Patient Self-Management of Oral Anticoagulant Therapy: An International Update

The clinical use of oral anticoagulant therapy has been complicated by the necessity for frequent determinations of the prothrombin time (PT) to ensure safety and therapeutic efficacy. This requirement has often imposed a significant burden on both providers and patients. In 1985 a German patient, Heike M?ller-Jung, initiated her own patient self-testing (PST) and patient self-management (PSM). Today there are over 15,000 patients in Germany managing their oral anticoagulant therapy with PSM options. Pilot PST and PSM programs are in place in many other countries. In the United States, two devices have recently been approved for PST. This method of monitoring has been shown to be as accurate as that of traditional central laboratory PT determinations, to improve the amount of time patients are within the therapeutic INR range, and to decrease the incidence of adverse events associated with anticoagulant therapy.     

Self-Management of Oral Anticoagulant Therapy: A Review

Patient self-management of oral anticoagulant therapy has over the last years gained increasing attention and widespread use. The method implies self-testing using a coagulometer (point-of-care device) and self-dosaging of coumarin. The method entails advantages for selected patients, who do not need to go to the hospital or family doctor for blood specimen and drug dosage adjustment. In contrast to patients on conventional management, patients performing self-managing have a reduced binding to the health care system, and it allows these patients unhindered to travel and manage their job or school. Therefore, the patients have a high degree of compliance because they are highly motivated. This has been the main justification for patient self-management. Furthermore, the conducted trials have also indicated a better quality of treatment compared to conventional management. In this paper the different aspects of this new treatment modality are critically reviewed, with special focus on the published clinical studies and the evaluation of the used coagulometers.     

Workshop: Patient Self-Management: Update of Ongoing Studies in Sweden

Identification of patients with acute cardiac ischemia (ACI) remains challenging. The object of this study was to examine the role of clinical findings in the diagnosis/triage of emergency department (ED) patients with symptoms suggestive of ACI. The study was designed as a secondary data analysis of a multicenter prospective controlled clinical trial. It was set in 10 midwest, southeast, and northeast U.S. hospitals, and 10,689 patients with chest pain or other symptoms suggesting ACI presenting from May 1993 to December 1993, participated. The results indicated that ACI patients were more likely to have chest pain as a chief complaint or presenting symptom (P = 0.001). The presenting symptom of nausea was more commonly associated with a final diagnosis of ACI (P = 0.003). Shortness of breath as the chief complaint and presenting symptoms of abdominal pain, nausea, dizziness, and fainting were less frequent among patients with a final diagnosis of ACI (P = 0.001). A past history of diabetes mellitus, myocardial infarction, or angina pectoris was more frequently associated with a final diagnosis of ACI (P = 0.001). A lower pulse rate in patients with a final diagnosis of ACI (P = 0.001) was not considered clinically significant. Median first and highest systolic blood pressures (SBPs) were higher, median lowest SBPs were lower, median diastolic blood pressure of the lowest SBPs were lower, and initial and highest pulse pressures were wider in patients with a final diagnosis of ACl (P = 0.001). On arrival, these blood pressure variables in AMI patients, subsequently classified as Killip class 4, were above the threshold for this classification. Rales were more commonly present in patients with a final diagnosis of ACI (P= 0.001). All primary ST-segment abnormalities, Q waves, and T-wave abnormalities, except T-wave flattening, were seen more frequently in patients with a final diagnosis ACI (P= 0.001). Normal ECGs were more frequently associated with a non-ACI final diagnosis, yet 20% of AMI patients and 37% of Unstable Angina Pectoris (UAP) patients had normal ECGs. It can be concluded that certain clinical features can help to identify ED patients with ACI. Initially normal ECGs can be seen in 20% of patients with AMI and 37% of patients with UAP. Patients with ACI can present with normal blood pressures and develop cardiogenic shock. Clinical outcome data for ACI patients are presented.     

Physicians' Use of Heparin Following Thrombolytic Therapy: An International Perspective

Background: The current prevalence, timing, and route of heparin use after thrombolytic therapy for acute myocardial infarction both within and outside the United States (U.S.) have not been extensively studied. Method: An 18-item questionnaire was mailed to cardiologists and emergency medicine practitioners in the U.S. and to physicians in 5 countries considering participation in an international trial of thrombolytic therapy. Results: Almost all used some form of heparin after recombinant tissue-plasminogen activator; 8% withheld heparin after streptokinase. Non-U.S. physicians used subcutaneous heparin more frequently than did U.S. physicians (26% vs. 4%). Time to heparin initiation varied greatly. Most physicians used the activated partial thromboplastin time to monitor anticoagulation, although there was little consensus about the appropriate way to determine the efficacy of heparin therapy. Conclusions: This survey shows considerable disagreement about the preferred administration of heparin among physicians treating patients with myocardial infarction. This lack of agreement reflects uncertainty about how heparin therapy should be used. When the results of well-designed clinical trials examining the optimal dosing, timing, and monitoring of heparin therapy have been published, perhaps the clinical community can reach a consensus.     

Acute ethanol does not protect against ischemic/ reperfusion injury in rabbit myocardium

Moderate use of alcohol has shown protective effects in coronary artery disease, while excessive use has been associated with cardiomyopathy and hypertension. Since alcohol is a vasodilator, we postulated that it might have protective effects when administered acutely in the setting of ischemia/reperfusion. Therefore, we studied the acute effects of alcohol on myocardial infarction in a rabbit model. Anesthetized, open chest rabbits were subjected to a 30 minute coronary artery occlusion followed by 4 hours of reperfusion. Rabbits were randomized to a control group (n = 20), receiving an infusion of 10 ml normal saline, intravenously, over 10 minutes via a Harvard pump, or an alcohol group (n = 20), receiving a diluted solution of 100% ethanol (1 ml/kg diluted in normal saline to 10 ml total solution) infused in a similar fashion. This infusion regimen resulted in an average blood alcohol level of 110 mg/dl (range 77–129) tested in five rabbits within the study. Ten minutes after infusion, a marginal branch of the circumflex artery was occluded. Regional myocardial blood flow during coronary occlusion and reperfusion was measured using radioactive microspheres. Myocardial ischemic area at risk (AR) was assessed by blue dye injection and myocardial necrosis (AN) by triphenyltetrazolium chloride (TTC) staining. The mean regional coronary blood flow in ischemic tissue was 0.04 ± 0.01 ml/min/g in the control group versus 0.03 ± 0.01 ml/min/g in the experimental group (p = NS) and averaged 1.74 ml/min/g (control) to 1.98 ml/min/g (alcohol) in the nonischemic tissue. All rabbits received comparable ischemic insult: Collateral blood flow and AR were similar in both groups. An overall analysis showed no significant reduction in infarct size (expressed as the percent of necrotic tissue within the area at risk) in the alcohol group (23 ± 3%) compared with the control group (27 ± 4%). In conclusion, alcohol did not reduce infarct size in the rabbit model.     

The impact of time to thrombolytic treatment on outcome in patients with acute myocardial infarction. For the CORE investigators (Collaborative Organisation for RheothRx Evaluation)

OBJECTIVES—To examine the impact of time to thrombolytic treatment on multiple acute outcome variables in a single trial of thrombolysis in acute myocardial infarction.
DESIGN AND PATIENTS—Mortality and reinfarction rate were measured in 2770 patients with acute myocardial infarction who received thrombolysis within 12 hours in CORE, an international, dose ranging trial of poloxamer 188. Tc-99m sestamibi infarct size and radionuclide angiographic ejection fraction substudies included 1099 and 1074 patients, respectively.
RESULTS—Time to thrombolysis, subgrouped by intervals (< 2, 2-4,  4-6, and  6 hours), was significantly associated with infarct size (median 15.0%, 18.5%, 22.0%, 18.5% of left ventricle; p = 0.033), mean (SD) ejection fraction (51.5 (12.0)%, 48.3 (13.9)%, 48.2 (13.3)%, 48.2 (15.0)%; p = 0.006), 35 day mortality (5.7%, 7.1%, 7.9%, 12.5%; p = 0.0004), six month mortality (7.3%, 8.6%, 10.4%, 15.5%; p < 0.0001), and 35 day reinfarction rate (6.1%, 3.2%, 4.0%, 0.9%; p = 0.0001).
CONCLUSIONS—In this single large trial, the beneficial effect of time to thrombolysis on infarct size and ejection fraction was restricted to treatment given within two hours of symptom onset, while the effect on mortality was evident over all time intervals. Reinfarction rate was higher in patients treated with earlier thrombolysis.


Keywords: myocardial infarction; thrombolysis; infarct size     

Effect of spontaneous reperfusion on myocardial infarct size

The effect of perfusion of the infarct artery on myocardial infarct size was studied in 39 patients who had not received interventive therapy. At predischarge coronary angiography, 19 patients had subtotal and 20 total occlusion of the infarct artery. The early ST-segment elevation recorded on a 12-lead electrocardiogram was used as an index of the amount of initially jeopardized myocardium. Infarct size was estimated by peak serum creatine kinase and, at discharge, by a QRS score, sigma Q and sigma R on a 12-lead electrocardiogram, and by radionuclide global and infarct segment left ventricular ejection fraction. Despite a similar degree of initial ischemia (sigma ST), infarct size was smaller in the 11 patients with anterior infarction and subtotal occlusion than in the 9 patients with anterior infarction and total occlusion when measured by peak serum creatine kinase (2114 +/- 1192 U/l vs. 3653 +/- 1059 U/l, p less than 0.02), QRS score (5.0 +/- 2.7 vs. 9.6 +/- 3.5, p less than 0.01), sigma Q (3.25 +/- 2.74 mV vs. 5.92 +/- 3.56 mV, p less than 0.10), sigma R (4.36 +/- 1.25 mV vs. 2.16 +/- 0.91 mV, p less than 0.001), global left ventricular ejection fraction (45.0 +/- 12.2% vs. 33.4 +/- 6.7%, p less than 0.05), and infarct segment ejection fraction (40.4 +/- 8.2% vs. 30.3 +/- 5.4%, p less than 0.05). In the inferior infarct patients, both the degree of initial ischemia and final infarct size were similar in the 8 patients with subtotal and in the 11 patients with total occlusion.(ABSTRACT TRUNCATED AT 250 WORDS)     

Infarct size limitation: Acute N-acetylcysteine defense (ISLAND trial): Preliminary analysis and report after the first 30 patients

Our previous experimental research and initial clinical observations regarding the use of N-acetylcysteine in the treatment of ischemic and reperfusion injury in acute myocardial infarction gave rise to a study entitled the Infarct Size Limitation: Acute N-acetylcysteine Defense (ISLAND) trial. Today, this randomized, echocardiographically and angio-graphically controlled study includes the first 30 patients with a first anterior wall myocardial infarction: Group A (n = 10) consisting of patients with successful recanalization of the in-farct-related left anterior descending artery by streptokinase without any further treatment, Group B (n = 10) consisting of patients with failed infarct-related artery recanalization, and Group C (n = 10) comprising patients who had successful streptokinase-induced recanalization of the left anterior descending artery plus N-acetylcysteine administration at a dose of 100 mg/kg body weight. The parameters monitored in our study include changes in global and regional left ventricular ejection fraction of the infarct-related segment using echocar-diography and, using electrocardiograms and the Wagner QRS scoring system, the amounts of acutely jeopardized and finally infarcted myocardium. In Group A, global left ventricular ejection fraction rose nonsignificantly within 2 weeks from 37.5 ± 9.6% to 38.5 ± 13.8%; it declined significantly in Group B from 36.2 ± 6.1% to 30.1 ±6.7% (p < 0.05), while it considerably improved in Group C from 41.7 ± 4.1 % to 59.6 ±8.1 % (p < 0.001). Regional left ventricular ejection fraction changed significantly only in Group C: from — 4.5 ± 27.3 to 45.6 ± 16.3 (p < 0.001). In Group A, in which the amount of acutely jeopardized myocardium was 21.7 ± 7.2, infarction actually occurred in 20.4 ± 9.7% (practically no myocardial salvage). In Group B, risk area was 18.1 ± 4.3%, but infarct size rose to a resulting 29.1 ±6.0%. Significant myocardial salvage was accomplished only in Group C: of 26.2 ±8.1% of jeopardized myocardium, infarct size was reduced to 10.8 ± 7.1% (salvage by 58.8%). Also, basic division of patients by therapy showed that, although those with nonidentical findings on their coronary arteries were included into the same groups, patients treated with streptokinase plus N-acetylcysteine had significantly more favorable values of the monitored parameters than those treated with streptokinase alone. We conclude our interim analysis suggests that N-acetylcysteine has a beneficial effect, reducing the functional and structural impacts of myocardial infarction.     

Morbidity during five years after myocardial infarction and its relation to infarct size

In 809 patients with a recent myocardial infarction, morbidity during 5-year follow-up was assessed. The overall 5-year mortality rate was 33% (39% in patients with larger infarcts and 26% in patients with smaller infarcts) as judged from maximum serum enzyme activity (p less than .001). In terms of morbidity, no significant association with estimated infarct size was observed. Patients with smaller infarcts tended to have a higher reinfarction rate and were rehospitalized more often, whereas a similar proportion of patients with large and small infarcts developed stroke. Among survivors, chest pain tended to be more common in patients having smaller infarcts, whereas symptoms of dyspnea and claudicatio intermittens were similar in both groups, as were smoking habits, work capability, and varying forms of medication. We thus conclude that during a 5-year follow-up after acute myocardial infarction, mortality, but not morbidity, was related to the original infarct size.     

心电图法评估心肌梗死面积

急性心肌梗死是严重威胁人类健康的重要疾病。心肌梗死面积越大,预后越差。梗死面积对于预测心功能、评估治疗方法具有重要意义。现对心电图评估心肌梗死面积的各种方法作一综述。     

Low-Dose Glucose-Insulin-Potassium Is Ineffective in Acute Myocardial Infarction: Results of a Randomized Multicenter Pol-GIK Trial

Summary. We aimed to assess the clinical efficacy of glucose-insulin-potassium (GIK) in acute myocardial infarction. Experimental data provided evidence of the beneficial effects of GIK on ischemic myocardium. The clinical trials, mostly uncontroled and conducted mainly before the thrombolytic era, were inconclusive due to the small number of patients and discrepancies in protocols. In order to evaluate the efficacy of this intervention, we have performed a prospective multicenter randomized study. The study consisted of 954 patients with acute myocardial infarction (MI) randomized within 24 hours from the onset of symptoms to low-dose GIK (n = 494), which consisted of 1000 mL 10% dextrose, 32–20 U insulin, and 80 mEq K+, or to the control group (n = 460), which was given 1000 mL 0.09% sodium chloride, by intravenous 24-hour infusion at a rate of 42 mL/h. Cardiac mortality and the occurrence of cardiac events at 35 days did not differ between GIK and control-allocated patients (32 (6.5%) vs. 21 (4.6%), respectively; OR 1.45, 95% CI 0.79–2.68, P = 0.20; and 214 (43.3%) vs. 192 (41.7%), OR 1.07, 95% CI 0.82–1.38, P = 0.62). Total mortality at 35 days was significantly higher in the GIK than in the control group (44 (8.9%) vs. 22 (4.8%), respectively, OR 1.95, 95% CI 1.12–3.47, P = 0.01). The excess of noncardiac deaths in the GIK group may have occurred by chance. Low-dose GIK treatment does not improve the survival and clinical course in acute MI.     

This section edited by Bruce Waller,M.D. Usefulness of the 12-lead electrocardiogram in detection of myocardial infarction: Electrocardiographic-anatomic correlations—Part I

This two-part review evaluates a 56-year period (1938–1994) of electrocardiographic-necropsy correlation studies. Part I focuses on definitions of infarct location and evaluates anterior infarctions. Part II will focus on lateral and posterior infarcts.     

Reassessing the clinical significance of electrocardiographically unrecognized myocardial infarctions: Radionuclide infarct size and its impact on long-term prognosis

Background

Silent or unrecognized myocardial infarction (UMI) diagnosed by surveillance electrocardiography (ECG) carries similarly poor prognosis as recognized MI (RMI) for poorly understood reasons.

Methods

This study included 5430 consecutive patients who presented to the nuclear laboratory and underwent 2-day stress and rest Tc-^99m sestamibi and ECG studies between March 1991 and June 1999. UMI was diagnosed if ECG showed Q-wave MI in the absence of a history of RMI. We measured infarct size (% defect size as compared with the entire left ventricular sestamibi uptake), ejection fraction (EF, %), and summed difference score (SDS, sestamibi uptake by myocardium in stress minus sestamibi uptake in rest images as a marker of ischemia). Survival was determined by follow-up survey (median 6 years).

Results

We identified 346 UMIs, 628 RMIs, and 4456 subjects without MI (No MI). As compared with RMI, UMI patients had lesser abnormalities on nuclear scans (p < .0001 for all), including smaller infarct size (5.7% vs. 12.2%), higher EF (58% vs. 53%), and lesser ischemia (SDS; 3.9% vs. 2.7%). UMI prognosis was as poor as that of RMI (annual mortality rate 4.7% vs. 4.8% with No MI rate of 2.9%; p < .001 for all comparisons), and this persisted after multivariate analysis. Infarct size quantification successfully risk-stratified ECG-UMI patients, but UMI patients continued to predict mortality even if the infarct size was 0%.

Conclusions

Although UMI patients have lesser abnormalities on nuclear scans, ECG-based UMI continues to independently predict mortality, indicating the continuing relevance of ECG in clinical practice.     

Ineffectiveness of methylprednisolone to reduce infarct size in experimental coronary occlusion

Summary Two medium-sized branches of the left coronary artery were prepared in each of 10 anesthetized open chest dogs for later occlusion. The first artery was occluded during 90 minutes and reperfused thereafter. This occlusion produced the control infarct. Methylprednisolone (50 mg/kg i.v.) was injected, and the second artery was occluded also for 90 minutes and reperfused thereafter. Both infarcts were made visible by staining left ventricular rings with p-nitrobluetetrazolium. Infarct size was compared with the size of the perfusion area, which we obtained from the postmortem angiogram. Both infarcts were equal in size and comprised 50% of the area of perfusion of the occluded artery. Methylprednisolone in a single high dose given prophylactically did not influence infarct size nor any of the measured parameters.

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Zusammenfassung An 10 Hunden wurde die Wirkung von Methylprednisolon auf die Myokarddurchblutung und die resultierende Infarktgröße nach experimentellem Koronarverschluß untersucht. An jedem Herzen wurden hintereinander zwei mittelgroße Äste der linken Koronararterie für 90 min okkludiert und anschließend reperfundiert. Der Verschluß der 1. Arterie erfolgte unter Kontrollbedingungen, es resultierte der Kontrollinfarkt. Vor dem Verschluß der 2. Arterie wurde Methylprednisolon (50 mg/kg Körpergewicht i.v.) injiziert, es resultierte der Testinfarkt. Die hämodynamischen Parameter (LVP, LV-dp/dt, AOP, HR) wurden kontinuierlich registriert, der myokardiale Sauerstoffverbrauch wurde vom Computer mit Hilfe der Bretschneider-Formel kalkuliert. Die myokardiale Durchblutung wurde mit Hilfe der Tracer microsphere-Technik bestimmt. Das Gebiet der myokardialen Nekrose wurde mit Hilfe der p-NBT-Färbung definiert, das Perfusionsgebiet wurde mit Hilfe der Post-mortem-Angiographie bestimmt Die Infarktgröße wurde als Quotient aus Nekrose- und Perfusionsgebiet in Prozent ausgedrückt. Die hämodynamischen Bedingungen waren in beiden Verschlußperioden vergleichbar, der Kollateralfluß betrug im Gebiet der Kontrollarterie 13,9±6,2% und im Gebiet der Testarterie 14,5±7,8% der Normaldurchblutung. Die resultierenden Infarktgrößen waren ohne Unterschied, der Kontrollinfarkt betrug 51±22%, der Testinfarkt 48±25%. Durch Methylprednisolon konnte weder der Kollateralfluß noch die resultierende Infarktgröße nach Koronarligatur beeinflußt werden.

     

Simple clinical data are useful in predicting effect of exercise training after myocardial infarction

OBJECTIVES: The aim of the present study was to determine whether simpleclinical variables can predict the effect of intensive exercisetraining in an unselected population early after myocardialinfarction. METHODS: Starting 5 weeks after the qualifying myocardial infarction,105 patients, 68 years old or younger, completed a 4 week periodof intensive exercise training. The training effect was definedas an absolute increase in cumulative work at bicycle ergometry.Using univariate and multivariate analysis, 28 variables weretested against the training effect. RESULTS: The mean exercise capacity increased from 46.7 ± 22.7kJ to 69.5 ± 311 kJ (P=0.0001). Multivariate analysisidentified five independent predictors of the training effect.Myocardial infarct size was associated with a better trainingeffect (P=0.0018), as was male gender (P0.0042) and abilityto exercise to exhaustion at the baseline exercise test (P=0.0124).Older age (P=0.0017) and treatment with beta-adrenergic blockingagents (P=0.0241) were associated with a lower effect from training.These five variables explained 33% of the variations in effectfrom training. Patients suffering in-hospital cardiac complicationsor congestive heart failure achieved a training effect at leastas great as patients without cardiac complications. CONCLUSIONS: Five simple clinical variables, including infarct size, canassist in the selection of patients for exercise training aftermyocardial infarction.     

Workshop: Patient Self-Management: Update of Ongoing Studies in Sweden

Anti-vitamin K (AVK) therapy (e.g., warfarin) requires regular blood tests for adequate dosing of the drug. The therapeutic window for these drugs is narrow, with a risk of bleeding if the dose is too high and of thrombotic complications if the dose is too low. Moreover, the required dose to achieve an optimal level of anticoagulation is individual and depends on such factors as the general health of the patient, food intake, and concomitant medication. Although control requires regular monitoring, most patients are reluctant to visit an anticoagulation clinic (ACC) more than 6-12 times yearly because each visit costs the patient both money and time. The development of prothrombin time (PT) monitors that are simple to operate and highly portable has made self-management possible for large groups of patients on long-term AVK therapy. Self-management increases the safety of AVK therapy through frequent testing (3-4 times per month) and timely dose adjustments when they are indicated. The concept of self-management of AVK therapy was introduced in Germany a decade ago with great success. Swedish patient education in self-management was started in September 1996. As of May 1997, 38 patients have completed the training program, 37 of whom have continued with self-management. Experience with the first seven groups of patients has convinced us that self-management is possible and has great potential. Randomized controlled studies are needed to determine the cost effectiveness of self-management with regard to a reduction in bleeding and thrombotic complications.     

Relationship between the Enzymatically Estimated Infarct Size and Clinical Findings in Acute Myocardial Infarction

ABSTRACT In 580 patients with a definite myocardial infarction (MI) and no previous MI, the enzymatically estimated infarct size was related to the clinical course including various complications. In all patients, heat-stable lactate dehydrogenase activity (EC 1.1.1.27, LD) was analyzed every 12 hours for 48–108 hours and in a subgroup (n=170) creatine kinase activity (EC 2.7.3.2, CK) and creatine kinase subunit B (CK B) were analyzed every 6 hours for 48 hours. The highest recorded enzyme activity was used as a rough estimate of infarct size. A positive correlation was found between serum enzyme activity and most of the clinical variables studied, such as incidence of congestive heart failure, treatment with furosemide, incidence of hypotension, cardiogenic shock, pericarditis, post myocardial infarction syndrome, AV block III, and the duration of hospitalization. We conclude that the enzymatically estimated infarct size determined by heat-stable LD, CK and CK B closely reflects the severity of the infarction.