No prospective, randomized trials exist in which placebo, antiplatelet or anticoagulant therapy in patients with congestive heart failure have been compared. Most studies have looked retrospectively at the impact of these treatments on systemic embolism and the ensuing morbidity and mortality, and none of the large trials of heart failure was initially designed to address this question.
The SOLVD Investigators: Effect of enalapril on survival in patients with reduced left ventricular ejection fractions and congestive heart failure. N Engl J Med1991, 325: 293–302. See [2].
2.
The SOLVD Investigators: Effect of enalapril on mortality and the development of heart failure in asymptomatic patients with reduced left ventricular ejection fractions. N Engl J Med1992, 327: 685–691. The authors [1,2] pointed out that that the role of the left atrium should not be overlooked in congestive heart failure. These two reports [1,2] address the issue of thromboembolism as a feature of congestive heart failure but underline its rarity as a cause of death.
3.
RedfieldMMGershBJBaileyKRBallardDJRodehefferRJ: Natural history of idiopathic dilated cardiomyopathy: Effect of referral bias and secular trend. Am J Coll Cardiol1993, 22: 1921–1926.
4.
VignaVRussoADe RitoVPernaGVillellaATestaM: Frequency of left atrial thrombi by transesophageal echocardiography in idiopathic and in ischemic dilated cardiomyopathy. Am J Cardiol1992, 70: 1500–1501. See comment on Siostrzonek et al. [5].
5.
SiostrzonekPKoppensteinerRGoessingerHZangenehMHeinzGKreinerG: Hemodynamic and hemorheologic determinants of left atrial spontaneous echo contrast and thrombus formation in patients with idiopathic dilated cardiomyopathy. Am Heart J1993, 125: 430–434. This article and that by Vigna et al. [4] show that the left ventricle is not the only source of emboli in cardiomyopathy.
6.
DunkmanBWJohnsonGRCarsonPEBhatGFarrellLCohnJN: Incidence of thromboembolic events in congestive heart failure. Circulation1993, 87 (suppl VI):VI94–VI101. A key article, even in view of the use of retrospective data on thromboembolism, in which anticoagulant agents were found not to be superior to aspiriny.
7.
The Stroke Prevention in Atrial Fibrillation Investigators: Predictors of thromboembolism in atrial fibrillation. II. Echocardiographic features of patients at risk. Ann Intern Med1992, 116: 6–12. A fundamental reference on the risk of embolism in patients with atrial fibrillation.
8.
FalkRHFosterECoatsMH: Ventricular thrombi and thromboembolism in dilated cardiomyopathy: A prospective follow-up study. Am Heart J1992, 123: 136–142. This study prospectively followed the course of patients with ventricular thrombi and showed that they predispose patients to embolism.
9.
KumagaiKFukunamiMOhmoriMKitabatakeAKamadaTHokiN: Increased intracardiovascular clotting in patients with chronic atrial fibrillation. J Am Coll Cardiol1990, 16: 377–380. See comment on Stavrinadi et al. [11].
10.
SbarouniEBradshawAAndreottiFTuddenhamEOakleyCMClelandJGF: Relationship between hemostatic abnormalities and neuroendocrine activity in heart failure. Am Heart J1994, 127: 607–612. See comment on Stavrinadi et al. [11].
11.
StavrinadiVAidonopoulosSChristopoulou-CokkinouVAthanassopoulosGCokkinosDV: Is a positive D-dimer a strong indication for esophageal echocardiographic investigation of intracardiac thrombogenic conditions [abstract]? Thromb Res1992, 65 (suppl 1):323. This study and those by Kumagai et al. [9] and Sbarouni et al. [10] addressed the issue of hematological markers, including increased viscosity and elevated levels of D-dimer and von Willebrand factor, and the risk of thromboembolism.
12.
BlondheimDSJacobsLEKotlerMNCostacurtaGAParryWR: Dilated cardiomyopathy with mitral regurgitation: Decreased survival despite a low frequency of left ventricular thrombus. Am Heart J1991, 122: 763–771. See comment on Karatasakis et al. [13].
13.
KaratasakisGGotsisAKafantogiasAKalkandiHCokkinosDV: The effect of mitral regurgitation on left atrial thrombus formation studied by transesophageal echocardiography [abstract]. Eur Heart J1993, 114 (suppl):357. This article and that by Blondheim et al. [12] emphasize that mitral regurgitation diminishes the risk of thrombus formationy.
14.
ShermanDGDykenMLFisherMHarrisonMJGHartRG: Antithrombotic therapy for cerebrovascular disorders. Chest1989, 95 (suppl 2):140S–155S.
15.
ConnollySJLaupacisAGentMRobertsRSCairnsJAHoynerC: Canadian Atrial Fibrillation Anticoagulation (CAFA) Study. J Am Coll Cardiol1991, 18: 349–355.
16.
CaroJJGroomePAFlegelKM: Atrial fibrillation and anticoagulation: From randomised trials to practice. Lancet1993, 341: 1381–1384. This article places in its proper perspective the risks versus the benefits of anticoagulation in atrial fibrillation and states that the harm of hemorrhage versus that of embolism should exceed 6:1 to justify not giving anticoagulation.
17.
FalkRH: A plea for a clinical trial of anticoagulation in dilated cardiomyopathy. Am J Cardiol1990, 65: 914–915. We all repeat the plea for a prospective comparison of anticoagulant agents with placebo to be carried out.
18.
KatzSDMarantzPRBiasucciLJondeauGLeeKBrennanC: Low incidence of stroke in ambulatory patients with heart failure: A prospective study. Am Heart J1993, 126: 141–146. This is a pivotal study which showed that stroke in congestive heart failure is less frequent than previously believed.
19.
FusterVGershBJGiulianiERTajikAJFreyRL: The natural history of idiopathic dilated cardiomyopathy. Am J Cardiol1981, 47: 525–531. See comment on Kyrle et al. [20].
20.
KyrlePAKorningerCGossingerHGlogarDLechnerKNiessnerH: Prevention of arterial and pulmonary embolism by oral anticoagulants in patients with dilated cardiomyopathy. Thromb Haemost1985, 54: 521–523. This study and that by Fuster et al. [19] belong to the first generation of trials showing a high incidence of stroke and a great benefit from anticoagulation in patients with dilated cardiomyopathy.
21.
FalkRHPollakATandonPK: The effect of warfarin on prevalence of stroke in patients with severe heart failure [abstract]. J Am Coll Cardiol1993, 21: 218A.
22.
PetersenPBoysenGGodtfredsenJAndersenEDAndersenB: Placebo-controlled, randomised trial of warfarin and aspirin for prevention of thromboembolic complications in chronic atrial fibrillation. The Copenhagen AFASAK study. Lancet1989, 28: 175–179. See comment on SPAF II [24].
23.
Stroke Prevention in Atrial Fibrillation Investigators: Stroke Prevention in Atrial Fibrillation Study: Final results. Circulation1991, 84: 527–539. See comment on SPAF II [24].
24.
Stroke Prevention in Atrial Fibrillation Investigators: Warfarin versus aspirin for prevention of thromboembolism in atrial fibrillation: Stroke Prevention in Atrial Fibrillation II Study. Lancet1994, 343: 687–691. Connolly et al. [15], Petersen et al. [22], and the SPAF investigators [23,24] have shown that anticoagulant agents diminish the risk of embolism in atrial fibrillation. The SPAF I study [23] also showed evidence of a benefit from aspirin. In SPAF II, aspirin proved to be only marginally inferior to warfarin.
25.
The Boston Area Anticoagulation Trial for Atrial Fibrillation Investigators: The effect of low-dose warfarin on the risk of stroke in patients with nonrheumatic atrial fibrillation. N Engl J Med1990, 323: 1505–1511. One of the first large studies of anticoagulation in atrial fibrillation, in which anticoagulants proved to be superior to placebo.
26.
KistlerJPSingerDEHughesRAGressDRSheehanMAMaraventanoSW: Atrial fibrillation: Stroke incidence and prevention. In Thrombosis: An Update. Edited by Neri SerneriGGGensiniGFAbbateRPriscoD.Florence: Scientific Press; 1992: 391–399.
