Diego Sangiorgi

Stent thrombosis with drug-eluting and bare-metal stents: evidence from a comprehensive network meta-analysis

BACKGROUND The relative safety of drug-eluting stents and bare-metal stents, especially with respect to stent thrombosis, continues to be debated. In view of the overall low frequency of stent thrombosis, large sample sizes are needed to accurately estimate treatment differences between stents. We compared the risk of thrombosis between bare-metal and drug-eluting stents. METHODS For this network meta-analysis, randomised controlled trials comparing different drug-eluting stents or drug-eluting with bare-metal stents currently approved in the USA were identified through Medline, Embase, Cochrane databases, and proceedings of international meetings. Information about study design, inclusion and exclusion criteria, sample characteristics, and clinical outcomes was extracted. FINDINGS 49 trials including 50,844 patients randomly assigned to treatment groups were analysed. 1-year definite stent thrombosis was significantly lower with cobalt-chromium everolimus eluting stents (CoCr-EES) than with bare-metal stents (odds ratio [OR] 0·23, 95% CI 0·13-0·41). The significant difference in stent thrombosis between CoCr-EES and bare-metal stents was evident as early as 30 days (OR 0·21, 95% CI 0·11-0·42) and was also significant between 31 days and 1 year (OR 0·27, 95% CI 0·08-0·74). CoCr-EES were also associated with significantly lower rates of 1-year definite stent thrombosis compared with paclitaxel-eluting stents (OR 0·28, 95% CI 0·16-0·48), permanent polymer-based sirolimus-eluting stents (OR 0·41, 95% CI 0·24-0·70), phosphorylcholine-based zotarolimus-eluting stents (OR 0·21, 95% CI 0·10-0·44), and Resolute zotarolimus-eluting stents (OR 0·14, 95% CI 0·03-0·47). At 2-year follow-up, CoCr-EES were still associated with significantly lower rates of definite stent thrombosis than were bare-metal (OR 0·35, 95% CI 0·17-0·69) and paclitaxel-eluting stents (OR 0·34, 95% CI 0·19-0·62). No other drug-eluting stent had lower definite thrombosis rates compared with bare-metal stents at 2-year follow-up. INTERPRETATION In randomised studies completed to date, CoCr-EES has the lowest rate of stent thrombosis within 2 years of implantation. The finding that CoCr-EES also reduced stent thrombosis compared with bare-metal stents, if confirmed in future randomised trials, represents a paradigm shift. FUNDING The Cardiovascular Research Foundation.

Systemic cardiac amyloidoses: disease profiles and clinical courses of the 3 main types.

Background— Most studies of amyloidotic cardiomyopathy consider as a single entity the 3 main systemic cardiac amyloidoses: acquired monoclonal immunoglobulin light-chain (AL); hereditary, mutated transthyretin-related (ATTRm); and wild-type transthyretin-related (ATTRwt). In this study, we compared the diagnostic/clinical profiles of these 3 types of systemic cardiac amyloidosis. Methods and Results— We conducted a longitudinal study of 233 patients with clear-cut diagnosis by type of cardiac amyloidosis (AL, n=157; ATTRm, n=61; ATTRwt, n=15) at 2 large Italian centers providing coordinated amyloidosis diagnosis/management facilities since 1990. Average age at diagnosis was higher in AL than in ATTRm patients; all ATTRwt patients except 1 were elderly men. At diagnosis, mean left ventricular wall thickness was higher in ATTRwt than in ATTRm and AL. Left ventricular ejection fraction was moderately depressed in ATTRwt but not in AL or ATTRm. ATTRm patients less often displayed low QRS voltage (25% versus 60% in AL; P<0.0001) or low voltage-to-mass ratio (1.1±0.5 versus 0.9±0.5; P<0.0001). AL patients appeared to have greater hemodynamic impairment. On multivariate analysis, ATTRm was a strongly favorable predictor of survival, and ATTRwt predicted freedom from major cardiac events. Conclusions— AL, ATTRm, and ATTRwt should be considered 3 different cardiac diseases, probably characterized by different pathophysiological substrates and courses. Awareness of the diversity underlying the cardiac amyloidosis label is important on several levels, ranging from disease classification to diagnosis and clinical management.

Short- Versus Long-Term Dual Antiplatelet Therapy After Drug-Eluting Stent Implantation: An Individual Patient Data Pairwise and Network Meta-Analysis

BACKGROUND Randomized controlled trials comparing short- (≤6 months) with long-term (≥1 year) dual antiplatelet therapy (DAPT) after drug-eluting stent(s) (DES) placement have been insufficiently powered to detect significant differences in the risk of major adverse cardiac events (MACE). OBJECTIVES This study sought to compare clinical outcomes between short- (≤6 months) and long-term (1 year) DAPT and among 3 months, 6 months, and 1 year of DAPT post-DES placement by performing an individual patient data pairwise and network meta-analysis. METHODS Randomized controlled trials comparing DAPT durations after DES placement were searched through the MEDLINE, EMBASE, and Cochrane databases and in international meeting proceedings. The primary study outcome was 1-year risk of MACE (cardiac death, myocardial infarction, or definite/probable stent thrombosis). RESULTS Four trials including 8,180 randomized patients were identified. At 1-year follow-up, short-term DAPT was associated with similar rates of MACE (hazard ratio [HR]: 1.11; 95% confidence interval [CI]: 0.86 to 1.43; p = 0.44), but significantly lower rates of bleeding (HR: 0.66; 95% CI: 0.46 to 0.94; p = 0.03) versus prolonged DAPT. Comparable results were apparent in the landmark period between DAPT discontinuation and 1-year follow-up (for MACE: HR: 1.20; 95% CI: 0.77 to 1.89; p = 0.42) (for bleeding: HR: 0.44; 95% CI: 0.21 to 0.91; p = 0.03). There were no significant differences in 1-year rates of MACE among 3-month versus 1-year DAPT, 6-month versus 1-year DAPT, or 3-month versus 6-month DAPT. CONCLUSIONS Compared with prolonged DAPT, short-term DAPT is associated with similar rates of MACE but lower rates of bleeding after DES placement.

Stent Thrombosis With Everolimus-Eluting Stents Meta-Analysis of Comparative Randomized Controlled Trials

Background— Some but not all studies have reported reduced rates of stent thrombosis (ST) with everolimus-eluting stents (EES) compared with other drug-eluting stents (DES). All of these studies were insufficiently powered to reliably detect differences in ST. We therefore performed a meta-analysis of randomized controlled trials comparing the risk of 2-year definite ST between EES and other DES. Methods and Results— Randomized controlled trials comparing EES versus other DES were searched through MEDLINE, EMBASE, Cochrane databases, and proceedings of international meetings. Information on study design, inclusion and exclusion criteria, sample characteristics, and clinical outcomes was extracted. Eleven randomized controlled trials (16 775 patients) were analyzed, including 5 trials (n=7113) of EES versus paclitaxel-eluting stents, 5 trials (n=7370) of EES versus sirolimus-eluting stents, and 1 trial (n=2292) of EES versus zotarolimus-eluting stents. By 2 years definite ST with EES compared with pooled DES occurred in 0.5% versus 1.3% patients, respectively (relative risk, 0.38; 95% CI, 0.24–0.59; P<0.0001). Similar results were observed when the broader definition of definite/probable ST was considered (relative risk, 0.46; 95% CI, 0.33–0.66; P<0.0001). EES compared with other DES reduced the relative risk of early ST (within 30 days), late ST (31 days to 1 year), cumulative 1-year ST, and very late ST (1–2 years). The reduced rate of definite ST observed with EES was consistent across all DES comparators with no interactions apparent during any time interval. Conclusions— EES compared with a pooled group of paclitaxel-eluting stents, sirolimus-eluting stents, and zotarolimus-eluting stents is associated with a significant reduction of definite ST, an effect that appears early and increases in magnitude through at least 2 years.

Ostial and midshaft lesions vs. bifurcation lesions in 1111 patients with unprotected left main coronary artery stenosis treated with drug-eluting stents: results of the survey from the Italian Society of Invasive Cardiology

AIMS In this study, we compared the cumulative risk of major adverse cardiac events (MACE) of patients with distal unprotected left main coronary artery (ULMCA) stenosis with those of patients with ostial and midshaft lesions treated with drug-eluting stent (DES). METHODS AND RESULTS The survey promoted by the Italian Society of Invasive Cardiology on ULMCA stenosis was an observational study involving 19 high-volume Italian centres. We enrolled 1111 patients with ULMCA stenosis treated with DES. Major adverse cardiac events were defined as death, myocardial infarction, and target lesion revascularization. Three hundred and thirty-four patients had ostial or midshaft lesions (group 1) and 777 bifurcations (group 2). The adjusted hazards ratio of the risk of 2 year MACE of patients in group 2 vs. patients in group 1 was 1.50 (P = 0.024). However, we observed that there was a significant difference between patients with bifurcations treated with two stents and those in group 1 (P = 0.001), but not between patients with bifurcations treated with one stent and those in group 1 (P = 0.38). CONCLUSION Patients with bifurcations have a worse outcome than patients with ostial and midshaft lesions. However, the technique used to treat bifurcations has a significant impact on clinical outcomes.

Phrenic stimulation: a challenge for cardiac resynchronization therapy.

Background—Phrenic stimulation (PS) may hinder left ventricular (LV) pacing. We prospectively observed its prevalence in consecutive patients with cardiac resynchronization therapy (CRT) devices. Methods and Results—In the years 2003 to 2006, 197 patients received a CRT device. PS and LV threshold measurements were carried out at implantation and at 6-month follow-up. LV reverse remodeling was assessed by echocardiography before implantation and at follow-up. LV lead placement was lateral/posterolateral in 86% of patients. Both PS and LV reverse remodeling occurred most frequently at the lateral/posterolateral LV pacing sites (P<0.001). PS was detected in 73 (37%) of patients and was clinically relevant in 41 (22%). The detection of PS at implantation had a poor sensitivity, as it occurred only in left lateral or sitting position in 27 patients. Ten patients (5%) underwent repeated surgery and 4 (2%) had their CRT turned off because of PS. At follow-up, we could manage PS noninvasively in 32 patients with a small PS-LV threshold difference: in 20 by cathode programmability (3 also thanks to automatic management of LV output) and in 12 (without cathode programmability) by programming the LV output as threshold +1 V. Conclusions—PS may seriously hinder CRT. A bipolar LV lead and cathode programmability are mandatory to avoid PS by changing the LV pacing vector at target sites for CRT. LV stability at target sites despite PS should also be pursued by these means. The automatic adjustment of LV pacing output is complementary in patients with a small PS-LV threshold difference.Background— Phrenic stimulation (PS) may hinder left ventricular (LV) pacing. We prospectively observed its prevalence in consecutive patients with cardiac resynchronization therapy (CRT) devices. Methods and Results— In the years 2003 to 2006, 197 patients received a CRT device. PS and LV threshold measurements were carried out at implantation and at 6-month follow-up. LV reverse remodeling was assessed by echocardiography before implantation and at follow-up. LV lead placement was lateral/posterolateral in 86% of patients. Both PS and LV reverse remodeling occurred most frequently at the lateral/posterolateral LV pacing sites ( P <0.001). PS was detected in 73 (37%) of patients and was clinically relevant in 41 (22%). The detection of PS at implantation had a poor sensitivity, as it occurred only in left lateral or sitting position in 27 patients. Ten patients (5%) underwent repeated surgery and 4 (2%) had their CRT turned off because of PS. At follow-up, we could manage PS noninvasively in 32 patients with a small PS-LV threshold difference: in 20 by cathode programmability (3 also thanks to automatic management of LV output) and in 12 (without cathode programmability) by programming the LV output as threshold +1 V. Conclusions— PS may seriously hinder CRT. A bipolar LV lead and cathode programmability are mandatory to avoid PS by changing the LV pacing vector at target sites for CRT. LV stability at target sites despite PS should also be pursued by these means. The automatic adjustment of LV pacing output is complementary in patients with a small PS-LV threshold difference. Received December 14, 2008; accepted June 10, 2009. # CLINICAL PERSPECTIVE {#article-title-2}

Impact of Bifurcation Technique on 2-Year Clinical Outcomes in 773 Patients With Distal Unprotected Left Main Coronary Artery Stenosis Treated With Drug-Eluting Stents

Background—Distal unprotected left main coronary artery (ULMCA) stenosis represents a technical challenge for interventional cardiologists. In this study, we compared 2-year clinical outcomes of different stenting strategies in patients with distal ULMCA stenosis treated with drug-eluting stents. Methods and Results—The survey promoted by the Italian Society of Invasive Cardiology on ULMCA stenosis was an observational study on patients with ULMCA stenosis treated with percutaneous coronary intervention. In this study, we selected patients with distal ULMCA stenosis treated with drug-eluting stents. Seven hundred seventy-three patients were eligible for this study: 456 were treated with 1 stent (group 1) and 317 with 2 stents (group 2). The primary end point of the study was the incidence of major adverse cardiac events (MACEs), defined as the occurrence of mortality, myocardial infarction, and target lesion revascularization. During a 2-year follow-up, risk-adjusted survival free from MACE was significantly higher in patients in group 1 than in patients in group 2. The propensity-adjusted hazard ratio for the risk of 2-year MACE in patients in group 1 versus group 2 was 0.53 (95% CI, 0.37 to 0.76). The propensity-adjusted hazard ratio for the risk of 2-year cardiac mortality and myocardial infarction in patients in group 1 versus group 2 was 0.38 (95% CI, 0.17 to 0.85). Conclusions—Compared with the 2-stent technique, the 1-stent technique is associated with a better 2-year MACE-free survival. The stenting strategy is a prognostic factor that should be taken into account when deciding the optimal revascularization treatment.

Risk of Stroke With Coronary Artery Bypass Graft Surgery Compared With Percutaneous Coronary Intervention

OBJECTIVES This study sought to determine whether coronary artery bypass graft (CABG) surgery is associated with an increased risk of stroke compared with percutaneous coronary intervention (PCI). BACKGROUND Some, but not all, randomized trials have reported increased rates of stroke with CABG compared with PCI. However, all these studies were powered insufficiently to examine differences in the risk of stroke reliably. METHODS We performed a meta-analysis of 19 trials in which 10,944 patients were randomized to CABG versus PCI. The primary end point was the 30-day rate of stroke. We also determined the rate of stroke at the midterm follow-up and investigated whether there was an interaction between revascularization type and the extent of coronary artery disease on the relative risk of stroke. RESULTS The 30-day rate of stroke was 1.20% after CABG compared with 0.34% after PCI (odds ratio: 2.94, 95% confidence interval: 1.69 to 5.09, p < 0.0001). Similar results were observed after a median follow-up of 12.1 months (1.83% vs. 0.99%, odds ratio: 1.67, 95% confidence interval: 1.09 to 2.56, p = 0.02). The extent of coronary artery disease (single vessel vs. multivessel vs. left main) did not affect the relative increase in the risk of stroke observed with CABG compared with PCI at either 30 days (p = 0.57 for interaction) or midterm follow-up (p = 0.08 for interaction). Similar results were observed when the outcomes in 33,980 patients from 27 observational studies were analyzed. CONCLUSIONS Coronary revascularization by CABG compared with PCI is associated with an increased risk of stroke at 30 days and at the mid-term follow-up.

Two-Year Clinical Outcome With Drug-Eluting Stents Versus Bare-Metal Stents in a Real-World Registry of Unprotected Left Main Coronary Artery Stenosis from the Italian Society of Invasive Cardiology

Data are limited about the relative efficacy of drug-eluting stents (DESs) versus bare-metal stents (BMSs) for the treatment of unprotected left main coronary artery (ULMCA) stenosis. The survey promoted by the Italian Society of Invasive Cardiology on ULMCA stenosis was an observational study involving 19 high-volume Italian centers of patients with ULMCA stenosis treated using percutaneous coronary intervention (PCI). From January 2002 to December 2006, of 1,453 patients identified with ULMCA stenosis treated with PCI, 1,111 were treated with DESs and 342 were treated with BMSs. During a 2-year follow-up, risk-adjusted survival free from cardiac death was significantly higher in patients treated with DESs than in those treated with BMSs. The propensity-adjusted hazard ratio for risk of 2-year cardiac mortality after DES versus BMS implantation was 0.49 (95% confidence interval 0.32 to 0.77). The benefit of DESs in reducing cardiac mortality was obtained in the period from 3 to 6 months and maintained up to 2 years. In conclusion, for patients with ULMCA stenosis undergoing PCI, DES implantation was associated with higher adjusted rates of 2-year survival free from cardiac death. The benefit of DESs in reducing cardiac mortality was obtained in the period in which clinical manifestations of restenosis usually peak.

Longevity of implantable cardioverter-defibrillators: implications for clinical practice and health care systems

AIMS Comparative studies on the longevity of implantable cardioverter-defibrillators (ICDs) among different manufacturers have never been reported. Longevity of ICD devices implanted from 1 January 2000 to 31 December 2002 was prospectively investigated according to their type and manufacturer. METHODS AND RESULTS Longevity of single-chamber (SC), double-chamber (DC), and biventricular (CRT-D) ICDs from Medtronic (MDT), Guidant (GDT), and St Jude Medical (SJM) was measured in all the patients who required device replacement. The observation follow-up ended on 31 December 2007; patients who died prematurely or were transplanted before battery exhaustion were excluded from the analysis. Factors associated with longevity (number of delivered shocks, pacing activity) were researched. One hundred and fifty-three patients received an ICD in the abovementioned period. Six underwent heart transplantation, and 23 died before device replacement; 80 had an SC device, 59 had DC device, and 14 had CRT-D device. Longevity of MDT was superior to GDT and SJM, replacement rates being, respectively, 42%, 95.3%, and 97.2%. Only MDT manufacturers and SC type were associated with greater ICD longevity. Longevity had an impact on the cost/month of treatment of replaced ICDs. CONCLUSION Battery longevity is significantly different among manufacturers. ICD cost is strictly dependent on device longevity, whereas device up-front cost is of limited clinical meaning. Appropriate assessment of cost-effectiveness should be based on ICD longevity in the real-life scenario.