Impact of diabetes on clinical outcome among elderly patients with acute coronary syndrome treated with percutaneous coronary intervention: insights from the ELDERLY ACS 2 trial.

BACKGROUND: Despite recent improvements in percutaneous coronary revascularization and antithrombotic therapies for the treatment of acute coronary syndromes, the outcome is still unsatisfactory in high-risk patients, such as the elderly and patients with diabetes. The aim of the current study was to investigate the prognostic impact of diabetes on clinical outcome among patients included in the Elderly-ACS 2 trial, a randomized, open-label, blinded endpoint study carried out at 32 centers in Italy. METHODS: Our population is represented by 1443 patients included in the Elderly-ACS 2 trial. Diabetes was defined as known history of diabetes at admission. The primary endpoint of this analysis was cardiovascular mortality, while secondary endpoints were all-cause death, recurrent myocardial infarction, Bleeding Academic Research Consortium type 2 or 3 bleeding, and rehospitalization for cardiovascular event or stent thrombosis within 12 months after index admission. RESULTS: Diabetes was present in 419 (29%) out of 1443 patients. Diabetic status was significantly associated with major cardiovascular risk factors and history of previous coronary disease, presentation with non-ST segment elevation myocardial infarction (P = 0.01) more extensive coronary disease (P = 0.02), more advanced Killip class at presentation (P = 0.003), use at admission of statins (P = 0.004) and diuretics at discharge (P < 0.001). Median follow-up was 367 days (interquartile range: 337-378 days). Diabetic status was associated with an absolute increase in the rate of cardiovascular mortality as compared with patients without diabetes [5.5 vs. 3.3%, hazard ratio (HR) 1.7 (0.99-2.8), P = 0.054], particularly among those treated with clopidogrel [HR (95% confidence interval (CI)) = 1.89 (0.93-3.87), P = 0.08]. However, this difference disappeared after correction for baseline differences [Adjusted HR (95% CI) 1.1(0.4-2.9), P = 0.86]. Similar findings were observed for other secondary endpoints, except for bleeding complications, significantly more frequent in diabetic patients [HR (95% CI) 2.02 (1.14-3.6), P = 0.02; adjusted HR (95% CI) = 2.1 (1.01-4.3), P = 0.05]. No significant interaction was observed between type of dual antiplatelet therapy, diabetic status and outcome. CONCLUSION: Among elderly patients with acute coronary syndromes, diabetic status was associated with higher rates of comorbidities, more severe cardiovascular risk profile and major bleeding complications fully accounting for the absolute increase in mortality. In fact, diabetes mellitus did not emerge as an independent predictor of survival in advanced age.

Impact of body mass index on clinical outcome among elderly patients with acute coronary syndrome treated with percutaneous coronary intervention: Insights from the ELDERLY ACS 2 trial.

BACKGROUND AND AIM: Elderly patients are at increased risk of hemorrhagic and thrombotic complications after an acute coronary syndrome (ACS). Frailty, comorbidities and low body weight have emerged as conditioning the prognostic impact of dual antiplatelet therapy (DAPT). The aim of the present study was to investigate the prognostic impact of body mass index (BMI) on clinical outcome among patients included in the Elderly-ACS 2 trial, a randomized, open-label, blinded endpoint study comparing low-dose (5 mg) prasugrel vs clopidogrel among elderly patients with ACS. METHODS AND RESULTS: Our population is represented by 1408 patients enrolled in the Elderly-ACS 2 trial. BMI was calculated at admission. The primary endpoint of this analysis was cardiovascular (CV) mortality. Secondary endpoints were all-cause death, recurrent MI, Bleeding Academic Research Consortium (BARC) type 2 or 3 bleeding, and re-hospitalization for cardiovascular reasons or stent thrombosis within 12 months after index admission. Patients were grouped according to median values of BMI (

Outcomes of Elderly Patients with ST-Elevation or Non-ST-Elevation Acute Coronary Syndrome Undergoing Percutaneous Coronary Intervention.

INTRODUCTION: Acute coronary syndromes (ACS) have been classified according to the finding of ST-segment elevation on the presenting electrocardiogram, with different treatment strategies and practice guidelines. However, a comparative description of the clinical characteristics and outcomes of acute coronary syndrome elderly patients undergoing percutaneous coronary intervention during index admission has not been published so far. METHODS: Retrospective cohort study of patients enrolled in the Elderly ACS-2 multicenter randomized trial. Main outcome measures were crude cumulative incidence and cause-specific hazard ratio (cHR) of cardiovascular death, noncardiovascular death, reinfarction, and stroke. RESULTS: Of 1443 ACS patients aged >75 years (median age 80 years, interquartile range 77-84), 41% were classified as ST-elevation myocardial infarction (STEMI), and 59% had non-ST-elevation ACS (NSTEACS) (48% NSTEMI and 11% unstable angina). As compared with those with NSTEACS, STEMI patients had more favorable baseline risk factors, fewer prior cardiovascular events, and less severe coronary disease, but lower ejection fraction (45% vs 50%, P < .001). At a median follow-up of 12 months, 51 (8.6%) STEMI patients had died, vs 39 (4.6%) NSTEACS patients. After adjusting for sex, age, and previous myocardial infarction, the hazard among the STEMI group was significantly higher for cardiovascular death (cHR 1.85; 95% confidence interval [CI], 1.02-3.36), noncardiovascular death (cHR 2.10; 95% CI, 1.01-4.38), and stroke (cHR 4.8; 95% CI, 1.7-13.7). CONCLUSIONS: Despite more favorable baseline characteristics, elderly STEMI patients have worse survival and a higher risk of stroke compared with NSTEACS patients after percutaneous coronary intervention.

Comparison of Reduced-Dose Prasugrel and Standard-Dose Clopidogrel in Elderly Patients With Acute Coronary Syndromes Undergoing Early Percutaneous Revascularization.

BACKGROUND: Elderly patients are at elevated risk of both ischemic and bleeding complications after an acute coronary syndrome and display higher on-clopidogrel platelet reactivity compared with younger patients. Prasugrel 5 mg provides more predictable platelet inhibition compared with clopidogrel in the elderly, suggesting the possibility of reducing ischemic events without increasing bleeding. METHODS: In a multicenter, randomized, open-label, blinded end point trial, we compared a once-daily maintenance dose of prasugrel 5 mg with the standard clopidogrel 75 mg in patients >74 years of age with acute coronary syndrome undergoing percutaneous coronary intervention. The primary end point was the composite of mortality, myocardial infarction, disabling stroke, and rehospitalization for cardiovascular causes or bleeding within 1 year. The study was designed to demonstrate superiority of prasugrel 5 mg over clopidogrel 75 mg. RESULTS: Enrollment was interrupted, according to prespecified criteria, after a planned interim analysis, when 1443 patients (40% women; mean age, 80 years) had been enrolled with a median follow-up of 12 months, because of futility for efficacy. The primary end point occurred in 121 patients (17%) with prasugrel and 121 (16.6%) with clopidogrel (hazard ratio, 1.007; 95% confidence interval, 0.78-1.30; P=0.955). Definite/probable stent thrombosis rates were 0.7% with prasugrel versus 1.9% with clopidogrel (odds ratio, 0.36; 95% confidence interval, 0.13-1.00; P=0.06). Bleeding Academic Research Consortium types 2 and greater rates were 4.1% with prasugrel versus 2.7% with clopidogrel (odds ratio, 1.52; 95% confidence interval, 0.85-3.16; P=0.18). CONCLUSIONS: The present study in elderly patients with acute coronary syndromes showed no difference in the primary end point between reduced-dose prasugrel and standard-dose clopidogrel. However, the study should be interpreted in light of the premature termination of the trial. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01777503.

Treatment of coronary artery disease with a new-generation drug-coated balloon: final results of the Italian Elutax SV rEgistry-DCB-RISE.

AIMS: Drug-coated balloons (DCBs) are a recognized alternative to stents for the treatment of in-stent restenosis (ISR), and there is some initial clinical evidence about their efficacy for the treatment of small coronary vessels. Newer-generation DCBs were developed to overcome the reduced deliverability of the previous generation, also warranting a more effective drug delivery to vessel wall. However, the vast majority of new-generation DCBs still lack of reliability due to paucity of clinical data. METHODS: Between 2012 and 2015, all patients treated with Elutax SV DCB (Aachen Resonance, Germany) at nine Italian centers were enrolled in this retrospective registry. Primary outcome was the occurrence of target-lesion revascularization (TLR) at the longest available follow-up. Secondary endpoints were procedural success and occurrence of device-oriented adverse cardiovascular events including cardiac death, target-vessel myocardial infarction, stroke, and TLR. A minimum 6-month clinical follow-up was required. RESULTS: We enrolled 544 consecutive patients treated at 583 sites. Fifty-three per cent of the patients had ISR, and the rest native vessel coronary artery disease. Procedural success occurred in 97.5%. At the longest available clinical follow-up (average 13.3 ±â€Š7.4 months), 5.9% of the patients suffered a TLR and 7.1% a device-oriented adverse cardiovascular event. We did not register cases of target-vessel abrupt occlusion. At multivariate analysis, severe calcification at the lesion site was the first determinant for the occurrence of TLR. CONCLUSION: This registry on the performance of a new-generation DCB shows an adequate profile of safety and efficacy at mid-term clinical follow-up.

IVUS-Guided Stent Implantation to Improve Outcome: A Promise Waiting to be Fulfilled.

The use of intravascular ultrasound (IVUS) to improve acute angiographic results was already shown in the prestent era. Various studies demonstrated the efficacy of IVUS in balloon sizing and estimating the extent of positive remodeling. With the introduction of drug-eluting stents (DES) the rate of restenosis has been significantly reduced but a new concern, the risk of stent thrombosis, has emerged. The association of stent underexpansion with stent thrombosis was observed for bare metal stents (BMS) and DES. Until now, the criteria for IVUS optimization used in different studies have relied on distal reference or on mean reference vessel for stent or postdilatation balloon sizing. Furthermore, an important recent innovation not available in previous studies is the use of noncompliant balloons to perform high pressure post-dilatation. Universal and easily applicable IVUS criteria for optimization of stent implantation as well as randomized studies on IVUS-guided DES implantation are necessary to minimize stent malapposition and underexpansion, which in turn can positively influence the rates of stent restenosis and thrombosis.

Late and very late stent thrombosis following drug-eluting stent implantation in unprotected left main coronary artery: a multicentre registry.

AIMS: To evaluate the occurrence of late and very late stent thrombosis (ST) following elective drug-eluting stent (DES) implantation in unprotected left main coronary artery (LMCA) stenosis in a large multicentre registry. METHODS AND RESULTS: All 731 consecutive patients who had sirolimus- or paclitaxel-eluting stent electively implanted in de novo lesions on unprotected LMCA in five centres were included. ST was defined according to Academic Research Consortium definitions. Four (0.5%) patients had a definite ST: three early (two acute and one subacute) and one late ST, no cases of very late definite ST were recorded. All patients survived from the event. Three patients had a probable ST. Therefore, 7/731 (0.95%) patients had a definite or a probable ST and all were on dual antiplatelet therapy at the time of the event. Possible (eight late and 12 very late) ST occurred in 20 (2.7%) patients. At 29.5 ± 13.7 months follow-up, a total of 45 (6.2%) patients had died; 31 (4.2%) of cardiac death. Ninety five (12.9%) patients had a target-vessel and 76 (10.4%) a target-lesion revascularization. Angiographic follow-up was performed in 548 patients (75%): restenosis occurred in 77 (14.1%) patients. CONCLUSION: Elective treatment of LMCA stenosis with DES appears safe with a 0.9% incidence of definite and probable ST at 29.5 ± 13.7 months.

Dual antiplatelet therapy after percutaneous coronary intervention with stent implantation in patients taking chronic oral anticoagulation.

OBJECTIVES: The purpose of this study was to evaluate the safety of dual antiplatelet therapy in patients in whom long-term anticoagulation (AC) with warfarin is recommended. BACKGROUND: The optimal antithrombotic strategy after percutaneous coronary intervention (PCI) for patients receiving AC is unclear. METHODS: Consecutive patients who underwent stent implantation and were discharged on triple therapy (defined as the combination of aspirin and thienopyridines and AC) were analyzed. RESULTS: Of the 127 patients with 224 lesions, 86.6% were men, with a mean age of 69.9 +/- 8.8 years. Drug-eluting stents (DES) were positioned in 71 (55.9%), and bare-metal stents (BMS) were positioned in 56 (44.1%) patients. Atrial fibrillation (AF) was the main indication (59.1%) for AC treatment. The mean triple therapy duration was 5.6 +/- 4.6 months, and clinical follow-up was 21.0 +/- 19.8 months. During the triple therapy period, 6 patients (4.7%) developed major bleeding complications; 67% occurred within the first month. No significant differences between DES and BMS were observed in the incidence of major (5.6% vs. 3.6%, respectively, p = 1.0) and minor (1.4% vs. 3.6%, respectively, p = 0.57) bleeding and mortality (5.6% vs. 1.8%, respectively, p = 0.39). A significant difference was observed in favor of DES in target vessel revascularization (14.1% vs. 26.8%, p = 0.041). CONCLUSIONS: While receiving triple therapy, major bleeding occurred in 4.7% of patients; one-half of the events were lethal, and most occurred within the first month.

Favorable long-term outcome after drug-eluting stent implantation in nonbifurcation lesions that involve unprotected left main coronary artery: a multicenter registry.

BACKGROUND: The presence of a lumen narrowing at the ostium and the body of an unprotected left main coronary artery but does not require bifurcation treatment is a class I indication of surgical revascularization. METHODS AND RESULTS: A total of 147 consecutive patients who had a stenosis in the ostium and/or the midshaft of an unprotected left main coronary artery (treatment of the bifurcation not required) and were electively treated with percutaneous coronary intervention and sirolimus-eluting stents (n=107) or paclitaxel-eluting stents (n=40) in 5 centres were included in this registry. In 72 patients (almost 50%), intravascular ultrasound guidance was performed. Procedural success was achieved in 99% of the patients; in 1 patient with stenosis in the left main coronary artery ostium, a >30% residual stenosis persisted at the end of the procedure, and the patient was referred for coronary artery bypass graft surgery. During hospitalization, no patients experienced a Q-wave myocardial infarction or died. One patient died 19 days after the procedure because of pulmonary infection. At long-term clinical follow-up (886+/-308 days), 5 patients had died; 7 patients had target vessel revascularization (5 repeat percutaneous coronary interventions and 2 coronary artery bypass graft surgeries), and of these only 1 patient had a target lesion revascularization. Angiographic follow-up was performed in 106 patients (72%) with a late loss of -0.01 mm. Restenosis in the left main trunk occurred only in 1 patient (0.9%). CONCLUSIONS: Percutaneous coronary intervention with sirolimus-eluting stents or paclitaxel-eluting stents implantation in nonbifurcation left main coronary artery lesions appears safe with a long-term major adverse clinical event rate of 7.4% and a restenosis rate of 0.9%.

Comparison of sirolimus versus paclitaxel eluting stents for treatment of coronary in-stent restenosis.

In patients with in-stent restenosis (ISR) inside bare metal stents, drug-eluting stents reduce the recurrence of restenosis compared with balloon angioplasty. However, few data are available about this therapeutic modality in the case of diffuse restenosis. The aim of this study was to evaluate the immediate and mid-term outcome of sirolimus- and paclitaxel-eluting stent implantation in diffuse ISR and determine the predictors of clinical and angiographic restenosis recurrence. A series of 161 consecutive patients with 194 diffuse ISR lesions (>10 mm) treated with drug-eluting stent implantation were evaluated. Major adverse cardiac events were defined as death, myocardial infarction, and the need for target lesion revascularization. During a mean follow-up of 8.2 +/- 3.4 months, the cumulative incidence of major adverse cardiac events was 19% in the SES group and 24% in the PES group (p = 0.56). Angiographic follow-up was performed in 80% of the lesions. The overall restenosis rate was 22% and was not significantly different between lesions treated with sirolimus-eluting (20%) or paclitaxel-eluting (25%, p = 0.55) stents. The incidence of restenosis was higher in diabetics (32%) than in nondiabetics (16%, odds ratio 2.5, 95% confidence interval 1.1 to 5.5, p = 0.02). By multivariate analysis, diabetes was confirmed to be the only independent predictor of recurrent restenosis (odds ratio 3.53, 95% confidence interval 1.39 to 9.02, p = 0.008). In conclusion, drug-eluting stent implantation for diffuse ISR is associated with acceptable clinical and angiographic results. The association of diffuse restenosis and diabetes mellitus is an unfavorable condition leading to a high risk of recurrence.

Treating chronic total occlusions using subintimal tracking and reentry: the STAR technique.

Successful recanalization of coronary total occlusions (CTOs) remains an area where improvements are needed. We propose an approach similar to the one utilized in treating some peripheral artery occlusions and aimed to create a subintimal dissection with distal reentry. A 0.014' hydrophilic wire with a J-configuration is utilized for this purpose. We applied this technique to CTO of native coronaries in 31 patients where previous attempts failed in 21 of them (67%). The right coronary artery (RCA) was the index vessel in 87% of patients. Recanalization of the vessel and of most of distal branches was achieved in 21 patients; patency of at least one major distal branch was achieved in 9 patients. Drug-eluting stents (DESs) were implanted in 53% of patients. Three patients had intraprocedural vessel perforation without consequences. Five patients (16%) had in-hospital non-Q-wave myocardial infarction. No other adverse events occurred at a mean follow-up of 5.1 +/- 3.7 months except for one noncardiac death. Angiographic follow-up was performed in 21 (67%) patients and 53% of them developed restenosis. Reintervention on the target vessel was performed in 11 patients (52%). Complete success with the procedure was originally obtained in 8 of the 10 patients who did not develop restenosis and in 8 of them DESs were originally implanted. This technique appears a promising approach to recanalize difficult total occlusions, particularly the ones localize on the RCA, which has the most important side branches located distally.

Is overdilatation of 3.0 mm sirolimus-eluting stent associated with a higher restenosis rate?

We evaluated the safety and effectiveness of postdilating a 3.0 mm sirolimus-eluting stents (SESs; six cells) with a 3.5-4.0 mm balloon. We identified 254 consecutive patients who underwent percutaneous coronary interventions using SESs with a nominal diameter of 3.0 mm (six cells). Patients were divided into two groups based on whether they were subsequently postdilated with a 3.0 mm (group 1: 168 patients, 251 lesions) or a 3.5-4 mm balloon (group 2: 86 patients, 102 lesions). There were no significant differences regarding the incidence of in-hospital and long-term follow-up. Angiographic follow-up was available in 72% and 74% of groups 1 and 2, respectively. The two groups had no significant differences regarding late lumen loss (0.51 +/- 0.36 vs. 0.52 +/- 0.33; P = 0.3) and binary restenosis rates (10.7% vs. 8.8%; P = 0.1). Six-month clinical follow-up was available in all patients. At long-term follow-up (mean: 10.6 +/- 3.7 for group 1 and 11.3 +/- 3.9 months for group 2), there were no significant differences between the two groups regarding major adverse cardiac events (8.9% vs. 9.2%; P = 0.9). Implantation of a 3.0 mm SES with postdilation with a 3.5-4 mm balloon did not result in any significant difference in complications, in-hospital non-Q-wave myocardial infarction, binary restenosis, or target lesion revascularization. These data should lessen concern that overdilation may dilute the beneficial effects of SESs.

Safety and feasibility of Bivalirudin with either Cypher and Taxus drug-eluting stent during percutaneous coronary intervention.

OBJECTIVE: This open label, prospective, non-comparative trial is the first to evaluate the safety and feasibility of bivalirudin (Angiomax(R), the Medicines Company, Parsippany, NJ), during PCI with implantation of the sirolimus eluting stent (Cypher, Cordis a J & J, Warren, NJ) or the paclitaxel eluting stent (Taxus, Boston Scientific, Natick, MA). METHODS: Patients who were referred for elective PCI suitable for stent implantation were recruited. Bivalirudin was administrated as a bolus of 1.0 mg/kg followed by 2.5 mg/kg/hour infusion for up to 4 hours in the first 68 patients. Following REPLACE 2 study, patients were treated with a lower dose of bivalirudin (0.75 mg/kg followed by 1.75 mg/kg/hour infusion). RESULTS: 111 patients with 139 lesions were included in the study. Thirty-one (27.9%) were diabetics, 14 (12.6%) had unstable angina and 79 (66.6%) had multivessel disease. Complex lesion morphology was present in 65 (46.7%), in-stent restenosis in 32 (23%), total occlusion 7 (5%) and bifurcations 22 (15.8%). Activated clotting time (ACT) was verified to be therapeutic following bivalirudin administration. During the index procedure no patients required provisional use of glycoprotein (GP) IIb/IIIa inhibitors. One patient had intracoronary thrombosis which resolved after stenting. An additional 2 patients had non-Q wave myocardial infarction (MI). No patients died, had major bleeding, required transfusions or sustained vascular complications. 1 patient developed thrombosis at 4 months with a documented MI. At 6 month follow-up, 3 (2.7%) patients died and 12 (10.8%) patients had target lesion revascularization (1 CABG and 11 re-PCI). Angiographic follow-up was achieved in 98 patients (89.9%). CONCLUSIONS: This study indicates the safety and feasibility of Cypher or Taxus stent implantation in conjunction with bivalirudin administration, with no elective use of GP IIb/IIIa inhibitors.

Comparison of clinical and angiographic outcome of sirolimus-eluting stent implantation versus cutting balloon angioplasty for coronary in-stent restenosis.

Sixty in-stent restenotic lesions were treated with sirolimus-eluting stent implantation and retrospectively compared with a group of matched lesions treated with cutting balloon angioplasty. The results indicate a good safety profile of the procedure and a 57% reduction in the incidence of recurrent restenosis in comparison with cutting balloon angioplasty.

Effectiveness of sirolimus-eluting stent implantation for treatment of in-stent restenosis after brachytherapy failure.

The impact of the use of sirolimus-eluting stents (SESs) in the treatment of in-stent restenosis in previously irradiated sites has not been adequately evaluated. Fifteen consecutive patients who underwent percutaneous coronary interventions using SESs in lesion sites previously intervened with intracoronary radiation therapy were identified. All stents were implanted successfully, and there were no major in-hospital complications. At 30-day follow-up, there was 1 case of subacute thrombosis that led to target lesion revascularization (TLR). At 6 months, 2 patients underwent TLR because of recurrent angina with angiographic restenosis, and 1 patient underwent target vessel revascularization distally to the SES site; no other major adverse cardiac events occurred at long-term follow-up (mean 17 +/- 8 months).

Intraprocedural stent thrombosis during implantation of sirolimus-eluting stents.

BACKGROUND: Intraprocedural stent thrombosis (IPST) is a rare event (<0.01% in our experience with bare metal stents), with the exception of specific settings such as acute myocardial infarction, thrombus-containing lesions, and dissections. We report the occurrence of this event during elective implantation of sirolimus-eluting stents. METHODS AND RESULTS: Between April 2002 and August 2003, 670 patients with 1362 lesions were treated with Cypher (Cordis, Johnson and Johnson Co) sirolimus-eluting stent implantation in San Raffaele Hospital and EMO Centro Cuore Columbus. Diabetes mellitus was present in 142 patients (21%), and 164 (24.5%) had unstable angina. Pretreatment with glycoprotein IIb/IIIa (GP IIb/IIIa) inhibitors was carried out in 235 patients (35%). Total stent length per vessel was 42.9+/-28.3 mm. IPST occurred in 5 patients (0.7%). None of the patients with IPST were pretreated with GP IIb/IIIa inhibitors. Using univariate exact logistic regression, only total stent length per vessel, in millimeters (exact OR, 1.03; 95% CI, 1.011 to 1.046; P=0.0028), was associated with the occurrence of IPST. CONCLUSIONS: Stent length was associated with the occurrence of IPST. Particular attention will need to be directed to this potential complication when long sirolimus-eluting stents are being used.