Thomas Ischinger

Biolimus-eluting stent with biodegradable polymer versus sirolimus-eluting stent with durable polymer for coronary revascularisation (LEADERS): a randomised non-inferiority trial

BACKGROUND A novel stent platform eluting biolimus, a sirolimus analogue, from a biodegradable polymer showed promising results in preliminary studies. We compared the safety and efficacy of a biolimus-eluting stent (with biodegradable polymer) with a sirolimus-eluting stent (with durable polymer). METHODS We undertook a multicentre, assessor-blind, non-inferiority study in ten European centres. 1707 patients aged 18 years or older with chronic stable coronary artery disease or acute coronary syndromes were centrally randomised by a computer-generated allocation sequence to treatment with either biolimus-eluting (n=857) or sirolimus-eluting (n=850) stents. The primary endpoint was a composite of cardiac death, myocardial infarction, or clinically-indicated target vessel revascularisation within 9 months. Analysis was by intention to treat. 427 patients were randomly allocated to angiographic follow-up, with in-stent percentage diameter stenosis as principal outcome measure at 9 months. The trial is registered with ClinicalTrials.gov, number NCT00389220. FINDINGS We analysed all randomised patients. Biolimus-eluting stents were non-inferior to sirolimus-eluting stents for the primary endpoint at 9 months (79 [9%] patients vs 89 [11%], rate ratio 0.88 [95% CI 0.64-1.19], p for non-inferiority=0.003, p for superiority=0.39). Frequency of cardiac death (14 [1.6%] vs 21 [2.5%], p for superiority=0.22), myocardial infarction (49 [5.7%] vs 39 [4.6%], p=0.30), and clinically-indicated target vessel revascularisation (38 [4.4%] vs 47 [5.5%], p=0.29) were similar for both stent types. 168 (79%) patients in the biolimus-eluting group and 167 (78%) in the sirolimus-eluting group had data for angiographic follow-up available. Biolimus-eluting stents were non-inferior to sirolimus-eluting stents in in-stent percentage diameter stenosis (20.9%vs 23.3%, difference -2.2% [95% CI -6.0 to 1.6], p for non-inferiority=0.001, p for superiority=0.26). INTERPRETATION Our results suggest that a stent eluting biolimus from a biodegradable polymer represents a safe and effective alternative to a stent eluting sirolimus from a durable polymer in patients with chronic stable coronary artery disease or acute coronary syndromes. FUNDING Biosensors Europe SA, Switzerland.

A Randomized Study of Coronary Angioplasty Compared with Bypass Surgery in Patients with Symptomatic Multivessel Coronary Disease

BACKGROUND The standard treatment for patients with symptomatic multivessel coronary artery disease is coronary-artery bypass grafting (CABG). Percutaneous transluminal coronary angioplasty (PTCA) is widely used as an alternative approach to revascularization, but a systematic comparison of the two procedures is needed. We compared the outcomes in patients one year after complete revascularization with CABG or PTCA. METHODS A total of 8981 patients with multivessel coronary disease were screened at eight clinical sites, and 359 patients were randomly assigned to undergo CABG (177 patients) or PTCA (182 patients). Enrollment required that complete revascularization of at least two major vessels supplying different myocardial regions be deemed clinically necessary and technically feasible. RESULTS Among the patients in the CABG group, an average of 2.2 +/- 0.6 vessels were grafted, and among those in the PTCA group, 1.9 +/- 0.5 vessels were dilated. After CABG, hospitalization was longer (median, 19, as compared with 5 days for PTCA), and Q-wave myocardial infarction in relation to the procedure was more frequent (8.1 percent, as compared with 2.3 percent after PTCA; P = 0.022), whereas in-hospital mortality did not differ significantly between the two groups (2.5 percent in the CABG group and 1.1 percent in the PTCA group). At discharge 93 percent of the patients in the CABG group were free of angina, as compared with 82 percent of those in the PTCA group (P = 0.005). During the first year of follow-up, further interventions were necessary in 44 percent of the patients in the PTCA group (repeated PTCA in 23 percent, CABG in 18 percent, and both in 3 percent) but in only 6 percent of the patients in the CABG group (repeated CABG in 1 percent and PTCA in 5 percent; P < 0.001). Seventy-four percent of the patients in the CABG group and 71 percent of those in the PTCA group were free of angina one year after treatment. Exercise capacity improved similarly in both groups. However, 22 percent of the CABG group, as compared with only 12 percent of the PTCA group, did not require antianginal medication (P = 0.041). CONCLUSIONS In selected patients with multivessel coronary disease, PTCA and CABG as initial treatments resulted in equivalent improvement in angina after one year. However, in order to achieve similar clinical outcomes, the patients treated with PTCA were more likely to require further interventions and antianginal drugs, whereas the patients treated with CABG were more likely to sustain an acute myocardial infarction at the time of the procedure.

Comparison of zotarolimus-eluting and everolimus-eluting coronary stents.

BACKGROUND New-generation coronary stents that release zotarolimus or everolimus have been shown to reduce the risk of restenosis. However, it is unclear whether there are differences in efficacy and safety between the two types of stents on the basis of prospectively adjudicated end points endorsed by the Food and Drug Administration. METHODS In this multicenter, noninferiority trial with minimal exclusion criteria, we randomly assigned 2292 patients to undergo treatment with coronary stents releasing either zotarolimus or everolimus. Twenty percent of patients were randomly selected for repeat angiography at 13 months. The primary end point was target-lesion failure, defined as a composite of death from cardiac causes, any myocardial infarction (not clearly attributable to a nontarget vessel), or clinically indicated target-lesion revascularization within 12 months. The secondary angiographic end point was the extent of in-stent stenosis at 13 months. RESULTS At least one off-label criterion for stent placement was present in 66% of patients. The zotarolimus-eluting stent was noninferior to the everolimus-eluting stent with respect to the primary end point, which occurred in 8.2% and 8.3% of patients, respectively (P<0.001 for noninferiority). There were no significant between-group differences in the rate of death from cardiac causes, any myocardial infarction, or revascularization. The rate of stent thrombosis was 2.3% in the zotarolimus-stent group and 1.5% in the everolimus-stent group (P=0.17). The zotarolimus-eluting stent was also noninferior regarding the degree (+/-SD) of in-stent stenosis (21.65+/-14.42% for zotarolimus vs. 19.76+/-14.64% for everolimus, P=0.04 for noninferiority). In-stent late lumen loss was 0.27+/-0.43 mm in the zotarolimus-stent group versus 0.19+/-0.40 mm in the everolimus-stent group (P=0.08). There were no significant between-group differences in the rate of adverse events. CONCLUSIONS At 13 months, the new-generation zotarolimus-eluting stent was found to be noninferior to the everolimus-eluting stent in a population of patients who had minimal exclusion criteria. (ClinicalTrials.gov number, NCT00617084.)

Long-term clinical outcomes of biodegradable polymer biolimus-eluting stents versus durable polymer sirolimus-eluting stents in patients with coronary artery disease (LEADERS): 4 year follow-up of a randomised non-inferiority trial.

BACKGROUND The effectiveness of durable polymer drug-eluting stents comes at the expense of delayed arterial healing and subsequent late adverse events such as stent thrombosis (ST). We report the 4 year follow-up of an assessment of biodegradable polymer-based drug-eluting stents, which aim to improve safety by avoiding the persistent inflammatory stimulus of durable polymers. METHODS We did a multicentre, assessor-masked, non-inferiority trial. Between Nov 27, 2006, and May 18, 2007, patients aged 18 years or older with coronary artery disease were randomly allocated with a computer-generated sequence to receive either biodegradable polymer biolimus-eluting stents (BES) or durable polymer sirolimus-eluting stents (SES; 1:1 ratio). The primary endpoint was a composite of cardiac death, myocardial infarction, or clinically-indicated target vessel revascularisation (TVR); patients were followed-up for 4 years. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00389220. FINDINGS 1707 patients with 2472 lesions were randomly allocated to receive either biodegradable polymer BES (857 patients, 1257 lesions) or durable polymer SES (850 patients, 1215 lesions). At 4 years, biodegradable polymer BES were non-inferior to durable polymer SES for the primary endpoint: 160 (18·7%) patients versus 192 (22·6%) patients (rate ratios [RR] 0·81, 95% CI 0·66-1·00, p for non-inferiority <0·0001, p for superiority=0·050). The RR of definite ST was 0·62 (0·35-1·08, p=0·09), which was largely attributable to a lower risk of very late definite ST between years 1 and 4 in the BES group than in the SES group (RR 0·20, 95% CI 0·06-0·67, p=0·004). Conversely, the RR of definite ST during the first year was 0·99 (0·51-1·95; p=0·98) and the test for interaction between RR of definite ST and time was positive (p(interaction)=0·017). We recorded an interaction with time for events associated with ST but not for other events. For primary endpoint events associated with ST, the RR was 0·86 (0·41-1·80) during the first year and 0·17 (0·04-0·78) during subsequent years (p(interaction)=0·049). INTERPRETATION Biodegradable polymer BES are non-inferior to durable polymer SES and, by reducing the risk of cardiac events associated with very late ST, might improve long-term clinical outcomes for up to 4 years compared with durable polymer SES. FUNDING Biosensors Europe SA, Switzerland.

Risk of side branch occlusion during coronary angioplasty.

To assess the risk of side branch occlusion during percutaneous transluminal coronary angioplasty (PTCA), 600 consecutive procedures were analyzed. On the basis of pre-PTCA angiograms of 557 patients in whom the balloon was actually inflated, 365 side branches in 302 patients (54% of patients) were deemed in jeopardy. A total of 122 side branches in 102 patients (18%) originated from the lesion segment itself, i.e., their take-off was narrowed (Group I, 33% of side branches at risk), whereas 243 side branches in 214 patients (38%) originated from the immediate vicinity of the stenosis in a way that they were subjected to temporary occlusion during balloon dilatation (Group II, 67% of side branches at risk). Patency of side branches was determined by consensus of 2 observers. Criteria for occlusion were disappearance, filling by collaterals, or stagnation of flow. After PTCA, 20 of 365 side branches (5%) were occluded and associated with chest pain in 5 patients, creatine kinase increase in 6, left anterior hemiblock, septal Q waves and transient atrial fibrillation in 1 and non-sustained ventricular tachycardia in 1 of the 20 patients. Exercise tolerance did not decrease. No local predilection for side branch occlusion was evident. Seventeen of 122 side branches (14%) occluded in Group I, compared with 3 of 243 (1%) in Group II (p less than 0.001). Thus, more than half of the patients who underwent PTCA had side branches at risk for iatrogenic occlusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Percutaneous transluminal coronary angioplasty in patients with prior coronary bypass surgery

To improve symptomatic status and avoid reoperation, 122 initial and 7 repeat percutaneous transluminal coronary angioplasty procedures were performed in 116 patients with disabling angina pectoris at a mean of 26.8 months (range 2 to 132) after coronary bypass surgery. Marked angiographic improvement (greater than 30% reduction in diameter stenosis) was obtained in 107 (88%) of the 122 initial procedures and in all 7 repetitions. Mean stenosis was reduced from 78 +/- 13% (mean +/- standard deviation) to 25 +/- 13% (p less than 0.0001) and mean pressure gradient from 49 +/- 15 to 11 +/- 8 mm Hg (p less than 0.0001). Complications were: emergency surgery (three patients), Q wave infarction (one patient), myocardial infarction by enzyme criteria only (four patients) and non-occluding coronary dissection (one patient). There were no neurologic or peripheral vascular complications and no early deaths. One late death occurred 14 months after an unsuccessful but uncomplicated angioplasty procedure. At a mean follow-up of 8.3 months, 88 patients (76%) were free of angina or in improved condition. In patients followed up for at least 6 months, evidence of restenosis occurred in 9 (53%) of 17 saphenous veins, 1 (50%) of 2 proximal graft anastomoses, 4 (18%) of 22 distal graft anastomoses and 5 (14%) of 37 native coronary arteries. When coronary anatomy is suitable, percutaneous transluminal angioplasty is an attractive alternative to reoperation in symptomatic patients with prior coronary bypass surgery.

Value of the SYNTAX score for risk assessment in the all-comers population of the randomized multicenter LEADERS (Limus Eluted from A Durable versus ERodable Stent coating) trial

OBJECTIVES We aimed to assess the predictive value of the SYNTAX score (SXscore) for major adverse cardiac events in the all-comers population of the LEADERS (Limus Eluted from A Durable versus ERodable Stent coating) trial. BACKGROUND The SXscore has been shown to be an effective predictor of clinical outcomes in patients with multivessel disease undergoing percutaneous coronary intervention. METHODS The SXscore was prospectively collected in 1,397 of the 1,707 patients enrolled in the LEADERS trial (patients after surgical revascularization were excluded). Post hoc analysis was performed by stratifying clinical outcomes at 1-year follow-up, according to 1 of 3 SXscore tertiles. RESULTS The 1,397 patients were divided into tertiles based on the SXscore in the following fashion: SXscore<or=8 (SXlow) (n=464), SXscore>8 and <or=16 (SXmid) (n=472), and SXscore>16 (SXhigh) (n=461). At 1-year follow-up, there was a significantly lower number of patients with major cardiac event-free survival in the highest tertile of SXscore (SXlow=92.2%, SXmid=91.1%, and SXhigh=84.6%; p<0.001). Death occurred in 1.5% of SXlow patients, 2.1% of SXmid patients, and 5.6% of SXhigh patients (hazard ratio [HR]: 1.97, 95% confidence interval [CI]: 1.29 to 3.01; p=0.002). The myocardial infarction rate tended to be higher in the SXhigh group. Target vessel revascularization was 11.3% in the SXhigh group compared with 6.3% and 7.8% in the SXlow and SXmid groups, respectively (HR: 1.38, 95% CI: 1.1 to 1.75; p=0.006). Composite of cardiac death, myocardial infarction, and clinically indicated target vessel revascularization was 7.8%, 8.9%, and 15.4% in the SXlow, SXmid, and SXhigh groups, respectively (HR: 1.47, 95% CI: 1.19 to 1.81; p<0.001). CONCLUSIONS The SXscore, when applied to an all-comers patient population treated with drug-eluting stents, may allow prospective risk stratification of patients undergoing percutaneous coronary intervention. (LEADERS Trial Limus Eluted From A Durable Versus ERodable Stent Coating; NCT00389220).

Acute occlusion after percutaneous transluminal coronary angioplasty--a new approach.

Between July 1980 and November 1982, there were 935 coronary angioplasties attempted at Emory University Hospital. Of these patients, 20 developed acute occlusion. Of these 20, 19 presented within 3 hr of surgery or within 3 hr after stopping a continuous heparin infusion. Five patients required emergency surgery, but in 15 nitrates, nifedipine, and/or repeat angioplasty reopened the artery and the patient could be stabilized on continuous infusions of heparin and nitroglycerin. In only one case was an occluding thrombus evident on angiographic examination. The mechanism of acute occlusion is unknown, but coronary artery spasm may play a role.

Repeat Coronary Angioplasty

The potential of repeat percutaneous transluminal coronary angioplasty as a mode of therapy for recurrence of stenosis after initially successful angioplasty was examined on the basis of data on all 514 patients with successful angioplasty at Emory University before April 1982. Recurrence was found in 171 (33%) of the 514 patients. Repeat angioplasty was attempted in 95 patients with a significantly higher primary success rate (97 versus 85%, p less than 0.001) and a lower complication rate (8 versus 15%, p less than 0.10) than those of initial angioplasty. Follow-up documentation was available in all 92 patients with successful repeat angioplasty. A second recurrence of stenosis was found in 26% (24 of 92). A third angioplasty was performed in seven patients; six procedures were successful and there have been no recurrences of stenosis. Repeat coronary angioplasty provides a means to treat recurrence of stenosis. It proved to be very successful and safe and yielded good long-term results. It also increased the percent of patients with documented lasting success after angioplasty from 63 to 78%.

Does length or eccentricity of coronary stenoses influence the outcome of transluminal dilatation

In 526 patients undergoing a first percutaneous transluminal coronary angioplasty (PTCA) of a single native vessel, we studied the influence of length and eccentricity of the lesion on complications and primary success. Long stenoses (3a 5 mm, n = 153) did not differ from short stenoses (S 4 mm, n = 265) in terms of overall complications or gain in lumen diameter and distal pressure. Eccentric stenoses (n = 155) showed a lower rate of primary success than concentric stenoses (n = 338) (80% vs 89%, p < 0.05). Inability to cross the stenosis was the main reason for failure. Stenoses that were long and eccentric (n = 51) had the highest incidence of complications (24%) and stenoses that were short and concentric (n = 177) the lowest (12%, p < 0.05). However, the average outcome expressed by gain in lumen diameter and distal pressure was equal in both groups and is obviously more dependent on technical factors than on anatomy. Nevertheless, length and, particularly, eccentricity of a lesion constitute risk factors for PTCA. They may be overcome by technical skill and sophisticated equipment, such as steerable catheters.