Recurrent angina and cardiac ischaemia as a presentation of pheochromocytoma: a case report.

Background: We present a case of a pregnant patient with recurrent angina, in which her symptoms were initially attributed to coronary artery spasm. However, during follow-up, she was diagnosed as having pheochromocytoma, a rare neuroendocrine tumour. Case summary: The 35-year-old patient was admitted to the hospital because of chest pain and elevated cardiac troponins after the use of MDMA. Physical examination, electrocardiogram, echocardiography, coronary angiogram, and cardiac MRI were normal. Symptoms were attributed to coronary spasm, and a calcium antagonist was started. Ten months later, when 36 weeks pregnant, her symptoms returned. One week later, the patient was readmitted to the hospital with signs of acute left ventricular (LV) failure, highly elevated troponins, and severe global LV dysfunction. Urgent section caesarean was performed due to maternal morbidity and foetal tachycardia. During section, flushes and marked variability in blood pressure were noted. Laboratory metanephrines testing was performed. LV function recovered within 3 days without any therapeutic intervention. However, chest pain reoccurred, now accompanied with headaches, malignant hypertension, and accelerated idiopathic ventricular rhythms. (Nor)metanephrines tests were positive. A solid lesion in the right adrenal on CT scan confirmed the diagnosis of pheochromocytoma. Fluid repletion and alpha-blocker therapy were started. Due to persistent symptoms, urgent laparoscopic adrenalectomy was performed. Hereafter, the patient remained without symptoms. Discussion: A pheochromocytoma may present with recurrent angina and can result in a catecholamine-induced cardiomyopathy. It is important to timely recognize this diagnosis in order to minimize morbidity and mortality.

Migraine and cardiovascular disease: what cardiologists should know.

Migraine is a chronic neurovascular disease with a complex, not fully understood pathophysiology with multiple causes. People with migraine suffer from recurrent moderate to severe headache attacks varying from 4 to 72 h. The prevalence of migraine is two to three times higher in women compared with men. Importantly, it is the most disabling disease in women <50 years of age due to a high number of years lived with disability, resulting in a very high global socioeconomic burden. Robust evidence exists on the association between migraine with aura and increased incidence of cardiovascular disease (CVD), in particular ischaemic stroke. People with migraine with aura have an increased risk of atrial fibrillation, myocardial infarction, and cardiovascular death compared with those without migraine. Ongoing studies investigate the relation between migraine and angina with non-obstructive coronary arteries and migraine patients with patent foramen ovale. Medication for the treatment of migraine can be preventative medication, such as beta-blockers, angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, antiepileptics, antidepressants, some of the long-acting calcitonin gene-related peptide receptor antagonists, or monoclonal antibodies against calcitonin gene-related peptide or its receptor, or acute medication, such as triptans and calcitonin gene-related peptide receptor antagonists. However, these medications might raise concerns when migraine patients also have CVD due to possible (coronary) side effects. Specifically, knowledge gaps remain for the contraindication to newer treatments for migraine. All cardiologists will encounter patients with CVD and migraine. This state-of-the-art review will outline the basic pathophysiology of migraine and the associations between migraine and CVD, discuss current therapies, and propose future directions for research.

Efficacy and safety of alirocumab and evolocumab: a systematic review and meta-analysis of randomized controlled trials.

AIMS: The effect of low-density lipoprotein cholesterol-lowering therapy with alirocumab or evolocumab on individual clinical efficacy and safety endpoints remains unclear. We aimed to evaluate the efficacy and safety of alirocumab and evolocumab in patients with dyslipidaemia or atherosclerotic cardiovascular disease. METHODS AND RESULTS: We performed a review of randomized controlled trials (RCTs) comparing treatment with alirocumab or evolocumab vs. placebo or other lipid-lowering therapies up to March 2018. Primary efficacy endpoints were all-cause death, cardiovascular death, myocardial infarction (MI), and stroke. We estimated risk ratios (RR) and 95% confidence intervals (CI) using random effect models. We included 39 RCTs comprising 66 478 patients of whom 35 896 were treated with proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitors (14 639 with alirocumab and 21 257 with evolocumab) and 30 582 with controls. Mean weighted follow-up time across trials was 2.3 years with an exposure time of 150 617 patient-years. Overall, the effects of PCSK9 inhibition on all-cause death and cardiovascular death were not statistically significant (P = 0.15 and P = 0.34, respectively). Proprotein convertase subtilisin-kexin type 9 inhibitors were associated with lower risk of MI (1.49 vs. 1.93 per 100 patient-year; RR 0.80, 95% CI 0.74-0.86; I  2 = 0%; P < 0.0001), ischaemic stroke (0.44 vs. 0.58 per 100 patient-year; RR 0.78, 95% CI 0.67-0.89; I  2 = 0%; P = 0.0005), and coronary revascularization (2.16 vs. 2.64 per 100 patient-year; RR 0.83, 95% CI 0.78-0.89; I  2 = 0%; P < 0.0001), compared with the control group. Use of these PCSK9 inhibitors was not associated with increased risk of neurocognitive adverse events (P = 0.91), liver enzymes elevations (P = 0.34), rhabdomyolysis (P = 0.58), or new-onset diabetes mellitus (P = 0.97). CONCLUSION: Proprotein convertase subtilisin-kexin type 9 inhibition with alirocumab or evolocumab was associated with lower risk of MI, stroke, and coronary revascularization, with favourable safety profile.

One-Year COMBO Stent Outcomes in Acute Coronary Syndrome: from the COMBO Collaboration.

PURPOSE: The COMBO biodegradable polymer sirolimus-eluting stent includes endothelial progenitor cell capture (EPC) technology for rapid endothelialization, which may offer advantage in acute coronary syndromes (ACS). We sought to analyze the performance of the COMBO stent by ACS status and ACS subtype. METHODS: The COMBO collaboration (n = 3614) is a patient-level pooled dataset from the MASCOT and REMEDEE registries. We evaluated outcomes by ACS status, and ACS subtype in patients with ST segment elevation myocardial infarction (STEMI) or non-STEMI (NSTEMI) versus unstable angina (UA). The primary endpoint was 1-year target lesion failure (TLF), composite of cardiac death, target vessel myocardial infarction, or clinically driven target lesion revascularization. Secondary outcomes included stent thrombosis (ST). RESULTS: We compared 1965 (54%) ACS and 1649 (46.0%) non-ACS patients. ACS presentations included 40% (n = 789) STEMI, 31% (n = 600) NSTEMI, and 29% (n = 576) UA patients. Risk of 1-year TLF was greater in ACS patients (4.5% vs. 3.3%, HR 1.51 95% CI 1.01-2.25, p = 0.045) without significant differences in definite/probable ST (1.1% vs 0.5%, HR 2.40, 95% CI 0.91-6.31, p = 0.08). One-year TLF was similar in STEMI, NSTEMI, and UA (4.8% vs 4.8% vs. 3.7%, p = 0.60), but definite/probable ST was higher in STEMI patients (1.9% vs 0.5% vs 0.7%, p = 0.03). Adjusted outcomes were not different in MI versus UA patients. CONCLUSIONS: Despite the novel EPC capture technology, COMBO stent PCI was associated with somewhat greater risk of 1-year TLF in ACS than in non-ACS patients, without significant differences in stent thrombosis. No differences were observed in 1-year TLF among ACS subtypes.

Final five-year results of the REMEDEE Registry: Real-world experience with the dual-therapy COMBO stent.

OBJECTIVES: This final report from the REMEDEE Registry assessed the long-term safety and efficacy of the dual-therapy COMBO stent in a large unselected patient population. BACKGROUND: The bio-engineered COMBO stent (OrbusNeich Medical BV, The Netherlands) is a dual-therapy pro-healing stent. Data of long-term safety and efficacy of the this stent is lacking. METHODS: The prospective, multicenter, investigator-initiated REMEDEE Registry evaluated clinical outcomes after COMBO stent implantation in daily clinical practice. One thousand patients were enrolled between June 2013 and March 2014. RESULTS: Five-year follow-up data were obtained in 97.2% of patients. At 5-years, target lesion failure (TLF) (composite of cardiac death, target-vessel myocardial infarction, or target lesion revascularization) was present in 145 patients (14.8%). Definite or probable stent thrombosis (ST) occurred in 0.9%, with no additional case beyond 3-years of follow-up. In males, 5-year TLF-rate was 15.6 versus 12.6% in females (p = .22). Patients without diabetes mellitus (DM) had TLF-rate of 11.4%, noninsulin-treated DM 22.7% (p = .001) and insulin-treated DM 41.2% (p < .001). Patients presenting with non-ST segment elevation acute coronary syndrome (NSTE-ACS) had higher incidence of TLF compared to non-ACS (20.4 vs. 13.3%; p = .008), while incidence with STE-ACS was comparable to non-ACS (10.7 vs. 13.3%; p = .43). CONCLUSION: Percutaneous coronary intervention with the dual-therapy COMBO stent in unselected patient population shows low rates of TLF and ST to 5 years. Remarkably, no case of ST was noted beyond 3 years.

Indirect comparison of the efficacy and safety of alirocumab and evolocumab: a systematic review and network meta-analysis.

AIMS: Although alirocumab and evolocumab have both been associated with improved outcomes in patients with dyslipidaemia or established atherosclerotic cardiovascular disease, data on their respective performances are scarce. This study aimed at providing an indirect comparison of the efficacy and safety of alirocumab vs. evolocumab. METHODS AND RESULTS: We conducted a systematic review and network meta-analysis of randomized trials comparing alirocumab or evolocumab to placebo with consistent background lipid-lowering therapy up to November 2018. We estimated the relative risk (RR) and the 95% confidence intervals (CIs) using fixed-effect model in a frequentist pairwise and network meta-analytic approach. A total of 30 trials, enrolling 59 026 patients were included. Eligibility criteria varied significantly across trials evaluating alirocumab and evolocumab. Compared with evolocumab, alirocumab was associated with a significant reduction in all-cause death (RR 0.80, 95% CI 0.66-0.97) but not in cardiovascular death (RR 0.83, 95% CI 0.65-1.05). This study did not find any significant differences in myocardial infarction (RR 1.15, 95% CI 0.99-1.34), stroke (RR 0.96, 95% CI 0.71-1.28), or coronary revascularization (RR 1.13, 95% CI 0.99-1.29) between the two agents. Alirocumab was associated with a 27% increased risk of injection site reaction compared to evolocumab; however, no significant differences were found in terms of treatment discontinuations, systemic allergic reaction, neurocognitive events, ophthalmologic events, or new-onset of or worsening of pre-existing diabetes. CONCLUSION: Alirocumab and evolocumab share a similar safety profile except for injection site reaction. No significant differences were observed across the efficacy endpoints, except for all-cause death, which may be related to the heterogeneity of the studied populations treated with the two drugs.

Sex differences in 1-year clinical outcomes after percutaneous coronary intervention with COMBO stents: From the COMBO collaboration.

BACKGROUND: The COMBO drug eluting stent is a novel device with luminal endothelial progenitor cell capture technology for rapid homogeneous endothelialization. METHODS AND RESULTS: We examined for sex differences in 1-year outcomes after COMBO stenting from the COMBO collaboration, a pooled patient-level dataset from the MASCOT and REMEDEE multicenter registries. The primary endpoint was 1-year target lesion failure (TLF), composite of cardiac death, target vessel-myocardial infarction (TV-MI), or clinically driven target lesion revascularization (CD-TLR). Secondary outcomes included stent thrombosis (ST). Adjusted outcomes were assessed using Cox regression methods. The study included 861 (23.8%) women and 2,753 (76.2%) men. Women were older with higher prevalence of several comorbidities including diabetes mellitus. Risk of 1-year TLF was similar in both sexes (3.8% vs. 3.9%, HR 0.92, 95% CI 0.59-1.42, p = .70), without sex differences in the incidence of cardiac death (1.6% vs. 1.5%, p = .78), TV-MI (1.5% vs. 1.1%, p = .32), or CD-TLR (2.0% vs. 2.2%, p = .67). Definite or probable ST occurred in 0.4% women and 1.0% men (HR 0.26, 95% CI 0.06-1.11, p = .069). CONCLUSIONS: Despite greater clinical risks at baseline, women treated with COMBO stents had similarly low 1-year TLF and other ischemic outcomes compared to men.

One-year clinical outcomes in patients with chronic kidney disease treated with COMBO stents: From the COMBO collaboration.

BACKGROUND: Chronic kidney disease (CKD) patients undergoing percutaneous coronary intervention (PCI) experience greater ischemic events including clinically driven target lesion revascularization (CD-TLR). Whether the COMBO biodegradable-polymer sirolimus-eluting stent promotes better outcomes in these patients by virtue of endothelial progenitor cell capture technology is unknown. OBJECTIVE: We examined one-year outcomes by CKD status from the COMBO collaboration. METHODS: The COMBO collaboration was a patient-level pooled dataset from the REMEDEE and MASCOT registries (3,614 patients) of all-comers undergoing attempted COMBO stent PCI. The primary endpoint was one-year target lesion failure (TLF), composite of cardiac death, target-vessel myocardial infarction (TV-MI) or CD-TLR. Secondary endpoints included stent thrombosis (ST). RESULTS: The study included 6.4% (n = 231) CKD and 93.6% (n = 3,361) non-CKD patients. CKD patients were older and included more women with greater prevalence of several comorbidities but similar rate of acute coronary syndrome (50.6% vs. 54.5%, p = .26). CKD patients underwent radial PCI less often (56.1% vs. 70.3%, p < .001) and received clopidogrel (78.6% vs. 68.3%) more often (p = .004). One-year TLF occurred in 7.9% CKD vs. 3.7% non-CKD patients, p = .001. CKD patients also demonstrated greater incidence of cardiac death (6.2% vs. 1.2%, p < .0001), TV-MI (2.7% vs. 1.1%, p = .04) but similar CD-TLR (2.7% vs 2.2%, p = .61) and definite/probable ST (1.4% vs. 0.8%, p = .42), compared to non-CKD patients. CONCLUSIONS: CKD patients treated with COMBO stents had significantly greater incidence of one-year TLF compared to non-CKD patients driven by cardiac death and to a lesser extent TV-MI but not CD-TLR. They had similar rates of definite/probable ST.

1-Year COMBO stent outcomes stratified by the PARIS bleeding prediction score: From the MASCOT registry.

BACKGROUND: The COMBO stent is a biodegradable-polymer sirolimus-eluting stent with endothelial progenitor cell capture technology for faster endothelialization. OBJECTIVE: We analyzed COMBO stent outcomes in relation to bleeding risk using the PARIS bleeding score. METHODS: MASCOT was an international registry of all-comers undergoing attempted COMBO stent implantation. We stratified patients as low bleeding-risk (LBR) for PARIS score ≤ 3 and intermediate-to-high (IHBR) for score > 3 based on baseline age, body mass index, anemia, current smoking, chronic kidney disease and need for triple therapy. Primary endpoint was 1-year target lesion failure (TLF), composite of cardiac death, myocardial infarction (MI) not clearly attributed to a non-target vessel or clinically-driven target lesion revascularization (TLR). Bleeding was adjudicated using the Bleeding Academic Research Consortium (BARC) definition. Dual antiplatelet therapy (DAPT) cessation was independently adjudicated. RESULTS: The study included 56% (n = 1270) LBR and 44% (n = 1009) IHBR patients. Incidence of 1-year TLF was higher in IHBR patients (4.1% vs. 2.6%, p = 0.047) driven by cardiac death (1.7% vs. 0.7%, p = 0.029) with similar rates of MI (1.8% vs. 1.1%, p = 0.17), TLR (1.5% vs. 1.6%, p = 0.89) and definite/ probable stent thrombosis (1.2% vs. 0.6%, p = 0.16). Incidence of 1-year major BARC 3 or 5 bleeding was significantly higher in IHBR patients (2.3% vs. 0.9%, p = 0.0094), as was the incidence of DAPT cessation (29.3% vs. 22.8%, p < 0.01), driven by physician-guided discontinuation. CONCLUSIONS: Patients with intermediate-to-high PARIS bleeding risk in the MASCOT registry experienced greater incidence of 1-year TLF, major bleeding and DAPT cessation than LBR patients, without significant differences in stent thrombosis.

Feasibility and Utility of a Cardiovascular Risk Screening Tool in Women Undergoing Routine Gynecology Evaluation.

Background: The goals of this multicenter survey were to examine the prevalence and patient awareness of cardiovascular risk factors, and the association between history of adverse pregnancy outcomes (APO­including gestational hypertension, gestational diabetes, and preeclampsia) and prevalence of cardiovascular risks among women presenting to outpatient obstetrics/gynecology (OB/GYN) clinics. Materials and Methods: We surveyed 2,946 female patients attending 16 outpatient OB/GYN clinics across the United States between January 2010 and January 2012. Main outcome measures were self-reported cardiovascular risk factors and symptoms such as angina and dyspnea. Results: Mean age of the patients was 51 ± 13.6 years. Cardiovascular risks and symptoms were highly prevalent (86.0% and 40.1%, respectively). Many patients did not know if they had common risk factors such as hypertension, hypercholesterolemia, or diabetes (18.4%, 32.0%, and 17.9%, respectively). Women with a history of APO were slightly more likely to be aware of common risk factors, including abnormal blood pressure (17% vs. 18.6%), high cholesterol (31.7% vs. 32%), and obesity/elevated body mass index (43.9% vs. 49.7%). Compared with patients with no history of APO, patients with APO (n = 380, 12.9%) were more likely to have risk factors (89.5% vs. 83.9%, p = 0.002) and symptoms (45.5% vs. 39.3%, p = 0.02). Conclusions: Awareness of cardiovascular risk factors and symptoms among all women surveyed in this study was poor, although awareness for some risk factors was relatively higher among patients with APO. This study demonstrates the feasibility of cardiovascular assessment in OB/GYN clinics using a simple questionnaire and its potential role for early recognition and timely intervention.

1-Year Outcomes with COMBO Stents in Small-Vessel Coronary Disease: Subgroup Analysis From the COMBO Collaboration.

BACKGROUND: Small vessel diameter is associated with higher risk of target lesion revascularization (TLR) after percutaneous coronary intervention (PCI). The COMBO sirolimus-eluting biodegradable-polymer stent has a proprietary anti-CD34 antibody layer to enhance homogeneous endothelialization, which may be advantageous in treating small vessels. OBJECTIVE: We examined for differences in 1-year clinical outcomes after PCI by maximum implanted stent diameter from the COMBO collaboration. METHODS: The COMBO collaboration (n = 3614) is a patient-level pooled dataset of patients undergoing PCI with COMBO stents in the MASCOT and REMEDEE multicenter registries. Stent diameter was available in 3590 (99.3%) patients. We compared patients receiving COMBO stents <3 mm versus ≥3 mm. The primary endpoint was 1-year target lesion failure (TLF), composite of cardiac death, target vessel-myocardial infarction (TV-MI) or clinically driven TLR. Secondary outcomes included stent thrombosis (ST). Adjusted outcomes were assessed using Cox regression methods. RESULTS: The study included 792 (22%) patients with small stents <3 mm and 2798 (78%) patients with large stents ≥3 mm. Small stent patients included more women with lower body mass index and higher prevalence of diabetes but similar prevalence of acute coronary syndrome. Risk of 1-year TLF was similar in small and large stent groups (4.4% vs. 3.8%, HR 1.12, 95% CI 0.74-1.72, p = 0.58). There were no differences in the rates of cardiac death (1.7% vs. 1.5%, p = 0.74), TV-MI (1.4% vs. 1.2%, p = 0.58) or TLR (2.7% vs. 2.1%, p = 0.31). Definite or probable ST occurred in 1.3% of the small stent and 0.7% of the large stent PCI patients, p = 0.14, HR 2.13, 95% CI 0.93-5.00, p = 0.07. CONCLUSIONS: One-year ischemic outcomes after COMBO PCI were similar irrespective of stent diameter in this all-comers international cohort.

Comparison of One-Year Outcomes in Patients >75 Versus ≤75 Years With Coronary Artery Disease Treated With COMBO Stents (From The MASCOT Registry).

Older patients who undergo coronary interventions are at greater risk of ischemic events and less likely to tolerate prolonged dual antiplatelet therapy (DAPT) due to bleeding risk. The COMBO biodegradable polymer sirolimus-eluting stent promotes rapid endothelialization through endothelial progenitor cell capture technology which may be advantageous in elderly patients. We compared 1-year clinical outcomes and DAPT cessation events in patients >75 versus ≤75 years from the MASCOT registry. MASCOT was a prospective, multicenter cohort study of all-comers undergoing attempted COMBO stenting. The primary endpoint was 1-year target lesion failure (TLF), composite of cardiac death, myocardial infarction (MI) not clearly attributed to a nontarget vessel or clinically driven target lesion revascularization. Bleeding was adjudicated using the Bleeding Academic Research Consortium criteria. Adjusted outcomes were analyzed using Cox regression methods. The study included 18% (n = 479) patients >75 years and 72% (n = 2,135) patients ≤75 years. One-year TLF occurred in 4.6% patients >75 years versus 3.1% patients ≤75years of age, p = 0.10; adj hazard ratio 1.36, 95% confidence intervals 0.77 to 2.38, p = 0.29. There were no significant differences in cardiac death (1.7% vs 1.3%, p = 0.55), MI (2.1% vs 1.2%, p = 0.14), target lesion revascularization (1.7% vs 1.4%, p = 0.60) and definite stent thrombosis (0.8% vs 0.4%, p = 0.19). Major Bleeding Academic Research Consortium 3,5 bleeding (3.1% vs 1.5%, p = 0.01) and DAPT cessation rates (32.4% vs 23.0%, p <0.001) were significantly higher in elderly patients. In conclusion, elderly patients >75 years treated with COMBO stents had similar TLF but significantly greater incidence of bleeding than younger patients and DAPT cessation in one-third of patients over 1 year.

1-Year Clinical Outcomes of All Comers Treated With 2 Bioresorbable Polymer-Coated Sirolimus-Eluting Stents: Propensity Score-Matched Comparison of the COMBO and Ultrathin-Strut Orsiro Stents.

OBJECTIVES: The aim of this study was to determine 1-year safety and efficacy after treatment with the COMBO and Orsiro stents. BACKGROUND: The COMBO stainless-steel stent has an anti-CD34+ antibody coating to capture endothelial progenitor cells, thereby promoting faster endothelialization. The Orsiro is an ultrathin-strut cobalt-chromium stent, covered by an extremely thin layer of amorphous silicon carbide to minimize ion leakage. Both devices elute sirolimus from biodegradable polymers. METHODS: For this analysis we included European patients from the COMBO collaboration, a patient-level pooling of 2 prospective all-comers registries of COMBO stent implantation (n = 2,775), and all patients randomized to the Orsiro stent (n = 1,169) from the Dutch BIO-RESORT (Comparison of Biodegradable Polymer and Durable Polymer Drug-Eluting Stents in an All Comers Population) randomized trial. The main outcome of interest was 1-year target lesion failure, a composite of cardiac death, target vessel myocardial infarction, and clinically driven target lesion revascularization evaluated using propensity score-matched analysis. RESULTS: At baseline, COMBO patients were older and had more insulin-treated diabetes, renal insufficiency, and other comorbidities. However, Orsiro patients included more current smokers and more acute coronary syndrome presentations. Orsiro patients also received longer stents and had more complex target lesions. After propensity score-matched analysis (n = 862/arm), 1-year target lesion failure occurred in 4.1% of COMBO-treated and 2.7% of Orsiro-treated patients (hazard ratio: 1.55; 95% confidence interval: 0.92 to 2.62; p = 0.10). Definite stent thrombosis occurred in 0.5% of COMBO-treated and 0.5% of Orsiro-treated patients (p = 0.99). CONCLUSIONS: A propensity score-matched comparison of all comers treated with the COMBO or Orsiro stent showed no statistically significant differences. Stent thrombosis risk was low and similar between the stents. (Comparison of Biodegradable Polymer and Durable Polymer Drug-Eluting Stents in an All Comers Population [BIO-RESORT], NCT01674803; MASCOT-Post Marketing Registry [MASCOT], NCT02183454; Prospective Registry to Assess the Long-term Safety and Performance of the Combo Stent [REMEDEE Reg], NCT01874002).

1-year results after PCI with the COMBO stent in all-comers in Asia versus Europe: Geographical insights from the COMBO collaboration.

BACKGROUND: The COMBO drug-eluting stent combines sirolimus-elution from a biodegradable polymer with an anti-CD34+ antibody coating for early endothelialization. OBJECTIVE: We investigated for geographical differences in outcomes after percutaneous coronary intervention (PCI) with the COMBO stent among Asians and Europeans. METHODS: The COMBO Collaboration is a pooled patient-level analysis of the MASCOT and REMEDEE registries of all-comers undergoing attempted COMBO stent PCI. The primary outcome was 1-year target lesion failure (TLF), composite of cardiac death, target vessel myocardial infarction (TV-MI) and target lesion revascularization (TLR). RESULTS: This study included 604 Asians (17.9%) and 2775 Europeans (82.1%). Asians were younger and included fewer females, with a higher prevalence of diabetes mellitus but lower prevalence of other comorbidities than Europeans. Asians had a higher prevalence of ACC/AHA C type lesions and received longer stent lengths. More Asians than Europeans were discharged on clopidogrel (86.5% vs 62.8%) rather than potent P2Y12 inhibitors. One-year TLF occurred in 4.0% Asians and 4.1% of Europeans, p = 0.93. The incidence of cardiac death was higher in Asians (2.8% vs. 1.3%, p = 0.007) with similar rates of TV-MI (1.5% vs. 1.2%, p = 0.54) and definite stent thrombosis (0.3% vs. 0.5%, p = 0.84) and lower incidence of TLR than Europeans (1.0% vs. 2.5%, p = 0.025). After adjustment, differences for cardiac death and TLR were no longer significant. CONCLUSIONS: In the COMBO collaboration, although 1-year TLF was similar regardless of geography, Asians experienced higher rates of cardiac death and lower TLR than Europeans, while incidence of TV-MI and ST was similar in both regions. Adjusted differences did not reach statistical significance. CLINICALTRIAL. GOV IDENTIFIER-NUMBERS: NCT01874002 (REMEDEE Registry), NCT02183454 (MASCOT registry).

The influence of implantation techniques on lesion oriented-outcomes in Absorb BVS and Xience EES lesions treated in routine clinical practice at complete three year follow-up: AIDA trial QCA substudy.

It has been hypothesized that dedicated optimized Absorb BVS implantation techniques might mitigate the risk of adverse events such as target vessel failure and device thrombosis. In this explorative AIDA trial QCA substudy, we sought to investigate the influence of implantation techniques on lesion-oriented outcomes in both the Absorb BVS and Xience EES arm at complete 3-year follow-up. The current analysis includes 2152 study lesions treated with at least one study device, of which the baseline angiogram was suited for offline QCA analysis, including Dmax analysis. The lesion-oriented composite outcome (LOCE) of this analysis was a composite of definite device thrombosis, target lesion revascularization and target-vessel myocardial infarction. In Absorb BVS, the Lesion-oriented composite endpoint (LOCE) occurred numerically less in correctly QCA sized vessels when compared to incorrectly sized vessels 8.5% (58/696) versus 11.1% (39/358), p = 0.151. In Xience EES, LOCE had occurred more frequently in incorrectly sized devices according to device diameter/RVD matching; 2.2% (4/187) in correctly sized devices versus 7.1% (63/911) in incorrectly sized devices (p = 0.014). In this AIDA trial QCA substudy, rates of LOCE were significantly lower in Xience EES treated lesions in which devices were correctly sized according to the definitions of device diameter/RVD matching.

A paradox in sex-specific clinical outcomes after bioresorbable scaffold implantation: 2-year results from the AIDA trial.

BACKGROUND: Females are underrepresented in clinical trials evaluating new stent technologies whilst results may differ between the sexes. Females are known to have smaller, more tortuous coronary arteries and have generally more comorbidities. On the other hand, they may have smaller plaque burden. This subgroup-analysis sought to assess sex-specific outcomes after Absorb bioresorbable vascular scaffold (BVS) or XIENCE everolimus-eluting stent (EES) implantation. METHODS: The AIDA trial was an investigator-initiated, non-inferiority, all-comers trial, in which 1845 patients were randomly assigned to either Absorb BVS or XIENCE EES. Baseline clinical, angiography and procedural variables, as well as 2-year clinical outcomes were analyzed by sex and device modality. RESULTS: Of the 1845 randomized patients, 475 (25.7%) were females. The 2-year rates of target vessel failure (TVF) with Absorb BVS versus XIENCE EES in females were 6.4% versus 10.6% (HR 0.59; 95% CI: 0.31-1.11; p = 0.10) and in males 12.7% versus 9.7% (HR 1.34; 95% CI: 0.98-1.85; p = 0.07). Males treated with Absorb BVS were at higher risk for TVF compared to females treated with Absorb BVS (HR 2.06; 95% CI 1.21-3.53; p = 0.007). Definite/probable device thrombosis occurred in females with Absorb BVS versus XIENCE EES in 1.6% versus 1.4% (HR 1.15; 95% CI: 0.26-5.12; p = 0.86) and in males 3.9% versus 0.7% (HR 5.55; 95% CI: 2.11-14.35; p < 0.001). A statistical significant interaction between sex and device was present for TVF (p = 0.02), but was not seen for definite/probable device thrombosis (p = 0.08). CONCLUSIONS: In this subgroup analysis, Absorb BVS used in routine practice tends to result in better clinical outcomes in females compared to males.

Long-Term Performance of the COMBO Dual-Therapy Stent: Results from the REMEDEE Registry.

BACKGROUND: Data of long-term safety and efficacy of the COMBO dual-therapy stent is lacking. REMEDEE Registry evaluated the COMBO stent and showed low clinical event rates up to 3 year. We report the clinical outcomes at 4-year follow-up of this registry. METHODS: The REMEDEE Registry is a prospective, multicenter registry with minimal exclusion criteria, evaluating clinical outcomes after treatment with the COMBO stent. A 1000 patients were enrolled between June 2013 and March 2014. Target lesion failure (TLF), defined as a composite of cardiac death, target-vessel myocardial infarction (TV-MI) and target lesion revascularization (TLR), at 4-year follow-up was the primary focus of this analysis. RESULTS: Four-year follow-up data were obtained in 97.3% of patients. TLF was present in 117 patients (11.9%). Cardiac death occurred in 45 patients (4.6%), TV-MI was observed in 25 patients (2.6%) and TLR was performed in 73 patients (7.5%). Of the 7.5% TLR at 4 years, 1.5% were beyond 2 years. Definite ST was seen in 7 patients (0.7%) and probable ST in 1 (0.1%). No definite or probable ST occurred between 3 and 4 years follow-up. At 4-year follow-up, 93.1% of patients were free of ischemic symptoms. CONCLUSION: This registry showed excellent 4-year results after COMBO stent placement, with no ST beyond 3 years.

Residual Inflammatory Risk in Patients With Low LDL Cholesterol Levels Undergoing Percutaneous Coronary Intervention.

BACKGROUND: Data on the impact of residual inflammatory risk (RIR) in patients undergoing percutaneous coronary intervention (PCI) with baseline low-density lipoprotein cholesterol (LDL-C) ≤70 mg/dl are scarce. OBJECTIVES: The purpose of this study was to characterize the prevalence and impact of persistent high RIR after PCI in patients with baseline LDL-C ≤70 mg/dl. METHODS: All patients undergoing PCI between January 2009 and December 2016 in a single tertiary center, with baseline LDL-C ≤70 mg/dl and serial high-sensitivity C-reactive protein (hsCRP) assessments (at least 2 measurements ≥4 weeks apart) were retrospectively analyzed. High RIR was defined as hsCRP >2 mg/l. Patients were categorized as persistent low RIR (first low then low hsCRP), attenuated RIR (first high then low hsCRP), increased RIR (first low then high hsCRP), or persistent high RIR (first high then high hsCRP). Primary endpoint of interest was major adverse cardiac and cerebrovascular accident (MACCE) (death, myocardial infarction, or stroke), within 1 year of the second hsCRP measurement. RESULTS: A total of 3,013 patients were included, with persistent low, attenuated, increased, and persistent high RIR in 1,225 (41.7%), 414 (13.7%), 346 (11.5%), and 1,028 (34.1%) patients, respectively. Overall, there was a stepwise increase in the incidence rates of MACCE, transitioning from the persistent low to the attenuated, increased, and persistent high RIR (respectively, 64.4 vs. 96.6 vs. 138.0 vs. 152.4 per 1,000 patient-years; p < 0.001). After adjustment, the presence of persistent high RIR remained strongly associated with MACCE (adjusted hazard ratio: 2.10; 95% confidence interval: 1.45 to 3.02; p < 0.001). CONCLUSIONS: Among patients undergoing PCI with baseline LDL-C ≤70 mg/dl, persistent high RIR is frequent and is associated with increased risk of MACCE. Targeting residual inflammation in patients with optimal LDL-C control may further improve outcomes after PCI.

The relationship of pre-procedural Dmax based sizing to lesion level outcomes in Absorb BVS and Xience EES treated patients in the AIDA trial.

Due to expansion limits of the Absorb bioresorbable scaffold a meticulous implantation with correct sizing is required. We sought to investigate the clinical outcomes based on the sizing of the device related to the maximal lumen diameter measured by quantitative coronary angiography in Absorb BVS and Xience EES treated lesions in the AIDA trial. Sizing of Absorb bioresorbable vascular scaffold (BVS) and Xience everolimus eluting stent (EES) was graded according to the definitions of device non-oversize and device oversize on pre-procedural angiography. Lesion-oriented outcomes (LOCE) (device thrombosis, TLR and TVMI) that occurred during 2 years follow-up were related to device non-oversized or oversized status. In the Absorb BVS group, LOCE occurred in 48 (7.4%) lesions in the oversized group and in 32 (8.2%) lesions in the non-oversized group (HR 0.91; 95% CI 0.58-1.42; p = 0.681), whereas TLR occurred in 34 (5.3%) lesions and in 23 lesions (5.9%), respectively (HR 0.89; 95% CI 0.52-1.51; p = 0.666). Definite scaffold thrombosis occurred in 11 (1.7%) device oversized treated lesions against 16 (4.1%) device non-oversized treated lesions (HR 0.41; 95% CI 0.19-0.89; p = 0.020). There were no differences in event rates between oversized and non-oversized groups in lesions treated with Xience EES. There was no significant difference in LOCE between oversized and non-oversized treated Absorb BVS and Xience EES treated lesions. Non-oversized Absorb BVS implantation was associated with a higher risk of scaffold thrombosis at complete 2 years follow-up. The majority of very late scaffold thrombosis occurred in properly sized devices.