Summary Background Third-generation, permanent-polymer-based drug-eluting stents with novel, flexible designs might be more easily delivered than previous generations of stents in complex coronary ...lesions, but might be less longitudinally stable. We aimed to assess the safety and efficacy in all-comer patients of two third-generation stents that are often used clinically, but that have not yet been compared, and one of which has not previously been assessed in a randomised trial. Methods In this investigator-initiated, single-blind, multicentre, randomised, two-arm, non-inferiority trial, patients aged 18 years and older who required a percutaneous coronary intervention with implantation of a drug-eluting stent were recruited from four study sites in the Netherlands. We randomly assigned patients by independently managed computer-generated allocation sequences in a 1:1 ratio to receive either cobalt-chromium-based zotarolimus-eluting stents (Resolute Integrity, Medtronic, Santa Rosa, CA, USA) or platinum-chromium-based everolimus-eluting stents (Promus Element, Boston Scientific, Natick, MA, USA). Patients and analysts were masked to the allocated stent, but treating clinicians were not. The primary endpoint of target-vessel failure was a composite of safety (cardiac death or target-vessel-related myocardial infarction) and efficacy (target-vessel revascularisation) at 12 months, analysed by intention to treat (with a non-inferiority margin of 3·6%). This trial is registered with ClinicalTrials.gov , number NCT01331707. Findings Between Nov 25, 2010, and May 24, 2012, 1811 eligible all-comer patients, with 2371 target lesions, were enrolled in the study. 370 (20%) patients presented with ST-elevation myocardial infarction and 447 (25%) with non-ST-elevation myocardial infarction. 906 patients were assigned to receive zotarolimus-eluting stents and 905 to receive everolimus-eluting stents. Ease of stent delivery was shown by very low numbers of patients requiring treatment other than their assigned study treatment (six 1% in the zotarolimus-eluting stent group vs five 1% in the everolimus-eluting stent group; p=0·22). 12-month follow-up results were available for 1810 patients (one patient in the zotarolimus-eluting stent group withdrew consent). The primary endpoint was met by 55 (6%) of 905 patients in the zotarolimus-eluting stent group and 47 (5%) of 905 in the everolimus-eluting stent group. The zotarolimus-eluting stent was non-inferior to the everolimus-eluting stent (absolute risk difference 0·88%, 95% CI −1·24% to 3·01%; upper limit of one-sided 95% CI 2·69%; non-inferiority p=0·006). We noted no significant between-group differences in individual components of the primary endpoint. Definite stent thrombosis occurred in three (0·3%) patients in the zotarolimus-eluting stent group and six (0·7%) patients in the everolimus-eluting stent group (p=0·34). Longitudinal stent deformation was seen only in the everolimus-eluting stent group (nine 1·0% of 905 vs 0 of 906, p=0·002; nine of 1591 0·6% everolimus-eluting stents implanted became deformed), but was not associated with any adverse events. Interpretation Both stents were similarly efficacious and safe, and provided excellent clinical outcomes, especially in view of the large number of patients who presented with acute myocardial infarctions. Funding Boston Scientific, Medtronic.
The study sought to evaluate for the first time the 5-year outcomes after treating an all-comers population with newer-generation cobalt chromium-based Resolute Integrity zotarolimus-eluting stents ...(ZES) (Medtronic, Santa Rosa, California) versus platinum chromium-based PROMUS Element everolimus eluting stents (EES) (Boston Scientific, Natick, Massachusetts).
The DUTCH PEERS (TWENTE II) (DUrable polymer-based sTent CHallenge of Promus ElemEnt versus ReSolute integrity: TWENTE II) trial is a randomized, multicenter, single-blinded, investigator-initiated all-comers trial that found at its main analysis similar 1-year safety and efficacy for both drug-eluting stents. It is the first randomized trial ever to investigate the Resolute Integrity ZES and the first trial to compare both devices.
In total, 1,811 patients were 1:1 randomized to ZES versus EES. We performed a pre-specified assessment of the 5-year clinical outcomes in terms of safety and efficacy. The main endpoint target vessel failure (TVF) is a composite of cardiac death, target vessel-related myocardial infarction, or target vessel revascularization. Secondary endpoints included the individual components of TVF, and stent thrombosis. The study was independently monitored, and adverse clinical events were independently adjudicated.
Five-year clinical follow-up data was available in 1,798 (99.3%) patients. The ZES and EES groups showed favorable outcomes, with similar 5-year incidence of TVF (13.2% vs. 14.2%; p
= 0.62) and its individual components: cardiac death (4.5% vs. 4.9%; p
= 0.69), target vessel-related myocardial infarction (3.1% vs. 2.6%; p
= 0.47), and target vessel revascularization (7.6% vs. 8.6%; p
= 0.46). The 5-year incidence of definite or probable stent thrombosis was similar (1.5% vs. 1.3%; p
= 0.83).
At 5-year follow-up, the Resolute Integrity ZES and PROMUS Element EES showed similar and sustained results in terms of safety and efficacy for treating a broad population of all-comers.
Background Drug-eluting stents (DES) are increasingly used for the treatment of coronary artery disease. An optimized DES performance is desirable to successfully treat various challenging coronary ...lesions in a broad population of patients. In response to this demand, third-generation DES with an improved deliverability were developed. Promus Element (Boston Scientific, Natick, MA) and Resolute Integrity (Medtronic Vascular, Santa Rosa, CA) are 2 novel third-generation DES for which limited clinical data are available. Accordingly, we designed the current multicenter study to investigate in an all-comers population whether the clinical outcome is similar after stenting with Promus Element versus Resolute Integrity. Methods DUTCH PEERS is a multicenter, prospective, single-blinded, randomized trial in a Dutch all-comers population. Patients with all clinical syndromes who require percutaneous coronary interventions with DES implantation are eligible. In these patients, the type of DES implanted will be randomized in a 1:1 ratio between Resolute Integrity versus Promus Element. The trial is powered based on a noninferiority hypothesis. For each stent arm, 894 patients will be enrolled, resulting in a total study population of 1,788 patients. The primary end point is the incidence of target vessel failure at 1-year follow-up. Summary DUTCH PEERS is the first randomized multicenter trial with a head-to-head comparison of Promus Element and Resolute Integrity to investigate the safety and efficacy of these third-generation DES.
The aim of this report was to assess the three-year safety and efficacy of implanting newer-generation Resolute Integrity zotarolimus-eluting stents (ZES) versus PROMUS Element everolimus-eluting ...stents (EES) in all-comers.
In the randomised, multicentre, investigator-initiated DUTCH PEERS trial, a total of 1,811 all-comers were 1:1 randomly assigned to treatment with ZES versus EES. A total of 1,293 patients (72%) were treated for complex lesions and 455 patients (25%) were treated for multiple lesions. The primary endpoint target vessel failure (TVF) is a composite of cardiac death, target vessel-related myocardial infarction or target vessel revascularisation. Adverse clinical events were independently adjudicated. Three-year follow-up data were obtained in 1,807 patients (99.8%, four withdrawals). Both the ZES and EES groups showed favourable outcomes with a similar incidence of TVF (10.7% vs. 10.3%; pLog-rank=0.77) and the individual components thereof: cardiac death (3.2% vs. 3.1%; pLog-rank=0.87), target vessel-related myocardial infarction (2.8% vs. 2.2%; pLog-rank=0.44) and target vessel revascularisation (6.0% vs. 6.2%; pLog-rank=0.87). In addition, the incidence of definite or probable stent thrombosis was similar for patients treated with ZES versus EES (1.4% vs. 1.1%; pLog-rank=0.66).
The safety and efficacy of treating all-comers with newer-generation Resolute Integrity and PROMUS Element stents was found to be extended up to three years.
This study assessed clinical events and patient-reported chest pain 2 years after treatment of all-comers with Resolute Integrity zotarolimus-eluting stents (Medtronic Vascular, Santa Rosa, ...California) and Promus Element everolimus-eluting stents (Boston Scientific, Natick, Massachusetts).
For both drug-eluting stents (DES), no all-comer outcome data from >12 months of follow-up have been published. Although there is increasing interest in patient-reported chest pain following stenting, data with novel DES are scarce.
The DUTCH PEERS multicenter trial (TWENTE II) (DUrable Polymer-Based STent CHallenge of Promus ElemEnt Versus ReSolute Integrity) Randomized Trial TWENTE II) randomized 1,811 all-comer patients to treatment with 1 type of DES. Monitoring and event adjudication were performed by independent contract research organizations.
The 2-year follow-up of 1,810 patients (99.9%) was available. The primary composite endpoint target vessel failure occurred in 8.6% and 7.8% of patients treated with zotarolimus- and everolimus-eluting stents, respectively (p = 0.55). Rates of components of target vessel failure were: cardiac death (2.4% vs. 1.9%, p = 0.42); target vessel-related myocardial infarction (2.4% vs. 1.8%, p = 0.33); clinically-indicated target vessel revascularization (4.6% vs. 4.9%, p = 0.83). At 1- and 2-year follow-up, >80% of patients were free from chest pain (no between-stent difference). In addition, >87% of patients were either free from chest pain or experienced pain only at maximal physical exertion, but not during normal daily activities. Patients with chest pain after 12 months at no more than moderate physical effort had a higher risk of target vessel revascularization during the following year (hazard ratio: 1.89 95% confidence interval: 1.05 to 3.39, p = 0.03).
During the second year of follow-up, the incidence of adverse clinical endpoints remained similar and low for both DES. The vast majority of patients were free from chest pain.
Background
Percutaneous coronary intervention (PCI) in bifurcated lesions with second-generation drug-eluting stents (DES) was associated with increased myocardial infarction (MI) rates. Flexible ...stent designs that accommodate well to vessel tapering may be of benefit in challenging anatomies such as bifurcated target lesions, but so far data are scarce.
Methods
We analyzed the 2-year follow-up data of the DUTCH PEERS (TWENTE II) trial, which randomized 1811 all-comer patients to PCI with newer generation resolute integrity zotarolimus-eluting (Medtronic) or promus element everolimus-eluting stents (Boston Scientific). In bifurcated lesions, provisional stenting was generally performed. Target vessel failure is a composite endpoint, consisting of cardiac death, target vessel MI, or target vessel revascularization.
Results
Patients with at least one bifurcated lesion (
n
= 465, 25.7 %) versus patients with non-bifurcated target lesions only (
n
= 1346, 74.3 %) showed similar rates of clinical endpoints including target vessel failure (9.2 versus 7.9 %,
p
= 0.36) and definite stent thrombosis (0.4 versus 1.0 %,
p
= 0.38). Target vessel MI was more common in patients with bifurcated lesions (3.4 versus 1.6 %,
p
= 0.02); but after multivariate analysis with propensity score adjustment, bifurcation treatment was found not to be an independent predictor of target vessel MI (HR 1.40, 95 % CI 0.71–2.76;
p
= 0.34). Among patients with bifurcated lesions, DES type and side-branch size did not affect outcome, but periprocedural MI occurred more often after two-stent approaches (9.0 versus 2.1 %;
p
= 0.002).
Conclusion
All-comer patients treated for bifurcated and non-bifurcated target lesions showed similar and low rates of clinical endpoints, suggesting that the DES used are efficacious and safe for treating bifurcated target lesions.
Limited data is available on the long-term outcome of patients with increased cardiovascular event risk, treated with newer-generation durable polymer drug-eluting stents (DES).
We therefore assessed ...3-year follow-up data of high-risk versus low- to intermediate-risk patients of the randomized DUTCH PEERS trial (NCT01331707). In both risk groups we also compared patients treated with Resolute Integrity versus Promus Element DES. Patients were categorized as "high-risk" if they met ≥1 of the following criteria: (1) diabetes (17.9%); (2) previous myocardial infarction (21.9%); (3) previous coronary revascularization (25.8%); (4) chronic renal failure (3.5%); (5) left ventricular ejection fraction ≤30% (1.5%); and (6) age ≥75 years (17.3%).
At the 3-year follow-up, the incidence of the composite endpoint target vessel failure (TVF) (13.2 vs. 7.5%; logrank p < 0.001) and 2 of its components - cardiac death (4.7 vs. 1.5%; logrank p < 0.001) and target vessel revascularization (7.3 vs. 4.7%; logrank p = 0.03) - was higher in high-risk (n = 957) versus low- to intermediate-risk patients (n = 854). Among high-risk patients, treatment with Resolute Integrity (n = 481) and Promus Element stents (n = 476) was similarly safe and efficacious (TVF: 13.3 vs. 13.1%; logrank p = 0.95; definite-or-probable stent thrombosis: 1.7 vs. 1.7%; logrank p = 1.00).
The newer-generation Resolute Integrity and Promus Element stents showed similar results in terms of safety and efficacy for treating high-risk patients, who had significantly higher event rates than patients with low-to-intermediate risk.
Background Spinal cord stimulation is known to be a successful treatment for chronic intractable angina pectoris. Its effect may be anti-ischemic. It is uncertain if the clinical effect is partly ...caused by a placebo effect of surgery for implantation of a stimulator. In this study, clinical efficacy is investigated, together with a possible placebo effect.
Methods and Results Efficacy of spinal cord stimulation as a treatment for chronic intractable angina pectoris was studied for 6 weeks in 13 treated patients and 12 control patients with chronic angina. Assessments were exercise capacity and ischemia, daily frequency of anginal attacks and nitrate tablet consumption, and quality of life (perceived quality of life and pain). Compared with control, exercise duration (
P =.03) and time to angina (
P = .01) increased; anginal attacks and sublingual nitrate consumption (
P = .01) and ischemic episodes on 48-hour electrocardiogram (
P = .04) decreased. ST-segment depression on the exercise electrocardiogram decreased at comparable workload (
P = .01). Anginal attacks and consumption of sublingual nitrates decreased (
P = .01), perceived quality of life increased (
P = .03), and pain decreased (
P = .01).
Conclusions Spinal cord stimulation is effective in chronic intractable angina pectoris, and its effect is exerted through anti-ischemic action. Efficacy is unlikely to be explained as a placebo effect from surgery. (Am Heart J 1998;136:1114-20.)
The anatomy of cardiac activity-regulating circuitry was studied with retrograde transneuronal viral labelling after pseudorabies virus injections into different parts of the rat heart. Transection ...of the spinal cord at Th1 was used to reveal selectively the parasympathetic neuronal networks. Virus-labelled sympathetic preganglionic cells were found in the Th1-Th7 thoracic intermediolateral cell groups, with some additional infections at Th8-Th11 after inoculations of the ventricular myocardium. After ventricular injections the thoracic spinal labelling pattern was bilateral and after right atrial infection it was contralateral. Approximately 20% of the parasympathetic preganglionic cells were located in the dorsal motor vagus nucleus; the rest occupied positions in the peri-ambiguus area ventrolateral to the nucleus ambiguus. Here and in the ventrolateral reticular formation myocardiotopy was found. Supraspinal transneuronal infections were bilateral, showed no apparent side dominance and were found in the nucleus of the solitary tract, the area postrema, the raphe nuclei, the A5 group, the parabrachial region, the periaqueductal grey, the hypothalamus, the amygdala and the cortex, in particular the anterior cingulate, the frontal, prelimbic, infralimbic and insular cortices. Spinal transections at Th1 reduced the number of labelled cells, gave a right side labelling dominance and affected the infection patterns in the ventrolateral reticular area, the raphe nuclei, the periaqueductal grey matter, the perifornical and retrochiasmatic area and the rostral parts of the insular cortex. The latter structures are linked selectively to the sympathetic innervation of the heart. The anatomical and functional aspects of these findings are discussed in relation to the autonomic control of heart activity.
Spinal cord stimulation in angina pectoris increases exercise capacity and reduces both anginal attacks and ischemic electrocardiographic signs. This suggests an anti-ischemic action, perhaps through ...changes in myocardial blood flow. In 9 patients, regional myocardial blood flow was studied with positron emission tomography before and after 6 weeks of spinal cord stimulation, both at rest and during a dipyridamole stress test. Frequency of anginal attacks ana consumption of short-acting nitrates were assessed by patient diaries. Exercise duration and time to angina were measured with treadmill exercise tests. After 6 weeks of stimulation, both frequency of daily anginal attacks and nitrogen consumption decreased (3.7 ± 1.7 vs 1.4 ± 1.0 p < 0.01 and 2.8 ± 2.2 vs 1.1 ± 1.2 tablets p = 0.01, respectively); exercise duration and time to angina increased (358 ± 165 vs 493 ± 225 seconds p < 0.01 and 215 ± 115 vs 349 ± 213 seconds p = 0.02, respectively); and ST-segment depression during dipyridamole stress testing was reduced (0.17 0 to 0.5 mV vs 0.09 0 to 0.2 mV, p = 0.04) (all data mean ± SD). Total resting blood flow remained unchanged (115 ± 29 vs 127 ± 31 ml/min/100 g, p = 0.31), but flow reserve decreased (146 ± 43% vs 122 ± 39%, p = 0.04). The coefficient of variation of flow, representing flow heterogeneity, decreased after treatment, both at rest (20.1 ± 3.8% vs 17.4 ± 2.6%, p = 0.04) and after dipyridamole stress (26.2 ± 4.4% vs 22.9 ± 5.5%, p = 0.02). Thus, spinal cord stimulation is clinically effective due to homogenization of myocardial blood flow. Since flow reserve decreases despite clinical improvement, the dipyridamole effect may be blunted by spinal cord stimulation.
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