A polymer-based, paclitaxel-eluting stent in patients with coronary artery disease☆

Background: A substantial proportion of patients receiving fibrinolytic therapy for myocardial infarction with ST-segment elevation have inadequate reperfusion or reocclusion of the infarct-related artery, leading to an increased risk of complications and death. Methods: We enrolled 3491 patients, 18 to 75 years of age, who presented within 12 hours after the onset of an ST-elevation myocardial infarction and randomly assigned them to receive clopidogrel 8300-mg loading dose, followed by 75 mg once daily) or placebo. Patients received a fibrinolytic agent, aspirin, and when appropriate, heparin (dispensed according to body weight) and were echeduled to undergo angiography 48 to 192 hours after the start of study medication. The primary efficacy end point was a composite of an ocluded infarct-related artery (defined by a Thrombolysus in Myocardial Infarction flow grade of 0 or 1) on angiography or death or recurrent myocardial infarction before angiography. Results: The rates of the primary efficacy end point were 21.7 percent in the placebo group and 15.0 percent in the clopidogrel group, representing an absolute reduction of 6.7 percentage points in the rate and a 36 percent reduction in the odds of the end point with clopidogrel therapy (95 percent confidence interval, 24 to 47 percent; P<0.001). By 30 days, clopidogrel therapy reduced the odds ol the composite end point of death from cardiovascular causes, recurrent myocardial infarction, or recurrent ischemia leading to the need for urgent revascularization by 20 percent (from 14.1 to 11.6 percent, P=0.03). The rates of major bleeding and intracranial hemorrhage were similar in the two groups. Conclusions: In patients 75 years of age or younger who have myocardial infarction with ST-segment elevation and who receive aspirin and a standard fibrinolytic regimen, the addition of clopidogrel improves the patency rate of the infarct-related artery and reduces ischemic complications.

Addition of clopidogrel to aspirin and fibrinolytic therapy for myocardial infarction with ST-segment elevation

Background: The results from small clinical studies suggest that therapy with adult bone marrow (BM)– derived cells (BMCs) reduces infarct size and improves left ventricular function and perfusion. However, the effects of BMC transplantation in patients with ischemic heart disease remains unclear. Methods: We searched MEDLINE, EMBASE, Science Citation Index, CINAHL (Cumulative Index to Nursing and Allied Health), and the Cochrane Central Register of Controlled Trials (CENTRAL) (through July 2006) for randomized controlled trials and cohort studies of BMC transplantation to treat ischemic heart disease. We conducted a random-effects meta-analysis across eligible studies measuring the same outcomes. Results: Eighteen studies (N=999 patients) were eligible. The adult BMCs included BM mononuclear cells, BM mesenchymal stem cells, and BM-derived circulating progenitor cells. Compared with controls, BMC transplantation improved left ventricular ejection fraction (pooled difference, 3.66%; 95% confidence interval [CI], 1.93% to 5.40%; P.001); reduced infarct scar size (�5.49%; 95% CI, �9.10% to �1.88%; P=.003); and reduced left ventricular end-systolic volume (�4.80 mL; 95% CI, �8.20 to �1.41 mL; P=.006). Conclusions: The available evidence suggests that BMC transplantation is associated with modest improvements in physiologic and anatomic parameters in patients with both acute myocardial infarction and chronic ischemic heart disease, above and beyond conventional therapy. Therapy with BMCs seems safe. These results support conducting large randomized trials to evaluate the impact of BMC therapy vs the standard of care on patient-important outcomes. Arch Intern Med. 2007;167:989-997

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Adult bone marrow-derived cells for cardiac repair: a systematic review and meta-analysis.

Cytochrome P450 (CYP)2C19 catalyzes the bioactivation of the antiplatelet prodrug clopidogrel, and CYP2C19 loss-of-function alleles impair formation of active metabolites, resulting in reduced platelet inhibition. In addition, CYP2C19 loss-of-function alleles confer increased risks for serious adverse cardiovascular (CV) events among clopidogrel-treated patients with acute coronary syndromes (ACSs) undergoing percutaneous coronary intervention (PCI). Guideline updates include emphasis on appropriate indication for CYP2C19 genotype–directed antiplatelet therapy, refined recommendations for specific CYP2C19 alleles, and additional evidence from an expanded literature review (updates at http://www.pharmgkb.org).

https://ascpt.onlinelibrary.wiley.com/doi/epdf/10.1038/clpt.2013.105

Clinical Pharmacogenetics Implementation Consortium Guidelines for CYP2C19 Genotype and Clopidogrel Therapy: 2013 Update

The search strategy included MEDLINE, EMBASE, the Cochrane Library, and Current Controlled Trials Register through to August 2007 for randomized controlled trials of BMSC treatment for AMI. Thirteen trials (14 compari- sons) with a total of 811 participants were included. Data were analysed using a random effects model. Overall, stem cell therapy improved left ventricular ejection fraction (LVEF) by 2.99% (95% confidence interval (CI), 1.26-4.72%, P ¼ 0.0007), significantly reduced left ventricular end-systolic volume (LVESV) by 4.74 mL (95% CI, 27.84 to 21.64 mL, P ¼ 0.003), and myocardial lesion area by 3.51% (95% CI, 25.91 to 21.11%, P ¼ 0.004) compared with controls. Subgroup analysis revealed that there was statistical significant difference in LEVF in favour of BMSCs when cells were infused within 7 days following AMI and when the BMSC dose administered was higher than 10 8 BMSCs. In addition, there were trends in favour of benefit for most clinical outcomes examined, although it should be acknowledged that the 95%CI included no significant difference. Conclusion Stem cell treatment for AMI still holds promise. Clinically, these data suggest that improvement over conventional therapy can be achieved. Further, adequately powered trials using optimal dosing, longer term outcome assessments, more reliable, and more patient-centred outcomes are required.

Autologous bone marrow stem cells to treat acute myocardial infarction: a systematic review.

Objective: To study whether emergent intracoronary autologous bone marrow cell transplantation (BMT) is applicable for the treatment of acute myocardial infarction (AMI).

Methods: 20 patients admitted within 24 h after the onset of a first AMI were randomly allocated to receive intracoronary autologous BMT (n  =  10) or bone marrow supernatant (controls, n  =  10) immediately after primary percutaneous coronary intervention. Left ventricular ejection fraction (LVEF), left ventricular end diastolic internal diameter (LVDd) and myocardial perfusion defect scores were examined respectively by echocardiography and single-photon emission computed tomography at one week and six months after AMI.

Results: From one week to six months after AMI, LVEF was enhanced from mean 53.8 (SD 9.2)% to 58.6 (9.9)% (p 0.05); LVDd remained unchanged (52.5 (2.8) v 52.1 (3.2) mm, p > 0.05) in the BMT group but was significantly enlarged in the control group (50.4 (6.0) v 55.2 (7.1) mm, p 0.05).

Conclusion: Emergent intracoronary transplantation of bone marrow mononuclear cells after AMI is practicable, and it improved cardiac function, prevented myocardial remodelling and increased myocardial perfusion at six months’ follow up.

/pdf/efficacy-of-emergent-transcatheter-transplantation-of-stem-hd95v9pxo5.pdf

Efficacy of Emergent Transcatheter Transplantation of Stem Cells for Treatment of Acute Myocardial Infarction (TCT-STAMI)

Aims

We sought to determine whether repeat administration of bone marrow mononuclear cells (BMC) can improve left ventricular function compared with a single infusion in patients with large acute myocardial infarction (AMI).



Methods and results

Thirty-nine patients with a ST-elevation AMI of the anterior wall and a significantly decreased left ventricular ejection fraction (LVEF 20–39%) were randomly assigned to three groups following primary percutaneous coronary intervention: Group A (n = 12) received a single intracoronary infusion of BMC (1.9 ± 1.2 × 108) at 3–7 days after AMI; Group B (n = 15) received BMC administration both at 3–7 days (2.0 ± 1.4 × 108) and at 3 months (2.1 ± 1.7 × 108); and the control group (CON, n = 12) received one placebo injection at 3–7 days. We noted no severe complications associated with the BMC transfer. The increase in LVEF evaluated by magnetic resonance imaging (MRI) after 12 months in Group B (11.7 ± 2.6%) was significantly greater than that in Group A (7.2 ± 1.6%, P < 0.001) or in CON (2.9 ± 2.0%, P < 0.001). Magnetic resonance imaging-derived myocardial infarct size decreased significantly in Group B compared with Group A (11.3 ± 2.7% vs. 6.3 ± 1.6%, P < 0.001).



Conclusion

Data from this preliminary study suggest that repeated BMC administration might be a safe and feasible therapeutic strategy for patients with large AMI.

https://onlinelibrary.wiley.com/doi/pdf/10.1093/eurjhf/hfp062

Repeated autologous bone marrow mononuclear cell therapy in patients with large myocardial infarction.

Background: Although the sirolimus-eluting stent (CYPHER®, Cordis, USA) has shown a dramatic reduction of restenosis, there are still some concerns about its efficacy and safety. Its durable polymer coating may enhance neointimal proliferation and residual sirolimus, which cannot be released from polymer, may result in incomplete reendothelization. As a drug reservoir, bioabsorbable polymer (polylactic acid, PLA) is more rational. Objective: We aimed to determine the safety and efficacy of sirolimus-eluting stent coated with PLA (EXCEL®, JW Medical Systems, China) in the treatment of human coronary arterial diseases. Methods: The study included 31 patients with de novo coronary lesions, with vessels 2.5–3.5 mm in diameter. The primary end points included the percentage of in-stent restenosis of the luminal diameter and in-stent late luminal loss at 6 months, as determined by quantitative angiography. The secondary end point was the major adverse cardiac events (MACE) 30 days and 6 months after the index procedure. Results: Forty-eight EXCEL stents were successfully delivered in the 34 lesions, and multiple stents were implanted in 35.3% of lesions. All patients were discharged without clinical complications and completed clinical follow-up at 1 and 6 months. No MACE had occurred. Twenty patients (30 stents) completed 6 months of angiographic follow-up. No in-stent or in-lesion restenosis (diameter stenosis ≥≥50%) was observed. In-stent late loss was (0.07 ± 0.17) mm. Conclusions: The implantation of EXCEL stent is feasible and safe and elicits minimal neointimal proliferation. This new stent has potential advantages regarding the long-long-term result over the commercially stent as the new stent has no sustained stimulation to the local tissue. © 2006 Wiley-Liss, Inc.

Effectiveness and safety of the sirolimus-eluting stents coated with bioabsorbable polymer coating in human coronary arteries.

Objective. To investigate acute recoil of bioabsorbable poly-L-lactic acid (PLLA) stent. Background. As newly developed coronary stent, bioabsorbable PLLA stent still encountered concern of acute stent recoil. Methods. Sixteen minipigs were enrolled in our study. Eight PLLA XINSORB stents (Weite Biotechnology Co., Ltd., China) and eight metallic stents (EXCEL, Jiwei Co., Ltd. China) were implanted into coronary arteries. Upon quantitative coronary angiography analysis, acute absolute recoil was defined as the difference between mean diameter of inflated balloon (X) and mean lumen diameter of stent immediately after deployment (Y), while acute percent recoil was defined as (X&#x2212;Y)/X and expressed as a percentage. Intravascular ultrasound (IVUS) was performed immediately after implantation and 24 hours later to compare cross-sectional area (CSA) between two groups and detect stent malapposition or collapse. Results. Acute absolute recoil in XINSORB and EXCEL was &#x2009;mm and &#x2212;&#x2009;mm respectively (). Acute percent recoil in XINSORB and EXCEL was &#x25; and &#x2212;&#x25;, respectively (). CSA of XINSORB was similar to that of EXCEL immediately after implantation, so was CSA of XINSORB at 24-hours followup. Within XINSORB group, no difference existed between CSA after implantation and CSA at 24-hours followup. No sign of acute stent malapposition was detected by IVUS. Conclusions. The acute stent recoil of XINSORB is similar to that of EXCEL. No acute stent malapposition or collapse appeared in both kinds of stent. This preclinical study was designed to provide preliminary data for future studies of long-term efficacy and safety of XINSORB stent.

/pdf/comparison-of-acute-recoil-between-bioabsorbable-poly-l-4kt2em48q9.pdf

Comparison of Acute Recoil between Bioabsorbable Poly-L-lactic Acid XINSORB Stent and Metallic Stent in Porcine Model

BACKGROUND Large discrepancy of the incidence of myocardial bridging (MB) has been reported either among the postmortem studies or among the studies with coronary angiogram. This study was to investigate the prevalence of MB in large number of coronary angiograms and the angiographic characteristics of MB. METHODS A total of 5525 consecutive patients who underwent first diagnostic coronary angiography from January 2003 to March 2006 in Zhongshan Hospital were enrolled in this study. MB was diagnosed when the angiographical "milking effect", defined as the systolic compression and complete or partly release of the compression in diastole, was seen in the epicardial coronary arteries. Angiography was routinely repeated after intracoronary injection of 200 microg nitroglycerin. The systolic compression and length of MB were compared before and after the administration of nitroglycerin and also before and after stent implantation in patients with significant stenosis in segment proximal to the MB. RESULTS Among 5525 patients, MBs were found in a total of 888 patients angiographically with the prevalence of 16.1%. Atherosclerotic lesions were found more often in the segment proximal to the MB with 344/854 (40.3%) patients than in the segment distal to the MB with 47/854 (5.5%) (P < 0.01). The systolic compression ((43.3 +/- 13.7)% at baseline vs (54.2 +/- 14.0)% after nitroglycerine) and the average length ((20.9 +/- 7.5) mm at baseline vs (22.7 +/- 8.0) mm after nitroglycerine) of the MB segment were increased after intracoronary injection of nitroglycerin (both P < 0.01). Stent implantation was performed in 88 patients with significant stenosis in the segment proximal to the MB. The systolic compression and the length of the MB segment were increased after stenting compared with those before stenting (systolic compression, (49.4 +/- 14.6)% at baseline vs (57.3 +/- 12.3)% after stenting, and length of MB, (19.5 +/- 6.1) mm at baseline vs (21.8 +/- 6.3) mm after stenting, P < 0.01). CONCLUSIONS MB was a frequent finding in coronary angiogram with an incidence of 16.1%. Intracoronary administration of nitroglycerin and stent implantation in the segment proximal to the MB could enhance the systolic compression and the length of the MB angiographically.

Qibing Wang

Papers

Efficacy of Emergent Transcatheter Transplantation of Stem Cells for Treatment of Acute Myocardial Infarction (TCT-STAMI)

Repeated autologous bone marrow mononuclear cell therapy in patients with large myocardial infarction.

Effectiveness and safety of the sirolimus-eluting stents coated with bioabsorbable polymer coating in human coronary arteries.

Comparison of Acute Recoil between Bioabsorbable Poly-L-lactic Acid XINSORB Stent and Metallic Stent in Porcine Model

Prevalence and characteristics of myocardial bridging in coronary angiogram--data from consecutive 5525 patients.