Benefit of Adding Low Molecular Weight Heparin to the Conventional Treatment of Stable Angina Pectoris A Double‐Blind, Randomized, Placebo‐Controlled Trial

BackgroundPatients with chronic coronary artery disease exhibit a dysfunctioning endothelium, which may be responsible for exercise-induced platelet activation and expression of a procoagulant moiety. In this study, we evaluated the therapeutic efficacy of a low molecular weight heparin (Parnaparin) in patients with stable angina pectoris. Methods and ResultsAccording to a double-blind, randomized, placebo-controlled trial, 29 patients with stable exercise-induced angina pectoris and angiographically proven coronary artery disease received a single daily subcutaneous injection of Parnaparin or placebo on top of aspirin and conventional antianginal medication over 3 months. Patients randomized to Parnaparin showed a significant decrease in the fibrinogen level (P=.035) and an improvement in both the time to 1-mm ST segment depression (P=.008) and the peak ST segment depression (P=.015). The Canadian Cardiovascular Society class for angina pectoris was also improved by Parnaparin (P=.016). Parnaparin did not affect ADP and collagen-induced platelet aggregation, whereas thrombin-induced aggregation was reduced (P=.0001). The bleeding time was slightly prolonged, but this was not associated with any significant bleeding. Conclsions. Patients with stable angina pectoris may be treated with Parnaparin in addition to aspirin and conventional antianginal medication. Side effects are negligible, and compliance is excellent.

[1]  A. Branzi,et al.  Comparison of efficacy of low molecular weight heparin (parnaparin) with that of unfractionated heparin in the presence of activated platelets in healthy subjects. , 1993, The American journal of cardiology.

[2]  W. Casscells,et al.  Thrombin inhibitors in unstable angina: rebound or continuation of angina after argatroban withdrawal? , 1993, Journal of the American College of Cardiology.

[3]  E. Jones,et al.  Coronary surgery and coronary angioplasty in patients with two-vessel coronary artery disease. , 1993, The American journal of cardiology.

[4]  E. Palazzini,et al.  Dose-effect relationship in the prevention of post-surgical thromboembolism by a low-molecular-weight heparin: a multicenter study , 1993 .

[5]  N. Edvardsson,et al.  Double-blind trial of aspirin in primary prevention of myocardial infarction in patients with stable chronic angina pectoris , 1992, The Lancet.

[6]  V. Fuster,et al.  Clinical-pathological correlations of coronary disease progression and regression. , 1992, Circulation.

[7]  A. Quyyumi,et al.  Platelet hyperaggregability across the coronary bed in response to rapid atrial pacing in patients with stable coronary artery disease. , 1992, Circulation.

[8]  U. Thadani,et al.  Effects of 8:00 a.m. and 2:00 p.m. doses of isosorbide-5-mononitrate during twice-daily therapy in stable angina pectoris. , 1992, The American journal of cardiology.

[9]  W. Nichols,et al.  Adjunctive therapy with low molecular weight heparin with recombinant tissue-type plasminogen activator causes sustained reflow in canine coronary thrombosis. , 1992, American heart journal.

[10]  M. Babbini,et al.  Human pharmacology of a low‐molecular‐weight heparin (ALFA‐LMWH): An update , 1992, Medicinal research reviews.

[11]  A. Branzi,et al.  Effects of two dosages of subcutaneous low molecular weight heparin (Parnaparin) and of unfractionated heparin on fibrin formation and lipolysis in acute myocardial infarction. , 1992, Thrombosis research.

[12]  G. Raskob,et al.  Subcutaneous low-molecular-weight heparin compared with continuous intravenous heparin in the treatment of proximal-vein thrombosis. , 1992, The New England journal of medicine.

[13]  H. Büller,et al.  Comparison of subcutaneous low-molecular-weight heparin with intravenous standard heparin in proximal deep-vein thrombosis , 1992, The Lancet.

[14]  V. Fuster,et al.  The pathogenesis of coronary artery disease and the acute coronary syndromes (2). , 1992, The New England journal of medicine.

[15]  M. Rosolowsky,et al.  ADP plays an important role in mediating platelet aggregation and cyclic flow variations in vivo in stenosed and endothelium-injured canine coronary arteries. , 1992, Circulation research.

[16]  P C Elwood,et al.  Fibrinogen, Viscosity, and White Blood Cell Count Are Major Risk Factors for Ischemic Heart Disease: The Caerphilly and Speedwell Collaborative Heart Disease Studies , 1991, Circulation.

[17]  C. Lambert.  Pathophysiology of stable angina pectoris. , 1991, Cardiology Clinics.

[18]  G. Ciuffetti,et al.  Efficacy of Low-Molecular-Weight Heparin in the Management of Intermittent Claudication , 1991, Angiology.

[19]  C. Legnani,et al.  Perioperative Prophylaxis with a Low Molecular Weight Heparin Reduces Late PAI-1 Levels after Gynaecological Surgery , 1990 .

[20]  E. Nabel,et al.  Paradoxical narrowing of atherosclerotic coronary arteries induced by increases in heart rate. , 1990, Circulation.

[21]  T. Meade,et al.  Arterial disease risk factors and angiographic evidence of atheroma of the carotid artery. , 1989, Stroke.

[22]  J. Badimón,et al.  Mechanisms of arterial thrombosis in nonparallel streamlines: platelet thrombi grow on the apex of stenotic severely injured vessel wall. Experimental study in the pig model. , 1989, The Journal of clinical investigation.

[23]  J. Eidt,et al.  Specific Platelet Mediators and Unstable Coronary Artery Lesions: Experimental Evidence and Potential Clinical Implications , 1989, Circulation.

[24]  James Vayda,et al.  Aspirin, heparin, or both to treat acute unstable angina , 1989 .

[25]  A. Angelini,et al.  Factors influencing the presence or absence of acute coronary artery thrombi in sudden ischaemic death. , 1989, European heart journal.

[26]  R. Mesa-Tejada,et al.  Identification and Distribution of Fibrinogen, Fibrin, and Fibrin(ogen) Products in Atherosclerosis: Use of Monoclonal Antibodies , 1989, Arteriosclerosis.

[27]  A. Bini.  Identification and distribution of fibrinogen, fibrin and fibrin (ogen) degradation products in atherosclerosis , 1989 .

[28]  C. Legnani,et al.  Pharmacodynamic effects on blood coagulation of a new low molecular weight heparin (alfa-LMWH) in healthy volunteers and gynecological surgery patients. , 1989, International angiology : a journal of the International Union of Angiology.

[29]  C. Benedict,et al.  Transcardiac serotonin concentration is increased in selected patients with limiting angina and complex coronary lesion morphology. , 1989, Circulation.

[30]  E. Dall’aglio,et al.  Clinical pharmacology of a new low molecular weight heparin (Alfa LMWH-Fluxum). , 1988, International angiology : a journal of the International Union of Angiology.

[31]  R. D'Agostino,et al.  Fibrinogen and risk of cardiovascular disease. The Framingham Study. , 1987, JAMA.

[32]  S. Rahimtoola,et al.  Changes in blood rheology in patients with stable angina pectoris as a result of coronary artery disease. , 1987, Circulation.

[33]  M. Fujita,et al.  Acceleration of coronary collateral development by heparin in conscious dogs. , 1987, Japanese circulation journal.

[34]  R. Lobb,et al.  Induction of angiogenesis by bovine brain derived class 1 heparin-binding growth factor. , 1985, Biochemistry.

[35]  S. Thompson,et al.  The effect of physiological levels of fibrinogen on platelet aggregation. , 1985, Thrombosis research.

[36]  L. Wilhelmsen,et al.  Fibrinogen as a risk factor for stroke and myocardial infarction. , 1984, The New England journal of medicine.

[37]  L. Hillis,et al.  Release of prostaglandins and thromboxane into the coronary circulation in patients with ischemic heart disease. , 1981, The New England journal of medicine.

[38]  T W Meade,et al.  Haemostatic function and ischaemic heart disease. , 1981, Lancet.

[39]  H. Goldsmith,et al.  Particle flow behaviour in models of branching vessels: I. Vortices in 90 degrees T-junctions. , 1979, Biorheology.

[40]  M. Lie,et al.  Evaluation of an amidolytic heparin assay method: increased sensitivity by adding purified antithrombin III. , 1977, Thrombosis research.

[41]  M. Lie,et al.  Assay of heparin in plasma using a chromogenic substrate for activated factor X. , 1976, Thrombosis research.

[42]  Bridget Wilcken,et al.  Pathogenesis of coronary artery disease , 1969 .