HEPARIN IN ACUTE MYOCARDIAL INFARCTION—Observations Indicating the Potential Advantages of Using It as the Sole Anticoagulant in Therapy

There is a considerable body of experimental evidence that heparin is superior as an anticoagulant to any prothrombin depressing drugs. Furthermore its lipemia-clearing action affords other benefits which result from the removal of fat from the bloodstream. Important among these beneficial effects is the increased tissue and myocardial oxygen consumption which results from the injection of heparin in atherosclerotic patients.Because of these advantages of heparin over oral anticoagulants, the use of heparin as the sole anticoagulant for three weeks in patients with severe acute myocardial infarction was evaluated as opposed to the customary therapy where heparin is given for several days and then oral anticoagulants are used. The mortality in the dicoumarin treated group was 38 per cent, as compared with 28 per cent in the patients who received only heparin for three weeks.     

Risks of discontinuing anticoagulant therapy in a selected group of patients with atherosclerotic heart disease: a prospective study

In 134 patients with coronary artery disease, long-term oral anticoagulant therapy (mean duration, 56 months) for acute myocardial infarction (98 patients), acute coronary insufficiency (25 patients) or severe chronic angina (11 patients) was terminated abruptly in 50 patients (group 1) and gradually in 84 (group 2). The 134 patients represented a homogeneous population of patients with coronary artery disease since most patients older than 75 years and those with conditions known to increase the risks of thromboembolic complications were excluded. The two groups were comparable in terms of sex, age, presence of risk factors, duration of anticoagulant therapy, and presence of angina and abnormal resting electrocardiograms during therapy. Patients were evaluated 6 months after cessation of anticoagulant therapy and, since abrupt withdrawal of therapy did not carry a higher risk than gradual discontinuation, data for groups 1 and 2 were tabulated together.Of the 84 patients with angina at the end of therapy 15 experienced an increase in its severity and this symptom appeared in another patient (relapse rate, 18%). Angina progressed to fatal acute myocardial infarction in four (mortality, 3%) and nonfatal infarction in two; however, all six had extensive coronary artery disease and poor left ventricular function. The results of this study suggest that neither abrupt nor gradual cessation of anticoagulant therapy is associated with an inordinate exacerbation of heart disease.     

Anticoagulant Therapy in Coronary Artery Disease: A Therapeutic Enigma

The authors'' experience with anticoagulant therapy in both the acute phase and the long-term management of myocardial infarction has proved disappointing. A review of the literature has failed to establish benefit when all patients with coronary artery disease are treated with anticoagulant drugs. A need for well-controlled studies still exists.     

Clinical effects of anticoagulant therapy in suspected acute myocardial infarction: systematic overview of randomised trials.

OBJECTIVES: Most randomised trials of anticoagulant therapy for suspected acute myocardial infarction have been small and, in some, aspirin and fibrinolytic therapy were not used routinely. A systematic overview (meta-analysis) of their results is needed, in particular to assess the clinical effects of adding heparin to aspirin. DESIGN: Computer aided searches, scrutiny of reference lists, and inquiry of investigators and companies were used to identify potentially eligible studies. On central review, 26 studies were found to involve unconfounded randomised comparisons of anticoagulant therapy versus control in suspected acute myocardial infarction. Additional information on study design and outcome was sought by correspondence with study investigators. SUBJECTS: Patients with suspected acute myocardial infarction. INTERVENTIONS: No routine aspirin was used among about 5000 patients in 21 trials (including half of one small trial) that assessed heparin alone or heparin plus oral anticoagulants, and aspirin was used routinely among 68,000 patients in six trials (including the other half of one small trial) that assessed the addition of intravenous or high dose subcutaneous heparin. MAIN OUTCOME MEASUREMENTS: Death, reinfarction, stroke, pulmonary embolism, and major bleeds (average follow up of about 10 days). RESULTS: In the absence of aspirin, anticoagulant therapy reduced mortality by 25% (SD 8%; 95% confidence interval 10% to 38%; 2P = 0.002), representing 35 (11) fewer deaths per 1000. There were also 10 (4) fewer strokes per 1000 (2P = 0.01), 19 (5) fewer pulmonary emboli per 1000 (2P < 0.001), and non-significantly fewer reinfarctions, with about 13 (5) extra major bleeds per 1000 (2P = 0.01). Similar sized effects were seen with the different anticoagulant regimens studied. In the presence of aspirin, however, heparin reduced mortality by only 6% (SD 3%; 0% to 10%; 2P = 0.03), representing just 5 (2) fewer deaths per 1000. There were 3 (1.3) fewer reinfarctions per 1000 (2P = 0.04) and 1 (0.5) fewer pulmonary emboli per 1000 (2P = 0.01), but there was a small non-significant excess of stroke and a definite excess of 3 (1) major bleeds per 1000 (2P < 0.0001). CONCLUSIONS: The clinical evidence from randomised trials dose not justify the routine addition of either intravenous or subcutaneous heparin to aspirin in the treatment of acute myocardial infarction (irrespective of whether any type of fibrinolytic therapy is used).     

Prevention of cardiovascular complications in manifest arteriosclerosis by the use of Micristine]

A long-term clinical trial in micristin-treated patients suffering from organic arterial circulatory disturbances is reported. Problems of therapy monitoring by determination of the ASA level in plasma and of control of platelet aggregation are discussed. Acute cardiovascular complications (myocardial infarction, stroke, acute vascular occlusion, amputation and angiographically demonstrated progression) were observed. The observation time did not suffice to establish statistically significant differences between micristin therapy anticoagulant treatment and basic cardiovascular therapy. The results are suggestive of a more beneficial effect of anticoagulant treatment.     

Dependence of a drop in blood pressure in pulmonary circulation and in the right heart on dosage of isosorbide dinitrate]

An effect of isosorbide dinitrate on blood pressure values in the pulmonary circulation and the right heart has been investigated in 25 patients with a history of the first transmural myocardial infarction. Group I including 12 patients has been given 5 mg isosorbide nitrate in a 60-minute intravenous infusion while group II of 13 patients has been given 10 mg of the drug in the same way. Both groups have been matched in clinical data and blood pressure value in the pulmonary circulation which has been normal. Pulmonary blood pressure has been measured with Swan-Ganz catheter prior to the administration of drug, and 15, 30, 45 and 60 minutes following an infusion. Isosorbide dinitrate in a dose of 5 mg did not decrease blood pressure in the pulmonary circulation statistically significantly. The differences in blood pressure falls did exceed 9%. Filling pressure in the right ventricle did not change either while systolic blood pressure decrease by 16.6%. A double dose of isosorbide dinitrate reduced blood pressure in the pulmonary artery by about 1/3 of the baseline value, and blood pressure in the right ventricle (mean right atrial pressure) by 57.2%. Both systolic and diastolic arterial pressures were reduced. Isosorbide dinitrate reduced blood pressure in the pulmonary circulation in patients who underwent myocardial infarction, and hypotensive effect has been dose-related. A reduction in the right ventricular filling pressure has been a one of important mechanisms decreasing pulmonary pressures.     

Relation of trauma to disease; aspects of correlation in cases involving compensation

As a general rule, it is not believed possible to classify patients with acute myocardial infarction as to the future severity of their illness at the time of the initial examination. However, classifications are possible from complete clinical data of the first few days with regard to the predicted mortality rates. Whether to manage the patient in the hospital or at home depends on the community facilities. The patient should be in bed for a period of two to three weeks if unquestioned infarction has occurred. The main avenue of investigation as to lowering of mortality needs to be directed toward the prevention of heart failure or sudden unexpected death probably related to arrhythmia. If the patient is hospitalized and laboratory facilities are available, anticoagulant therapy can be safely and effectively carried out without undue risk or prohibitive increase in the cost of management. The experience of the author and his colleagues has led to the belief that anticoagulants given routinely to patients with myocardial infarction are effective in decreasing the incidence of thromboembolic complications.     

ACUTE MYOCARDIAL INFARCTION—A Discussion of Certain Controversial Issues

As a general rule, it is not believed possible to classify patients with acute myocardial infarction as to the future severity of their illness at the time of the initial examination. However, classifications are possible from complete clinical data of the first few days with regard to the predicted mortality rates. Whether to manage the patient in the hospital or at home depends on the community facilities. The patient should be in bed for a period of two to three weeks if unquestioned infarction has occurred.The main avenue of investigation as to lowering of mortality needs to be directed toward the prevention of heart failure or sudden unexpected death probably related to arrhythmia. If the patient is hospitalized and laboratory facilities are available, anticoagulant therapy can be safely and effectively carried out without undue risk or prohibitive increase in the cost of management. The experience of the author and his colleagues has led to the belief that anticoagulants given routinely to patients with myocardial infarction are effective in decreasing the incidence of thromboembolic complications.     

The effect of insulin on the heart

Insulin infusion has been advocated in the treatment of myocardial ischaemia and myocardial infarction. There is evidence from experimental animal studies for a protective effect of high-dose insulin administration in myocardial ischaemia and myocardial infarction. In some relatively small study populations a reduction in mortality was reported in those patients who received glucose-insulin-potassium (GIK) during myocardial infarction, which was confirmed in two meta-analyses. However, it has not been possible to reproduce these positive results in large randomised clinical trials. (Neth Heart J 2010;18:255-9.)     

T wave alternans and ventricular tachyarrhythmia risk stratification: a review

Sudden cardiac death (SCD) is one of the leading causes of mortality in industrialized countries. Thus, identifying patients at high risk of SCD is an important goal. T wave alternans (TWA) is a new method for identifying patients with lethal ventricular tachyarrhythmias, and is dependent on heart rate. The maximal predictive accuracy is achieved at heart rates between 100 and 120 bpm, so that TWA is usually measured during exercise, pharmacological stress, or atrial pacing. It has been shown that TWA has high sensitivity and negative predictive value for predicting SCD after myocardial infarction and is also useful for predicting SCD in patients with nonischemic cardiomyopathy. Although the implantable cardioverter defibrillator (ICD) is now the primary therapy for preventing SCD, it is difficult to identify those patients who are susceptible to lethal ventricular tachyarrhythmias for primary prevention. In the prediction of SCD, TWA can be used as a screening test of appropriate patients for further electrophysiological examination and therapy.     

Long-term beta blockade: possible protection from myocardial infarction.

The clinical behaviour of 90 patients on beta-blocking drugs for established coronary heart disease who were admitted to a coronary care unit with prolonged ischaemic myocardial pain was compared with that of 90 similar patients not on this therapy. Transmural myocardial infarction was confirmed in 30 of the patients on beta-blockers and in 62 controls. A diagnosis of myocardial necrosis without infarction was made in 20 patients on beta-blockers and in 14 controls. Coronary insufficiency was diagnosed in 40 patients on beta-blockers and in 14 controls. The incidence of simus bradycardia, hypotension, syncope, and radiological pulmonary oedema was similar in the two groups. Established beta-blockade, therefore, has not been shown to prejudice the outcome of patients with coronary heart disease admitted to hospital with prolonged ischaemic myocardial pain. On the contrary, it may protect some patients from the development of a myocardial infarction.     

Construction and characterization of a novel staphylokinase variant with thrombin-inhibitory activity

Staphylokinase (SAK) is an effective thrombolysis agent for therapy of myocardial infarction. We have constructed a fusion SAK variant (SAK-HV) with a thrombin-binding domain composed of 12 amino acids from hirudin and expressed it in Escherichia coli and purified the resultant protein. SAK-HV maintained fibrinolytic activity similar to SAK and had anticoagulant activity attributable to its hirudin segment. Measurement of thrombin-binding activity in vitro demonstrated that SAK-HV possessed binding activity with thrombin while SAK did not. SAK-HV might thus be a more potent thrombolytic agent with anticoagulation property than SAK.     

Increased Sensitivity to Heparin Following Acute Myocardial Infarction

In vivo increased sensitivity to heparin has been demonstrated in patients following an acute myocardial infarction. An intravenous injection of 10,000 units of heparin was given to each of 18 patients with recent myocardial infarction in order to compare them with 17 patients who were not suffering from any acute illness. The changes in whole blood clotting time, recalcified plasma clotting time and prothrombin time were greater and more prolonged in the patients with recent myocardial infarction. Of the three tests, the one-stage prothrombin time provided the simplest and the most precise measurement of heparin sensitivity. The reason for this was not clear: it is possible that it is related to shock and congestive heart failure which were complications of the clinical course following myocardial infarction.     

New aspects of ICD therapy: from rhythm therapy to complex cardiac monitoring. Development of an implantable, ICD-assisted, intrathoracic 6-channel ECG for continuous monitoring of high infarct risk patients]

Implantable defibrillator systems (ICD) are therapy of choice for the treatment of life-threatening ventricular arrhythmias and in prevention of sudden cardiac death. In more than 80% of patients who receive an ICD, the underlying cardiac disease is a coronary heart disease. Since arrhythmogenic sudden cardiac death can be reliably prevented in these patients by the use of ICD technology, the cardiac prognosis for these patients is determined by the occurrence of myocardial ischemia and myocardial infarction, as well as from the heart failure which develops in consequence. An intrathoracic 6-channel ECG comparable to the standard surface ECG can be reconstructed by further technical development of the electrode configurations currently present in ICD systems. The importance of this development in early diagnosis of myocardial ischemias and myocardial infarction can hardly be adequately estimated at the moment. The chronic consequences of myocardial infarction can be completely prevented or at least greatly reduced by means of such diagnostics and inclusion of immediate initiation of effective, appropriate early therapeutic measures before more serious symptoms even occur. In the development and pilot studies thus far, it has been found that the intrathoracic 6-channel ECG which can be generated in the ICD is capable of reliably recognizing acute myocardial ischemia, irrespective of localization or extent earlier and better than the standard surface ECG. Continuous preventive ischemia monitoring using the implanted ICD thus appears possible in patients at risk of infarction.     

A Survey of Cardiac Infarctions: Hospital Experience

A study of patients with cardiac infarction, treated in hospital between 1950 and 1954 and followed up to the present, is reported. One hundred and forty-two patients suffered 169 attacks. In 95 attacks, the patients received anticoagulant therapy, with 15 acute deaths. Fifty-six were not so treated; among these there were 21 deaths. The rate of survival was best in younger patients with their first episode of infarction, without preexisting hypertension, cardiac failure, or systolic blood pressure persistently below 100. Angina preceding infarction disappeared in one-half of the subjects after the episode; half the survivors suffered recurrent myocardial infarction within five years. Moderate hypertension had no effect upon immediate or 10-year survival. No patient received long-term anticoagulant therapy. Of the survivors of acute infarction, 16 died in the first year after the acute attack, nine in the second year, nine in the third, six in the fourth and five in the fifth. At the end of five years, 51 subjects had survived 60 episodes. At the end of 10 years, 43 living patients had sustained 45 myocardial infarctions.     

Myocardial infarction after taking zolmitriptan

We report the case of a patient with mild non-obstructive coronary artery disease who sustained an inferior wall myocardial infarction shortly after taking zolmitriptan as abortive therapy for migraine headaches. A Medline search was performed to review all reported cases of myocardial infarction related to migraine therapy with zolmitriptan and related medications. Zolmitriptan may cause myocardial infarction (MI) even in the absence of significant coronary artery disease.     

National Assessment of Statin Therapy in Patients Hospitalized with Acute Myocardial Infarction: Insight from China PEACE-Retrospective AMI Study, 2001, 2006, 2011

BackgroundStatin therapy is among the most effective treatments to improve short- and long-term mortality after acute myocardial infarction. The use of statin, and the intensity of their use, has not been described in acute myocardial infarction patients in China, a country with a rapidly growing burden of cardiovascular disease.ConclusionsThe use of statin therapy has dramatically increased over the past decade in Chinese patients with acute myocardial infarction. However, half of patients still did not receive intensive statin therapy in 2011.Given that guidelines strongly endorse intensive statin therapy for acute myocardial infarction patients, initiatives promoting the use of statin therapy, with attention to treatment intensity, would support further improvements in practice.     

Targeted anti-estrogens to treat and prevent diseases in women

The estrogen receptor has been successfully targeted with the anti-estrogen tamoxifen to treat all stages of breast cancer. Because tamoxifen is a partial agonist, it exhibits target-site specificity: it acts as an anti-estrogen in the breast to inhibit tumor growth, while exhibiting estrogenic effects on bones and lipid metabolism. Therefore, tamoxifen has the added benefit of maintaining bone density and reducing the risk of myocardial infarction in postmenopausal women.However, undesirable side effects of tamoxifen preclude its use as a hormone replacement therapy for otherwise healthy women. New anti-estrogens are currently being developed that may prevent osteoporosis, breast and endometrial cancer, and reduce the risk of myocardial infarction.     

Digitalis use in acute myocardial infarction: current concepts

Digitalis is one of the oldest and most commonly prescribed medications. There has been continuing controversy regarding its use in acute myocardial infarction. Recent information from animal experiments and clinical investigation serves as a guide for its appropriate use in this situation. When it is used appropriately and judiciously there is no increase in toxicity or cardiac arrhythmias. In fact, there is benefit to the patient who has a failing myocardium associated with acute myocardial infarction.     

Propofol protects the autophagic cell death induced by the ischemia/reperfusion injury in rats

Autophagy has been implicated in cardiac cell death during ischemia/reperfusion (I/R). In this study we investigated how propofol, an antioxidant widely used for anesthesia, affects the autophagic cell death induced by the myocardial I/R injury. The infarction size in the myocardium was dramatically reduced in rats treated with propofol during I/R compared with untreated rats. A large number of autophagic vacuoles were observed in the cardiomyocytes of I/R-injured rats but rarely in I/R-injured rats treated with propofol. While LC3-II formation, an autophagy marker, was up-regulated in the I/R-injured myocardium, it was significantly down-regulated in the myocardial tissues of I/R-injured and propofol-treated rats. Moreover, propofol inhibited the I/R-induced expression of Beclin-1, and it accelerated phosphorylation of mTOR during I/R and Beclin-1/Bcl-2 interaction in cells, which indicates that it facilitates the inhibitory pathway of autophagy. These data suggest that propofol protects the autophagic cell death induced by the myocardial I/R injury.