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Aims The BRIE trial is a registry evaluating the safety and performance of90 Sr delivered locally (Beta-Cath TM system of Novoste) to de-novo and restenotic lesions in patients with up to two discrete lesions in different vessels.Methods and Results In total, 149 patients (175 lesions) were enrolled; 62 treated with balloons and 113 with stents. The restenosis rate, the minimal luminal diameter and the late loss were determined in three regions of interest: (a) in a subsegment of 5mm containing the original minimal luminal diameter pre-intervention termed target segment; (b) the irradiated segment, 28mm in length, and (c) the entire analysed segment, 42mm in length, termed the vessel segment. Binary restenosis was 9·9% for the target segment, 28·9% for the irradiated segment, and 33·6% for the vessel segment. These angiographic results include 5·3% total occlusions. Excluding total occlusions binary restenosis was 4·9%, 25% and 29·9%, respectively. At 1 year the incidence of major adverse cardiac events placed in a hierarchical ranking were: death 2%, myocardial infarction 10·1%, CABG 2%, and target vessel revascularization 20·1%. The event-free survival rate was 65·8%. Non-appropriate coverage of the injured segment by the radioactive source termed geographical miss affected 67·9% of the vessels, and increased edge restenosis significantly (16·3% vs 4·3%, P=0·004). It accounted for 40% of the treatment failures.Conclusion The results of this registry reflect the learning process of the practitioner. The full therapeutic potential of this new technology is reflected by the restenosis rate at the site of the target segment. It can only be unravelled once the incidence of late vessel occlusion and geographical miss has been eliminated by the prolonged use of thienopyridine, the appropriate training of the operator applying this new treatment for restenosis prevention, and the use of longer sources. Copyright 2002 The European Society of Cardiology. Published by Elsevier Science Ltd. All rights reserved. [ABSTRACT FROM PUBLISHER]

Background Edge restenosis is a major problem after radioactive stenting. The cold-end stent has a radioactive mid-segment (15·9mm) and non-radioactive proximal and distal 5·7mm segments. Conceptually this may negate the impact of negative vascular remodelling at the edge of the radiation.Method and Results ECG-gated intravascular ultrasound with three-dimensional reconstruction was performed post-stent implantation and at the 6-month follow-up to assess restenosis within the margins of the stent and at the stent edges in 16 patients. Angiographic restenosis was witnessed in four patients, all in the proximal in-stent position. By intravascular ultrasound in-stent neointimal hyperplasia, with a >50% stented cross-sectional area, was seen in eight patients. This was witnessed proximally (n=2), distally (n=2) and in both segments (n=4). Echolucent tissue, dubbed the ‘black hole’ was seen as a significant component of neointimal hyperplasia in six out of the eight cases of restenosis. Neointimal hyperplasia was inhibited in the area of radiation: Δ neointimal hyperplasia=3·72mm3(8·6%); in-stent at the edges of radiation proximally and distally Δ neointimal hyperplasia was 7·9mm3(19·0%) and 11·4mm3(25·6%), respectively (P=0·017). At the stent edges there was no significant change in lumen volume.Conclusions Cold-end stenting results in increased neointimal hyperplasia in in-stent non-radioactive segments. [ABSTRACT FROM PUBLISHER]

Aims This study reports the clinical outcome, up to 17 years, of the first 856 consecutive patients treated by coronary angioplasty at a single centre and attempts to identify a subgroup of patients at low risk of adverse events.Methods and Results Follow-up status was established via hospital and general practitioner records and the civil registry. Median follow-up was 16 years. The overall 5-, 10-, 15- and 17-year survival was 90%, 78%, 64% and 58%, respectively and corresponding event-free survival was 53%, 33%, 22% and 19%. After 32% of patients had experienced a major adverse cardiac event in the first year, the annual coronary re-intervention incidence thereafter and, even beyond year 10, remained at 2%–3%. Using multivariable Cox regression, significant independent predictors of mortality were advanced age, diabetes, multivessel disease and impaired left ventricular function at the time of PTCA. A subgroup of 26% of the patients with none of these risk factors had a survival rate similar to the general Dutch population matched for age and gender (at 5 years: 96%, at 10 years: 89% and at 15 years: 83%).Conclusion Although the majority of patients (>80%) experienced a further cardiac event during the 17 years after their first angioplasty procedure, in those non-diabetics under 60 years with single-vessel disease and good left ventricular function, prognosis was similar to the general population. [ABSTRACT FROM PUBLISHER]

This study investigated the relation between the extent of morphological damage, observed 2 hours after reperfusion which followed either 30 or 60 minutes of ischaemia, and the long-term recovery of regional myocardial function after the same periods of ischaemia. The nature of the morphological changes in this in vivo pig model is akin to that described in an Langendorff preparation. It is shown that sarcolemmal disruption, after 60 minutes of ischaemia followed by reperfusion, is associated with aggregation of sarcolemmal intramembranous particles and formation of multilamellar, lipidic structures suggesting a reorganization of the phospholipids, lateral phase separation and fusion events. However, thirty minutes of ischaemia with reperfusion did not lead to sarcolemmal disruption although extrusion of lipidic material, observed in a fraction of the mitochondria in each muscle cell, occurred independent of the duration of ischaemia. In another group of animals the regional myocardial function was assessed by cross-sectional echocardiography after 2 weeks of recovery. This correlated with the degree to which sarcolemmal integrity in the biopsies was maintained. The observed destruction of the sarcolemma was best explained in terms of bilayer destabilization, mediated by an increase in calcium and hydrogen ions in the cytosol of the myocardial cell. [ABSTRACT FROM PUBLISHER]

A new model for the electrical induction of coronary thrombosis in the pig is described. In 35 out of 47 experiments (74%) a 100% occluding thrombus developed. In 16 experiments (34%), at least one episode of coronary spasm occurred at the site of electrical stimulation. Flow in the region of the left ventricle supplied by the thrombosed coronary artery decreased from 1·04 ± 0·21 to 0·09 ± 0·04 ml/min/g tissue (mean ± SD). Histological examination showed that the lesion caused by the electrical current occurred through the arterial wall and was quite discrete, measuring a few millimetres in length. Scanning and transmission electron microscopy revealed that the occlusions were caused by typical platelet thrombi. Lysis of the thrombi by the intracoronary administration of porcine plasmin was successful in 15 out of 19 animals (79%). Preliminary results show that thrombolysis after 40 min occlusion restores flow to nearly base-line values, but does not improve regional function in the first 3 h. [ABSTRACT FROM PUBLISHER]

During the last 10 years there has been a growing interest in the use of domestic pigs in the study of various aspects of nivocardial ischemia. While most studies are still performed on dogs, a number of scientific and non-scientific (emotional) reasons have led to a shift from the use of the former to that of domestic pigs. In this paper the suitability of the pig for cardiovascular studies is dealt with, with special attention to the coronary and collateral circulation. A number of manifestations of myocardial ischemia and reperfusion of previously underperfused myocardium such as ventricular arrhythmias, metabolism and recovery of function are discussed. Where possible, the comparison is made with findings in the dog. [ABSTRACT FROM PUBLISHER]

Aims: To report the 4-month angiographic and 6-month clinical follow-up in first-in-man study using the tacrolimus-eluting bioabsorbable polymer-coated cobalt-chromium MAHOROBA stent., Methods and Results: A total of 47 patients with either stable angina or unstable angina, or silent myocardial ischaemia, based on a de novo coronary stenosis that could be covered by a single 18 mm stent in a native coronary artery with a diameter between 3.0 and 3.5 mm were enrolled at three sites. The primary endpoint was in-stent late loss at 4 months. The secondary endpoints include %volume obstruction of the stents assessed by intravascular ultrasound (IVUS) at 4 months and major adverse cardiac events (MACE) at 6 months. Forty-seven patients were enrolled. Procedural success was achieved in 97.9%. At 4-month follow-up, in-stent late loss was 0.99 +/- 0.46 mm, whereas in-stent %volume obstruction in IVUS was 34.8 +/- 15.8%. At 6 months, there were no deaths, but 2 patients suffered from a myocardial infarction and 11 patients required ischaemia-driven repeat revascularization. The composite MACE rate was 23.4%., Conclusion: This tacrolimus-eluting stent failed to prevent neointimal hyperplasia, despite the theoretical advantages of the tacrolimus, which has less inhibitory effects on endothelial cells than smooth muscle cells.

Aims: Stem cell therapy after myocardial infarction (MI) has been studied in models of permanent coronary occlusion. We studied the effect of intracoronary administration of unselected bone marrow (BM) and mononuclear cells (MNC) in a porcine model of reperfused MI., Methods and Results: In 34 swine, the left circumflex coronary artery was balloon-occluded for 2 h followed by reperfusion. Ten swine without MI served as controls. All swine underwent magnetic resonance imaging (MRI) 1 week post-MI. The next day, 10 of the 30 surviving MI swine received BM, 10 other MI swine received MNC, and the remaining MI swine received medium intracoronary. Four weeks later, all swine underwent a follow-up MRI. One week after MI, end-diastolic volume (92+/-16 mL) and left ventricular (LV) weight (78+/-12 g) were greater, whereas ejection fraction (40+/-8%) was lower than in controls (69+/-11 mL, 62+/-13 g, and 53+/-6%). Injection of BM or MNC had no effect on the MI-induced changes in global or regional LV-function. However, there was a significant reduction in infarct size 4 weeks after MNC injection (-6+/-3%) compared with the medium (-3+/-5%)., Conclusion: Intracoronary injection of BM or MNC in swine does not improve regional or global LV-function 4 weeks after injection. However, a reduction in infarct-size was noted after MNC injection.

Aims: To compare the global characteristics of patients with and without evidence of plaque rupture (PR) in their coronary tree and to evaluate the phenotype of ruptured plaques using intravascular ultrasound (IVUS) radiofrequency data analysis (IVUS-VH)., Methods and Results: Forty patients underwent three-vessel IVUS-VH interrogation. Twenty-eight PRs were diagnosed in 26 vessels (25.7% of the vessels studied) of 20 patients (50% of the population). Ruptures located in the left anterior descending were clustered in the proximal part of the vessel, whereas ruptures located in the right coronary artery were more distally located (P=0.02). Patients with at least one PR presented larger body mass index (BMI) (28.4+/-3.7 vs. 25.8+/-2.6 kg/m(2), P=0.01) and plaque burden (40.7+/-7.6 vs. 33.7+/-8.4%, P=0.01) than patients without rupture, despite showing similar lumen cross-sectional area (9.6+/-3.3 vs. 9.2+/-2.3 mm(2), P=0.60). Among current smokers, 66.7% presented a PR in their coronary tree. Finally, PR sites showed a higher content of necrotic core compared with minimum lumen area sites (17.48+/-10.8 vs. 13.10+/-6.5%, P=0.03) and a trend towards higher calcified component., Conclusion: Patients with at least one PR in their coronary tree presented larger BMI and worse IVUS-derived characteristics compared with patients without PR.

In order to study the safety of 'rescue' strategies in the treatment of patients with failed thrombolysis, all 548 patients admitted with evolving myocardial infarction to the Thoraxcenter, Rotterdam, from January 1997 until April 1999 were reviewed. Of these patients, 49% had received thrombolysis. Of patients treated with thrombolysis and not referred from other hospitals (n = 154) 36% received rescue therapy for failed thrombolysis. Three rescue therapies were used after failed thrombolysis: percutaneous coronary intervention (74%), retreatment with thrombolysis (39%) and platelet glycoprotein (GP) IIb/IIIa receptor blockers (53%), often in combination. Platelet GP IIb/IIIa receptor blockers were administered in 64% of patients treated with rescue percutaneous coronary intervention. Major bleeding occurred in 14% of all thrombolysis treated patients, and in 30% of patients who received multiple rescue therapies. Bleeding was related to heparin usage and platelet GP IIb/IIIa receptor blockers, as was the insertion of catheters for percutaneous coronary intervention or intra-aortic balloon pumps. Major bleeding resulted in one death due to a ruptured ventricle, one haemorrhagic stroke, and three cases of tamponade for which surgery was needed. Four of these patients had received combination rescue therapy. Rescue therapy is a widely used strategy for failed thrombolysis, but is associated with a high bleeding rate. Alternative reperfusion strategies to avoid failed thrombolysis should be considered in high risk patients., (Copyright 2002 The European Society of Cardiology.)

Aims: The BRIE trial is a registry evaluating the safety and performance of (90)Sr delivered locally (Beta-Cath TM system of Novoste) to de-novo and restenotic lesions in patients with up to two discrete lesions in different vessels., Methods and Results: In total, 149 patients (175 lesions) were enrolled; 62 treated with balloons and 113 with stents. The restenosis rate, the minimal luminal diameter and the late loss were determined in three regions of interest: (a) in a subsegment of 5mm containing the original minimal luminal diameter pre-intervention termed target segment; (b) the irradiated segment, 28 mm in length, and (c) the entire analysed segment, 42 mm in length, termed the vessel segment. Binary restenosis was 9.9% for the target segment, 28.9% for the irradiated segment, and 33.6% for the vessel segment. These angiographic results include 5.3% total occlusions. Excluding total occlusions binary restenosis was 4.9%, 25% and 29.9%, respectively. At 1 year the incidence of major adverse cardiac events placed in a hierarchical ranking were: death 2%, myocardial infarction 10.1%, CABG 2%, and target vessel revascularization 20.1%. The event-free survival rate was 65.8%. Non-appropriate coverage of the injured segment by the radioactive source termed geographical miss affected 67.9% of the vessels, and increased edge restenosis significantly (16.3% vs 4.3%, P=0.004). It accounted for 40% of the treatment failures., Conclusion: The results of this registry reflect the learning process of the practitioner. The full therapeutic potential of this new technology is reflected by the restenosis rate at the site of the target segment. It can only be unravelled once the incidence of late vessel occlusion and geographical miss has been eliminated by the prolonged use of thienopyridine, the appropriate training of the operator applying this new treatment for restenosis prevention, and the use of longer sources., (Copyright 2002 The European Society of Cardiology. Published by Elsevier Science Ltd. All rights reserved.)

Aims: Intracoronary radiation is a promising therapy potentially reducing restenosis following catheter-based interventions. Currently, only limited data on this treatment are available. The feasibility and outcome in daily routine practice, however, is unknown., Methods and Results: In 100 consecutive patients, intracoronary beta-radiation was performed with a (90)Strontium system (Novoste Beta-Cathtrade mark) following angioplasty. Predominantly complex (73% type B2 and C) and long lesions (length 24.3+/-15.3 mm) were included (37% de novo, 19% restenotic and 44% in-stent restenotic lesions). Radiation success was 100%. Mean prescribed dose was 19.8+/-2.5 Gy. A pullback procedure was performed in 19% lesions. Geographic miss occurred in 8% lesions. Periprocedural thrombus formation occurred in four lesions, dissection in nine lesions. During hospital stay, no death, acute myocardial infarction, or repeat revascularization was observed. Major adverse cardiac events occurred predominantly between 6 and 12 months after the index procedure with major adverse cardiac event-free survival of 66% at 12 months (one death, 10 Q-wave myocardial infarctions, 23 target vessel revascularizations; ranked for worst event)., Conclusion: Routine catheter-based intracoronary beta-radiation therapy after angioplasty is safe and feasible with a high acute procedural success. The clinical 1-year follow-up showed delayed occurrence of major adverse cardiac events between 6 and 12 months after the index procedure., (Copyright 2001 The European Society of Cardiology. Published by Elsevier Science Ltd. All rights reserved.)

Aims: We sought to compare the effect of intracoronary beta-radiation on the vessel dimensions in de novo lesions using three-dimensional intravascular ultrasound quantification after balloon angioplasty and stenting., Methods and Results: Forty patients (44 vessels; 28 balloon angioplasty and 16 stenting) treated with catheter-based beta-radiation and 18 non-irradiated control patients (18 vessels; 10 balloon angioplasty and 8 stenting) were investigated by means of three-dimensional volumetric intravascular ultrasound analysis post-procedure and at 6-8 months follow-up. Total vessel (EEM) volume enlarged after both balloon angioplasty and stenting (+37 mm(3) vs +42 mm(3), P=ns), but vessel wall volume (plaque plus media) also increased similarly (+33 mm(3) vs +49 mm(3), P=ns) in the irradiated patients. Lumen volume remained unchanged in both groups (+3 mm(3) vs -7 mm(3), P=ns). In the stent-covered segments, neointima at follow-up was significantly smaller in the irradiated group than the control group (8 mm(3) vs 27 mm(3), P=0.001, respectively), but the total amount of tissue growth was similar in both groups (33 mm(3) vs 29 mm(3), P=ns)., Conclusions: Intracoronary beta-radiation induces vessel enlargement after balloon angioplasty and/or stenting, accommodating tissue growth. Additional stenting may not play an important role in the prevention of constrictive remodelling in the setting of catheter-based intracoronary beta-radiotherapy., (Copyright 2002 The European Society of Cardiology.)

Aims: Coronary stenting is limited by a 10%-60% restenosis rate due to neointimal hyperplasia. Sirolimus is a macrocyclic lactone agent that interacts with cell-cycle regulating proteins and inhibits cell division between phases G1 and S1. The hypothesis tested in this study is that local delivery of sirolimus with an eluting stent can prevent restenosis., Methods and Results: Fifteen patients were treated with 18 mm sirolimus eluting BX VELOCITY stents. Quantitative angiography and three-dimensional quantitative intravascular ultrasound were performed at implantation and at the 6 months follow-up. All stent implantations were successful. One patient died on day 2, of cerebral haemorrhage and one patient suffered a subacute stent occlusion due to edge dissection (re-PTCA, CKMB 42). At 9 months no further adverse events had occurred and all patients were angina free. Quantitative coronary angiography revealed no change in minimal lumen diameter and percent diameter stenosis and hence no in-lesion or in-stent restenosis. Quantitative intravascular ultrasound showed that intimal hyperplasia volume and percent obstruction volume at follow-up were negligible at 5.3 mm(3)and 1.8%, respectively. No edge effect was observed in the segments proximal and distal to the stents., Conclusion: Implantation of a sirolimus-eluting stent seems to effectively prevent intimal hyperplasia., (Copyright 2001 The European Society of Cardiology.)

Background: Edge restenosis is a major problem after radioactive stenting. The cold-end stent has a radioactive mid-segment (15.9 mm) and non-radioactive proximal and distal 5.7 mm segments. Conceptually this may negate the impact of negative vascular remodelling at the edge of the radiation., Method and Results: ECG-gated intravascular ultrasound with three-dimensional reconstruction was performed post-stent implantation and at the 6-month follow-up to assess restenosis within the margins of the stent and at the stent edges in 16 patients. Angiographic restenosis was witnessed in four patients, all in the proximal in-stent position. By intravascular ultrasound in-stent neointimal hyperplasia, with a >50% stented cross-sectional area, was seen in eight patients. This was witnessed proximally (n=2), distally (n=2) and in both segments (n=4). Echolucent tissue, dubbed the 'black hole' was seen as a significant component of neointimal hyperplasia in six out of the eight cases of restenosis. Neointimal hyperplasia was inhibited in the area of radiation: Delta neointimal hyperplasia=3.72 mm3 (8.6%); in-stent at the edges of radiation proximally and distally Delta neointimal hyperplasia was 7.9 mm3 (19.0%) and 11.4 mm3 (25.6%), respectively (P=0.017). At the stent edges there was no significant change in lumen volume., Conclusions: Cold-end stenting results in increased neointimal hyperplasia in in-stent non-radioactive segments., (Copyright 2001 The European Society of Cardiology.)

Aims: This study is the contribution by the Thoraxcenter, Rotterdam, to the European(32)P Dose Response Trial, a non-randomized multicentre trial to evaluate the safety and efficacy of the radioactive Isostent in patients with single coronary artery disease., Methods and Results: The radioactivity of the stent at implantation was 6--12 microCi. All patients received aspirin indefinitely and either ticlopidine or clopidogrel for 3 months. Quantitative coronary angiography measurements of both the stent area and the target lesion (stent area and up to 5 mm proximal and distal to the stent edges) were performed pre- and post-procedure and at the 5-month follow-up. Forty-two radioactive stents were implanted in 40 patients. Treated vessels were the left anterior descending coronary artery (n=20), right coronary artery (n=10) or left circumflex artery (n=10). Eight patients received additional non-radioactive stents. Lesion length measured 10+/-3 mm with a reference diameter of 3.07+/-0.69 mm. Minimal lumen diameter increased from 0.98+/-0.53 mm pre-procedure to 2.29+/-0.52 mm (target lesion) and 2.57+/-0.44 mm (stent area) post-procedure. There was one procedural non-Q wave myocardial infarction, due to transient thrombotic closure. Thirty-six patients returned for angiographical follow-up. Two patients had a total occlusion proximal to the radioactive stent. Of the patent vessels, none had in-stent restenosis. Edge restenosis was observed in 44%, occurring predominantly at the proximal edge. Target lesion revascularization was performed in 10 patients and target vessel revascularization in one patient. No additional clinical end-points occurred during follow-up. The minimal lumen diameter at follow-up averaged 1.66+/-0.71 mm (target lesion) and 2.12+/-0.72 (stent area); therefore late loss was 0.63+/-0.69 (target lesion) and 0.46+/-0.76 (stent area), resulting in a late loss index of 0.65+/-1.15 (target lesion) and 0.30+/-0.53 (stent area)., Conclusion: These results indicate that the use of radioactive stents is safe and feasible, however, the high incidence of edge restenosis makes this technique currently clinically non-applicable., (Copyright 2001 The European Society of Cardiology.)

Aims: There is increased late loss in luminal diameter following long-term coronary stenting, compared with balloon angioplasty. We evaluated short- and long-term vessel wall injury after experimental implantation of two stent designs as well as balloon angioplasty and their relationship to neointimal hyperplasia., Methods and Results: Wiktor stents and Palmaz-Schatz stents were implanted in normal coronary arteries of pigs (balloon/artery ratio: 0.9-1.1). In control coronary arteries, balloon angioplasty was performed. At 1, 4 and 12 weeks, the vessel injury score, neointimal thickness and inflammatory response were assessed by histology. The vessel injury score increased over time in both Wiktor and Palmaz-Schatz stents: 0.9 +/- 0.1, 1.5 +/- 0.5 and 1.7 +/- 0.6 (mean +/- SD) for Wiktor stents and 0.7 +/- 0.2, 1.0 +/- 0.1 and 1.2 +/- 0.3 for Palmaz-Schatz stents at 1, 4 and 12 weeks follow-up, respectively. No increase in injury was seen in balloon angioplasty controls. Inflammation was seen in both stented groups but was absent 12 weeks after balloon angioplasty. No strong correlation between injury and neointimal thickness was apparent., Conclusion: Stents induce chronic injury in contrast to balloon angioplasty. Stent design (coil vs slotted tube) as well as inflammation may influence vessel response.

We studied the acute effects of the calcium antagonist nisoldipine in 10 conscious pigs with chronic heart failure. Left ventricular dysfunction was induced by permanent ligation of the left circumflex coronary artery. Two to three weeks after myocardial infarction the effects of four consecutive 10 min intravenous infusions of nisoldipine (0.05; 0.1; 0.25 and 0.5 micrograms kg-1 min-1) or its solvent on systemic haemodynamics were evaluated. In addition, we used the radioactive microsphere technique to study the distribution of cardiac output after each dose of nisoldipine. Nisoldipine significantly (P less than 0.05) increased heart rate (from 144 +/- 9 to 161 +/- 8 beats min-1), cardiac output (from 2.1 +/- 0.1 to 2.9 +/- 0.2 l min-1), stroke volume (from 14 +/- 1 to 18 +/- 1 ml) and left ventricular dP/dtmax (from 2600 +/- 100 to 3500 +/- 250 mmHg s-1), but had no effect on arterial blood pressure. Left ventricular end-diastolic pressure (from 19 +/- 2 to 16 +/- 1 mmHg) and systemic vascular resistance (from 52 +/- 3 to 37 +/- 3 mmHg min l-1) decreased after nisoldipine. The nisoldipine-induced increase in cardiac output did not affect blood flow to the kidneys, brain, liver or skin, but perfusion of the stomach (84%), adrenals (84%) and normal myocardium (from 200 +/- 25 to 321 +/- 38 ml min-1 100 g-1) as well as infarcted myocardium (from 41 +/- 8 to 61 +/- 19 ml min-1 100 g-1) increased significantly.(ABSTRACT TRUNCATED AT 250 WORDS)

An overview is provided of current thinking regarding the origin(s) of atherosclerosis on the basis of clinical evidence, experimental models and pharmacological investigations with calcium antagonists. Because this group of drugs inhibits the influx of Ca2+ into the smooth muscle cell of the cardiovascular wall, it has been argued that when endothelial damage is anticipated or has occurred, the 'protective' action of calcium antagonists might avoid, delay or even help to repair the calcium overload seen with cell membrane damage. In the real world the situation must be far more complex as will become evident but as a concept the avoidance of Ca2+ overloading is enticing. In fact, based on circumstantial evidence, a major clinical trial is currently in progress in which the long term effect of nifedipine on coronary atherosclerosis is being evaluated in a double blind randomized fashion. The end-point of this study lies in the reduction of the severity and number of coronary artery lesions. Although not yet completed, the design and goals of that study are provided.