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Coronary stent implantation is being performed in an increasing number of patients with a wide spectrum of clinical and lesion characteristics. A variety of stent designs are now available and continuous efforts are being made to improve the stent placement procedure. The objective of this study was to perform a comprehensive analysis of the relation between clinical, lesion, and procedural factors, and restenosis after intracoronary stenting in a large and unselected population of patients. A consecutive series of 4,510 patients with coronary stent placement was analyzed. Exclusion criteria were only a failed procedure and an adverse outcome within the first month after the intervention. Follow-up angiography was performed in 80% of patients at 6 months. Clinical, lesion, and procedural data from all 3,370 patients (4,229 stented lesions) with follow-up angiography were analyzed in a logistic regression model for restenosis (> or =50% diameter stenosis). Clinical factors contributed to the predictive power of the model much less than lesion and procedural factors. The strongest risk factor for restenosis was a small vessel size, with a 79% increase in the risk for a vessel of 2.7 mm versus a vessel of 3.4 mm in diameter. Stent design was the second strongest factor; the incidence of restenosis ranged from 20.0% to 50.3% depending on the stent type implanted. In conclusion, this study demonstrates the predominant role of lesion and procedural factors in determining the occurrence of restenosis after coronary stent placement. Among these factors, stent design appears to play a particularly important role in the hyperplastic response of the vessel wall.

Background-The modified American College of Cardiology/American Heart Association (ACC/AHA) lesion morphology criteria are predictive of early outcome after various coronary catheter interventions. Their potential prognostic value after stent implantation and, in particular, for restenosis and long-term clinical outcome has not been studied. We assessed the prognostic value of the modified ACC/AHA criteria for the long-term angiographic and clinical outcome of patients after coronary stenting. Methods and Results-This study includes 2944 consecutive patients with symptomatic coronary artery disease treated with coronary stent placement. Modified ACC/AHA lesion morphology criteria were used to qualitatively assess the angiograms; type A and B1 lesions were categorized as simple, and type B2 and C lesions were designated complex. Primary end points were angiographic restenosis and 1-year event-free survival. Restenosis rate was 33.2% in complex lesions and 24.9% in simple lesions (P<0.001). It was 21. 7% for type A, 26.3% for type B1, 33.7% for type B2, and 32.6% for type C lesions. One-year event-free survival was 75.6% for patients with complex lesions and 81.1% for patients with simple lesions (P<0. 001). It was 85.2% for patients with type A, 79.4% for type B1, 75. 9% for type B2, and 75.2% type C lesions. The higher risk for restenosis and an adverse outcome associated with complex lesions was also maintained after multivariate adjustment for other clinical and angiographic characteristics. Conclusions-The modified ACC/AHA lesion morphology scheme has significant prognostic value for the outcome of patients after coronary stent placement. Lesion morphology is able to influence the restenosis process and thus the entire 1-year clinical course of these patients.

Background: High-pressure dilatation is considered a better stent placement strategy, but this has not yet been proved by appropriately designed studies. The objective of this randomized trial was to assess the role of high-pressure dilatation in the early and late outcome of patients undergoing coronary stent placement., Methods and Results: Consecutive patients with coronary stent placement were randomly assigned to high- (15 to 20 atm, 468 patients) or low- (8 to 13 atm, 466 patients) balloon-pressure dilatation. The primary end point of the study was the event-free survival at 1 year. Secondary end points were the incidence of stent thrombosis at 30 days and angiographic restenosis (>/=50% diameter stenosis) at 6 months. The incidence of stent thrombosis was 1.7% in the high-pressure and 1.9% in the low-pressure group (relative risk 0.89; 95% CI 0.30 to 2.56). During the first 30 days, although there was no significant difference in the incidence of Q-wave myocardial infarction, the incidence of non-Q-wave infarction was 6.4% in the high-pressure and 3.4% in the low-pressure group (relative risk 1. 87; 95% CI 1.02 to 3.42). The restenosis rate was 30.4% in the high-pressure and 31.4% in the low-pressure group (relative risk 0. 97; 95% CI 0.75 to 1.26). Event-free survival at 1 year was not significantly different between the groups, with 78.8% in high-pressure patients and 75.5% in patients assigned to low-pressure dilatation (hazard ratio 0.85; 95% CI 0.65 to 1.11)., Conclusions: The systematic use of high-balloon-pressure inflation (15 to 20 atm) during coronary stent placement is not associated with any significant influence on the 1-year outcome of patients undergoing this intervention.

Unlabelled: Coronary stent implantation is an increasingly accepted revascularization method. The 20%-30% restenosis rate during the first 6 mo requires a close follow-up of the patients. Since there is very little data available defining the role of perfusion scintigraphy in the management of this population, the aim of this study was to assess the diagnostic performance of stress myocardial perfusion imaging for detecting restenosis in patients after coronary stent implantation., Methods: In 82 patients, 93 rest or stress SPECT studies were performed using 201Tl and 99mTc-hexakis-2-methoxyisobutyl isonitrile to evaluate 99 vascular territories with implanted coronary stents. The average interval between the stent implantation and the scintigraphic study was 210.5 +/- 129.6 days. The scintiscans were visually evaluated. A stress-induced perfusion defect with reversibility at rest was used as the criterion for stent restenosis., Results: Coronary angiography revealed a stenosis of > 50% diameter in the region of the stent in 19 arteries, while in 80 arteries there was no evidence of restenosis angiographically. With perfusion scintigraphy, 15/19 vascular territories with restenosed stents showed stress-induced perfusion abnormalities (sensitivity = 79%), while 62/80 territories without restenosis did not (specificity = 78%). In territories without a myocardial infarction (n = 48), sensitivity and specificity values were 8/8 (100%) and 36/44 (82%), and in territories with a myocardial infarction (n = 47) 7/11 (64%) and 26/36 (72%), respectively. Side branch stenosis was fairly frequent in patients without stent restenosis but with a reversible perfusion pattern on their scintiscan (8/18); however, these stenoses were induced infrequently by the stents (3 cases)., Conclusion: Using the criterion of defect reversibility, stress perfusion SPECT can accurately detect restenoses of coronary artery stents. This method is most accurate for evaluating patients without a previous myocardial infarction in the stented vascular territory.

This study was designed to test the hypothesis that patients fulfilling intravascular ultrasound (IVUS) criteria for optimal coronary stent implantation show a reduction in the restenosis rate at 6 months. IVUS guidance for stent dilation may be associated with facilitated stent implantation and an increased acute luminal gain, but it has not yet been determined, whether and to what extent this procedure is associated with a reduction in the restenosis rate. IVUS-guided optimization of Palmaz-Schatz stent placement was performed in 125 consecutive patients, 64 of whom fulfilled IVUS-criteria for optimal stent placement. Another 125 patients served as the non-IVUS control group. In 107 patients (86%) of the non-IVUS control group and 105 patients (84%) of the IVUS group, angiographic follow-up was performed. The IVUS group of patients revealed a significantly lower restenosis rate of 20.9% as compared with 29.9% in the control group (P = 0.033). Patients that met IVUS criteria for optimal stent placement had a larger minimal lumen diameter immediately after stent implantation (3.13 +/- 0.44 vs. 2.95 +/- 0.47 mm; P = 0.045) and at 6-month follow-up (2.23 +/- 0.78 vs. 1.87 +/- 0.76 mm; P = 0.019) as well as a significantly lower restenosis rate (13.5% vs. 28.3%; P = 0.038) as compared with patients that did not fulfil these criteria. Our data suggest that patients fulfilling IVUS criteria for optimal stent placement demonstrate a reduced risk for the development of restenosis. Thus, IVUS investigation identifies factors predictive of restenosis after coronary stent placement.

This study was designed to assess the extent of potential discrepancies between intravascular ultrasound (IVUS) and quantitative coronary angiography (QCA) measurement of intrastent minimal luminal diameter and to evaluate the impact of dilation pressures and the balloon:artery ratio on the assessment of the minimal lumen diameter (MLD) by these imaging modalities. IVUS is recommended as an adjunct to angiography to assess stent expansion; however, the extent of potential discrepancies between the two imaging modalities is not well defined. Included were 225 patients in whom coronary Palmaz-Schatz stents were successfully placed after PTCA. IVUS and QCA were performed at the end of the intervention. We compared the MLD assessed by QCA and IVUS in the instent and reference site. The MLD assessed by IVUS and QCA were 2.68 +/- 0.41 mm and 3.08 +/- 0.47 mm (P < 0.001), respectively, at the tightest intrastent site and 3.19 +/- 0.50 mm and 3.17 +/- 0.52 ns at the reference site. There was a correlation between the dilation pressure and the difference between QCA- and IVUS-based intrastent MLD measurement (y = -0.05x + 1.11; r = -0.53; P < 0.0001). At low dilation pressures, a significant difference between the image modalities was found, but after high dilation pressures no discrepancies were detected. No relation was found with the balloon:artery ratio. These data provide clear evidence that in the case of low-pressure dilation, the exclusive reliance on data obtained by QCA will not yield sufficiently accurate information on intrastent MLD, whereas after high dilation pressure, the differences between the imaging modalities are minimized.

Objectives: This study sought to investigate the contribution of ticlopidine to the inhibition of platelet activation after coronary stent placement., Background: After coronary stenting, antiplatelet therapy with aspirin and ticlopidine improves stent patency compared with anticoagulation. However, the specific role of ticlopidine has not been elucidated., Methods: After successful coronary stent placement, we randomized 22 patients to receive ticlopidine and aspirin (ticlopidine group) and 25 to receive aspirin alone (aspirin group). Surface expression on platelets of the activated fibrinogen receptor and of P-selectin was assessed by flow cytometry., Results: In the aspirin group the percent of platelets with activated fibrinogen receptors increased between days 1 and 5 (p = 0.001), whereas there were no substantial changes in the ticlopidine group. The percent of P-selectin-positive platelets did not change significantly in the aspirin group but decreased in the ticlopidine group (p = 0.019). At day 5 after the intervention, the percent of platelets with activated fibrinogen receptors in the ticlopidine group was significantly lower (median [interquartile range]: 8.5 [3.1 to 17.8] vs. 18.1 [8.5 to 35.5], p = 0.025), and there was a trend to fewer P-selectin-positive platelets than in the aspirin group (5.8 [3.4 to 9.5] vs. 8.8 [4.0 to 15.8], p = 0.073)., Conclusions: Combined antiplatelet therapy with ticlopidine plus aspirin is superior to treatment with aspirin alone in suppressing platelet activation after coronary stenting.

Objectives: The Intracoronary Stenting and Antithrombotic Regimen (ISAR) trial is a randomized comparison of combined antiplatelet with anticoagulant therapy after coronary Palmaz-Schatz stent placement. The objective of this study was to compare early and late clinical and angiographic outcome in a subgroup of patients with stent placement for acute myocardial infarction., Background: Stenting has become a treatment option for acute myocardial infarction, but it is not known which antithrombotic regimen is more adequate after stent implantation., Methods: One hundred twenty-three patients with successful stenting after acute myocardial infarction were randomized to receive aspirin plus ticlopidine (n = 61) or intense anticoagulant therapy (n = 62). Six-month repeat angiography was performed in 101 (86.3%) eligible patients., Results: During the first 30 days after stenting, patients with antiplatelet therapy had a significantly lower clinical event rate (3.3% vs. 21.0%, p = 0.005) and stent vessel occlusion rate (0% vs. 9.7%, p = 0.03) and a trend to fewer cardiac events (1.6% vs. 9.7%, p = 0.12). After 6 months, the survival rate free of recurrent myocardial infarction was higher in patients with antiplatelet therapy (100% vs. 90.3%, p = 0.03), and the rate of stent vessel occlusion was lower (1.6% vs. 14.5%, p = 0.02). Both groups had comparable restenosis rates (26.5% vs. 26.9%, p = 0.87)., Conclusions: This study demonstrates that combined antiplatelet therapy after stent placement in patients with acute myocardial infarction is associated with an overall better clinical and angiographic outcome than anticoagulant therapy.

Objective: To test the efficacy of intravascular ultrasound (IVUS)-guided stent placement and to determine the clinical outcome during the first 30 days in those patients who were treated with antiplatelet therapy rather than anticoagulants because they met the IVUS criteria for optimal stent placement., Design: Prospective observational study., Patients: 126 patients with successful, non-elective Palmaz-Schatz stent placement., Interventions: IVUS was performed to assess the attachment of stent struts, the coverage of the dissection, and the intrastent minimal lumen area., Main Outcome Measures: Intrastent lumen area, clinical outcome during the first 30 days., Results: In all patients IVUS showed complete apposition and coverage of the dissection. In 23 patients (18%) the IVUS lumen area criterion was achieved. In 75 patients, further balloon dilatation was performed and in 41 IVUS criteria were finally fulfilled. The minimal intrastent lumen area increased from a mean (SD) of 6.81 (1.15) mm2 to 9.56 (2.61) mm2 (P < or = 0.01) between the first and final IVUS investigations. 64 patients (51%) who met the IVUS criteria were treated with aspirin (100 mg) and ticlopidine (250 mg) twice a day. During the first 30 days none of the following events occurred: death, myocardial infarction, repeat intervention, aortocoronary bypass surgery, and subacute stent thrombosis., Conclusion: The additional information provided by IVUS examination helped the operator to decide whether further dilatation was needed after a coronary stent had been placed. For patients who met the IVUS criteria for optimal stent placement, antiplatelet therapy was associated with an excellent clinical outcome during the first 30 days.

Background: The clinical benefit of coronary-artery stenting performed in conjunction with coronary angioplasty is limited by the risk of thrombotic occlusion of the stent as well as hemorrhagic and vascular complications of intensive anticoagulation. We compared antiplatelet therapy with conventional anticoagulant therapy with respect to clinical outcomes 30 days after coronary-artery stenting., Methods: After successful placement of Palmaz-Schatz coronary-artery stents, 257 patients were randomly assigned to receive antiplatelet therapy (ticlopidine plus aspirin) and 260 to receive anticoagulant therapy (intravenous heparin, phenprocoumon, and aspirin). The primary cardiac end point was a composite measure reflecting death from cardiac causes or the occurrence of myocardial infarction, aortocoronary bypass surgery, or repeat angioplasty. The primary noncardiac end point comprised death from noncardiac causes, cerebrovascular accident, severe hemorrhage, and peripheral vascular events., Results: Of the patients assigned to antiplatelet therapy, 1.6 percent reached a primary cardiac end point, as did 6.2 percent of those assigned to anticoagulant therapy (relative risk, 0.25; 95 percent confidence interval, 0.06 to 0.77). With antiplatelet therapy, there was an 82 percent lower risk of myocardial infarction than in the anticoagulant-therapy group, and a 78 percent lower need for repeat interventions. Occlusion of the stented vessel occurred in 0.8 percent of the antiplatelet-therapy group and in 5.4 percent of the anticoagulant-therapy group (relative risk, 0.14; 95 percent confidence interval, 0.02 to 0.62). A primary noncardiac end point was reached by 1.2 percent of the antiplatelet-therapy group and 12.3 percent of the anticoagulant-therapy group (relative risk, 0.09; 95 percent confidence interval, 0.02 to 0.31). Hemorrhagic complications occurred only in the anticoagulant-therapy group (in 6.5 percent). An 87 percent reduction in the risk of peripheral vascular events was observed with antiplatelet therapy., Conclusions: As compared with conventional anticoagulant therapy, combined antiplatelet therapy after the placement of coronary-artery stents reduces the incidence of both cardiac events and hemorrhagic and vascular complications.

Ultrasound heart catheters are used to measure the velocity in coronary arteries. However, the act of introducing a catheter into the vessel disturbs the very flow being measured. We used laser Doppler anemometry to measure the velocity distribution in an axially symmetric model, both with and without a catheter inserted. The catheter reduced the center-line velocity by as much as 60 percent at a distance of 2 mm downstream from the catheter, and by as much as 25 percent at a distance of 10 mm. This means the velocity measured with an ultrasound catheter does not show the maximum velocity of the undisturbed flow in the tube center. In the constriction, however, the measured velocities with the LDA and ultrasound catheter are almost the same. Thus, catheter measurements in the stenosis achieve accurate results. The velocity profile in the stenosed areas is flattened over nearly the whole cross section. The velocity is extremely reduced only close to the wall. The measurements outside of the stenosis lead to large differences which need to be studied carefully in the future. The disturbed flow finally disappeared 15 mm downstream of the catheter. The measurements were done at steady flow using a glycerine water solution with a dynamic viscosity of 4.35 mPas. In future studies, these experiments will be repeated for pulsatile flow conditions using non-Newtonian blood-like fluids.

Background: Coronary stenting in conjunction with coronary angioplasty is a valuable tool for treatment of severe coronary dissection and is effective in reducing the frequency of restenoses. Evidence is increasing that the lumen gain within the stent is negatively correlated with the rate of subacute closures and restenoses. Since the assessment of radiolucent coronary stents and complex lumen morphologies by angiography is limited, we hypothesized that the use of a balloon catheter with integrated intravascular ultrasound (IVUS) facility for stent deployment and guidance of its expansion could improve the acute lumen gain without relevant procedural prolongation., Methods and Results: Deployment of a single Palmaz-Schatz coronary stent with the combined imaging balloon catheter alone was successful in 18 of 20 patients eligible for this study. Corresponding measurements of minimal lumen diameter (MLD) by angiography and IVUS could be performed in 16 patients, revealing a close correlation between the two methods within the reference segments (3.10 +/- 0.38 and 3.08 +/- 0.43 mm, r = .79). Despite an adequate angiographic result in most patients after stent deployment, IVUS showed smaller MLD within the stented segment (2.15 +/- 0.23 mm) compared with angiography (2.63 +/- 0.26 mm, P < .0001) with a poor correlation (r = .27). To achieve IVUS criteria for optimal stent expansion (ratio of 0.9 between IVUS-assessed cross-sectional area of stent and reference segment), an average of three additional balloon inflations with higher pressure and/or a larger balloon diameter were performed without adverse effects in 15 of 16 patients who initially did not fulfill these criteria. This resulted in a significant increase in stent MLD to 2.63 +/- 0.27 mm (IVUS, P < .0001 versus initial MLD) and 2.89 +/- 0.32 mm (angiography, P < .0002 versus initial MLD) and a better correlation between the two methods (r = .60). The IVUS guidance led to a 40 +/- 15% increase of the minimal stent cross-sectional area with an additional time consumption of 21 minutes on average., Conclusions: This study demonstrates the application of a combined imaging balloon catheter for delivery and ultrasound-guided expansion of Palmaz-Schatz coronary stents. IVUS offered a comprehensive insight into the stented coronary segments, revealing a substantial overestimation of stent dimensions by angiography. IVUS guidance led to a significant improvement of stent expansion. This additional lumen gain, which was not discernible by angiography in most patients, might result in a reduction of subacute stent thromboses as well as restenoses.

Studies of the efficacy of molsidomine, previously performed on our service, demonstrated that a clear antianginal effect in the longterm treatment of angina pectoris could only be achieved with a regimen of the standard 2 mg dose when given six times daily. Consequently, since a mode of administration with a longer duration of action was implicitly desirable, the present study, carried out in eleven patients with coronary artery disease and stable, exertional angina pectoris, was undertaken to assess the antiischemic effects of 8 mg molsidomine in sustained-release form as compared with the standard 2 mg formulation according to a double-blind, randomized, crossover, placebo-controlled protocol. Additionally, plasma concentrations of molsidomine were determined to elucidate the bioavailability as well as possible correlations between plasma concentrations and antiischemic effect. As compared with placebo, after administration of 8 mg molsidomine sustained-release there were reduction in the ST-segment depression at one, three, five and eight hours of 74% (p less than 0.001), 61% (p less than 0.001), 44% (p less than 0.025), and 31% (p less than 0.01), respectively; after 2 mg molsidomine, 74% (p less than 0.001), 37% (p less than 0.025), 7% (ns) and 6% (ns), respectively. Analysis of the response of the ST-segment in the individual patients showed an unequivocal antiischemic effect with a reduction in ST-segment depression of at least 1 mm after 8 mg molsidomine sustained-release at the specified points in time in ten, five, six and four patients, respectively, and after 2 mg molsidomine in nine, five, one and no patients, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Within a relatively short period of time, nitroglycerin patches have come into widespread use for treatment of coronary artery disease in the absence of sufficient clinical data in support of their efficacy. Presently, there is still considerable controversy regarding the extent and duration of action as well as the dosage requirements. Accordingly, a study was carried out in six patients with angiographically-documented coronary artery disease, stable exercise-induced angina pectoris and reproducible ST-segment depression to analyze the effects of nitroglycerin patches, formulated to deliver 5 mg, 10 mg, 20 mg as well as 30 mg per 24 hours, respectively, on the extent of ST-segment depression. In a further study, the extent and duration of antianginal and anti-ischemic effects of nitroglycerin patches delivering 30 mg/24 hours were investigated in ten patients according to a randomized, double-blind, crossover placebo-controlled protocol. In seven of these patients, testing was again performed at 2.5 hours after repeated application (second application at 24 hours) (Figure 1). Nitroglycerin patches delivering 5 mg, 10 mg, 20 mg as well as 30 mg/24 hours, respectively, led to significant reductions in ST-segment depression at 2.5 hours of 59% (range 25 to 100%; p less than 0.025), 63% (0 to 100%, p less than 0.01), 77% (50 to 100%, p less than 0.001) as well as 82% (50 to 100%, p less than 0.005) as compared with control values (Figure 2).(ABSTRACT TRUNCATED AT 250 WORDS)

Based on studies carried out according to randomized, double-blind, crossover, placebo-controlled protocols, analysis was performed to assess the antiischemic effects of (a) 40 mg ISDN, both after acute administration and during long-term treatment with four doses daily, (b) treatment with 20 mg ISDN twice daily (at 8 a.m. and 1 p.m.), and (c) 0.8 mg sublingually administered NTG during treatment with 40 mg ISDN four times daily. After acute administration of 40 mg ISDN there was a reduction in ST-segment depression from 2.05 to 0.18 mm (p less than 0.01). During chronic treatment, statistically-significant changes were no longer detectable. Sublingual administration of 0.8 mg NTG led to a reduction of ST-segment depression during the acute phase of ISDN from 1.20 to 0.15 mm (-87%; p less than 0.01) and during chronic treatment from 1.90 to 0.90 mm (-53%; p less than 0.01). Accordingly, as compared with changes induced in the acute and placebo phases, the effectiveness of NTG during chronic ISDN treatment was diminished. After acute administration of 20 mg ISDN, ST-segment depression was reduced from 2.15 to 0.40 mm (p less than 0.01) and to a comparable degree during long-term twice-daily treatment, from 2.25 to 0.40 mm (p less than 0.01). There was a significant reduction in the rate of anginal attacks and nitrate consumption. Thus, with respect to the anti-ischemic effectiveness of ISDN, tolerance development is incurred during repeated administration. Concomitantly, the effectiveness of NTG is not essentially negated, but rather diminished.(ABSTRACT TRUNCATED AT 250 WORDS)

This study was designed to compare the antihypertensive and anti-ischemic effects of the newly developed cardioselective beta-blocking agent, betaxolol, with the non-selective agent, nadolol, both of which have hydrophilic long acting properties, over a period of 48 hours. Additionally, the study was intended to determine whether betaxolol exerts a lesser influence on pulmonary function and whether beta-1- and beta-2-adrenergic blocking agents also induce a decrease in blood glucose levels during standard bicycle ergometry for three to nine minutes, similar to that reported in association with exercise of longer duration and, if so, whether this effect can be circumvented by the use of a selective agent. Ten patients with angiographically documented CAD, stable exercise angina pectoris and reproducible ST-segment depression of at least 1 mm received on day 1, in a single blind fashion, one tablet of placebo, on day 2 and day 7, in a double-blind, randomized and cross-over fashion, 20 mg betaxolol or 80 mg nadolol, respectively. Bicycle ergometry was performed before, four, 24 and 48 hours after drug with fixed work loads, blood glucose determination before and after ergometry four hours after drug and airway resistance and maximal ventilatory capacity studies were carried out five hours after drug administration. As compared with placebo, betaxolol and nadolol led to reductions of ST-segment depression of 65% (p less than 0.01) and 74% (p less than 0.005) at four hours, of 53% (p less than 0.025) and 56% (p less than 0.01) at 24 hours and 41% (p less than 0.05) and 44% (p less than 0.05) at 48 hours.(ABSTRACT TRUNCATED AT 250 WORDS)

In previous studies it had been shown that during longterm treatment of coronary artery disease with isosorbide dinitrate (ISDN) in sustained-release form, there was no reduction in exercise-induced ST-segment depression, no decrease in the rate of anginal attacks or nitrate consumption and no changes in blood pressure or heart rate [1, 4]. To determine to what extent tolerance development is a fundamental property of longterm administration of ISDN, this study, carried out according to a randomized, double-blind, cross-over, placebo-controlled protocol (Figure 1), was undertaken. The anti-ischemic effects of 40 mg ISDN were analyzed after acute administration and during longterm treatment with 40 mg four times daily in eleven patients with stable angina pectoris and reproducible ST-segment depression. Additionally, the influence of this therapy on the anti-ischemic effects of 0.8 mg sublingually-administered nitroglycerin (GTN) was assessed in ten of the eleven patients. On acute administration, 40 mg ISDN led to a reduction in ST-segment depression at one hour from 2.05 to 0.18 mm (p less than 0.01), and at six hours from 2.35 to 1.20 mm (p less than 0.01) (Figure 2, Table 1). During chronic treatment, statistically significant changes were no longer detectable. In eight of the eleven patients there was a complete loss of effects; in the remaining three, a marked attenuation was observed (Figure 3). Acute administration of 40 mg ISDN resulted in plasma concentrations of 221 ng/ml 5-ISMN, 53 ng/ml 2-ISMN and 23 ng/ml ISDN (Figure 6, Table 2).(ABSTRACT TRUNCATED AT 250 WORDS)

A number of carefully controlled studies in recent years have unequivocally documented evidence of tolerance development with respect to anti-ischemic effects during longterm treatment with nitrates [1, 3, 4, 5, 7, 8]. To determine to what extent tolerance development can be circumvented through an interval regimen, a study was performed in ten patients with stable angina pectoris and reproducible ST-segment depression according to a randomized, double-blind, cross-over, placebo-controlled protocol. Analysis of the anti-ischemic effect of 20 mg ISDN was carried out after acute administration and during chronic treatment on an interval regimen with the administration of 20 mg ISDN in the morning (at 8 a.m.) and at midday (1 p.m.) (Figure 1). On acute administration, 20 mg ISDN led to a reduction in ST-segment depression from 2.15 to 0.40 mm (p less than 0.01) and during longterm treatment from 2.25 to 0.40 mm (p less than 0.01) (Figure 2, Table 1). After acute administration the plasma concentration of ISDN was 9 ng/ml, 2-ISMN 34 ng/ml and 5-ISMN 149 ng/ml (Figure 5, Table 2). Of the control values during longterm treatment, a detectable level was found only for 5-ISMN with a concentration of 36 ng/ml while that of both 2-ISMN and ISDN was 0 ng/ml. On renewed administration, there was an increase of ISDN to 9 ng/ml, 2-ISMN to 37 ng/ml and 5-ISMN to 208 ng/ml.(ABSTRACT TRUNCATED AT 250 WORDS)

Nisoldipine (Bay K5552), a newly-developed dehydropyridine derivative with calcium antagonistic properties, was found to have a duration of action twice as long as its parent compound, nifedipine, in laboratory experiments. To evaluate the anti-ischemic potency and duration of action, the effects of 10 mg nisoldipine after acute administration and at the end of three weeks of treatment with 10 mg twice daily were compared with those of 120 mg verapamil three times daily in a double-blind, randomized, crossover, placebo-controlled study. In twelve patients with angiographically-documented coronary artery disease and stable exertional angina pectoris, bicycle ergometry was performed before and at three and seven hours after medication on the first and 21st days of the three respective treatment phases. The control value at 8 a.m. on the 21st day corresponded with the ten-hour value on the 20th day of treatment. Between the three treatment phases, there was a one-week wash-out period during which the patients received placebo three times daily. At the time of the ergometric studies, blood was drawn for determination of verapamil plasma concentrations and, additionally, each patient recorded anginal attacks and nitrate consumption. Analysis was carried out for ST-segment depression in each patient at the highest comparable workload achieved in all treatment phases, the time to onset of 1 mm ST-segment depression as well as the response of the heart rate, systolic arterial blood pressure and the heart rate-blood pressure double-product both at rest and during exercise.(ABSTRACT TRUNCATED AT 250 WORDS)

Nitrendipine is a newly-developed calcium channel blocker derived from the dehydropyridine series which, according to experimental studies, affects marked dilation of the peripheral and coronary vessels. As compared with the parent compound nifedipine, nitrendipine exhibits a clearly more prolonged elimination half-time. This study was designed to evaluate the antihypertensive efficacy, in particular, with respect to the duration of action as well as the anti-ischemic effectiveness with a protocol encompassing as many factors as possible. In 13 patients with angiographically-documented coronary artery disease and elevated blood pressure at rest and/or during exercise, on two days separated by a three-day washout period, we investigated the effects of 20 mg nitrendipine, as compared with placebo, in a double-blind, randomized, crossover study. The systolic and diastolic arterial blood pressure as well as the heart rate were recorded prior to, at two, five, eight and twelve hours after medication and the blood pressure only at 24 hours. Blood pressure and heart rate were assessed during active standing at two hours, passive tilt at 2 1/2 hours and, together with analysis of the ST segments, before and during semisupine bicycle ergometry performed at three hours after tablet administration.(ABSTRACT TRUNCATED AT 250 WORDS)