Impact of acute coronary syndrome on clinical outcomes after revascularization with the dual-therapy CD34 antibody-covered sirolimus-eluting Combo stent and the sirolimus-eluting Orsiro stent.

OBJECTIVES: To compare the efficacy and safety of the dual-therapy CD34 antibody-covered sirolimus-eluting Combo stent (DTS) and the sirolimus-eluting Orsiro stent (O-SES) in patients with and without acute coronary syndrome (ACS) included in the SORT OUT X study. BACKGROUND: The incidence of target lesion failure (TLF) after treatment with modern drug-eluting stents has been reported to be significantly higher in patients with ACS when compared to patients without ACS. Whether the results from the SORT OUT X study apply to patients with and without ACS remains unknown. METHODS: In total, 3146 patients were randomized to stent implantation with DTS (n = 1578; ACS: n = 856) or O-SES (n = 1568; ACS: n = 854). The primary end point, TLF, was a composite of cardiac death, target-lesion myocardial infarction (MI), or target lesion revascularization (TLR) within 1 year. RESULTS: At 1 year, the rate of TLF was higher in the DTS group compared to the O-SES group, both among patients with ACS (6.7% vs. 4.1%; incidence rate ratio: 1.65 [95% confidence interval, CI: 1.08-2.52]) and without ACS (6.0% vs. 3.2%; incidence rate ratio: 1.88 [95% CI: 1.13-3.14]). The differences were mainly explained by higher rates of TLR, whereas rates of cardiac death and target lesion MI did not differ significantly between the two stent groups in patients with or without ACS CONCLUSION: Compared to the O-SES, the DTS was associated with a higher risk of TLF at 12 months in patients with and without ACS. The differences were mainly explained by higher rates of TLR.

Randomized Clinical Comparison of the Dual-Therapy CD34 Antibody-Covered Sirolimus-Eluting Combo Stent With the Sirolimus-Eluting Orsiro Stent in Patients Treated With Percutaneous Coronary Intervention: The SORT OUT X Trial.

BACKGROUND: Target lesion failure remains an issue with contemporary drug-eluting stents. Thus, the dual-therapy sirolimus-eluting and CD34+ antibody-coated Combo stent (DTS) was designed to further improve early healing. This study aimed to investigate whether the DTS is noninferior to the sirolimus-eluting Orsiro stent (SES) in an all-comers patient population. METHODS: The SORT OUT X (Combo Stent Versus Orsiro Stent) trial, was a large-scale, randomized, multicenter, single-blind, 2-arm, noninferiority trial with registry-based follow-up. The primary end point target lesion failure was a composite of cardiac death, myocardial infarction, or target lesion revascularization within 12 months, analyzed using intention-to-treat. The trial was powered for assessing target lesion failure noninferiority of the DTS compared with the SES with a predetermined noninferiority margin of 0.021. RESULTS: A total of 3146 patients were randomized to treatment with the DTS (1578 patients; 2008 lesions) or SES (1568 patients; 1982 lesions). At 12 months, intention-to-treat analysis showed that 100 patients (6.3%) assigned the DTS and 58 patients (3.7%) assigned the SES met the primary end point (absolute risk difference, 2.6% [upper limit of 1-sided 95% CI, 4.1%]; P (noninferiority)=0.76). The SES was superior to the DTS (incidence rate ratios for target lesion failure, 1.74 [95% CI, 1.26-2.41]; P=0.00086). The difference was explained mainly by a higher incidence of target lesion revascularization in the DTS group compared with the SES group (53 [3.4%] vs. 24 [1.5%]; incidence rate ratio, 2.22 [95% CI, 1.37-3.61]; P=0.0012). CONCLUSIONS: The DTS did not confirm noninferiority to the SES for target lesion failure at 12 months in an all-comer population. The SES was superior to the DTS mainly because the DTS was associated with an increased risk of target lesion revascularization. However, rates of death, cardiac death, and myocardial infarction at 12 months did not differ significantly between the 2 stent groups. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03216733.

Impact of diabetes on clinical outcomes after revascularization with the dual therapy CD34 antibody-covered sirolimus-eluting Combo stent and the sirolimus-eluting Orsiro stent.

OBJECTIVES: To compare the efficacy and safety of the dual therapy CD34 antibody-covered sirolimus-eluting Combo stent (DTS) and the sirolimus-eluting Orsiro stent (SES) in patients with and without diabetes mellitus (DM) included in the Scandinavian Organization for Randomized Trials with Clinical Outcome (SORT OUT) X study. BACKGROUND: The incidence of target lesion failure (TLF) after treatment with modern drug-eluting stents has been reported to be significantly higher in patients with DM when compared to patients without DM. Thus, whether the results from the SORT OUT X study apply to patients with and without DM remains unknown. METHODS: In total 3146 patients were randomized to stent implantation with DTS (n = 1578; DM: n = 279) or SES (n = 1568; DM: n = 271). The primary end point, TLF, was a composite of cardiac death, target-lesion myocardial infarction (MI), or target lesion revascularization (TLR) within 1 year. RESULTS: At 1 year, the rate of TLF was increased in the DTS group compared to the SES group, both among patients with DM (9.3% vs. 4.8%; risk difference: 4.5%; incidence rate ratio: 1.99, 95% confidence interval [CI]: 1.02-3.90) and without DM (5.7% vs. 3.5%; incidence rate ratio: 1.67, 95% CI: 1.15-2.42). The differences were mainly explained by higher rates of TLR. CONCLUSION: Compared to the SES, the DTS was associated with an increased risk of TLF at 12 months in patients with and without DM. The differences were mainly explained by higher rates of TLR, whereas rates of cardiac death and target lesion MI did not differ significantly between the two stent groups in patients with or without DM.

16-year follow-up of the Danish Acute Myocardial Infarction 2 (DANAMI-2) trial: primary percutaneous coronary intervention vs. fibrinolysis in ST-segment elevation myocardial infarction.

AIMS: The DANish Acute Myocardial Infarction 2 (DANAMI-2) trial found that interhospital transport to primary percutaneous coronary intervention (pPCI) was superior to fibrinolysis at the local hospital in patients with ST-segment elevation myocardial infarction (STEMI) at 30 days. The present study investigates the 16-year cardiovascular outcomes. METHODS AND RESULTS: We randomized 1572 STEMI patients to pPCI or fibrinolysis at 24 referral hospitals and 5 invasive centres in Denmark. Patients randomized to pPCI at referral hospitals were immediately transported to the nearest invasive centre. The main endpoint of the current study was a composite of death or rehospitalization for myocardial infarction (MI). Outcome information beyond 3 years was obtained through Danish health registries. After 16 years, pPCI-treated patients had a sustained lower rate of composite endpoint compared to patients treated with fibrinolysis in the overall cohort [58.7% vs. 62.3%; hazard ratio (HR) 0.86, 95% confidence interval (CI) 0.76-0.98], and among patients transported for pPCI (58.7% vs. 64.1%; HR 0.82, 95% CI 0.71-0.96). No difference in all-cause mortality was found, but cardiac mortality was reduced by an absolute of 4.4% in favour of pPCI (18.3% vs. 22.7%; HR 0.78, 95% CI 0.63-0.98). pPCI postponed a main event with 12.3 months in average compared to fibrinolysis (95% CI 5.0-19.5). CONCLUSION: The benefit of pPCI over fibrinolysis was maintained at 16-year follow-up. pPCI reduced the composite endpoint of death or rehospitalization for MI, reduced cardiac mortality, and delayed average time to a main event by approximately 1 year.

Coronary microvascular dysfunction and myocardial contractile reserve in women with angina and no obstructive coronary artery disease.

BACKGROUND: Coronary microvascular dysfunction (CMD) is a potential cause of myocardial ischemia and may affect myocardial function at rest and during stress. We investigated whether CMD was associated with left ventricular diastolic and systolic function at rest and during pharmacologically induced hyperemic stress. METHODS: In a prospective cohort study, we included 963 women with angina, left ventricular ejection fraction (LVEF) >45%, and an invasive coronary angiogram without significant stenosis (<50%). Parameters of left ventricular diastolic function, LVEF, speckle tracking-derived global longitudinal strain (GLS), and coronary flow velocity reserve (CFVR) were assessed by transthoracic echocardiography at rest and during dipyridamole stress. The GLS and LVEF reserves were defined as the absolute increases in GLS and LVEF during stress. RESULTS: Coronary flow velocity reserve (CFVR) was measured in 919 women of whom 26% had CMD (defined as CFVR < 2). Coronary microvascular dysfunction (CMD) was associated with higher age and a higher resting heart rate. Women with CMD had a reduced GLS reserve (P = .005), while we found no association between CFVR and LVEF at rest, GLS at rest, or the LVEF reserve, respectively. Global longitudinal strain (GLS) reserve remained associated with CFVR (P = .002) in a multivariable regression analysis adjusted for age, hemodynamic variables, and GLS at rest. In age-adjusted analysis, women with low CFVR had no signs of left ventricular diastolic dysfunction measured by echocardiography at rest. CONCLUSION: The GLS reserve was significantly lower in women with CMD. The mechanisms underlying the association between CMD and GLS reserve warrant further study.

Dual-therapy CD34 antibody-covered sirolimus-eluting COMBO stents versus sirolimus-eluting Orsiro stents in patients treated with percutaneous coronary intervention: the three-year outcomes of the SORT OUT X randomised clinical trial.

BACKGROUND: Target lesion failure (TLF) remains an issue with contemporary drug-eluting stents. The dual-therapy sirolimus-eluting and CD34 antibody-coated COMBO stent (DTS) was designed to improve early healing. AIMS: We aimed to compare the 3-year outcomes of the DTS and the sirolimus-eluting Orsiro stent (SES) in all-comer patients treated with percutaneous coronary intervention. METHODS: The SORT OUT X trial is a prospective multicentre randomised clinical trial with a registry-based follow-up comparing DTS and SES. The primary endpoint, TLF, is a composite of cardiac death, myocardial infarction or target lesion revascularisation (TLR). RESULTS: A total of 3,146 patients were randomised to treatment with the DTS (1,578 patients) or the SES (1,568 patients). At 3 years, an intention-to-treat analysis showed that 155 patients (9.8%) who were assigned the DTS and 118 patients (7.5%) who were assigned the SES met the primary endpoint (incidence rate ratio for TLF=1.33, 95% confidence interval: 1.04-1.70; p=0.02). This difference was caused by a significantly higher TLF rate in the DTS group compared to the SES group within the first year, which was mainly explained by a higher incidence of TLR in the DTS group compared to the SES group. Of note, the TLF rates were almost identical from 1 year to 3 years in both stent groups. CONCLUSIONS: At 3 years, the SES was superior to the DTS, mainly because the DTS was associated with an increased risk of TLF within the first year but not from 1 to 3 years. CLINICALTRIALS: gov: NCT03216733.

Myocardial CT perfusion compared with transthoracic Doppler echocardiography in evaluation of the coronary microvascular function: An iPOWER substudy.

BACKGROUND: A significant number of women with angina and no obstructive coronary artery disease (CAD; <50% stenosis) have coronary microvascular dysfunction (CMD) which carries an adverse cardiovascular prognosis. Coronary microvascular function can be evaluated by transthoracic Doppler echocardiography (TTDE) as a coronary flow velocity reserve (CFVR) and by static CT myocardial perfusion (CTP) as a myocardial perfusion reserve (MPR). Whether these methods are correlated is not known. We assessed the correlation between CFVR and MPR and investigated whether women with angina, CMD and no obstructive CAD have reduced MPR compared with asymptomatic women. METHODS: Static CTP with adenosine-induced vasodilation and TTDE of the left anterior descending artery with dipyridamole-induced vasodilation were successfully performed and analysed in 99 women with stable angina and no obstructive CAD and 33 asymptomatic women with no obstructive CAD. CMD was defined as CFVR < 2. RESULTS: Correlation between rate-pressure product corrected MPR and CFVR was weak but significant (r = .23; p = .007). MPR was highest among asymptomatic women with normal CFVR (median [interquartile range; IQR] 158 [145-181] %). Symptomatic women with normal CFVR had reduced MPR (148 [134-162] %; age-adjusted p < .001); however, the lowest MPR was found in symptomatic women with CMD (140 [129-164] %; age-adjusted p < .001), independent of cardiovascular risk factors and haemodynamic parameters (p = .017). CONCLUSION: Women with angina, CMD and no obstructive CAD had markedly diminished MPR compared with asymptomatic women. Correlation between CFVR and MPR was weak, suggesting that CTP and TTDE are not interchangeable for detection of CMD.

10-Year Clinical Outcome After Randomization to Treatment by Sirolimus- or Paclitaxel-Eluting Coronary Stents.

BACKGROUND: First-generation drug-eluting coronary stents (DES) were introduced in 2003 to 2004, and their use resulted in a considerable reduction in the development of in-stent restenosis at the cost of an increased risk of late stent thromboses. OBJECTIVES: This study followed clinical outcomes of patients included in a large randomized trial for 10 years to enable detection of late changes in annual event rates that could necessitate medical attention. METHODS: A total of 2,098 unselected all-comer patients (50% with acute coronary syndrome) were randomly assigned to have a first-generation DES implanted. This study recorded the occurrence of a major adverse cardiac event (MACE) assessed as the composite of cardiac death, myocardial infarction, and target vessel revascularization. Stent thromboses were also assessed. RESULTS: Of the 2,098 unselected patients, 73.1% were still alive after 10 years. During the follow-up period, MACE occurred in 346 (32.5%) in the group receiving a sirolimus-eluting stent and in 342 (33.1%) in the group receiving a paclitaxel-eluting stent (hazard ratio: 0.96; 95% confidence interval: 0.83 to 1.11; p = 0.60), with a steady annual rate of 2.6% after the first year. Definite, probable, and possible stent thrombosis appeared in 279 patients (13.3%), with no difference between stent types and with a steady annual rate of 1.3% after the first year. CONCLUSIONS: Among the surviving patients, the long-term annual MACE rate and the stent thrombosis rate appeared constant for both stent types, with no apparent late changes. Although there is no need for extraordinary medical attention for these patients, the absence of declines in annual event rates calls for continuous surveillance. (Danish Organization on Randomized Trials With Clinical Outcome II [SORT OUT II]; NCT00388934).

Comparison of Durable-Polymer Zotarolimus-Eluting and Biodegradable-Polymer Biolimus-Eluting Coronary Stents in Patients With Coronary Artery Disease: 3-Year Clinical Outcomes in the Randomized SORT OUT VI Trial.

OBJECTIVES: The authors sought to compare the safety and efficacy of the biocompatible durable-polymer zotarolimus-eluting stent with the biodegradable-polymer biolimus-eluting stent in unselected coronary patients. BACKGROUND: Biodegradable-polymer biolimus-eluting stents are superior to first-generation durable-polymer drug-eluting stents in long-term randomized all-comer trials. Long-term data comparing them to second-generation durable-polymer drug-eluting stents are lacking. METHODS: The study was a randomized, multicenter, all-comer, noninferiority trial in patients with chronic stable coronary artery disease or acute coronary syndromes and at least 1 coronary artery lesion requiring treatment with a drug-eluting stent. Endpoints included major adverse cardiac events (MACE), a composite of safety (cardiac death and myocardial infarction not clearly attributable to a non-target lesion) and efficacy (target lesion revascularization); the individual endpoints of MACE; all-cause mortality; any myocardial infarction; target vessel revascularization; and definite or probable stent thrombosis at 36 months. RESULTS: From March 2011 to August 2012, 2,999 patients were randomly assigned (1:1) to receive either the zotarolimus-eluting (1,502 patients) or the biolimus-eluting (1,497 patients) stent. At 3-year follow-up, MACE occurred in 128 (8.6%) patients assigned to the durable-polymer zotarolimus-eluting stent and in 144 (9.6%) assigned to the biodegradable-polymer biolimus-eluting stent (p = 0.36). Occurrence of cardiac death (2.7% vs. 3.4%), myocardial infarction not clearly attributable to a non-target lesion (2.7% vs. 2.5%), and target lesion revascularization (5.4% vs. 5.5%) did not differ significantly between the 2 groups. Definite very late stent thrombosis occurred in 6 (0.4%) patients assigned to the durable-polymer zotarolimus-eluting stent and in 10 (0.7%) assigned to the biodegradable-polymer biolimus-eluting stent (p = 0.33). CONCLUSIONS: At 3-year follow-up, the durable-polymer zotarolimus-eluting stent and the biodegradable-polymer biolimus-eluting stent were similar in clinical outcome, with no significant difference in safety and efficacy outcomes, including stent thrombosis.

Coronary Flow Velocity Reserve Assessed by Transthoracic Doppler: The iPOWER Study: Factors Influencing Feasibility and Quality.

BACKGROUND: Coronary flow velocity reserve (CFVR) measured by transthoracic Doppler echocardiography is a noninvasive measure of microvascular function, but it has not achieved widespread use, mainly because of concerns of validity and feasibility. The aim of this study was to describe the feasibility and factors associated with the quality of CFVR obtained in a large prospective study of women suspected of having microvascular disease. METHODS: Women with angina-like chest pain and no obstructive coronary artery disease on coronary angiography (<50% stenosis) were consecutively examined by transthoracic Doppler echocardiography of the left anterior descending coronary artery to measure CFVR (n = 947). Quality was evaluated on the basis of (1) identification of the left anterior descending coronary artery, (2) maintained probe position throughout the examination, (3) visibility and configuration of the left anterior descending coronary artery in two-dimensional color Doppler mode, and (4) gradual, consistent increases of characteristic, well-defined flow velocity curves in pulsed-wave mode. RESULTS: The mean age (SD) was 62.1 ± 9.7 years. On the basis of the evaluations, patients were divided into four groups according to quality score: nonfeasible (n = 28 [3%]), low quality (n = 80 [8%]), medium quality (n = 451 [48%]), and high quality (n = 388 [41%]). Quality score was associated with diabetes (P < .01), body mass index (P = .02), waist circumference (P = .05), nonsignificant atherosclerosis on coronary angiography (P = .03), and operator experience (P < .01). Low examination quality was associated with lower CFVR (P = .03), also after multivariate adjustment. CONCLUSIONS: Transthoracic Doppler echocardiographic measurement of CFVR is highly feasible and of good quality in experienced hands. However, CFVR is possibly underestimated when examination quality is low. Awareness of pitfalls and potential bias may improve the validity and interpretation of the measures obtained.

Outcomes after revascularisation with everolimus- and sirolimus-eluting stents in patients with acute coronary syndromes and stable angina pectoris: a substudy of the SORT OUT IV trial.

AIMS: The aim of this substudy of the SORT OUT IV trial was to compare clinical outcomes among patients with acute coronary syndromes (ACS) and stable angina pectoris (SAP) treated with everolimus-eluting stents (EES) or sirolimus-eluting stents (SES). METHODS AND RESULTS: We performed a post hoc subgroup analysis of data from SORT OUT IV. Of 2,705 patients, 1,178 (43.5%) patients had ACS and were treated with EES (n=580) or SES (n=598), and 1,527 (56.5%) patients had SAP and were treated with EES (n=773) or SES (n=754). The primary composite endpoint was major adverse cardiac events (MACE): cardiac death, myocardial infarction (MI), stent thrombosis, or target vessel revascularisation within 18 months. Hazard ratios (HR) and 95% confidence intervals (CI) were calculated for the endpoints. At 18-month follow-up, patients with ACS had higher rates of MACE compared to patients with SAP (8.1% versus 6.7%; HR=1.23, 95% CI: 0.93-1.62). MACE did not differ significantly between ACS patients treated with EES or SES (7.3% versus 8.9%; HR=0.81, 95% CI: 0.54-1.22) nor between SAP patients treated with EES or SES (6.9% versus 6.5%; HR=1.05, 95% CI: 0.71-1.55). CONCLUSIONS: EES and SES performed similarly with respect to MACE at 18-month follow-up in patients with ACS and SAP.