Impact of premature coronary artery disease on adverse event risk following first percutaneous coronary intervention.

Objectives: We assessed differences in risk profile and 3-year outcome between patients undergoing percutaneous coronary intervention (PCI) for premature and non-premature coronary artery disease (CAD). Background: The prevalence of CAD increases with age, yet some individuals develop obstructive CAD at younger age. Methods: Among participants in four randomized all-comers PCI trials, without previous coronary revascularization or myocardial infarction (MI), we compared patients with premature (men <50 years; women <55 years) and non-premature CAD. Various clinical endpoints were assessed, including multivariate analyses. Results: Of 6,171 patients, 887 (14.4%) suffered from premature CAD. These patients had fewer risk factors than patients with non-premature CAD, but were more often smokers (60.7% vs. 26.4%) and overweight (76.2% vs. 69.8%). In addition, premature CAD patients presented more often with ST-segment elevation MI and underwent less often treatment of multiple vessels, and calcified or bifurcated lesions. Furthermore, premature CAD patients had a lower all-cause mortality risk (adj.HR: 0.23, 95%-CI: 0.10-0.52; p < 0.001), but target vessel revascularization (adj.HR: 1.63, 95%-CI: 1.18-2.26; p = 0.003) and definite stent thrombosis risks (adj.HR: 2.24, 95%-CI: 1.06-4.72; p = 0.034) were higher. MACE rates showed no statistically significant difference (6.6% vs. 9.4%; adj.HR: 0.86, 95%-CI: 0.65-1.16; p = 0.33). Conclusions: About one out of seven PCI patients was treated for premature CAD. These patients had less complex risk profiles than patients with non-premature CAD; yet, their risk of repeated revascularization and stent thrombosis was higher. As lifetime event risk of patients with premature CAD is known to be particularly high, further efforts should be made to improve modifiable risk factors such as smoking and overweight. TWENTE trials: (TWENTE I, clinicaltrials.gov: NCT01066650), DUTCH PEERS (TWENTE II, NCT01331707), BIO-RESORT (TWENTE III, NCT01674803), and BIONYX (TWENTE IV, NCT02508714).

First myocardial infarction in patients with premature coronary artery disease: insights into patient characteristics and outcome after treatment with contemporary stents.

AIMS: Patients with premature coronary artery disease (CAD) have a higher incidence of myocardial infarction (MI) than patients with non-premature CAD. The aim of the present study is to asess differences in clinical outcome after a first acute MI, percutaneously treated with new-generation drug-eluting stents between patients with premature and non-premature CAD. METHODS AND RESULTS: We pooled and analysed the characteristics and clinical outcome of all patients with a first MI (and no previous coronary revascularization) at time of enrolment, in four large-scale drug-eluting stent trials. Coronary artery disease was classified premature in men aged <50 and women <55 years. Myocardial infarction patients with premature and non-premature CAD were compared. The main endpoint was major adverse cardiac events (MACE): all-cause mortality, any MI, emergent coronary artery bypass surgery, or clinically indicated target lesion revascularization. Of 3323 patients with a first MI, 582 (17.5%) had premature CAD. These patients had lower risk profiles and underwent less complex interventional procedures than patients with non-premature CAD. At 30-day follow-up, the rates of MACE [hazard ratio (HR): 0.22, 95% confidence interval (CI): 0.07-0.71; P = 0.005), MI (HR: 0.22, 95% CI: 0.05-0.89; P = 0.020), and target vessel failure (HR: 0.30, 95% CI: 0.11-0.82; P = 0.012) were lower in patients with premature CAD. At 1 year, premature CAD was independently associated with lower rates of MACE (adjusted HR: 0.50, 95% CI: 0.26-0.96; P = 0.037) and all-cause mortality (adjusted HR: 0.24, 95% CI: 0.06-0.98; P = 0.046). At 2 years, premature CAD was independently associated with lower mortality (adjusted HR: 0.16, 95% CI: 0.05-0.50; P = 0.002). CONCLUSIONS: First MI patients with premature CAD, treated with contemporary stents, showed lower rates of MACE and all-cause mortality than patients with non-premature CAD, which is most likely related to differences in cardiovascular risk profile. TWENTE trials: TWENTE I, clinicaltrials.gov: NCT01066650), DUTCH PEERS (TWENTE II, NCT01331707), BIO-RESORT (TWENTE III, NCT01674803), and BIONYX (TWENTE IV, NCT02508714).

Risk of bleeding after percutaneous coronary intervention and its impact on further adverse events in clinical trial participants with comorbid peripheral arterial disease.

BACKGROUND: Both patients with obstructive coronary artery disease (CAD) and patients with peripheral arterial disease (PADs) have an increased bleeding risk. Information is scarce on bleeding in CAD patients, treated with percutaneous coronary intervention (PCI), who have comorbid PADs. We assessed whether PCI patients with PADs have a higher bleeding risk than PCI patients without PADs. Furthermore, in PCI patients with PADs we evaluated the extent by which bleeding increased the risk of further adverse events. METHODS: Three-year pooled patient-level data of two randomized PCI trials (BIO-RESORT, BIONYX) with drug-eluting stents were analyzed to assess mortality and the composite endpoint major adverse cardiac events (MACE: all-cause mortality, any myocardial infarction, emergent coronary artery bypass surgery, or target lesion revascularization). RESULTS: Among 5989 all-comer patients, followed for 3 years, bleeding occurred in 7.7% (34/440) with comorbid PADs and 5.0% (279/5549) without PADs (HR: 1.59, 95%CI: 1.11-2.23, p = 0.010). Of all PADs patients, those with a bleeding had significantly higher rates of all-cause mortality (HR: 4.70, 95%CI: 2.37-9.33, p < 0.001) and MACE (HR: 2.39, 95%CI: 1.23-4.31, p = 0.003). Furthermore, PADs patients with a bleeding were older (74.4 ± 6.9 vs. 67.4 ± 9.5, p < 0.001). After correction for age and other potential confounders, bleeding remained independently associated with all-cause mortality (adj.HR: 2.97, 95%CI: 1.37-6.43, p = 0.006) while the relation of bleeding with MACE became borderline non-significant (adj.HR: 1.85, 95%CI: 0.97-3.55, p = 0.06). CONCLUSION: PCI patients with PADs had a higher bleeding risk than PCI patients without PADs. In PADs patients, bleeding was associated with all-cause mortality, even after adjustment for potential confounders.

Clinical results after hybrid coronary revascularization with totally endoscopic coronary surgery.

BACKGROUND: The optimal revascularization strategy remains uncertain in multivessel coronary artery disease (MVCAD). The durability of the surgical grafts should be weighed against the decreased invasiveness of percutaneous coronary intervention (PCI). Hybrid coronary revascularization (HCR), a combination of PCI and surgery, could be a feasible alternative. This study aimed to investigate the occurrence of major adverse cardiac and cerebrovascular events (MACCE) and all-cause mortality after both endoscopic coronary artery bypass grafting (Endo-CABG) and the HCR procedure. METHODS: In this single-center retrospective observational study, 347 consecutive patients have been subjected to an Endo-CABG procedure, of which 103 underwent HCR between January 2016 and January 2018. A propensity score matching analysis was performed to match 103 Endo-CABG alone patients to the 103 HCR patients. The Endo-CABG procedure was performed through 3 endoscopic ports (5 mm) in the 2nd, 3rd, and 4th intercostal space and a utility port of 3 cm. RESULTS: In both the HCR and matched endo-CABG alone group, the 30-day mortality was acceptable (0% in the HCR group and 1.94% in the matched Endo-CABG alone group, p = 0.155). Additionally, the occurrence of MACCE after a mean follow-up of 1188 ± 538 days was similar in both groups (9.71% and 11.65% for the HCR and matched Endo-CABG alone group, respectively, p = 0.652). Still, the long-term all-cause mortality over this period was significantly higher in the matched Endo-CABG alone group (2.91% after the HCR procedure and 11.65% after matched Endo-CABG alone, p = 0.002). CONCLUSION: HCR has some advantages over Endo-CABG alone regarding the all-cause mortality, cross-clamping time, intensive care unit, and hospital length of stay. Therefore, HCR may be a suitable alternative therapy for patients with MVCAD.

New-generation drug-eluting coronary stents in octogenarians: Patient-level pooled analysis from the TWENTE I-IV trials.

BACKGROUND: Patients aged ≥80 years are often treated with new-generation drug-eluting stents (DES), but data from randomized studies are scarce owing to underrepresentation in most trials. We assessed 1-year clinical outcome of octogenarians treated with new-generation DES versus younger patients. METHODS: We pooled patient-level data of 9,204 participants in the TWENTE, DUTCH PEERS, BIO-RESORT, and BIONYX (TWENTE I-IV) randomized trials. The main clinical end point was target vessel failure (TVF), a composite of cardiac death, target vessel-related myocardial infarction (MI), or clinically indicated target vessel revascularization. RESULTS: The 671 octogenarian trial participants had significantly more comorbidities. TVF was higher in octogenarians than in 8,533 patients <80 years (7.3% vs 5.3%, hazard ratio [HR]: 1.36, 95% CI: 1.0-1.83, P = .04). The cardiac death rate was higher in octogenarians (3.9% vs 0.8%, P < .001). There was no significant between-group difference in target vessel MI (2.3% vs 2.3%, P = .88) and repeat target vessel revascularization (1.9% vs 2.8%, P = .16). In multivariate analyses, age ≥ 80 years showed no independent association with TVF (adjusted HR: 1.04, 95% CI: 0.76-1.42), whereas the risk of cardiac death remained higher in octogenarians (adjusted HR: 3.38, 95% CI: 2.07-5.52, P < .001). In 6,002 trial participants, in whom data on major bleeding were recorded, octogenarians (n = 459) showed a higher major bleeding risk (5.9% vs 1.9%; HR: 3.08, 95% CI: 2.01-4.74, P < .001). CONCLUSIONS: Octogenarian participants in 4 large-scale randomized DES trials had more comorbidities and a higher incidence of the main end point TVF. Cardiac mortality was higher in octogenarians, whereas there was no increase in MI or target vessel revascularization rates. Treatment of octogenarian patients with new-generation DES appears to be safe and effective.

Impact of long-term ticagrelor monotherapy following 1-month dual antiplatelet therapy in patients who underwent complex percutaneous coronary intervention: insights from the Global Leaders trial.

AIMS: To evaluate the impact of an experimental strategy [23-month ticagrelor monotherapy following 1-month dual antiplatelet therapy (DAPT)] vs. a reference regimen (12-month aspirin monotherapy following 12-month DAPT) after complex percutaneous coronary intervention (PCI). METHODS AND RESULTS: In the present post hoc analysis of the Global Leaders trial, the primary endpoint [composite of all-cause death or new Q-wave myocardial infarction (MI)] at 2 years was assessed in patients with complex PCI, which includes at least one of the following characteristics: multivessel PCI, ≥3 stents implanted, ≥3 lesions treated, bifurcation PCI with ≥2 stents, or total stent length >60 mm. In addition, patient-oriented composite endpoint (POCE) (composite of all-cause death, any stroke, any MI, or any revascularization) and net adverse clinical events (NACE) [composite of POCE or Bleeding Academic Research Consortium (BARC) Type 3 or 5 bleeding] were explored. Among 15 450 patients included in this analysis, 4570 who underwent complex PCI had a higher risk of ischaemic and bleeding events. In patients with complex PCI, the experimental strategy significantly reduced risks of the primary endpoint [hazard ratio (HR): 0.64, 95% confidence interval (CI): 0.48-0.85] and POCE (HR: 0.80, 95% CI: 0.69-0.93), but not in those with non-complex PCI (Pinteraction = 0.015 and 0.017, respectively). The risk of BARC Type 3 or 5 bleeding was comparable (HR: 0.97, 95% CI: 0.67-1.40), resulting in a significant risk reduction in NACE (HR: 0.80, 95% CI: 0.69-0.92; Pinteraction = 0.011). CONCLUSION: Ticagrelor monotherapy following 1-month DAPT could provide a net clinical benefit for patients with complex PCI. However, in view of the overall neutral results of the trial, these findings of a post hoc analysis should be considered as hypothesis generating.

Ticagrelor plus aspirin for 1 month, followed by ticagrelor monotherapy for 23 months vs aspirin plus clopidogrel or ticagrelor for 12 months, followed by aspirin monotherapy for 12 months after implantation of a drug-eluting stent: a multicentre, open-label, randomised superiority trial.

BACKGROUND: We hypothesised that ticagrelor, in combination with aspirin for 1 month, followed by ticagrelor alone, improves outcomes after percutaneous coronary intervention compared with standard antiplatelet regimens. METHODS: GLOBAL LEADERS was a randomised, open-label superiority trial at 130 sites in 18 countries. Patients undergoing percutaneous coronary intervention with a biolimus A9-eluting stent for stable coronary artery disease or acute coronary syndromes were randomly assigned (1:1) to 75-100 mg aspirin daily plus 90 mg ticagrelor twice daily for 1 month, followed by 23 months of ticagrelor monotherapy, or standard dual antiplatelet therapy with 75-100 mg aspirin daily plus either 75 mg clopidogrel daily (for patients with stable coronary artery disease) or 90 mg ticagrelor twice daily (for patients with acute coronary syndromes) for 12 months, followed by aspirin monotherapy for 12 months. Randomisation was concealed, stratified by centre and clinical presentation (stable coronary artery disease vs acute coronary syndrome), and blocked, with randomly varied block sizes of two and four. The primary endpoint at 2 years was a composite of all-cause mortality or non-fatal centrally adjudicated new Q-wave myocardial infarction as assessed by a core lab in a blinded manner. The key secondary safety endpoint was site-reported bleeding assessed according to the Bleeding Academic Research Consortium criteria (grade 3 or 5). Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT01813435, and is closed to new participants, with follow-up completed. FINDINGS: Between July 1, 2013, and Nov 9, 2015, 15 968 participants were randomly assigned, 7980 to the experimental group and 7988 to the control group. At 2 years, 304 (3·81%) participants in the experimental group had died or had a non-fatal centrally adjudicated new Q-wave myocardial infarction, compared with 349 (4·37%) participants in the control group (rate ratio 0·87 [95% CI 0·75-1·01]; p=0·073]). There was no evidence for a difference in treatment effects for the primary endpoint across prespecified subgroups of acute coronary syndromes and stable coronary artery disease (p=0·93). Grade 3 or 5 bleeding occurred in 163 participants in the experimental group and 169 in the control group (2·04% vs 2·12%; rate ratio 0·97 [95% CI 0·78-1·20]; p=0·77). INTERPRETATION: Ticagrelor in combination with aspirin for 1 month followed by ticagrelor alone for 23 months was not superior to 12 months of standard dual antiplatelet therapy followed by 12 months of aspirin alone in the prevention of all-cause mortality or new Q-wave myocardial infarction 2 years after percutaneous coronary intervention. FUNDING: AstraZeneca, Biosensors, and The Medicines Company.

Hemolysis after percutaneous paravalvular leak repair.

Paravalvular leak is a common complication after surgical mitral valve replacement. Surgically implanted prosthetic valves are complicated with paravalvular leaks in 17%.1 Surgical closure of paravalvular leaks is the most common therapy for these defects. Percutaneous closure is an alternative to repeat surgery for a selected high-risk population. We present a case of a patient who developed severe haemolytic anaemia and secondary renal failure after partially successful percutaneous closure of paravalvular leakage of a prosthetic mitral valve. The assumption is that the combination of a metallic foreign body and high shear stress caused haemolysis by damaging red blood cells.

Randomised study of a bioabsorbable polymer-coated sirolimus-eluting stent: results of the DESSOLVE II trial.

AIMS: To compare the efficacy and safety of the MiStent absorbable polymer sirolimus-eluting stent (APSES) with a zotarolimus-eluting stent (ZES). METHODS AND RESULTS: The trial was a 2:1 randomisation at 26 sites of 184 patients implanted with an APSES (n=123) versus a ZES (n=61). Following stent implantation, all patients underwent quantitative coronary angiography at baseline and at nine months of follow-up, while a select subgroup also underwent optical coherence tomography (OCT). The primary efficacy hypothesis was superiority of in-stent late lumen loss (LLL) of APSES compared to ZES. At nine months, the primary endpoint was met, with a mean in-stent LLL of 0.27±0.46 mm in 103 APSES patients versus 0.58±0.41 mm in 52 ZES patients (p<0.001). The proportion of uncovered stent struts by OCT at nine months was very low in both groups. The mean neointimal thickness of covered struts (p=0.002) and percent net volume obstruction (p≤0.003) were significantly lower in the APSES than in the ZES group. Major adverse cardiac event and stent thrombosis rates were low and comparable between groups. CONCLUSIONS: The DESSOLVE II trial demonstrated superiority in the primary efficacy endpoint of nine-month mean LLL for APSES compared to ZES. Strut coverage by OCT was high with both stents and the clinical safety endpoints including stent thrombosis were equally low in both groups. ClinicalTrials.gov Identifier: NCT01294748.

A case of myocardial infarction not to be stented too quickly...

This is a case of an interventional dilemma about how to manage a large thrombus, located distally from and adherent to a severe stenosis in a coronary venous bypass graft, with a TIMI-3 flow in a patient with a non-ST-elevation myocardial infarction. This case report concerns a 70-year-old female patient, diagnosed with unstable angina, 18 asymptomatic years after coronary bypass surgery. Although a high risk of a severe ischaemic event is present, immediate coronary intervention is not mandatory since perfusion is maintained, and given the real risk of embolisation of the large thrombus, even contra-indicated. From this perspective, the option to bail out and install an extensive antithrombotic therapy prior to delayed intervention is reasonable.

Cardiac rehabilitation reduces the rate of major adverse cardiac events after percutaneous coronary intervention.

BACKGROUND: Despite multiple publications on effects of rehabilitation in cardiac patients, rehabilitation is not fully known to be of value in post-percutaneous coronary intervention (PCI) patients. AIMS: To investigate the influence of cardiac rehabilitation on the incidence of major adverse cardiac events (MACEs) in post-PCI patients. METHODS: Retrospectively and nonrandomized 140 post-PCI patients (107 males, mean age 62 (7) years) participated in a 3-month rehabilitation program, starting 2 weeks post-PCI, while 83 post-PCI patients (54 males, mean age 68 (8) years) did not and were all followed up for 15 months. Data on cardiac medication prescription and incidence of MACE (including angina pectoris with or without reintervention, restenosis, myocardial infarction, revascularisation with re-PCI or CABG, and death) were collected. The relationship with cardiovascular risk factors including sex, smoking behaviour, obesity, diabetes mellitus, hypertension, familiar predisposition, and hypercholesterolemia was analysed. RESULTS: The incidence of total MACE in the rehabilitation group is significantly lower than in the control group (24% vs. 42%, respectively; P<0.005). The incidence of documented restenosis, angina pectoris with resulting reintervention, all revascularisations, and death is significantly lower in the rehabilitation group, compared with the control group. CONCLUSION: The incidence of MACE and restenosis is significantly lower when PCI patients are included in a cardiac rehabilitation program.

Immediate sheath removal after PCI using a Femostop is feasible and safe. Results of a registry.

BACKGROUND: Due to antithrombotic therapy before, during, and after percutaneous coronary intervention (PCI), and due sometimes to the need for an urgent reintervention, the arterial femoral sheath is generally not removed immediately after PCI, unless a vascular closing device is used. This strategy causes discomfort to the patient, increases the workload for the nursing staff, and bears a risk of local complications. OBJECTIVE: The purpose of this registry is to demonstrate that immediate sheath removal after PCI is safe and feasible with the ultimate goal of enhancing patient care and hospital efficiency. METHODS: In patients undergoing PCI, the femoral arterial sheath was removed immediately after PCI in the cath lab, using a Femostop, without manual compression. The patient's discomfort and the complication rate were measured. The overall time given to haemostasis was assessed. RESULTS: A total of 339 patients were included. Patient discomfort during Femostop placement was assessed as follows: 85% suffered none, 2% slight, 3% moderate, and 10% severe discomfort. Complication rates were: 36% ecchimosis, 10% haematoma < 6 cm, 5% haematoma > or = 6 cm (literature data of manual compression--LDMC--5.1% to 9%), 1% pseudoaneurysm (LDMC 1% to 1.8%), 0.6% need for transfusion (LDMC 2.5%), 0.3% need for vascular repair (LDMC 1.5% to 2.7%). The patient's immobilisation time after PCI was reduced from at least 10 hours to 6 hours. The time given to haemostasis was also reduced. CONCLUSION: Immediate sheath removal using a Femostop is feasible, safe, and improves the patient's comfort. The complication rate is equal or even lower to that reported after classical manual compression. Early ambulation improves the patient's comfort, and reduced time given to haemostasis causes organisational benefit. If a vascular closing device is not routinely used after PCI (for example, for economical reasons), immediate sheath removal after PCI could be the routine strategy.