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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.Hospital-based cohort study.Practices of 41 hospital-based cardiologists and internists in the Netherlands.7377 patients.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.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.

Patients who develop a reinfarction are at increased risk for subsequent reinfarctions and death. However, follow-up studies in these patients are rare.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.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.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%; p0.0001).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.

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.

SummaryVarious methods have been described to evaluate efficacy of anticoagulant therapy using the international normalized ration (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.

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.

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.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 CIISor = 40, CIIS 30-40 and CIIS 20-30 were significantly higher than in those with a CIIS20. 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 and40.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.

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.

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.

SummaryBecause 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 plethysmograph, 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 (Cl), 86 to 94%] and 94% (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 longterm follow-up studies.

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 (Dfl1=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 10784 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. ( JAMA . 1995;273:925-928)

SummaryA multi-centre, double blind randomized clinical triatr was designed to assess the efficacy and safety of orally administered 0-(β-hydroxyethyl)-rutosides (HR) capsules in the treatment of L0L patients with post-thrombotic syndrome. Seventeen patients were excluded from the analysis for violation of the study protocol, 4l received HR capsules (I,200 mg/day) and 43 placebo.Mean follow-up scores at the 4th and 8th week show that the HR patients displayed an improved state of tiredness as compared to the placebo's. The mean circumference of the calf for the HR group decreased from 390 (± 33) mm at visit one to 382 (± 33) mm at visit three, with a mean circumference reduction of 8.7 (± 8) mm, compared to a steady placebo circumference of 387 (± 31) mm at all 3 visits with a mean circumference reduction of only 2 mm (± 9). The estimated treatment effect at week 8 was −6.7 ffiffi, 95% confidence interval (−10.3, −3.0).The mean circumference of the ankle, decreased from 243 (± 20) mm to 238 (± 20) mm at the 4th week, contrasted with a constant placebo circumference of.24l (± 22) mm at both visits. The estimated treatment effect at week 4 was-5.4 ffiffi, 95% confidence intenral (−10.2, −0.6). However, at week 8, the estimated treatment effect was only −3.4 mm; 95% corrfidence interval (−8.6, + 1.8).In conclusion, HR capsules may show an improvement in the clinical symptoms and may show a mean circumference reduction of the calf and ankle at the 8th week, in patients with postthrombotic syndrome.

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-anticoagulant (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.

SummaryWe 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.

In a prospective cohort study, we evaluated X-ray VG in the management of non-surgical patients with clinically suspected PE. Thusfar follow up is available on 131 consecutive patients with suspected PE. In all patients a perfusion lungscan (PS) was carried out within 24 hours. In case of a normal PS (group A, n=32), no anticoagulant (AC) therapy was given. In case of an abnormal PS, AC therapy was started (heparin) and a bilateral ascending VG was carried out within 72 hours. In 46 patients (group C) venous thrombosis (DVT) was demonstrated by VG, and these patients were treated with AC for 6 months. In 53 patients with suspected PE and an abnormal lungscan, bilateral VG did not show DVT (group B). AC therapy was discontinued in these patients These patients were then screened for 14 days with fibrinogen legscanning and impedance plethysmography (IPG), followed by IPG alone every 2 months for at least 1 year. In group B, 6 patients died in the follow up period. None of the patients had signs of PE at autopsy. One additional patient in group B developed DVT documented by repeat VG, 6 months after entry into the trial. According to these preliminary data, it seems safe to base the decision whether or not to treat a patient with suspected PE with AC, on the presence or absence of DVT in the lower limbs as demonstrated by VG

Since the clinical diagnosis of deep vein thrombosis (DVT) is unreliable, several invasive and non-invasive methods have been developed recently. Of these, impedance plethysmography (IPG) is a widely employed technique based on measurement of changes in blood volume produced by temporary obstruction. IPG has been shovn in large prospective studies in symptomatic patients to be a safe and effective alternative to contrast venography, if used either in combination with 1251-fibrinogen legscanning or serially as a single test. Currently available impedance plethysmographs are limited by several technical and operational problems. Therefore, a new computerized impedance plethysmograph (CIP) was developed, having the following characteristics: portability, battery operated and fully automated. A prospective two-center study in 299 consecutive outpatients was done to compare the efficacy of CIP vs. venography in patients with symptomatic DVT. Using a blind design i.e. care was taken to insure that CIP and venography were performed and interpreted independently. The results in patients without venography proven thrombosis and those with proximal vein thrombosis were subjected to a discriminant analysis producing a line of best discrimination between normal and proximal vein thrombosis. In 14 patients it was not possible to obtain an adequate CIP tracing. 12 patients were not entered because of refusal to undergo venography and 15 patients were excluded from analysis because of poor opacification of the proximal veins. On the basis of discriminant analysis 138 of the CIP results were classified as normal and 120 as abnormal. 175 patients were normal on venography and 83 had proximal thrombosis. The sensitivity of CIP for proximal vein thrombosis was thus 95% while the speci-+ ficity was 77%. It is concluded that computerized impedance plethysmography is a potentially sensitive method to detect proximal vein thrombosis in patients with clinically suspected deep vein thrombosis.

The following tests were done in 61 well controlled diabetic patients: Platelet survival time (PST), platelet aggregation ratio acc. to Wu and Hoak (PAR), platelet aggregation test 1 acc. to Breddin (PAT 1), ADP-threshold concentration and filtragometer aggregation time acc. to Hornstra (Ta). The mean PST in 20 healthy volunteers was 99 hours ± 13,4 hrs.: in 12 pat. wihtout retinopathy 88,6 ± 12,8 hrs.; in 28 pat. with non-proliferative retinopathy 103,9 ± 18,2 hrs. and in 1 par. with proliferative retinopathy 105,8 ± 7,5 hrs. In 16 pat. with a disturbed nerve conduction time the mean PST was 102,2 ± 21,5 hrs. and 96,0 ± 21,9 hrs, in 28 pat. with a normal time. The PST was shortened (mean-1 ED) in 12 pat. out of 44 pat. The mean PAR was 0,37 ± 0,11 in 27 normal volunteers and 0,78 ± 0,12 in 61 diabetics. The PAR was < 0,71 in 16 out of 61 pat. The mean PAT 1 was 1,7 in 27 normal volunteers and 1,5 in 61 diabetics; the test was abnormal in 6 out of 61 pat. The ADP-threshold concentration was < 0,75 mumol ADP/L in only 4 out of 61 pat. The mean Ta was 242 ± 50,5 sec. in 16 normal volunteers and 167 ± 83 sec. in 44 pat.; the Ta was < 150 sec. in 23 out of 44 pat. There was no correlation between the severity of retino- and/or neuropathy with the PST, PAR, PAT 1, ADP-threshold or Ta or between the laboratory values. There was no abnormal laboratory test in 2 3 pat., one in 19, two in 16 and three in 3 pat. There was no relationship between the severity of retino- and/or neuropathy and number of abnormal laboratory tests.