Effect of 450-mg loading dose of clopidogrel on platelet function in Japanese patients undergoing coronary stent placement.

Usefulness of higher (>300 mg) loading doses of clopidogrel has been demonstrated in studies from the United States and Europe. The present study evaluated platelet aggregation after the administration of a 450-mg loading dose of clopidogrel in Japanese patients undergoing coronary stenting. Platelet aggregation was serially measured at baseline, and 2, 4, 6, and 8 h after 450-mg clopidogrel loading in 25 patients undergoing coronary stenting. Platelets were stimulated with 5 and 20 micromol/l adenosine diphosphate (ADP) and aggregation was assessed by optical aggregometry. Platelet aggregation (5 micromol/l ADP 42.8% +/- 13.5% and 20 micromol/l ADP 51.2% +/- 11.6%) was significantly suppressed

Ubiquitous atherosclerosis in coronary arteries without angiographically significant stenosis.

Previous intravascular ultrasound (IVUS) studies have shown coronary artery atherosclerosis even in angiographically normal reference segment. However, IVUS has not been performed in all of the three major coronary arteries. A total of 50 patients with single-vessel disease underwent IVUS evaluation in the proximal two-thirds of the three major coronary arteries. Lumen and external elastic membrane cross-sectional areas were measured at 1-mm intervals. To compensate the difference in pullback length among coronary arteries, normalized total plaque and media volume (TPV) was calculated as TPV/number of slices in pullback x median number of slices in study population. Percent plaque and media volume (PPV) was calculated as TPV/Sigma external elastic membrane cross-sectional area x 100. A cross section was defined as atherosclerotic if maximum intimal thickness exceeded 0.5 mm at any point in the vessel circumference. There was no significant difference in normalized TPV, PPV, and the incidence of abnormal intimal thickness between coronary arteries with and without significant stenosis. Frequency distribution of plaque burden was similar. Atherosclerosis is ubiquitous even in coronary arteries without angiographically significant stenosis. The extent of atherosclerosis is similar between coronary arteries with and without significant stenosis.

Antiplatelet effect of 50-mg maintenance dose of clopidogrel compared to 200 mg ticlopidine: a preliminary study.

In the United States and Europe, patients with coronary stents are maintained on 75 mg clopidogrel. Because the maintenance dose of ticlopidine in patients with coronary stents is 100 mg twice daily in Japan and 250 mg twice daily in the United States and Europe, in Japanese patients a lower dose of clopidogrel may achieve an antiplatelet effect comparable to 200 mg ticlopidine. Platelet aggregation was evaluated in 104 consecutive patients on 50 mg clopidogrel plus aspirin (n = 54) and 200 mg ticlopidine plus aspirin (n = 50). Platelets were stimulated with adenosine diphosphate (5 and 20 mumol/l) and aggregation was assessed by optical aggregometry. There was no significant difference in platelet aggregation induced with 5 (37% +/- 11% vs 38% +/- 15%, not significant) and 20 mumol/l adenosine diphosphate (48% +/- 13% vs 51% +/- 12%, not significant) between 50 mg clopidogrel and 200 mg ticlopidine. In Japanese patients, there is the possibility that a maintenance dose of 50 mg clopidogrel on platelet inhibition is comparable to 200 mg ticlopidine.

Early stent thrombosis because of stent dislodgement in a coronary artery aneurysm.

Stent thrombosis is one of the most feared complications after coronary stenting, because it often presents in a catastrophic way, triggering death or acute myocardial infarction. Previous studies report mechanical risk factors of stent thrombosis such as stent underexpansion and vessel dissection. This is a case report of early stent thrombosis associated with bare metal stent dislodgement because of dissolution of a mural thrombus in an unappreciated coronary artery aneurysm.

Silent very late thrombotic occlusion of sirolimus-eluting stent confirmed by directional coronary atherectomy.

Stent thrombosis is defined as thrombotic occlusion of a stent resulting in acute coronary syndrome (ACS). However, all thrombotic occlusions of stents might not result in ACS. The present case report describes silent, very late thrombotic occlusion of a drug-eluting stent that was confirmed from specimens removed by directional coronary atherectomy.

Prognostic significance of cystatin C in patients with ST-elevation myocardial infarction.

BACKGROUND: Cystatin C is reportedly a better endogenous marker of glomerular filtration rate than serum creatinine, so the prognostic value of cystatin C in patients with ST-elevation myocardial infarction (MI) was evaluated in the present study. METHODS AND RESULTS: A total of 71 patients who underwent percutaneous coronary intervention for ST-segment elevation MI <24 h from symptom onset were included. According to cystatin C level, patients were classified into 2 groups: (1) higher cystatin C group (n=33) and (2) lower cystatin C group (n=38). There was a trend toward more in-hospital deaths in patients with the higher cystatin C level compared with the lower cystatin C level group (15.2% vs 2.6%, P=0.06). Mean duration of clinical follow-up was 5.6 +/-2.8 months. There was no significant difference in death, reinfarction, disabling stroke or target lesion revascularization between the 2 groups. However, a higher incidence of rehospitalization for congestive heart failure was observed in patients with the higher cystatin C level than in those with the lower cystatin C level (15.2% vs 0%, P=0.01). CONCLUSIONS: Cystatin C may be associated with more cardiovascular events, mainly rehospitalization for congestive heart failure, after percutaneous coronary intervention in patients with ST-elevation MI.

Effect of balloon inflation time on expansion of sirolimus-eluting stent.

There is little information about the relationship between balloon inflation time and sirolimus-eluting stent (SES) expansion. In this randomized intravascular ultrasound (IVUS) study, 92 de novo lesions in native coronary arteries that underwent SES implantation were enrolled. Sirolimus-eluting stent was implanted using an inflation pressure of 14 atm. Stent balloon was gradually inflated until 14 atm in 10 s. In the short inflation group, it was deflated immediately after an image of the balloon inflated at 14 atm was taken. Stent balloon inflation lasted 60 s in the long inflation group. Intravascular ultrasound was then performed. The long balloon inflation resulted in a larger stent cross-sectional area (4.9 +/- 1.6 mm(2) vs 4.3 +/- 1.4 mm(2), P < 0.05) and expansion (71% +/- 13% vs 60% +/- 13%, P < 0.001) compared to the short balloon inflation, although stent expansion was relatively low in both groups. The relatively longer balloon inflation time using an inflation pressure of 14 atm results in better SES expansion. However, in the majority of lesions, adequate stent expansion is not achieved even using long balloon inflation, if it is inflated at 14 atm.

Multivessel coronary artery spasm refractory to intensive medical treatment.

This case report describes multivessel coronary artery spasm refractory to oral nifedipine, intravenous isosorbide dinitrate, diltiazem and nicorandil, and intracoronary nitroglycerin. Intracoronary administration of nicorandil only transiently relieved coronary artery spasm. Prednisolone was effective in preventing coronary artery spasm.

Effect of plaque volume on subsequent vessel remodeling at edges of sirolimus-eluting stents.

Serial (baseline and 9-month follow-up) intravascular ultrasound analysis was performed at 5-mm reference segments immediately proximal and distal to the sirolimus-eluting stent (SES) in 33 lesions. Proximal and distal reference segments were divided into 1-mm subsegments. Between postintervention and follow-up intravascular ultrasound studies, there were significant decreases in the lumen and increases in plaque & media areas in the subsegment closest to the distal edge, with no change in external elastic membrane area. There was no significant change in external elastic membrane, lumen, and plaque & media areas within the other subsegments. At the nearest 1-mm subsegment from the proximal and distal edges, baseline plaque & media area was associated with subsequent vessel remodeling. In conclusion, a large amount of plaque at the SES edge may be a risk of negative remodeling at follow-up (stent edge restenosis). It supports the importance of "normal-to-normal" SES deployment.

Long-term clinical outcomes after sirolimus-eluting stent implantation in dialysis patients.

There is little information about long-term (> 1 year) outcomes after sirolimus-eluting stent (SES) implantation in dialysis patients. Percutaneous coronary intervention (PCI) using SES was performed in 63 dialysis patients with 77 lesions. A control group for comparison was composed of 45 consecutive dialysis patients with 62 lesions who received PCI using bare metal stents (BMS). Clinical follow-up duration was 21.7 +/- 8.4 months in the SES group and 32.1 +/- 9.2 months in the BMS group (P < 0.01). There was no significant difference in the in-segment restenosis rate (30% versus 40%, P = 0.20) between the 2 groups. The 3-year mortality (22.5% versus 22.2%, P = 0.75), myocardial infarction (3.8% versus 4.9%, P = 0.93), target lesion revascularization (24.7% versus 31.0%, P = 0.61), and stent thrombosis rates (3.8% versus 2.4%, P = 0.73) were not significantly different between the SES and BMS groups. Compared to BMS, SES do not improve long-term clinical outcomes in dialysis patients.

Pioglitazone induces regression of coronary atherosclerotic plaques in patients with type 2 diabetes mellitus or impaired glucose tolerance: a randomized prospective study using intravascular ultrasound.

BACKGROUND: A large clinical trial clarified that pioglitazone reduces cardiovascular events in diabetic patients. However, effects of pioglitazone on structure of coronary atherosclerotic plaques have not been demonstrated. We examined whether pioglitazone reduces volumes of coronary atherosclerotic plaques using intravascular ultrasound (IVUS). METHODS: Twenty-six consecutive patients with type 2 diabetes mellitus (DM) or impaired glucose tolerance (IGT) undergoing percutaneous coronary intervention (PCI) were enrolled. Echolucent plaques without significant stenosis were selected in IVUS video images at non-PCI-influenced coronary segments and volumetric analysis of the targeted plaques was performed. The patients were randomly assigned into 2 groups: pioglitazone group consisted of 13 patients taking pioglitazone 15 mg/day for initial 14 days after PCI and subsequent 30 mg/day during 6-month follow-up, and control group with 13 patients as control. The plaque volumes and some parameters such as plasma lipid profiles and high-sensitive C-reacting protein (hs-CRP) levels were compared between baseline and the follow-up in those groups. RESULTS: In the pioglitazone group after 6 months, the plaque volume was significantly reduced (101.3+/-32.1 to 94.6+/-33.6 mm(3), -7.2%; p=0.0023), plasma triglyceride was significantly decreased (- 14.9%) and high density lipoprotein cholesterol was substantially increased (+20.0%) without any significant change in low density lipoprotein cholesterol (LDL-C). Also, hs-CRP level tended to be decreased. However, no significant change in plaque volumes and those parameters was observed in the control group. CONCLUSIONS: Pioglitazone may induce regression of coronary atherosclerotic plaques without LDL-C reduction in patients with DM and IGT.

Cost analysis of sirolimus-eluting stents in the Japanese health insurance system.

The cost-effectiveness of drug-eluting stents (DES) has been evaluated in the United States and Europe, however, there is little information from Japan. The present study evaluated the cost-effectiveness of sirolimus-eluting stents (SES) in Japan. In-hospital and follow-up costs of 25 consecutive patients undergoing SES implantation in a de novo lesion were evaluated. A control group for comparison was composed of 25 consecutive patients undergoing bare metal stent (BMS) implantation in a de novo lesion before the introduction of SES. There was no significant difference in resource use between the SES and BMS groups. Procedural cost (yen1,049,200 +/- 208,793 versus yen896,590 +/- 117,984, P = 0.01) was higher in the SES group than in the BMS group because of the higher reimbursement price of SES (yen378,000 versus yen258,000). In-hospital cost (yen1,202,891 +/- 208,793 versus yen1,050,280 +/- 177,984, P < 0.01) was higher in patients treated with SES. Less target lesion revascularization (4% versus 20%, P = 0.2) in patients with SES reduced the difference; aggregate 1-year cost was not significantly different (yen1,479,481 +/- 284,343 versus yen1,463,640 +/- 495,803, P = 0.9). It is concluded that SES may be cost-effective even in Japan.

Angiographic patterns of restenosis after sirolimus-eluting stent implantation.

BACKGROUND: Large-scale randomized trials demonstrate a high proportion of focal restenosis after drug-eluting stent (DES) implantation. On the other hand, recent reports have shown that in real-world practice a significant proportion of the restenosis is non-focal when DESs are used in unselected lesions. The present study evaluated angiographic patterns of restenosis after sirolimus-eluting stent (SES) implantation in Japan. METHODS AND RESULTS: Angiographic restenosis patterns of all consecutive restenotic lesions (n=124) after SES implantation were evaluated and classified according to the following scheme: focal (10 mm within the stent), proliferative (restenosis >10 mm in length extending outside the stent), and occlusive. There were 98 focal (79.0%), 15 diffuse (12.1%), and 5 proliferative restenoses (4.0%) and 6 total occlusions (4.8%). Focal intrastent restenosis was most dominant (42.7%). Proximal edge restenosis occurred in 22 lesions (17.7%). Multivariate analysis demonstrated diabetes mellitus (P<0.01) as an independent predictor of non-focal restenosis. CONCLUSIONS: Focal restenosis is predominant after SES implantation in real-world practice in Japan.

Re-restenosis and target lesion revascularization after treatment of sirolimus-eluting stent restenosis: retrospective analysis of 4 Japanese hospitals.

BACKGROUND: There is limited information about optimal management of drug-eluting stent (DES) restenosis. This study evaluated the incidences of re-restenosis and re-target lesion revascularization (TLR) after the treatment of sirolimus-eluting stent (SES) restenosis. METHODS AND RESULTS: A total of 102 lesions in 101 patients who underwent TLR for SES restenosis were classified according to: (1) focal (lesion length < or = 10 mm) or non-focal restenosis (>10 mm); and (2) use of DES for TLR: (1) focal restenosis treated with DES (focal-DES, n=40); (2) focal restenosis treated by balloon angioplasty (focal-balloon, n=31); (3) non-focal restenosis with DES (non-focal-DES, n=17); and (4) non-focal restenosis by balloon angioplasty (non-focal-balloon, n=14). Re-restenosis and re-TLR were observed in 6 (19.4%) and 5 lesions (12.5%) of the focal-DES group, in 13 (65.0%) and 11 (35.5%) of the focal-balloon group, in 7 (50.0%) and 6 (35.3%) of the non-focal-DES group, and in 8 (61.5%) and 7 (50.0%) of the non-focal-balloon group, respectively (P<0.05 for restenosis and TLR between the focal-DES group and other groups). CONCLUSIONS: Re-DES implantation for focal DES restenosis results in lower re-restenosis and re-TLR rates compared to re-DES implantation for non-focal DES restenosis or conventional balloon angioplasty either for focal or non-focal DES restenosis.

Fatal very late stent thrombosis in a young diabetic patient with severely diffuse coronary atherosclerosis.

Stent thrombosis is an infrequent event but a potentially fatal complication of coronary stenting. Adherence to long-term antiplatelet therapy plays an important role in the prevention of late stent thrombosis after drug-eluting stent (DES) implantation. Poor glycemic control due to nonadherence to diabetic treatments is likely to result in severely diffuse coronary atherosclerosis and diabetic microvascular complications. This case report describes fatal very late stent thrombosis in a young diabetic patient, which teaches us about the potential risk of DES in patients with acute myocardial infarction and the importance of patient education about long-term dual antiplatelet therapy after DES implantation. Furthermore, it demonstrates severely diffuse atherosclerosis in a young diabetic patient with nonadherence to diabetic treatments.