Lower Incidence Of Major Adverse Cardiac Events Research Articles

Immediate Results and Long-Term Clinical Outcome of Patients With Unprotected Distal Left Main Restenosis: The CORPAL Registry (Córdoba and Las Palmas)

The goal of this study was to assess the immediate and long-term outcomes in patients undergoing percutaneous coronary intervention (PCI) for in-stent restenosis (ISR) in an unprotected distal left main coronary artery (UDLM). PCI for UDLM-ISR can be complex. Limited information is available on procedural and clinical outcomes. Between May 2002 and February 2011, UDLM-ISR after drug-eluting stent implantation was observed in 79 of 1,102 patients (7%). Seventy-five were treated by repeat PCI using a simple approach (balloon/in-stent implantation) or a complex strategy (additional stent/double-stenting technique). A diagnosis of mild or severe restenosis was considered depending on the number of bifurcation segments affected (1 vs. >1). Major adverse cardiac events (MACE) were defined as cardiac death, target lesion revascularization, and myocardial infarction. ISR treatment was performed using a simple approach in 44 (58%) patients, and using a complex strategy in 31 (42%). After 46 ± 26 months, the MACE rate was 22%. Patients treated with a simple approach had a lower incidence of MACE at follow-up compared with patients treated with a complex strategy, regardless of the restenosis extent (mild restenosis: 93% vs. 67%, p < 0.05; severe: 70% vs. 23%, p < 0.05). On Cox regression analysis, diabetes was the only predictor of MACE (hazard ratio [HR]: 4.94; 95% confidence interval [CI]: 1.03 to 23.70; p < 0.05), whereas a simple strategy for ISR treatment was associated with lower risk (HR: 0.25; 95% CI: 0.08 to 0.79; p = 0.02). PCI for UDLM-ISR is safe and feasible, with a high rate of procedural success and an acceptable long-term MACE rate. A simple strategy, when applicable, appears to be a good treatment option, associated with a lower event rate at follow-up.

First- versus second-generation drug-eluting stents for the treatment of coronary bifurcations

Randomized controlled trials have demonstrated that second-generation drug-eluting stents (DESs) for the treatment of obstructive coronary artery disease are associated with comparable, if not improved, clinical outcomes as compared to those of their first-generation counterparts. The aim of this study was to compare the long-term clinical outcomes associated with first- versus second-generation DESs for the treatment of coronary bifurcation lesions. This was a retrospective study of consecutive de novo bifurcation lesions, excluding those at the left main, treated with either second-generation DES (everolimus-eluting or resolute zotarolimus-eluting stents) between October 2006 and October 2011 (199 bifurcation lesions in 192 patients) or first-generation DES (sirolimus-eluting or paclitaxel-eluting stents) between April 2002 and December 2005 (289 bifurcation lesions in 273 patients). Second-generation DES use in this setting was associated with less major adverse cardiac events (MACE) (23.1% vs. 14.4%, p=0.02) as well as lower target vessel revascularization (TVR) rates (15.5% vs. 8.3%, p=0.01) at 2-year follow-up. Target lesion revascularization, both per patient (12.6% vs. 7.4%, p=0.02) and per bifurcation (11.8% vs. 7.0%, p=0.03), was also improved with second-generation DES over the same follow-up period. Propensity-score adjusted analysis suggested that second-generation DES was associated with a lower incidence of MACE (HR, 0.53; 95% CI, 0.33-0.85; p=0.01) and TVR (HR, 0.44; 95% CI, 0.24-0.83; p=0.01). Our results suggest that the use of second-generation DES for the treatment of bifurcation lesions is associated with better clinical outcomes as compared to first-generation DES, largely due to a lower need for repeat revascularization.

Impact of low-density lipoprotein cholesterol/high-density lipoprotein cholesterol ratio as a risk factor of cardiovascular event after percutaneous coronary intervention in men

Background: Some clinical studies have demonstrated that Low-Density Lipoprotein Cholesterol/High-Density Lipoprotein Cholesterol (LDL-C/HDL-C) ratio was an excellent predictor of cardiovascular diseases. The aim of this study was to determine whether the LDL-C/HDL-C ratio may affect the outcomes after Percutaneous Coronary Intervention (PCI). Methods: Eight-hundred-seventy-seven male patients, who underwent successful PCI, were divided into the following three groups: those with LDL-C/HDL-C≤1.5 (n=178), 1.5-2.0 (n=261), >2.0 (n=438). In these groups, the incidence of Major Adverse Cardiac Events (MACE) was measured during the five years after PCI. MACE was defined as cardiac death, non-fatal myocardial infarction, new stenosis and restenosis. Results: Kaplan-Meier analysis demonstrated that patients with LDL-C/HDL-C≤1.5 had a significantly lower incidence of MACE than those with LDL-C/HDL-C>2.0 and also those with LDL-C/HDL-C of between 1.5 and 2 (P<0.001). In addition, Cox proportional hazards model indicated the LDL-C/HDL-C ratio was an independent risk factor of MACE. ![Figure][1] Cumulative incidence of MACE Conclusion: The LDL-C/HDL-C ratio was a valuable predictor of cardiovascular events in male patients. Furthermore, it is desirable to maintain the LDL-C/HDL-C raito to be less than 1.5 for secondary prevention after PCI. [1]: pending:yes

Ratio of Serum n-3 to n-6 Polyunsaturated Fatty Acids and the Incidence of Major Adverse Cardiac Events in Patients Undergoing Percutaneous Coronary Intervention

The relationship between major adverse cardiac events (MACE) and serum polyunsaturated fatty acid (PUFA) parameters has not been well documented in patients who have undergone percutaneous coronary intervention (PCI). The aim of the present study was to investigate this relationship. A total of 284 consecutive patients who underwent elective PCI were enrolled and stratified according to median serum levels of n-6 PUFAs (arachidonic acid [AA]), n-3 PUFAs (eicosapentaenoic acid [EPA] and docosahexaenoic acid [DHA]), and serum EPA/AA and DHA/AA ratios. The relationship between these PUFA parameters and the incidence of MACE including cardiac death, acute coronary syndrome, PCI for de novo lesions, and coronary artery bypass grafting, was analyzed. Multivariate analysis showed that among the PUFA parameters, only a high serum EPA/AA ratio was significantly associated with a low incidence of MACE in all the models tested (model A, without adjusted variables: hazard ratio [HR], 0.52; 95% confidence interval [CI]: 0.27-0.99, P = 0.048; model B, adjusted for age and diabetes: HR, 0.51; 95%CI: 0.26-0.98, P = 0.043; model C, adjusted for age, sex, diabetes, hypertension, smoking, and low-density lipoprotein cholesterol: HR, 0.49; 95%CI: 0.25-0.94, P = 0.033). The incidence of MACE in patients who have undergone PCI is significantly associated with serum EPA/AA ratio.

Titanium-nitride-oxIde-coated stents multicenter registry in diaBEtic patienTs: the TIBET registry

We sought to explore the immediate clinical and angiographic results of the Titan(®) stent implantation in diabetic patients, as well as the major adverse cardiac events (MACE) at 6-month follow-up. We enrolled 156 consecutive diabetic patients admitted to undergo percutaneous intervention for at least one significant (50%) coronary lesion. All lesions were treated with the Titan(®) stent implantation according to the contemporary interventional techniques. Patients were prospectively followed-up for at least 6months. The primary endpoint was MACE at 6-month follow-up [cardiac death, myocardial infarction (MI), or target lesion revascularization (TLR)]. Secondary endpoints included angiographic and clinical procedural success, in-hospital MACE, TLR at 6-month follow-up, and stent thrombosis. The mean age was 66.7±9.6years, (68.4% males). A total of 197 Titan(®) stents were implanted in 163 lesions. Direct stenting was performed in 45.2% of the cases. The mean stent diameter was 3.1±0.61mm, and the mean length was 18.0±8.9mm. Average stent deployment pressure was 13.9±4.2 bars. Angiographic procedural success was achieved in 154 (98.7%) cases, and clinical procedural success was achieved in 153 (98.1%) cases. One patient developed in-hospital non-Q-wave MI following the procedure. Clinical follow-up was completed in 155 (99.4%) patients. Three patients (1.9%) died of a cardiac or unknown cause, and two (1.3%) developed MI. TLR was performed in 11 patients (7.1%). Cumulative MACE at 6-month follow-up occurred in 16 (10.3%) patients. No patient suffered stent thrombosis. Titan(®) stent implantation in diabetic patients achieves an excellent immediate clinical and angiographic outcome, with a low incidence of MACE at mid-term follow-up.

Multivessel vs Single‐Vessel Revascularization in Patients With Non–ST‐Segment Elevation Acute Coronary Syndrome and Multivessel Disease in the Drug‐Eluting Stent Era

We sought to compare long-term outcomes for multivessel revascularization (MVR) vs single-vessel revascularization (SVR) with drug-eluting stents (DES) in patients with non-ST-segment elevation acute coronary syndrome (NSTE-ACS) and multivessel coronary artery disease (MVD). In DES era, MVR would improve long-term clinical outcomes in patients with NSTE-ACS. We studied 179 patients undergoing MVR and 187 patients undergoing SVR for NSTE-ACS and MVD. Major adverse cardiac events (MACE) were defined as death, myocardial infarction, or any revascularization. During follow-up (median 36 months), MACE occurred in 96 patients (26.2%); 35 (19.6%) in the MVR group and 61 (32.6%) in the SVR group (P=0.003). In multivariate analysis, MVR was associated with a lower incidence of MACE (hazard ratio [HR]: 0.50, 95% confidence interval [CI]: 0.30-0.85) and revascularization (HR: 0.43, 95% CI: 0.24-0.78), but not of death (HR: 0.69, 95% CI: 0.25-1.93) and myocardial infarction (HR: 0.39, 95% CI: 0.11-1.47). The incidence of periprocedural renal dysfunction was not significantly different between patients undergoing MVR vs SVR (3.4% vs 1.6%, P=0.33). Definite or probable stent thrombosis occurred at a similar rate (2.2% in the MVR group and 2.7% in the SVR group, P=0.99). In patients with NSTE-ACS and MVD, MVR using drug-eluting stents may reduce MACE. Our findings should be confirmed by a prospective, randomized trial.

The EXTREME registry: Titanium-nitride-oxide coated stents in small coronary arteries

We sought to explore the immediate results of Titan2 stent implantation in small coronary arteries, as well as the incidence of major adverse cardiac events (MACE) at six months follow-up. The safety of Titan2 stent has been confirmed in several studies in real-life unselected populations. We enrolled 311 consecutive patients admitted for percutaneous intervention for at least one significant (50%) de novo lesion in a native small coronary artery (2.0-2.75 mm). All lesions were treated with Titan2 stent implantation. Patients were prospectively followed up for at least six months. The primary endpoint was MACE at six months follow-up [death, myocardial infarction (MI), or target vessel revascularization (TVR)]. Secondary endpoints included angiographic and clinical procedural success, in-hospital MACE, target lesion revascularization (TLR) during follow-up, and stent thrombosis. The mean age was 67.3 +/- 10.9 years (65.9% males). A total of 356 Titan2 stents were implanted in 353 lesions. Angiographic and clinical procedural success was achieved in 344 (97.5%) patients. No case of in-hospital MACE or acute stent thrombosis was reported. Clinical follow-up was completed for an average of 8 +/- 2 months. Two patients (0.7%) died, and 6 (2.1%) developed MI. TLR was performed in 12 (4.2%) and TVR in 16 (5.5%) patients, all were clinically driven. Cumulative MACE occurred in 20 (6.9%) patients. One patient suffered subacute stent thrombosis, but no late stent thrombosis. Titan2 stent implantation in small coronary arteries achieves excellent immediate outcome, with a low incidence of MACE at mid-term follow-up.

Sicilian DES Registry: prospective in-hospital and 9-month clinical and angiographic follow-up in selected high restenosis risk patients

This is a multicentre, open label, prospective non-randomized registry, with 9-month angiographic follow-up, conducted to evaluate the safety and effectiveness of drug-eluting stents (DES) when used in high restenosis risk patients from the real world. From June 2004 to February 2005, a total of 1622 consecutive patients were enrolled to the Sicilian DES Registry, according to specific inclusion criteria. Both paclitaxel-eluting and sirolimus-eluting stents were used. The analysis was performed on 1472 patients because 150 patients were excluded from the study. The primary endpoint was to evaluate the rate of major adverse cardiac events (MACE) within 9 months after DES implantation. Major adverse cardiac events were defined as cardiac death, non-Q-wave or Q-wave myocardial infarction (MI) and target vessel revascularization (TVR). The secondary endpoints were procedural success, angiographic binary restenosis and stent thrombosis within 9 months post-procedure. Patients were more frequently male; 472 (32.1%) were diabetics, of whom 130 (27.5%) were treated with insulin. Mean ejection fraction of the left ventricle was 51.5 +/- 8.7%. Multivessel disease was found and treated in 627 patients (42.6%). A total of 2439 lesions were treated with DES. Final angiographic success was achieved in 2422 (99.3%) lesions. Procedural success was achieved in 1422 (96.6%) patients. The 9-month cumulative incidence of MACE was 7.3% with 0.8% of cardiac deaths, 0.8% non-fatal MI, 7.9% TVR. Binary restenosis was observed in 101 patients (8.3%). Stent thrombosis was documented in 11 patients (0.8%). Drug-eluting stents appear to be safe and associated with a low incidence of MACE at 9-month follow-up, even in patients selected for their complexity.

Abstract 2150: A European and Canadian Multicenter Randomized, Double-Blind Trial of the Sirolimus-Eluting Stent (SES) in Patients with De Novo Native Coronary Artery Lesions (NEW-SIRIUS): 5-Year Clinical Outcomes

Background : NEW-SIRIUS is the pooled analysis of the E-SIRIUS (n=352) and C-SIRIUS (n=100) studies, respectively, performed in Europe and Canada. Identical in design, these are multicenter randomized, double-blind trials examining the safety and efficacy of the sirolimus-eluting stent (SES) vs. an identical bare-metal stent (BMS) in 452 patients to treat de novo native long lesions in small coronary arteries, with adjunctive clopidogrel for only 2 months. Methods : The primary endpoint was in-stent minimum lumen diameter (MLD) at 8-month follow-up. Among the secondary endpoints were major adverse cardiac events(MACE) at 1, 6, 9 and 12 months, and annually up to 5 years post-procedure, as well as target lesion revascularization (TLR), target vessel revascularization (TVR) and protocol-defined stent thrombosis. Results : At 8 months, the MLD was 2.27±0.47mm in the SES vs. 1.36±0.66 mm in the BMS (p &lt; 0.001). The binary in-lesion restenosis rate was 5.1% in the SES vs. 44.2% in the BMS (p &lt; 0.001). At 4 years, there was a significantly lower incidence of MACE (SES: 15.1% vs BMS: 33.9%, p &lt; 0.001), primarily driven by a significant difference in clinically-driven TLR rates (SES: 7.1% vs. BMS: 26.0%, p &lt; 0.001). A subgroup analysis in diabetic patients (45 SES, 60 BMS) demonstrated that the in-stent MLD was larger in SES than in BMS (2.20±0.47 vs 1.14±0.64 mm, p &lt; 0.001) and the binary in-lesion restenosis rate was reduced from 56.1% (BMS) to 10.0% (RRR: 82.2%, p &lt; 0.001) at 8 months. At 4 years, the freedom from MACE in diabetic patients was 80.0% in the SES vs. 61.7% in the BMS (p = 0.031), again mainly driven by an improved freedom from clinically driven-TLR (SES: 90.8% vs. BMS: 66.9%, p=0.005), with no evidence of a late catch-up effect. Conclusion : Up to 4 years, SES were superior to BMS in the total cohort as well as in the diabetic subgroup without evidence of a late catch-up. Five-year follow-up data, including antiplatelet therapies utilization and a diabetic subgroup analyses will be available by July 2007 and presented.

Percutaneous Coronary Intervention Versus Coronary Artery Bypass Grafting in Patients with Coronary Artery Disease and Diabetic Nephropathy: A Single Center Experience

BackgroundPatients with diabetic nephropathy (DN) and coronary artery disease (CAD) represent a subset of patients with high cardiovascular morbidity and mortality. The optimal revascularization strategy using either percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) remains controversial. The purpose of this study was to compare the clinical outcomes of PCI to CABG in DN patients with CAD.MethodsThe clinical and angiographic records of DN patients with CAD who underwent either CABG (n=52) or PCI (n=48) were retrospectively analyzed.ResultsThe baseline characteristics were similar in the two groups except for the severity of the CAD. At 30 days, the death rate (PCI: 2.1% vs. CABG: 9.6%, p=0.21) and major adverse cardiac events (MACE) rate (PCI: 2.1% vs. CABG: 9.6%, p=0.21) were similar in comparisons between the PCI and CABG groups. At three years, the death rate (PCI: 18.8% vs. CABG: 19.2%, p=0.94) was similar between the PCI and CABG groups but the MACE rate (PCI: 47.9% vs. CABG: 21.2%, p=0.006) was higher in the PCI group compared to the CABG group. In addition, the repeat revascularization rate was higher in the PCI group compared to the CABG group (PCI: 12.5% vs. CABG: 1.9%, p=0.046).ConclusionsThe CABG procedure was associated with a lower incidence of MACE and repeat revascularization for up to three years of follow-up in DN patients with CAD. However, the overall survival rate was similar in the CABG and PCI groups. Therefore, CABG may be superior to PCI with regard to MACE and repeat revascularization.

Editorial Comment: Heart Transplantation, Cardiac Allograft Vasculopathy and Proliferation Signal Inhibitors

Editorial Comment: Heart Transplantation, Cardiac Allograft Vasculopathy and Proliferation Signal Inhibitors

The Impact of Proliferation Signal Inhibitors on the Healthcare Burden of Major Adverse Cardiac Events Following Heart Transplantation

Cardiac allograft vasculopathy (CAV) is a major burden on the long-term outcome of heart transplantation and is often only diagnosed following the occurrence of major adverse cardiac events (MACE). The proliferation signal inhibitors (PSIs) everolimus and sirolimus are being used with increasing frequency following heart transplantation due to their potent immunosuppressive and antiproliferative effects. In clinical trials in de novo and maintenance heart transplant recipients, PSIs are associated with a reduced incidence of CAV when compared with alternative immunosuppressive regimens. In further analysis of the incidence of MACE at four years post-transplant, everolimus was associated with a lower incidence of MACE in de novo recipients compared with azathioprine. The healthcare burden of these MACE was evaluated through the application of hospitalization costs from the 2003 US Healthcare Cost and Utilization Project. Everolimus treatment was associated with a reduction in the mean cost of MACE per patient in both the intent-to-treat population (57.2% reduction) and a sub-group of patients who underwent intravascular ultrasound examination (60.8% reduction). This model of healthcare cost analysis was subsequently applied to previously published data on the incidence of MACE in maintenance heart transplant recipients following conversion to sirolimus. The average cost of MACE per patient was US $9,117 in sirolimus-treated patients compared with US $37,830 in patients remaining on the original immunosuppressive regimen, a reduction of 75.9%. In conclusion, the antiproliferative benefits of PSI therapy in delaying the progression of CAV are associated with reduced healthcare costs, resulting from MACE in de novo and maintenance heart transplant recipients.

Spotlight on the Sirolimus-Eluting Stent in Coronary Artery Disease1

The sirolimus-eluting stent (CYPHER™) is a metal stent coated with 140 μg/cm2 of sirolimus blended with synthetic polymers. After stent implantation, sirolimus is slowly released causing localized cytostatic inhibition of proliferation of vascular smooth muscle cells in the peri-stent arterial wall over a period of about 1 month. Only minimal amounts of sirolimus enter the bloodstream and these appear to be insufficient to be of clinical relevance. In clinical trials that evaluated single de novo lesions and in-stent restenosis in patients with coronary artery disease, the sirolimus-eluting stent was associated with minimal neointimal hyperplasia. In four randomized trials in de novo lesions, sirolimus eluting stents produced a significantly lower incidence of major adverse cardiac events (MACE) than that observed in patients with uncoated stents, during periods of up to 2 years (p < 0.05 for all comparisons). The lower incidence of MACE was mostly due to a reduced requirement for repeat target vessel revascularization. At angiographic follow-up at periods of up to 8 months, late luminal loss was significantly smaller in the sirolimus-eluting stent groups than in the uncoated-stent groups (p < 0.001 in all studies). The sirolimus-eluting stent was well tolerated in clinical trials of up to 3 years’ follow-up. Because minimal blood levels of sirolimus are achieved, systemic adverse effects appear to be avoided. To date, there has been no evidence of any potential adverse effects resulting from the polymer coating or local drug toxicity. As yet, there is no evidence of an increased risk of subacute or late thrombosis, or aneurysm formation with the sirolimus-eluting stent compared with the uncoated stent. Long-term follow-up is needed to fully assess these theoretical concerns. Cost-effectiveness analyses over 12 months demonstrated a cost advantage for the sirolimus-eluting stent compared with an uncoated stent because of a reduced requirement for repeat target vessel revascularizations. Conclusion: Initial clinical trials with the sirolimus-eluting stent in patients with de novo coronary lesions have shown a significantly reduced incidence of MACE and of restenosis compared with a standard stent. Efficacy appears to be maintained throughout follow-up periods of up to 2 years in randomized trials, and to date, systemic or local adverse effects have been avoided. If efficacy and tolerability are consistently demonstrated over the long term, the sirolimus-eluting stent will be a major advance in the control of in-stent restenosis.

The sirolimus-eluting stent: a review of its use in the treatment of coronary artery disease.

The sirolimus-eluting stent (CYPHER( trade mark )) is a metal stent coated with 140 micro g/cm(2) of sirolimus blended with synthetic polymers. After stent implantation, sirolimus is slowly released causing localized cytostatic inhibition of proliferation of vascular smooth muscle cells in the peri-stent arterial wall over a period of about 1 month. Only minimal amounts of sirolimus enter the bloodstream and these appear to be insufficient to be of clinical relevance. In clinical trials that evaluated single de novo lesions and in-stent restenosis in patients with coronary artery disease, the sirolimus-eluting stent was associated with minimal neointimal hyperplasia. In four randomized trials in de novo lesions, sirolimus eluting stents produced a significantly lower incidence of major adverse cardiac events (MACE) than that observed in patients with uncoated stents, during periods of up to 2 years (p < 0.05 for all comparisons). The lower incidence of MACE was mostly due to a reduced requirement for repeat target vessel revascularization. At angiographic follow-up at periods of up to 8 months, late luminal loss was significantly smaller in the sirolimus-eluting stent groups than in the uncoated-stent groups (p < 0.001 in all studies). The sirolimus-eluting stent was well tolerated in clinical trials of up to 3 years' follow-up. Because minimal blood levels of sirolimus are achieved, systemic adverse effects appear to be avoided. To date, there has been no evidence of any potential adverse effects resulting from the polymer coating or local drug toxicity. As yet, there is no evidence of an increased risk of subacute or late thrombosis, or aneurysm formation with the sirolimus-eluting stent compared with the uncoated stent. Long-term follow-up is needed to fully assess these theoretical concerns. Cost-effectiveness analyses over 12 months demonstrated a cost advantage for the sirolimus-eluting stent compared with an uncoated stent because of a reduced requirement for repeat target vessel revascularizations. Initial clinical trials with the sirolimus-eluting stent in patients with de novo coronary lesions have shown a significantly reduced incidence of MACE and of restenosis compared with a standard stent. Efficacy appears to be maintained throughout follow-up periods of up to 2 years in randomized trials, and to date, systemic or local adverse effects have been avoided. If efficacy and tolerability are consistently demonstrated over the long term, the sirolimus-eluting stent will be a major advance in the control of in-stent restenosis.