in persons without clinical cardiovascular disease.Methods Noninvasive measurements of the intima and media of the common and internal carotid artery were made with high-resolution ultrasonography in 5858 subjects 65 years of age or older. Cardiovascular events (new myocardial infarction or stroke) served as outcome variables in subjects without clinical cardiovascular disease (4476 subjects) over a median follow-up period of 6.2 years.Results The incidence of cardiovascular events correlated with measurements of carotid-artery intima-media thickness. The relative risk of myocardial infarction or stroke increased with intima-media thickness (P<0.001). The relative risk of myocardial infarction or stroke (adjusted for age and sex) for the quintile with the highest thickness as compared with the lowest quintile was 3.87 (95 percent confidence interval, 2.72 to 5.51). The association between cardiovascular events and intima-media thickness remained significant after adjustment for traditional risk factors, showing increasing risks for each quintile of combined intima-media thickness, from the second quintile (relative risk, 1.54; 95 percent confidence interval, 1.04 to 2.28), to the third (relative risk, 1.84; 95 percent confidence interval, 1.26 to 2.67), fourth (relative risk, 2.01; 95 percent confidence interval, 1.38 to 2.91), and fifth (relative risk, 3.15; 95 percent confidence interval, 2.19 to 4.52). The results of separate analyses of myocardial infarction and stroke paralleled those for the combined end point.Conclusions Increases in the thickness of the intima and media of the carotid artery, as measured noninvasively by ultrasonography, are directly associated with an increased risk of myocardial infarction and stroke in order adults without a history of cardiovascular disease. (N Engl J Med 1999;340:14-22.) (C) 1999, Massachusetts Medical Society.

This paper presents a general approach for assessing the sensitivity of the point and interval estimates of the primary exposure effect in an observational study to the residual confounding effects of unmeasured variable after adjusting for measured covariates. The proposed method assumes that the true exposure effect can be represented in a regression model that includes the exposure indicator as well as the measured and unmeasured confounders. One can use the corresponding reduced model that omits the unmeasured confounder to make statistical inferences about the true exposure effect by specifying the distributions of the unmeasured confounder in the exposed and unexposed groups along with the effects of the unmeasured confounder on the outcome variable. Under certain conditions, there exists a simple algebraic relationship between the true exposure effect in the full model and the apparent exposure effect in the reduced model. One can then estimate the true exposure effect by making a simple adjustment to the point and interval estimates of the apparent exposure effect obtained from standard software or published reports. The proposed method handles both binary response and censored survival time data, accommodates any study design, and allows the unmeasured confounder to be discrete or normally distributed. We describe applications on two major medical studies.

BACKGROUND:The most important factor for improving out-of-hospital ventricular fibrillation survival rates is early defibrillation. This can be achieved if small, lightweight, inexpensive automatic external defibrillators are widely disseminated. Because automatic external defibrillator size and cost are directly affected by defibrillation waveform shape and because of the favorable experience with truncated biphasic waveforms in implantable cardioverter-defibrillators, we compared the efficacy of a truncated biphasic waveform with that of a standard damped sine monophasic waveform for transthoracic defibrillation.METHODS AND RESULTS:The principal goal of this multicenter, prospective, randomized, blinded study was to compare the first-shock transthoracic defibrillation efficacy of a 130-J truncated biphasic waveform with that of a standard 200-J monophasic damped sine wave pulse using anterior thoracic pads in the course of implantable cardioverter-defibrillator testing. Pad-pad ECGs were also examined after transthoracic defibrillation. After the elimination of data for 24 patients who did not meet all protocol criteria, the results from 294 patients were analyzed. The 130-J truncated biphasic pulse and the 200-J damped sine wave monophasic pulse resulted in first-shock efficacy rates of 86% and 86%, respectively (P = .97). ST-segment levels measured 10 seconds after the shock in 151 patients in sinus rhythm were -0.26 +/- 1.58 and -1.86 +/- 1.93 mm for the 130- and 200-J shocks, respectively (P < .0001).CONCLUSIONS:We found that 130-J biphasic truncated transthoracic shocks defibrillate as well as the 200-J monophasic damped sine wave shocks that are traditionally used in standard transthoracic defibrillators and result in fewer ECG abnormalities after the shock.

Warfarin is an established treatment for prevention of ischaemic stroke in patients with atrial fibrillation, but the value of this agent relative to aspirin is unclear. In the first Stroke Prevention in Atrial Fibrillation (SPAF-I) study, direct comparison of warfarin with aspirin was limited by the small number of thromboembolic events. SPAF-II aims to address this issue and also to assess the differential effects of the two treatments according to age.We compared warfarin (prothrombin time ratio 1.3-1.8, international normalised ratio 2.0-4.5) with aspirin 325 mg daily for prevention of ischaemic stroke and systemic embolism (primary events) in two parallel randomised trials involving 715 patients aged 75 years or less and 385 patients older than 75; we sought reductions in the absolute rate of primary events by warfarin compared with aspirin of 2% per year and 4% per year, respectively. In the younger patients, warfarin decreased the absolute rate of primary events by 0.7% per year (95% Cl - 0.4 to 1.7). The primary event rate per year was 1.3% with warfarin and 1.9% with aspirin (relative risk [RR] 0.67, p = 0.24). The absolute rate of primary events in low-risk younger patients (without hypertension, recent heart failure, or previous thromboembolism) on aspirin was 0.5% per year (95% Cl 0.1 to 1.9). Among older patients, warfarin decreased the absolute rate of primary events by 1.2% per year (95% Cl - 1.7 to 4.1). The primary event rate per year was 3.6% with warfarin and 4.8% with aspirin (RR 0.73, p = 0.39). In this older group, the rate of all stroke with residual deficit (ischaemic or haemorrhagic) was 4.3% per year with aspirin and 4.6% per year with warfarin (RR 1.1).Warfarin may be more effective than aspirin for prevention of ischaemic stroke in patients with atrial fibrillation, but the absolute reduction in stroke rate by warfarin is small. Younger patients without risk factors had a low rate of stroke when treated with aspirin. In older patients the rate of stroke (ischaemic and haemorrhagic) was substantial, irrespective of which agent was given. Patient age and the inherent risk of thromboembolism should be considered in the choice of antithrombotic prophylaxis for patients with atrial fibrillation.

HomeCirculationVol. 89, No. 6Guidelines for the management of transient ischemic attacks. From the Ad Hoc Committee on Guidelines for the Management of Transient Ischemic Attacks of the Stroke Council of the American Heart Association. Free AccessAbstractPDF/EPUBAboutView PDFSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessAbstractPDF/EPUBGuidelines for the management of transient ischemic attacks. From the Ad Hoc Committee on Guidelines for the Management of Transient Ischemic Attacks of the Stroke Council of the American Heart Association. W M Feinberg, G W Albers, H J Barnett, J Biller, L R Caplan, L P Carter, R G Hart, R W Hobson2nd, R A Kronmal and W S Moore W M FeinbergW M Feinberg , G W AlbersG W Albers , H J BarnettH J Barnett , J BillerJ Biller , L R CaplanL R Caplan , L P CarterL P Carter , R G HartR G Hart , R W Hobson2ndR W Hobson2nd , R A KronmalR A Kronmal and W S MooreW S Moore Originally published1 Jun 1994https://doi.org/10.1161/01.CIR.89.6.2950Circulation. 1994;89:2950–2965 Previous Back to top Next FiguresReferencesRelatedDetailsCited By Tuna M and Rothwell P (2021) Diagnosis of non-consensus transient ischaemic attacks with focal, negative, and non-progressive symptoms: population-based validation by investigation and prognosis, The Lancet, 10.1016/S0140-6736(20)31961-9, 397:10277, (902-912), Online publication date: 1-Mar-2021. Shahjouei S, Sadighi A, Chaudhary D, Li J, Abedi V, Holland N, Phipps M and Zand R (2021) A 5-Decade Analysis of Incidence Trends of Ischemic Stroke After Transient Ischemic Attack, JAMA Neurology, 10.1001/jamaneurol.2020.3627, 78:1, (77), Online publication date: 1-Jan-2021. Neves P, Fontes S, Fukujima M, Matas S and Prado G (2019) Profissionais da saúde, que assistem pacientes com Acidente Vascular Cerebral, necessitam de informação especializada, Revista Neurociências, 10.4181/RNC.2004.12.173, 12:4, (173-181) Honig S, Babiarz L, Honig E, Mirbagheri S, Urrutia V and Yousem D (2017) The impact of installing an MR scanner in the emergency department for patients presenting with acute stroke-like symptoms, Clinical Imaging, 10.1016/j.clinimag.2017.05.015, 45, (65-70), Online publication date: 1-Sep-2017. Landriel F, Ajler P and Yampolsky C (2016) Postoperative stroke in neurosurgery Treatment-Related Stroke, 10.1017/CBO9781139775397.004, (23-32) (2016) Iatrogenic ischemic strokes: peri- and postoperative strokes Treatment-Related Stroke, 10.1017/CBO9781139775397.002, (1-62) Atzema C, Grewal K, Lu H, Kapral M, Kulkarni G and Austin P (2015) Outcomes among patients discharged from the emergency department with a diagnosis of peripheral vertigo, Annals of Neurology, 10.1002/ana.24521, 79:1, (32-41), Online publication date: 1-Jan-2016. Peacock F, Beckley P, Clark C, Disch M, Hewins K, Hunn D, Kontos M, Levy P, Mace S, Melching K, Ordonez E, Osborne A, Suri P, Sun B and Wheatley M (2014) Recommendations for the Evaluation and Management of Observation Services, Critical Pathways in Cardiology: A Journal of Evidence-Based Medicine, 10.1097/HPC.0000000000000033, 13:4, (163-198), Online publication date: 1-Dec-2014. Hayashi T, Sehara Y, Kato Y, Fukuoka T, Deguchi I, Ohe Y, Maruyama H, Horiuchi Y, Sano H, Nagamine Y and Tanahashi N (2014) Clinical Characteristics of Cardioembolic Transient Ischemic Attack: Comparison with Noncardioembolic Transient Ischemic Attack, Journal of Stroke and Cerebrovascular Diseases, 10.1016/j.jstrokecerebrovasdis.2014.04.005, 23:8, (2169-2173), Online publication date: 1-Sep-2014. Hayashi T, Kato Y, Nagoya H, Ohe Y, Deguchi I, Fukuoka T, Maruyama H, Horiuchi Y, Nagamine Y, Sano H and Tanahashi N (2014) Prediction of Ischemic Stroke in Patients with Tissue-Defined Transient Ischemic Attack, Journal of Stroke and Cerebrovascular Diseases, 10.1016/j.jstrokecerebrovasdis.2013.11.020, 23:6, (1368-1373), Online publication date: 1-Jul-2014. Lackland D, Roccella E, Deutsch A, Fornage M, George M, Howard G, Kissela B, Kittner S, Lichtman J, Lisabeth L, Schwamm L, Smith E and Towfighi A (2013) Factors Influencing the Decline in Stroke Mortality, Stroke, 45:1, (315-353), Online publication date: 1-Jan-2014. Goldfinger J, Kronish I, Fei K, Graciani A, Rosenfeld P, Lorig K and Horowitz C (2012) Peer education for secondary stroke prevention in inner-city minorities: Design and methods of the prevent recurrence of all inner-city strokes through education randomized controlled trial, Contemporary Clinical Trials, 10.1016/j.cct.2012.06.003, 33:5, (1065-1073), Online publication date: 1-Sep-2012. Bentley R and March P (2011) Recurrent vestibular paroxysms associated with systemic hypertension in a dog, Journal of the American Veterinary Medical Association, 10.2460/javma.239.5.652, 239:5, (652-655), Online publication date: 1-Sep-2011. Howard G and Goff D (2011) Lipids and stroke: Looking for risk in all the wrong places?, Annals of Neurology, 10.1002/ana.22428, 69:4, (597-599), Online publication date: 1-Apr-2011. Ohara T, Yamamoto Y, Nagakane Y, Tanaka E, Morii F and Koizumi T (2011) Classification of etiologic subtypes for transient ischemic attacks: Clinical significance of lacunar transient ischemic attack, Rinsho Shinkeigaku, 10.5692/clinicalneurol.51.406, 51:6, (406-411), . Mahe G, Ronziere T, Laviolle B, Golfier V, Cochery T, De Bray J and Paillard F (2010) An unfavorable dietary pattern is associated with symptomatic ischemic stroke and carotid atherosclerosis, Journal of Vascular Surgery, 10.1016/j.jvs.2010.02.258, 52:1, (62-68), Online publication date: 1-Jul-2010. Matarin M, Singleton A, Hardy J and Meschia J (2010) The genetics of ischaemic stroke, Journal of Internal Medicine, 10.1111/j.1365-2796.2009.02202.x, 267:2, (139-155), Online publication date: 1-Feb-2010. Tateishi Y, Iguchi Y, Kimura K, Kobayashi K, Shibazaki K and Eguchi K (2009) Right-to-left shunts may be not uncommon cause of TIA in Japan, Journal of the Neurological Sciences, 10.1016/j.jns.2008.09.035, 277:1-2, (13-16), Online publication date: 1-Feb-2009. Messé S and Jauch E (2008) Transient Ischemic Attack: Diagnostic Evaluation, Annals of Emergency Medicine, 10.1016/j.annemergmed.2008.05.018, 52:2, (S17-S26), Online publication date: 1-Aug-2008. Jagoda A and Chan Y (2008) Transient Ischemic Attack Overview: Defining the Challenges for Improving Outcomes, Annals of Emergency Medicine, 10.1016/j.annemergmed.2008.04.030, 52:2, (S3-S6), Online publication date: 1-Aug-2008. Meurin P, Tabet J, Iliou M, Pierre B, Corone S, Cristofini P, Iung B and Driss A (2008) Thromboembolic events early after mitral valve repair: Incidence and predictive factors, International Journal of Cardiology, 10.1016/j.ijcard.2007.03.115, 126:1, (45-52), Online publication date: 1-May-2008. Koz C, Uzun M, Yokusoglu M, Ulas U, Baysan O, Genc C, Cansel M and Isik E (2008) Echocardiographic, Electrocardiographic, and Clinical Correlates of Recurrent Transient Ischemic Attacks: A Follow-up Study, Southern Medical Journal, 10.1097/SMJ.0b013e3181647071, 101:3, (246-251), Online publication date: 1-Mar-2008. Fagan S (2009) Urgent Need for Secondary Stroke Prevention After Transient Ischemic Attack, The Consultant Pharmacist, 10.4140/TCP.n.2008.131, 23:2, (131-140), Online publication date: 1-Feb-2008. Ruff N and Johnston S (2008) Chapter 23 Identification, risks, and treatment of transient ischemic attack Stroke Part II: Clinical Manifestations and Pathogenesis, 10.1016/S0072-9752(08)93023-2, (453-473), . Shaltoni H and Yatsu F (2007) Cerebrovascular Disease/Transient Ischemic Attack Cardiovascular Medicine, 10.1007/978-1-84628-715-2_92, (1911-1921), . Torres-Grate R, lvarez-Rodrguez E and Calvo Manuel E (2005) Historia natural de la arteriosclerosis. Expresividad cl?nica. Complicaciones agudas y cr?nicas, Medicine - Programa de Formaci?n M?dica Continuada Acreditado, 10.1016/S0211-3449(05)73755-3, 9:38, (2525-2535), Online publication date: 1-Sep-2005. Gladstone D (2015) COMMENTARY: Toward an emergency response to transient ischemic attacks, Postgraduate Medicine, 10.3810/pgm.2005.01.1562, 117:1, (9-14), Online publication date: 1-Jan-2005. Nguyen-Huynh M and Johnston S (2005) Transient ischemic attack: A neurologic emergency, Current Neurology and Neuroscience Reports, 10.1007/s11910-005-0018-z, 5:1, (13-20), Online publication date: 1-Jan-2005. (2003) Transient Ischemic Attack, New England Journal of Medicine, 10.1056/NEJM200304173481620, 348:16, (1606-1606), Online publication date: 17-Apr-2003. Eimil M and Egido J (2003) Ataque isquémico transitorio, FMC - Formación Médica Continuada en Atención Primaria, 10.1016/S1134-2072(03)75904-0, 10:5, (295-303), Online publication date: 1-Jan-2003. Hacke W, Kaste M, Olsen T, Orgogozo J and Bogousslavsky J (2003) Empfehlungen der Europäischen Schlaganfall-Initiative zur Versorgung und Behandlung des Schlaganfalls Die Notfalltherapie und Intensivtherapie bei Schlaganfall, 10.1007/978-3-642-57384-2_11, (96-112), . Swarztrauber K, Vickrey B and Mittman B (2002) Physicians' Preferences for Specialty Involvement in the Care of Patients With Neurological Conditions, Medical Care, 10.1097/00005650-200212000-00007, 40:12, (1196-1209), Online publication date: 1-Dec-2002. Johnston S (2002) Transient Ischemic Attack, New England Journal of Medicine, 10.1056/NEJMcp020891, 347:21, (1687-1692), Online publication date: 21-Nov-2002. Chang E, Holroyd B, Kochanski P, Kelly K, Shuaib A and Rowe B (2014) Adherence to Practice Guidelines for Transient Ischemic Attacks in an Emergency Department, Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques, 10.1017/S0317167100002225, 29:4, (358-363), Online publication date: 1-Nov-2002. Zerwic J, Ennen K and DeVon H (2016) Stroke, AAOHN Journal, 10.1177/216507990205000807, 50:8, (354-359), Online publication date: 1-Aug-2002. Caplan L (2002) Is the promise of randomized control trials ("evidence-based medicine") overstated?, Current Neurology and Neuroscience Reports, 10.1007/s11910-002-0044-z, 2:1, (1-8), Online publication date: 1-Feb-2002. Hellstrom H (1999) New evidence for the spasm-of-resistance-vessel concept of ischemic diseases, Medical Hypotheses, 10.1054/mehy.1998.0746, 53:3, (200-209), Online publication date: 1-Sep-1999. Rahmatullah A, Rahko P and Stein J (1999) Transesophageal echocardiography for the evaluation and management of patients with cerebral ischemia, Clinical Cardiology, 10.1002/clc.4960220605, 22:6, (391-396), Online publication date: 1-Jun-1999. Kasner S and Grotta J (1998) ISCHEMIC STROKE, Neurologic Clinics, 10.1016/S0733-8619(05)70068-2, 16:2, (355-372), Online publication date: 1-May-1998. Maxwell J, Rutledge R, Covington D, Churchill M and Clancy T (1997) A statewide, hospital-based analysis of frequency and outcomes in carotid endarterectomy, The American Journal of Surgery, 10.1016/S0002-9610(97)00202-X, 174:6, (655-661), Online publication date: 1-Dec-1997. Pedersen A, Lidegaard Ø, Kreiner S and Ottesen B (1997) Hormone replacement therapy and risk of non-fatal stroke, The Lancet, 10.1016/S0140-6736(97)06005-4, 350:9087, (1277-1283), Online publication date: 1-Nov-1997. Glusa E (1996) Acetylsalicylsäure im Vergleich zu anderen Thrombozytenfunktionshemmern — Nebenwirkungen und Interaktionen mit anderen Pharmaka Acetylsalicylsäure im Kardiovaskulären System, 10.1007/978-3-0348-7574-5_5, (89-110), . (1995) Admission Criteria for Stroke, Annals of Emergency Medicine, 10.1016/S0196-0644(95)70130-3, 26:4, (530-531), Online publication date: 1-Oct-1995. Gross S (1995) Transient Ischemic Attacks (TIA): Current Issues in Diagnosis and Management, Journal of the American Academy of Nurse Practitioners, 10.1111/j.1745-7599.1995.tb01158.x, 7:7, (329-338), Online publication date: 1-Jul-1995. June 1, 1994Vol 89, Issue 6 Advertisement Article InformationMetrics Copyright © 1994 by American Heart Associationhttps://doi.org/10.1161/01.CIR.89.6.2950 Originally publishedJune 1, 1994 PDF download Advertisement

BACKGROUNDEven with aggressive treatment, heart failure is associated with a substantial morbidity and mortality. This poor prognosis has led to increasing interest in primary prevention, and the identification of modifiable risk factors. Our objective was to determine whether modifiable cardiovascular risk factors, including systolic and diastolic blood pressure, fasting glucose level, cholesterol level, weight, and smoking, were independent risk factors for heart failure in patients with anatomically confirmed coronary artery disease.METHODSWe studied all patients with documented coronary artery disease eligible for the multicenter, randomized-controlled Coronary Artery Surgery Study. After excluding 79 prevalent cases, we identified incident cases of heart failure using hospital discharge abstracts, mortality records, or self-reported follow-up questionnaires. Criteria for self-reported cases were treatment with digitalis and/or furosemide plus two or more heart failure symptoms, including dyspnea on exertion, orthopnea, paroxysmal nocturnal dyspnea, or edema. Cox regression analysis was used to estimate adjusted relative risks.RESULTSAt 12-year follow-up, the cumulative incidence of heart failure was 20.6%. Smoking (relative risk, 1.47) and weight (relative risk, 1.15/10 kg) were independently associated with incident heart failure. Myocardial infarction during follow-up, age, female sex, and baseline left ventricular dysfunction were also risk factors for heart failure.CONCLUSIONSPatients with stable coronary artery disease are at high risk for developing heart failure, especially following myocardial infarction. However, interventions aimed at smoking cessation and weight reduction may prevent clinical heart failure in these patients.

OBJECTIVE:To compare the efficacy of commonly used forms of eye prophylaxis for newborns with no prophylaxis in the prevention of nongonococcal conjunctivitis.DESIGN:Randomized doubly masked clinical trial.SETTING:University of Washington Hospital and affiliated clinics, Seattle, between 1985 and 1990.SUBJECTS:The medical records of 8499 women were evaluated for possible participation; 2577 were eligible. Of the 758 enrolled, the infants of 630 were evaluable.INTERVENTION:Comparison of silver nitrate, erythromycin, and no eye prophylaxis given at birth for the prevention of conjunctivitis.MAIN OUTCOME MEASURES:Conjunctivitis during the first 60 days of life and nasolacrimal duct patency in the first 2 days of life.RESULTS:The frequency of impatent tear ducts at the 30- to 48-hour examination did not differ significantly by prophylaxis group. Among the 630 infants randomized and observed, 109 (17%) developed mild conjunctivitis. Sixty-nine (63%) of the cases appeared during the first 2 weeks of life. After 2 months of observation, infants allocated to silver nitrate eye prophylaxis at birth had a 39% lower rate of conjunctivitis (hazard ratio = 0.61, 95% confidence interval = 0.39 to 0.97), and those allocated to erythromycin had a 31% lower rate of conjunctivitis (hazard ratio = 0.69, 95% confidence interval = 0.44 to 1.07), than did those allocated to no prophylaxis.CONCLUSION:Silver nitrate eye prophylaxis caused no sustained deleterious effects and even provided some benefit to infants born to women without Neisseria gonorrhoeae. However, the effect was modest and against microorganisms of low virulence. The results suggest that parental choice of a prophylaxis agent including no prophylaxis is reasonable for women receiving prenatal care and who are screened for sexually transmitted diseases during pregnancy.

The authors conducted this study to determine the etiologic agents of conjunctivitis in early infancy. From 1985 to 1990, 630 infants enrolled in a randomized, controlled, double-masked study of eye prophylaxis were observed for 60 days after delivery for signs of conjunctivitis. The following isolates were categorized as pathogens: Haemophilus influenzae, Streptococcus pneumoniae, Neisseria cinerea, Klebsiella pneumoniae, and Chlamydia trachomatis. Using conditional logistic regression for analysis of 97 infant pairs, the authors identified isolates categorized as pathogens almost exclusively among cases (odds ratio (OR) = 18.0, 95% confidence interval (Cl) 2.3-128). Among the microorganisms which have not usually been regarded as pathogens in the etiology of infant conjunctivitis, Streptococcus mitis was the only microorganism associated with an increased risk of conjunctivitis (OR = 5.3, 95% Cl 1.8-15.0). The findings concerning the species of bacteria most often associated with conjunctivitis, as well as the finding that method of delivery is unimportant, suggest that bacteria were transmitted to the infants' eyes after birth and not from the birth canal.

Background and Objectives. The relation between cardiac mortality and antiarrhythmic drug administration has not been fully determined. This relation was analyzed in 1,330 patients enrolled in the Stroke Prevention in Atrial Fibrillation Study, a randomized clinical trial comparing warfarin, aspirin and placebo for the prevention of ischemic stroke or systemic embolism in patients with nonvalvular atrial fibrillation.Methods. Patients who received antiarrhythmic drug therapy for atrial fibrillation in this study were compared with patients not receiving antiarrhythmic agents. The relative risk of cardiac mortality, including arrhythmic death, in patients receiving antiarrhythmic drug therapy was determined and adjusted for other cardiac risk factors.Results. In patients receiving antiarrhythmic drug therapy, cardiac mortality was increased 2.5-fold (p = 0.006, 95% confidence interval [CI] 1.3 to 4.9) and arrhythmic death was increased 2.6-fold (p = 0.02, 95% CI 1.2 to 5.6). Among patients with a history of congestive heart failure, those given antiarrhythmic medications had a relative risk of cardiac death of 4.7 (p < 0.001, 95% CI 1.9 to 11.6) compared with that of patients not so treated; the relative risk of arrhythmic death in the treated group was 3.7 (p = 0.01, 95% CI 1.3 to 10.4). Patients without a history of congestive heart failure had no increased risk of cardiac mortality (relative risk 0.70, 95% CI 0.2 to 3.1) during antiarrhythmic drug therapy.After exclusion of 23 patients with documented ventricular arrhythmias and adjustment for other variables predictive of cardiac death, patients receiving antiarrhythmic drugs were not at increased risk of cardiac death or arrhythmic death. However, in patients with a history of heart failure who received antiarrhythmic drug therapy, the relative risk of cardiac death was 3.3 (p = 0.05, 95% CI 0.99 to 11.1) and that of arrhythmic death was 5.8 (p = 0.009, 95% CI 1.5 to 21.7) compared with the risk in patients not taking antiarrhythmic medications.Conclusions. Although antiarrhythmic drug therapy was not randomly determined in this trial, the data suggest that in patients with atrial fibrillation and a history of congestive heart failure, the risk of such therapy may outweigh the potential benefit of maintaining sinus rhythm.

Objective: To identify those patients with nonrheumatic atrial fibrillation who are at high risk and those at low risk for arterial thromboembolism. Design: Cohort study of patients assigned to placebo in a randomized clinical trial. Setting: Five hundred sixty-eight inpatients and outpatients with nonrheumatic atrial fibrillation assigned to placebo therapy at 15 U.S. medical centers from 1987 to 1989 in the Stroke Prevention in Atrial Fibrillation study. Patients were followed for a mean of 1.3 years. Measurements: Clinical variables were assessed at study entry and correlated with subsequent ischemic stroke and systemic embolism by multivariate analysis. Main Results: Recent (within 3 months) congestive heart failure, a history of hypertension, and previous arterial thromboembolism were each significantly and independently associated with a substantial risk for thromboembolism (> 7% per year; P less-than-or-equal-to 0.05). The presence of these three independent clinical predictors (recent congestive heart failure, history of hypertension, previous thromboembolism) defined patients with rates of thromboembolism of 2.5% per year (no risk factors), 7.2% per year (one risk factor), and 17.6% per year (two or three risk factors). Nondiabetic patients without these risk factors, comprising 38% of the cohort, had a low risk for thromboembolism (1.4% per year; 95% Cl, 0.05% to 3.7%). Patients without clinical risk factors who were under 60 years of age had no thromboembolic events. Conclusion: Patients with atrial fibrillation at high risk (> 7% per year) and low risk (< 3% per year) for thromboembolism can be identified by readily available clinical variables.

Objective: To identify echocardiographic predictors of arterial thromboembolism in patients with nonrheumatic atrial fibrillation and to determine whether these add to clinical variables for risk stratification. Design: Cohort study of patients assigned to placebo in a randomized clinical trial. Setting: Five hundred sixty-eight inpatients and outpatients with nonrheumatic atrial fibrillation assigned to placebo therapy at 15 U.S. medical centers from 1987 to 1989 in the Stroke Prevention in Atrial Fibrillation study. Patients were followed for a mean of 1.3 years. Measurements: M-mode and two-dimensional (2-D) echocardiograms performed at study entry and interpreted by local cardiologists. The predictive value of 14 echocardiographic variables for later ischemic stroke or systemic embolism was assessed by multivariate analysis. Main Results: Left ventricular dysfunction from 2-D echocardiograms (P = 0.003) and the size of the left atrium from M-mode echocardiograms (P = 0.02) were the strongest independent predictors of later thromboembolism. Multivariate analysis of these two independent echocardiographic predictors with the three independent clinical predictors of thromboembolism (history of hypertension, recent congestive heart failure, previous thromboembolism) identified 26% of the cohort with a low risk for thromboembolism (1.0% per year; 95% Cl, 0.2% to 4.0%). Compared with risk stratification using clinical variables alone, echocardiographic results altered thromboembolic risk stratification in 18% of the entire cohort and in 38% of those without clinical risk factors. Conclusions: Both left ventricular and left atrial variables are significant predictors of thromboembolism in patients with nonvalvular atrial fibrillation. Our results challenge traditional views of the pathogenesis of ischemic stroke in patients with atrial fibrillation and suggest that standard echocardiography contributes to risk stratification, differentiating the one third of patients without clinical risk factors who are at increased risk for stroke from the remainder who may not need antithrombotic prophylaxis.