Quality of secondary cardiovascular prevention in specialised care in the Netherlands: the SOLID study.

OBJECTIVE: To determine the extent to which Dutch patients with a history of cardiovascular disease and high cholesterol levels, treated in specialised care, are achieving low-cholesterol targets as defined by national guidelines. DESIGN: Hospital-based cohort study. SETTING: Practices of 41 hospital-based cardiologists and internists in the Netherlands. SUBJECTS: 7377 patients. RESULTS: Forty-one percent of the patients with an indication for secondary cardiovascular prevention by lipid-lowering drug treatment were receiving medication and were achieving cholesterol targets, 42% were receiving lipid-lowering medication but had cholesterol levels above target, 11% were not receiving treatment, and 5% had no recent lipid measurements. CONCLUSION: Compared with previous studies, the SOLID study shows that a relatively large percentage of the Dutch patients under specialised care with a history of cardiovascular disease and an indication for cholesterol-reducing therapy are currently being treated. A considerable proportion of the patients, however, are still not receiving optimal treatment and more than 10% are not being treated at all.

Dose-dependent efficacy of miglitol, an alpha-glucosidase inhibitor, in type 2 diabetic patients on diet alone: results of a 24-week double-blind placebo-controlled study.

AIMS: A double-blind randomised study was performed to compare the dose-effect and dose-tolerability relationships between the alpha-glucosidase inhibitor miglitol in doses of 25 mg, 50 mg, 100 mg and 200 mg all t.i.d. vs placebo t.i.d. in patients with Type 2 diabetes mellitus on diet only. METHODS: After a 6-week placebo run-in period 468 patients with a fasting blood glucose > or = 7 mmol/l as well as a HbA1c between 6.1% and 10.4% were randomised for a 24-week treatment period. RESULTS: The results of 465 patients were valid for safety analysis and of 384 patients for the efficacy analysis. In the placebo group the HbA1c level increased by 0.40+/-1.46% as compared with baseline. The decrease in the mean HbA1c values (corrected for differences in baseline values) was significant and dose-dependent for all miglitol groups compared with placebo, being -0.46% (95% CI: -0.91%, -0.01%) in the 25 mg group, -0.45% (95% CI: -0.90%, -0.003%) in the 50 mg group, -0.84% (95% CI: -1.31%, -0.37%) in the 100 mg group and -1.26% (95% CI: -1.76%, -0.76%) in the 200 mg group. Blood glucose levels following a standardised breakfast tolerance test were significantly and dose-dependently lower for all the miglitol doses at 12 and 24 wk of treatment compared to baseline: in comparison with baseline maximum blood glucose increased by 4% with placebo and decreased by 7%, 14%, 24% and 33% with miglitol 25 mg, 50 mg, 100 mg and 200 mg t.i.d. respectively. The same pattern was seen with postprandial maximal serum insulin levels which decreased by 8% under placebo and by 17%, 26%, 25% and 35% with the 25 mg to 200 mg doses of miglitol. The adverse events reported were mainly of gastrointestinal nature, mostly being flatulence, diarrhoea and abdominal pain and the incidence increased with increasing dose. Although the side effects were not serious, they were troublesome, leading to a considerable drop-out rate increasing with dose. CONCLUSIONS: The alpha-glucosidase inhibitor miglitol in Type 2 diabetic patients on diet alone decreases both HbA1c levels and postprandial glucose and insulin levels in a dose-dependent manner. Gastrointestinal side effects also showed dose-dependency. Combination of efficacy and safety results leads to the conclusion that the optimal dose of miglitol will be in the range of 50 to 100 mg t.i.d.

Prognostic significance of nonfatal myocardial reinfarction in survivors of a first infarction.

BACKGROUND: Patients who develop a reinfarction are at increased risk for subsequent reinfarctions and death. However, follow-up studies in these patients are rare. OBJECTIVE: The purpose of this study was to examine the risk of mortality after a first myocardial reinfarction and to determine the independent contribution of nonfatal reinfarction to the risk of subsequent mortality. METHODS: The prognostic value of nonfatal reinfarction was assessed in a large series (n=3097) of patients with a first myocardial infarction who participated in the ASPECT trial, comparing coumarin or matching placebo. RESULTS: A second myocardial infarction was documented in 299 patients (82% Q-wave infarctions), 45 (15%) of which were fatal. Of the 254 nonfatal reinfarctions, 31 patients (12%) died during subsequent follow-up. After adjustment for baseline characteristics, the relative risks of nonfatal reinfarction for subsequent cardiac mortality at one month were: 2.90 (1.49-5.64), at one year: 2.50 (1.47-4.23) and at three years: 2.71 (1.77-4.17). Rates of death or a second reinfarction in patients who did not undergo a revascularisation procedure after a first reinfarction were almost three times higher than in patients who did have PTCA or bypass surgery after a reinfarction (38% versus 14%; p<0.0001). CONCLUSION: This study population with three-year follow-up confirms that nonfatal reinfarction carries a strong and independent risk for recurrent reinfarction and subsequent mortality. Thus, prevention of reinfarction by intensive treatment might contribute in reduction of mortality.

Effects of nitrendipine and enalapril on left ventricular mass in patients with non-insulin-dependent diabetes mellitus and hypertension.

OBJECTIVE: To compare the effects of a calcium antagonist (nitrendipine) and an angiotensin converting enzyme inhibitor (enalapril) with those of placebo on left ventricular mass in patients with non-insulin-dependent diabetes mellitus and hypertension. DESIGN: A double-blind randomized, placebo-controlled trial. SETTING: General practitioners referred patients to the trial physician. PATIENTS: The study population comprised 121 patients with non-insulin-dependent diabetes mellitus. Inclusion criteria for blood pressure were diastolic blood pressure 90-115 mmHg and systolic blood pressure < or = 200 mmHg, while subjects were not being administered blood-pressure-lowering drugs for 3 weeks. INTERVENTION: Patients were randomly allocated to receive nitrendipine (n = 40), enalapril (n = 40) or placebo (n = 41). The treatment period was 48 weeks. MAIN OUTCOME MEASURES: The effect of nitrendipine was defined as the difference in change in left ventricular mass index from baseline between nitrendipine treatment and placebo after 48 weeks of treatment. The effects of nitrendipine compared with that of enalapril and of enalapril compared with placebo were defined similarly. Left ventricular mass was measured by M-mode echocardiography. RESULTS: Use of nitrendipine and enalapril led to significant and almost identical reductions in systolic and diastolic blood pressures. During 48 weeks left ventricular mass index decreased by 5% for patients in the nitrendipine group (decrease by 12 g/m2, 95% confidence interval 1-23), remained about the same for patients in the enalapril group (decrease by 1 g/m2, 95% confidence interval decrease by 10 to increase by 9) and increased by 9% for patients in the placebo group (increase by 9 g/m2, 95% confidence interval 2-16). CONCLUSION: These results indicate that administration of nitrendipine to patients with non-insulin-dependent diabetes mellitus and hypertension reduces left ventricular mass index. Enalapril appears not to induce regression, but perhaps prevents progression with an effect that is intermediate between those of nitrendipine and placebo.

The Cardiac Infarction Injury Score as a predictor for long-term mortality in survivors of a myocardial infarction.

AIMS: The Cardiac Infarction Injury Score (CIIS) is an electrocardiographic classification system that was developed as a diagnostic tool to assess the extent of cardiac injury in acute myocardial infarction. We investigated the prognostic value of the CIIS in post-myocardial infarction patients. METHODS AND RESULTS: The prognostic values of the CIIS for total and cardiac mortality was assessed in a large series (n = 3395) of patients who were enrolled in the ASPECT trial. Standard 12-lead electrocardiograms, recorded prior to hospital discharge were coded according to the CIIS and the Minnesota Code. Mean CIIS was 26 (range--8 to 59). After adjustment for other baseline characteristics, the CIIS was directly related to the risk of total mortality and cardiac mortality. At one-year follow-up the relative risks of CIIS > or = 40, CIIS 30-40 and CIIS 20-30 were significantly higher than in those with a CIIS < 20. The relative risks were, respectively, 2.3 (1.2-4.4), 2.2 (1.3-3.9) and 1.6 (0.9-2.9). At 3 year follow-up, the relative risks were, respectively, 2.1 (1.4-3.2), 1.7 (1.2-2.4) and 1.5 (1.0-2.1). The relative risks for total mortality were similar. When patients with major ECG abnormalities, as defined by the Minnesota code, were excluded, the associations were still significant in the CIIS classes 30-40 and > 40. CONCLUSION: The CIIS ECG scoring system is an important predictor for long-term cardiac mortality in post myocardial infarction patients. It can easily be automated and is efficient for classifying cardiac injury in epidemiological studies.

Efficiency optimization of the selection period in therapeutic trials.

To determine eligibility for a (randomized) clinical trial, measuring the inclusion and exclusion criteria can be extended over a period of time. During this period, known as the selection period, a patient is repeatedly examined at certain time intervals. This study describes an approach for optimizing the efficiency of the selection period. Efficiency is defined as the costs of randomizing one patient. The objective is to construct prediction models based on data obtained early in the selection period to predict subsequent exclusions. A prediction model increases the efficiency if after its application the costs per randomization are lower. The approach is illustrated using data from the selection period of the Rotterdam Cardiovascular Risk Intervention (ROCARI) trial which was composed of five consecutive patient visits. At each visit, data to determine eligibility was obtained. We found that logistic regression models based on data of the first and second visit could predict exclusions during the third visit. Application of the prediction models suggested that in this particular trial the costs per randomization would decrease by $52. As the initial costs per randomization were $1444, there would be a 3.6% (52/1444) savings in recruitment costs under the prediction models, accounting for a savings of more than $450,000. We conclude that the use of data obtained early in a selection period can predict subsequent exclusions, and therefore could increase the efficiency of such a period. The approach could be applied to data obtained in a pilot study as well as data obtained in the beginning of a prolonged intake period.

[Antithrombotic treatment following acute ischemic heart disease: acetylsalicylic acid and (or) oral anticoagulants?; ASPECT-II, a new study]. / Antitrombotische behandeling na een acute ischemische hartziekte: acetylsalicylzuur en (of) orale anticoagulantia?; ASPECT-II, een nieuw onderzoek.

In order to compare the efficacy and safety of three regimens of long-term antithrombotic treatment in patients with acute ischaemic syndromes, a prospective, randomized, open-label, multicentre study is being conducted in which 60-70 Dutch hospitals will participate. Eligible patients discharged following hospitalization for acute myocardial infarction or unstable angina pectoris are randomly assigned to receive either (a) adjusted full intensity oral anticoagulation (target range: 3.0-4.0 International Normalised Ratio (INR), (b) low dose aspirin or (c) combined therapy of low dose aspirin and adjusted low intensity oral anticoagulation (target range INR: 2.0-2.5). It is planned to enroll 8,700 patients within three years. During an estimated mean follow-up of 2.5 years the evolutions of total mortality, non-fatal myocardial infarction, non-fatal stroke and major bleeding complication will be assessed.

Optimal intensity of oral anticoagulant therapy after myocardial infarction.

OBJECTIVES: This study attempted to determine the optimal intensity of anticoagulant therapy in patients after myocardial infarction. BACKGROUND: Treatment with oral anticoagulant therapy entails a delicate balance between over- (risk of bleeding) and under-anticoagulation (risk of thromboemboli). The optimal intensity required to prevent the occurrence of either event (bleeding or thromboembolic) is not known. METHODS: A method was used to determine the optimal intensity of anticoagulant therapy by calculating incidence rates for either event associated with a specific international normalized ratio. The numerator included events occurring at given international normalized ratios, and the denominator comprised the total observation time. RESULTS: The study population included 3,404 myocardial infarction patients enrolled in the ASPECT (Anticoagulants in the Secondary Prevention of Events in Coronary Thrombosis) trial. Total treatment was 6,918 patient-years. Major bleeding occurred in 57 patients (0.8/100 patient-years), and thromboembolic complications in 397 (5.7/100 patient-years). The incidence of the combined outcome (bleeding or thromboembolic complications) with international normalized ratio <2 was 8.0/100 patient-years (283 events in 3,559 patient-years), with international normalized ratios between 2 and 3, 3.9/100 patient-years (33 events in 838 patient-years); 3.2/100 patient-years (57 events in 1,775 patient-years) for international normalized ratios between 3 and 4; 6.6/100 patient-years (37 events in 564 patient-years) for international normalized ratios between 4 and 5; and 7.7/100 patient-years (14 events in 182 patient-years) for international normalized ratios >5. After adjustment for achieved international normalized ratio levels, significant predictors were higher levels of systolic blood pressure and age. CONCLUSIONS: If equal weight is given to hemorrhagic and thromboembolic complications, these results suggest that the optimal intensity of long-term anticoagulant therapy for myocardial infarction patients lies between 2.0 and 4.0 international normalized ratio, with a trend to suggest an optimal intensity of 3.0 to 4.0.

Risk of stroke during long-term anticoagulant therapy in patients after myocardial infarction.

Myocardial infarction survivors have an increased risk of stroke, which is reduced with long-term anticoagulant therapy. However, an estimated 10-times increase in risk of bleeding during such treatment has been reported. We evaluated the risk of stroke in patients after a myocardial infarction and examined the relationship of the risk of intracranial hemorrhage or cerebral infarction and the intensity of anticoagulant therapy. The study population consisted of 3,404 post-myocardial infarction patients who took part in a randomized, double-blind, placebo-controlled trial. Patients were randomized to treatment with anticoagulants (international normalized ratio range, 2.8-4.8) or matching placebo. Mean follow-up was more than 3 years. The incidence of stroke analyzed on "intention-to-treat" was 0.7 per 100 patient-years in the anticoagulant patients against 1.2 in placebo, a hazard ratio of 0.60, with 95% confidence interval of 0.40 to 0.90. In the anticoagulation group, 15 patients had cerebral infarction and 17 an intracranial bleeding, 3 of which occurred after withdrawal of treatment. In the placebo group, the numbers were 43 and 2. Of the 14 intracranial bleeds during anticoagulation, 6 occurred at an international normalized ratio between 3.0 and 4.0 and 8 at greater than 4.0. These results confirm that long-term anticoagulant therapy substantially reduces the risk of stroke in post-myocardial infarction patients. The increased risk of bleeding complications associated with anticoagulant therapy is offset by a marked reduction in ischemic events. The risk of intracranial bleeding is directly related to the intensity of anticoagulant treatment.

Efficacy of long-term anticoagulant treatment in subgroups of patients after myocardial infarction.

OBJECTIVE: To investigate the efficacy of long term oral anticoagulant treatment in subgroups of patients after myocardial infarction. DESIGN: Analysis of the effect of anticoagulant treatment in subgroups of hospital survivors of myocardial infarction based upon age, gender, history of hypertension, previous myocardial infarction, smoking habits, diabetes mellitus, Killip class, anterior location of infarction, thrombolytic therapy, and use of beta blockers. SUBJECTS: Participants of a multicentre, randomised, double blind, placebo controlled trial that assessed the effect of oral anticoagulant treatment on mortality as well as cerebrovascular and cardiovascular morbidity in 3404 hospital survivors of acute myocardial infarction. MAIN OUTCOME MEASURES: The effect of anticoagulant treatment on recurrent myocardial infarction, cerebrovascular events, and vascular events (the composite endpoint of reinfarction, cerebrovascular event, and vascular death). RESULTS: Long term anticoagulant treatment was associated with a reduction in mortality of 10% (95% confidence interval -11% to 27%), recurrent myocardial infarction of 53% (41% to 62%), cerebrovascular events of 40% (10% to 60%) and vascular events of 35% (24% to 45%). Treatment effect with respect to recurrent myocardial infarction was comparable among all subgroups of patients. Although treatment effect appeared to be somewhat smaller in females than in males (-11% v -45%), and in patients with diabetes compared to those without (-14% v -42%) with respect to vascular events, none of these differences reached statistical significance. In multivariate analysis, more advanced age, previous myocardial infarction, diabetes mellitus, and heart failure during admission were independently associated with increased incidence of cardiovascular complications. CONCLUSIONS: The relative benefit of long term anticoagulant therapy in survivors of myocardial infarction is not modified by known prognostic factors for cardiovascular disease.

Characteristics and prognosis of non-participants of a multi-centre trial of long-term anticoagulant treatment after myocardial infarction.

Participants of a randomised trial may differ from eligible non-participants as a result of selection. We studied the distribution of prognostic factors and survival in eligible patients of a multi-centre trial of long-term oral anticoagulant treatment after myocardial infarction. All hospital survivors of myocardial infarction in one participating clinical centre of a multi-centre, randomised, double-blind, placebo-controlled trial of long-term anticoagulant treatment after myocardial infarction were screened for entry criteria. Subsequently, prognostic factors and survival of participants were compared with eligible but not randomised patients. The 350 participants were younger and were more often of male gender and more often smokers compared with 587 non-participants. Non-participants had more frequently suffered a previous myocardial infarction and were treated more often with diuretics and ACE-inhibitors, suggesting a higher proportion of patients with chronic heart failure in this group. Age, previous myocardial infarction and the use of diuretics at discharge were independent predictors of mortality, consent showed no association. Our findings indicate that participants of a clinical trial have a better prognosis during the first years following myocardial infarction compared to eligible non-participants as a result of a higher prevalence of cardiovascular risk factors associated with mortality in the non-participants.

[Adjustment to insulin of patients with type II diabetes mellitus in primary care; good results at low cost]. / Instelling op insuline van patiënten met diabetes mellitus type II in de eerste lijn; goede resultaten bij geringe kosten.

OBJECTIVE: Comparison of costs and results of different treatment policies for patients with diabetes mellitus type II (NIDDM) starting on insulin. DESIGN: Retrospective study using literature control data. SETTING: Diabetes Centre Rotterdam (DCR). METHODS: The effects of home treatment by the DCR were studied during one year in 52 NIDDM patients by measurement of glycosylated haemoglobin (HbA1c) values. These effects were compared with literature data. Cost data of insulin treatment were calculated for the different policies. RESULTS: After one year of insulin treatment, the DCR patients had 'satisfactory' HbA1c levels according to international standards. In comparable patients treated at an outpatient clinic these values were 'poor'. Home treatment versus treatment at an outpatient clinic or during hospitalisation constituted a cost reduction of NFL 416 and NFL 2480 per patient respectively. CONCLUSION: Insulin treatment in NIDDM patients at home has at least the same effects on HbA1c values as obtained in patients treated at an outpatient clinic, and reduces costs.

Costs and effects of long-term oral anticoagulant treatment after myocardial infarction.

OBJECTIVE: To investigate the costs and effects of long-term oral anticoagulant treatment after myocardial infarction. DESIGN: Cost-effectiveness analysis, based on a randomized, double-blind, placebo-controlled trial. SETTING: Sixty Dutch hospitals. PATIENTS: A total of 3404 hospital survivors of acute myocardial infarction randomized within a median period of 4 days after discharge to either oral anticoagulant treatment or placebo. The mean follow-up was 37 months. INTERVENTION: Oral anticoagulant treatment aimed at a target international normalized ratio of 2.8 to 4.8. MAIN OUTCOME MEASUREMENTS: Costs of hospital stay during readmissions, costs related to major cardiologic interventions, and costs of oral anticoagulant treatment. RESULTS: The costs of oral anticoagulant treatment were estimated at 394 Dutch guilders (Dfl) per patient-year (Dfl 1 = US $0.58). Placebo patients stayed 18,830 days in the hospital compared with 15,083 days for anticoagulation patients. Average costs per patient of medical care during follow-up were estimated at Dfl 10,784 for placebo patients and Dfl 9878 for anticoagulation patients. CONCLUSIONS: Costs of long-term anticoagulant treatment are outweighed by the costs of prevented clinical events.

Assessment of therapeutic quality control in a long-term anticoagulant trial in post-myocardial infarction patients.

Various methods have been described to evaluate efficacy of anticoagulant therapy using the international normalized ratio (INR). We compared the following approaches: (1) total INR's or the most recent measurement; (2) percent time within therapeutic range, with INR changing directly or halfway between visits; and (3) total observation time assuming INR changing linearly. The study population comprised 1700 post myocardial infarction patients. Treatment comprised 3725 patient-years. There were 61,471 INR assessments with target therapeutic level of 2.8-4.8. Acenocoumarol as well as phenprocoumon were employed. Therapeutic achievement in the first months of treatment was low: less than 60% of INR's were in range. Treatment stabilized after 6 months. Patients on acenocoumarol were within range 70% of the time compared to 80% for phenprocoumon. Method 3 is preferred because it incorporates time and is capable of calculating incidence rates at different INR levels. Our findings call for an urgent improvement of standard of anticoagulant control in the first months following commencement of treatment.

[Functioning of an Exercise electrocardiographic service for family physicians; a report of 498 patients]. / Het functioneren van een inspannings-elektrocardiografische service voor huisartsen; een beschrijving van 498 patiënten.

OBJECTIVE: In Rotterdam GPs have the possibility of requesting an exertion ECG for their patients from the Foundation Thrombosis Service and Physicians' Laboratory. A follow-up study was carried out in order to gain insight into the functioning of this service. PATIENTS AND METHODS: Over a period of three months, 266 GPs referred 498 patients to the service for an exertion ECG. The GPs received an enquiry form with questions on the referral and the functioning of the service. The patients were followed up for two weeks in connection with any (cardiovascular) events and with the management by the GP. An ECG was regarded as positive if the ST showed a depression greater than or equal to 1.5 mm. RESULTS: None of the patients died during the period of the investigation. Of the patients with positive and with negative ECGs, 41% and 37%, respectively, had no more complaints, 40% and 28% the same complaints, and 3% and 0.5% more complaints. Of the patients with a negative ECG (n = 439), 3.9% were referred to a cardiologist. If no ECG had been made, this proportion would have been 39%. CONCLUSION: The Foundation Thrombosis Service and Physicians' Laboratory Rotterdam provides an essential contribution to GPs' decision making concerning referral of patients with vague cardiac complaints to a cardiologist.

A new computerized impedance plethysmograph: accuracy in the detection of proximal deep-vein thrombosis in symptomatic outpatients.

Because of the lack of specificity of the clinical diagnosis it is appropriate in patients with clinically suspected deep-vein thrombosis to apply an objective test before starting anticoagulant treatment. Impedance plethysmography is a highly accurate technique for the detection of proximal-vein thrombosis with a reported sensitivity and specificity of 93 and 97%, respectively. In all previous reported evaluations of impedance plethysmography an apparatus which was developed in 1971 was used. A new computerized impedance plethysmography, using a novel device to measure impedance, was blindly compared against venography in 443 consecutive outpatients with clinically suspected deep-vein thrombosis. In the first phase of the study the computerized impedance plethysmography test results of 242 symptomatic patients were used to develop a discriminant line. Subsequently, this discriminant line was validated in the second phase of the study in another 201 symptomatic patients. The combined sensitivity and specificity of these two phases for proximal-vein thrombosis was 91% [95% confidence interval (CI), 86 to 94%] and 94% and (95% CI, 90 to 96%), respectively, which compares favourably with impedance plethysmography. It is concluded that computerized impedance plethysmography is a simple, portable, non-invasive technique with a high accuracy for the detection of proximal vein thrombosis. However, before computerized impedance plethysmography can be used as the only test in the diagnosis of deep-vein thrombosis, the safety of withholding anticoagulant treatment to patients with repeated normal computerized test results should be assessed during long-term follow-up studies.

Diagnostic value of D-dimer for deep venous thrombosis in outpatients.

We have studied the diagnostic value for deep venous thrombosis (DVT) of an enzyme immunoassay (EIA) for the detection of D-dimer in plasma of 239 consecutive outpatients suspected of having DVT by their general practitioner. DVT was confirmed by impedance plethysmography in 60 patients. Using the 95th percentile range of 42 healthy volunteers, the sensitivity for the detection of DVT was 92%, with a specificity of 21%. In our population with a prevalence of 25%, the D-dimer EIA showed a negative predictive value of 88% and a positive predictive value of 28%. We conclude that this D-dimer ELISA has limited value, either to confirm or to exclude DVT in outpatients.

Laboratory and therapeutic control in the Thrombosis Centre Rotterdam using chromogenic prothrombin time tests.

Growing interest is observed in chromogenic substrate assays, because of their better precision, performance and possibilities for automation. Applied to a Cobas Bio centrifugal analyzer, we compared Nycotest-Chrom (N-test) and Thromboquant-PT (Tbq) with Thrombotest (TT). Precision tests were performed with samples from 4 plasma pools: normal (45 sec), low (100 sec), middle (150 sec) and high (200 sec) segments of the therapeutic range of TT. N-test had the best precision profile in both intraassay and interassay determinations compared with Tbq. Both chromogenic substrate assays were better than TT in this respect. By orthogonal regression a provisional therapeutic range was calculated from 312 determinations and later adjusted in a confirmation experiment with natural logarithm regression in 946 determinations. Compared with a TT range of 105-180 sec, the therapeutic ranges were 71-120 sec for N-test and 63-103 sec for Tbq. In a clinical therapeutic control phase, 110 patients were randomized in equal proportions to two groups A and B. Every 2 weeks for a period of 16 weeks, blood samples were tested for N-test, Tbq and TT. In group A, dose adjustment was based on N-test, and in group B on Tbq. The monitoring physician was blinded for Tbq and TT in group A and for N-test and TT in group B. No differences were found between the groups for mean TT, N-test, Tbq or mean dosage, nor differences were found in complication rate. A definite therapeutic range was complied using sensitivity/specificity curves together with their 95% confidence limits. Given TT 105-180 sec, the therapeutic range of N-test is from 80 (95% confidence limits: 77-82) to 110 (95% confidence limits: 108-115) sec, and of Tbq from 68 (95% confidence limits: 66-71) to 95 (95% confidence limits: 91-98) sec. It was concluded that the two chromogenic substrate assays performed equally safe in the monitoring of patients on oral anticoagulant therapy, despite differences in diagnostic correspondence with the reference TT.

Is quantitative determination of fibrin(ogen) degradation products and thrombin-antithrombin III complexes useful to diagnose deep venous thrombosis in outpatients?

We studied the diagnostic value of recently introduced ELISA's for the determination of thrombin-antithrombin III (TAT) complexes, fibrin degradation products (FbDP), fibrinogen degradation products (FgDP) and total degradation products (TDP) for deep venous thrombosis (DVT) in plasma of 239 consecutive outpatients, suspected for DVT by their family doctor. DVT was confirmed by impedance plethysmography in 60 patients. Using the 95th percentile range of 42 healthy volunteers the sensitivity for the detection of DVT was: 37% for TAT, 95% for TDP, 92% for FbDP and 90% for FgDP. Specificity was: 88% for TAT, 16% for TDP, 20% for FbDP and 25% for FgDP. We conclude that these assays are of little value in the diagnosis of DVT in outpatients.