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J Dirschinger

Publications and source records attributed to J Dirschinger.

At least 37 records · Page 2Linked to original sources
PubMed1999

Influence of balloon pressure during stent placement in native coronary arteries on early and late angiographic and clinical outcome: A randomized evaluation of high-pressure inflation.

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.

Aged↗
PubMed1999

Influence of lesion length on restenosis after coronary stent placement.

The length of a coronary lesion is a significant predictor of restenosis after balloon angioplasty. The influence of lesion length has not comprehensively been assessed after coronary stent placement. This study includes 2,736 consecutive patients with coronary stent placement. Only patients with recent or chronic occlusions before the intervention were excluded. Patients were divided in 2 groups: 573 patients with long lesions (> or = 15 mm) and 2,163 patients with short lesions (< 15 mm). There were no significant differences between the groups with respect to the procedural success rate and incidence of subacute thrombosis. One-year event-free survival was lower in patients with long lesions (73.3% vs 80.0%, p = 0.001). Six-month angiography was performed in 82.5% of the eligible patients. The incidence of binary restenosis (> or = 50% diameter stenosis) was higher in patients with long lesions (36.9% vs 27.9%, p <0.001). Similarly, patients with long lesions presented more late lumen loss than those with short lesions (1.29 +/- 0.89 vs 1.07 +/- 0.77 mm, p <0.001). Multivariate models for both binary restenosis and late lumen loss demonstrated that lesion length was an independent risk factor for restenosis. The risk was further increased by multiple stent placement and overlapping stents that were also independent risk factors of restenosis. Stented segment length did not show any independent effect. Therefore, long lesions represent an independent risk factor for restenosis after coronary stent placement. The results of this study suggest that a possible way to reduce the risk is to cover the lesion with a minimal number of nonoverlapping stents.

Angioplasty, Balloon, Coronary↗
PubMed1999

Clinical and angiographic follow-up after balloon angioplasty with provisional stenting for coronary in-stent restenosis.

The objective of this study was to assess the angiographic and clinical outcome of patients with coronary in-stent restenosis treated with balloon angioplasty with provisional stenting. The study included 375 consecutive patients with in-stent restenosis managed with balloon angioplasty alone or combined with stenting. Clinical events were recorded during a 1-year follow-up period and quantitative analysis was performed on 6-month angiographic data. Of the 373 patients (451 lesions) with a successful procedure, 273 were treated with angioplasty alone and 100 with additional stenting. Target lesion revascularization was required in 23.7% of the patients: 20.7% in patients with angioplasty and 31.0% in patients with stenting. Angiographic restenosis rate was 38.9%: 35.8% in the angioplasty group and 47.7% in the stent group. Stenting in small vessels was associated with a much higher restenosis rate than in larger vessels (65.6% vs. 37.5%, respectively; P = 0.01). Thus, repeat balloon angioplasty with provisional stenting for in-stent restenosis is a safe treatment strategy associated with a relatively favorable long-term outcome. However, the long-term results might be improved if additional stenting is avoided especially in small vessels. Cathet. Cardiovasc. Intervent. 48:151-156, 1999.

Adult↗
PubMed1998

Effect of glycoprotein IIb/IIIa receptor blockade on recovery of coronary flow and left ventricular function after the placement of coronary-artery stents in acute myocardial infarction.

BACKGROUND: Apart from its established effects on vessel patency after percutaneous coronary revascularization, glycoprotein IIb/IIIa receptor blockade by abciximab may improve myocardial perfusion by inhibition of the interaction of platelets and platelet aggregates with the microvasculature. We investigated the effect of abciximab with stent placement in acute myocardial infarction. METHODS AND RESULTS: In a prospective randomized trial, patients undergoing stenting in acute myocardial infarction within 48 hours after onset of symptoms were randomly assigned to receive either standard-dose heparin or abciximab plus low-dose heparin. Immediately after the procedure and at 14-day angiographic follow-up, we assessed flow velocity in the recanalized vessel with the Doppler wire and regional wall motion by the centerline method. End points were changes in papaverine-induced peak flow velocities and in wall motion indices. We assigned 98 patients to standard heparin and 102 to abciximab. We obtained 152 paired flow measurements and 151 paired left ventricular function studies. Residual stenoses of the treated lesions did not differ between the 2 groups. Improvement of peak flow velocity (mean [95% CI]: 18.1 cm/s [13.6 to 22.6 cm/s], n=80, versus 10.4 cm/s [5.4 to 15.4 cm/s], n=72, P=0.024) and wall motion index (0.44 SD/chord [0.29 to 0.59 SD/chord], n=79 versus 0. 15 SD/chord [0.00 to 0.30 SD/chord], n=72, P=0.007) was significantly greater in patients assigned to abciximab than in those on heparin alone. At follow-up, the abciximab group had a higher global left ventricular ejection fraction than the heparin group (62% [59% to 65%] versus 56% [53% to 59%], P=0.003). CONCLUSIONS: Abciximab had important effects beyond the maintenance of large-vessel patency. It improved the recovery of microvascular perfusion and concomitantly enhanced the recovery of contractile function in the area at risk.

Abciximab↗
PubMed1998

Vessel size and long-term outcome after coronary stent placement.

BACKGROUND: The role of coronary stenting in the treatment of patients with small vessels is not well defined. The purpose of this study was to investigate the influence of vessel size on long-term clinical and angiographic outcome after coronary stent placement. METHODS AND RESULTS: The study comprised 2602 patients with successful stent implantation for symptomatic coronary artery disease. Patients were subdivided into 3 equally sized groups (tertiles) according to vessel size, with respective ranges of <2.8, 2.8 to 3.2, and >3.2 mm. Event-free survival at 1 year was 69.5% in the group with smaller vessels, 77.5% in the second group, and 81% in the group with larger vessels (P<0.001). Late lumen loss was similar between the 3 groups (1.12+/-0.73, 1.12+/-0.79, and 1.09+/-0. 88 mm, respectively). Angiographic restenosis rate was significantly higher in the small-vessel group (38.6%, 28.4%, and 20.4% in groups 1, 2, and 3, respectively; P<0.001). The analysis identified subgroups with different risk for restenosis even among patients with small vessels. Within this group, the restenosis rate may be as low as 29.6% in patients without additional risk factors and as high as 53.5% in patients with diabetes and complex lesions. CONCLUSIONS: Patients with small vessels present a higher risk for an adverse outcome after coronary stent placement because of a higher incidence of restenosis. However, the unusually high risk for restenosis is confined to those patients with small vessels who have concomitant risk factors such as diabetes and complex lesions.

Aged↗
PubMed1998

Clinical and angiographic outcome after stent placement for chronic coronary occlusion.

A consecutive series of 132 patients with total chronic coronary occlusions were compared with 1,966 patients with stenotic lesions in terms of angiographic and clinical outcome. We concluded that patients with chronically occluded coronary lesions present a higher rate of target lesion revascularizations and angiographic restenosis than patients with stenotic lesions.

Blood Vessel Prosthesis Implantation↗
PubMed1998

Intracoronary stenting and risk for major adverse cardiac events during the first month.

BACKGROUND: Our rationale for this study was to analyze the risk for procedural failure of attempted stenting and the risk for major adverse cardiac events (MACE) after success and to develop a risk stratification protocol for successful procedures. METHODS AND RESULTS: Stenting was attempted in 2894 procedures during the 5-year study period (success in 98.3% of 3815 lesions). After failure, the MACE rate was 42.6%. The risk for failure was higher for lesions in the left circumflex coronary artery or in venous bypass grafts and after an acute occlusion before stenting; it increased with stenosis length or grade and decreased with vessel size and growing institutional experience in stenting. After success, death occurred in 0.8%, death or myocardial infarction in 2.0%, and any MACE in 3.6%. Independent risk factors for MACE were older age, diabetes, acute myocardial infarction, unstable angina, impaired left ventricular function, residual dissections, stent overlap, longer stented segments, and a postprocedural regimen without ticlopidine. Procedural factors were substantially stronger predictors than operator-independent variables available before procedures. Overall, the risk declined after the first 3 days. Two major factors exhibited time-dependent variations of their influence: while residual dissections were the dominant risk factor within the first 3 days with a reduction after that, no protective effect of ticlopidine could be identified before day 3. From these results, we derived a risk stratification protocol for individual procedures. CONCLUSIONS: These results underscore the importance of optimal angiographic results and the need for antiplatelet regimens with immediate onset. Our risk stratification protocol may guide individual postprocedural care and allow us to compare risk profiles of different study populations and to devise quality control programs for stenting.

Aged↗
PubMed1998

Interlesion dependence of the risk for restenosis in patients with coronary stent placement in in multiple lesions.

BACKGROUND: Little is known about the behavior with regard to restenosis of multiple lesions within the same patient treated with intracoronary stenting. Our objective was to test the hypothesis that there is an intrapatient dependence of restenosis between lesions. METHODS AND RESULTS: Quantitative analysis was carried out on angiograms obtained before, immediately after, and at 6 months after coronary stent placement in 1734 lesions in 1244 patients. We used a specialized logistic regression that not only accounts for intraclass correlation but also quantifies it in the form of odds ratio (OR) as the change in risk of a lesion to develop restenosis if another companion lesion had restenosis. The model was based on 23 patient- and lesion-related variables with binary restenosis (diameter stenosis > or =50%) as end point. The overall restenosis rate was 27.5%: 24.4% for single-lesion, 28.6% for double-lesion, and 33.8% for > or =3-lesion interventions. After adjustment for the influence of significant factors (hypercholesterolemia, systemic arterial hypertension, diabetes mellitus, previous PTCA, ostial lesion, location in left anterior descending coronary artery, number of stents placed, vessel size, stenosis severity, balloon-to-vessel ratio, and final result), the analysis found a significant intrapatient correlation, OR 2.5 (1.8 to 3.6). This means that in patients with multilesion interventions, the risk of a lesion to develop restenosis is 2.5 times higher if a companion lesion has restenosis, independently of the presence or absence of analyzed patient risk factors (eg, diabetes). CONCLUSIONS: This study demonstrates that there is a dependence of restenosis between coronary lesions in patients who undergo a multilesion intervention. The likelihood of restenosis for a lesion is higher when another companion lesion has also developed restenosis. Other, as yet unidentified patient factors may be the source of this intrapatient correlation of restenosis.

Aged↗
PubMed1998

Diabetes mellitus and the clinical and angiographic outcome after coronary stent placement.

OBJECTIVES: The objectives of this study were to analyze the clinical and angiographic outcome of diabetic patients with successful coronary stent placement and to compare these results with those achieved after stenting in nondiabetic patients. BACKGROUND: The outcome of diabetic patients treated with stent placement due to coronary artery disease has not been assessed comprehensively. METHODS: This study analyzes a consecutive series of patients with successful stent placement comprising 715 patients with diabetes and 2,839 patients without diabetes. Clinical one year follow-up and angiographic control at 6 months were part of the protocol. Death, myocardial infarction and target lesion revascularization were considered as adverse events. An automated edge detection system was used for the angiographic assessment. The primary clinical endpoint was event-free survival at one year. The primary angiographic endpoint was restenosis rate at 6 months (> or = 50% diameter stenosis). RESULTS: Event-free survival was significantly lower in diabetic than in nondiabetic patients (73.1 vs. 78.5%, p < 0.001). Survival free of myocardial infarction was also significantly reduced in the diabetic group (89.9 vs. 94.4% in nondiabetics, p < 0.001). The incidence of both restenosis (37.5 vs. 28.3%, p < 0.001) and stent vessel occlusion (5.3 vs. 3.4%, p = 0.037) was significantly higher in diabetic patients. Diabetes was identified as an independent risk factor for adverse clinical events and restenosis in multivariate analyses. CONCLUSIONS: Patients with diabetes mellitus have a less favorable clinical outcome at one year after successful stent placement as compared to the nondiabetic patients. The clinical follow-up was characterized by a higher incidence of death, myocardial infarction and reinterventions. Diabetic patients also demonstrated an increased risk for restenosis.

Aged↗
PubMed1997

Bimodal distribution of angiographic measures of restenosis six months after coronary stent placement.

BACKGROUND: Restenosis has been perceived as the tail end of a normal distribution of the response of the vessel to the intervention. However, recent studies have described a bimodal distribution for de novo lesions after percutaneous transluminal coronary angioplasty. This finding suggests that some lesions may be more susceptible for restenosis. Whether this holds true for a wider spectrum of lesions undergoing stent placement is not yet known. The present study analyzes the frequency distribution of angiographic indexes of restenosis 6 months after coronary stent implantation. METHODS AND RESULTS: Quantitative angiographic evaluation was performed in 1084 lesions of 1084 patients before, immediately after, and 6 months after successful Palmaz-Schatz stent placement; this represented 80.4% of patients eligible for follow-up angiography. Principal end points of the analysis were angiographic indexes of restenosis at 6 months. Twenty-two lesions that became totally occluded at follow-up were excluded from most parts of the analysis. Diameter stenosis, minimal luminal diameter (MLD), and lumen loss at 6 months did not follow a normal pattern; the bimodal pattern was demonstrated through deconvolution that yielded two separate normal components delineating two lesion populations, which developed distinctively different degrees of lumen renarrowing. The first and larger subgroup of lesions, which was less prone to restenosis, was centered around a mean value of 27% for diameter stenosis and 2.19 mm for MLD, whereas the second subgroup, with a greater tendency for restenosis, was situated around a mean value of 68% for diameter stenosis and 0.76 mm for MLD. The intersection point between the two theoretical normal distribution components was 53.5% for diameter stenosis and 1.09 mm for MLD at follow-up. CONCLUSIONS: Frequency-distribution curves of angiographic indexes of restenosis after coronary stent placement have a bimodal pattern, suggesting the existence of two distinct populations with different propensity to restenosis. These findings may encourage future efforts for the timely identification of the subset with a higher risk as the target of specific antirestenotic strategies.

Aged↗
PubMed1997

Predictive factors of restenosis after coronary stent placement.

OBJECTIVES: The objective of this study was to identify clinical, lesional and procedural factors that can predict restenosis after coronary stent placement. BACKGROUND: Coronary stent placement reduces the restenosis rate compared with that after percutaneous transluminal coronary angioplasty (PTCA). However, restenosis remains an unresolved issue, and identification of its predictive factors may allow further insight into the underlying process. METHODS: All patients with successful coronary stent placement were eligible for this study unless they had had a major adverse cardiac event during the 1st 30 days after the procedure. Of the 1,349 eligible patients (1,753 lesions), follow-up angiography at 6 months was performed in 80.4% (1,084 patients, 1,399 lesions). Demographic, clinical, lesional and procedural data were prospectively recorded and analyzed for any predictive power for the occurrence of late restenosis after stenting. Restenosis was evaluated by using three outcomes at follow-up: binary restenosis as a diameter stenosis > or =50%, late lumen loss as lumen diameter reduction and target lesion revascularization (TLR) as any repeat PTCA or coronary artery bypass surgery involving the stented lesion. RESULTS: Multivariate analysis demonstrated that diabetes mellitus, placement of multiple stents and minimal lumen diameter (MLD) immediately after stenting were the strongest predictors of restenosis. Diabetes increased the risk of binary restenosis with an odds ratio (OR) [95% confidence interval] of 1.86 [1.56 to 2.16] and the risk of TLR with an OR of 1.45 [1.11 to 1.80]. Multiple stents increased the risk of binary restenosis with an OR of 1.81 [1.55 to 2.06] and that of TLR with an OR of 1.94 [1.66 to 2.22]. An MLD <3 mm at the end of the procedure augmented the risk of binary restenosis with an OR of 1.81 [1.55 to 2.06] and that of TLR with an OR of 2.05 [1.77 to 2.34]. Classification and regression tree analysis demonstrated that the incidence of restenosis may be as low as 16% for a lesion without any of these risk factors and as high as 59% for a lesion with a combination of these risk factors. CONCLUSIONS: Diabetes, multiple stents and smaller final MLD are strong predictors of restenosis after coronary stent placement. Achieving an optimal result with a minimal number of stents during the procedure may significantly reduce this risk even in patients with adverse clinical characteristics such as diabetes.

Aged↗
PubMed1997

Restenosis after coronary stent placement and randomization to a 4-week combined antiplatelet or anticoagulant therapy: six-month angiographic follow-up of the Intracoronary Stenting and Antithrombotic Regimen (ISAR) Trial.

BACKGROUND: Platelets and mural thrombus at the lesion site may play a key role in initiating the restenosis process after coronary interventions. The ISAR Trial provides a comparison of the outcomes of patients randomized to two different antithrombotic regimens administered for 4 weeks after successful coronary stent placement: combined antiplatelet therapy (aspirin plus ticlopidine) or a conventional anticoagulant regimen (phenprocoumon with initial overlapping heparin plus aspirin). Within the first 4 weeks after stent placement, combined antiplatelet therapy has been associated with a significant reduction of ischemic complications. In the present study, we examined whether combined antiplatelet therapy administered for 4 weeks after stent placement is able to reduce the process of restenosis at 6 months. METHODS AND RESULTS: Of 517 patients initially randomized, 496 were eligible for 6-month angiographic follow-up. Scheduled angiography was performed in 432 of the eligible patients (87.1%), 216 in each group. In a comparison of the two groups, there were no significant differences in clinical and procedural variables or in qualitative and quantitative lesion characteristics before and after stenting. At 6 months, minimal luminal diameter was 1.95+/-0.86 mm in the group with initial combined antiplatelet therapy and 1.90+/-0.87 mm in the group with initial anticoagulant therapy (P=.55). Late lumen loss was 1.10+/-0.81 and 1.15+/-0.75 mm (P=.54), and the restenosis rate was 26.8% and 28.9%, respectively (P=.70). Target lesion revascularization rate was 14.6% in the antiplatelet therapy group and 15.6% in the anticoagulant therapy group (P=.85). CONCLUSIONS: This study shows that combined antiplatelet therapy (aspirin plus ticlopidine) administered for 4 weeks after coronary Palmaz-Schatz stent placement does not result in a detectable benefit for the prevention of restenosis compared with conventional anticoagulant therapy (phenprocoumon with initial overlapping heparin plus aspirin).

Administration, Oral↗
PubMed1997

Coronary stent placement in patients with acute myocardial infarction: comparison of clinical and angiographic outcome after randomization to antiplatelet or anticoagulant therapy.

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.

Anticoagulants↗
PubMed1997

Comparative in-vitro validation of eight first- and second-generation quantitative coronary angiography systems.

BACKGROUND: It is known that first-generation quantitative coronary angiography (QCA) systems overestimate small vessel sizes owing to the point-spread function of the respective X-ray imaging chain. With second-generation systems new algorithms were introduced to correct for this source of error. OBJECTIVE: To evaluate the efficiency of the modified contour detection algorithms. METHODS: Six second-generation QCA systems (CMS, QANSAD, AWOS, CAAS II, Cardio 500, and Angioimage) were validated and compared with first-generation systems (CAAS and ARTREK). By using an arterial phantom consisting of stenotic and nonstenotic glass tubes (of diameters 0.5-5.0 mm) the accuracy and precision of each analysis system, as well as their additional accuracy and precision values for phantom diameters < or = 1.0 mm were determined. RESULTS: All systems had high accuracy and precision values, but first-generation systems overestimated small vessel diameters. With second-generation systems a significantly improved accuracy in the submillimeter range (an accuracy within +/-0.028 mm) was obtained. This improvement was accompanied by a moderate reduction in precision in the submillimeter range. CONCLUSION: The new algorithms of the second-generation QCA systems allow accurate and reliable measurements of small coronary dimensions and, therefore, precise analysis of coronary stenoses of moderate-to-high grade seems feasible with the improved accuracy of the new systems.

Algorithms↗
PubMed1992

McLeod syndrome: a distinct form of neuroacanthocytosis. Report of two cases and literature review with emphasis on neuromuscular manifestations.

McLeod syndrome was originally described on the basis of a specific blood group phenotype with weak expression of Kell antigens. This erythrocyte abnormality also causes acanthocytosis. The haematological findings are associated with abnormalities in other organ systems, including neuromuscular manifestations. A 51-year-old patient was followed up for 11 years. He presented with persistent muscle creatine kinase elevation and progressive heart disease and later developed a slowly progressive neuropathy and choreic movements. His younger brother presented with grand mal seizures, involuntary movements and high muscle creatine kinase when aged 43 years. Clinical myopathy was absent in both, yet muscle biopsy showed mild myopathic changes. The presence of a motor axonopathy was supported by electrophysiological findings. One brother also showed sensory axonopathy. The movement disorder suggested accompanying basal ganglia dysfunction. Earlier reports of McLeod syndrome are reviewed with respect to neuromuscular involvement. Absence of the Kx membrane protein seems to be the cause of this multi-system disorder.

Acanthocytes↗
PubMed1991

Clinical comparison of nitrates and sydnonimines.

Organic nitrates and the sydnominine-derivative, molsidomine, exhibit similar pharmacodynamic actions. Venous vasodilatation leads to a decrease in ventricular pressures and volumes and, consequently, to a reduction in myocardial oxygen requirement; coronary vasodilatation enhances myocardial oxygen supply to hypoperfused poststenotic regions. At the molecular level, relaxation of vascular smooth muscle is due to nitric oxide (NO) delivery; with nitrates, this is coupled to the presence of thiol groups, the depletion of which is considered the cause of nitrate tolerance. At least one further site in the nitrate bioconversion cascade, possibly at the level of NO generation appears to be involved in tolerance development, which may also affect the non-nitrate vasodilator SIN-1. Nitrate tolerance is a clinically relevant problem incurred with multiple daily doses or continuous nitrate administration which lead to nearly constant, high plasma concentrations. Effective long-term therapy with nitrates can only be carried out with an interval treatment which is associated with relatively low and substantially fluctuating plasma concentrations. In contrast, during long-term treatment with molsidomine, tolerance development is not a clinically-relevant problem, so that with multiple daily doses, an effect can be provided over 24 h. With regard to maximal anti-ischaemic and haemodynamic effects, organic nitrates and molsidomine are similar. Molsidomine represents an alternative to nitrate interval treatment, or, respectively can be used as an adjunct to interval treatment should it be necessary to bridge the therapeutic gap.

Coronary Disease↗
PubMed1990

Nitrate therapy in patients with coronary artery disease--preparations and doses with and without development of tolerance.

Rapid tolerance development with respect to hemodynamic, anti-anginal and anti-ischemic effects is a relevant clinical problem associated with any longterm treatment with nitroglycerin, isosorbide dinitrate or isosorbide 5-mononitrate. Tolerance occurs with any dosing regimen that results in nitrate accumulation in the plasma or nearly-constant plasma concentrations, as is the case with multiple daily doses of oral nitrates or continuous application of transdermal patch systems. Nitrate tolerance can be prevented by the interval treatment. This encompasses incorporation of an application-free interval which prevents meaningful nitrate accumulation such that, from a low baseline level, renewed drug administration leads to an increase in the nitrate plasma concentration greater than 2.5-fold. From controlled studies, dosing regimens for interval treatment proven to be effective have been designated for isosorbide dinitrate and isosorbide 5-mononitrate, as well as for transdermal nitroglycerin patch systems. The early attenuation of nitroglycerin, seen within the first 12 h of its use, according to the results of a recently completed study, can be counteracted through continuously increasing plasma concentrations during this period. Interval treatment does not enable 24-h therapeutic protection. Studies with ST-Holter monitoring, however, have shown that adequate coverage can be provided for the period during which the vast majority of ischemic episodes occur. Clinically-relevant rebound phenomena do not occur during interval treatment. Pharmacological approaches to prevent nitrate tolerance, on the basis of the limited and, in part, conflicting data available, do not provide an alternative to interval treatment.

Administration, Cutaneous↗