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Background: Calcium channel blockers (CCBs) are commonly used to treat conditions such as arterial hypertension and supraventricular dysrhythmias. Poisoning from these drugs can lead to severe morbidity and mortality. We aimed to determine the utility of extracorporeal treatments (ECTRs) in the management of CCB poisoning. Method(s): We conducted systematic reviews of the literature, screened studies, extracted data, summarized findings, and formulated recommendations following published EXTRIP methods. Result(s): A total of 83 publications (6 in vitro and 1 animal experiments, 55 case reports or case series, 19 pharmacokinetic studies, 1 cohort study and 1 systematic review) met inclusion criteria regarding the effect of ECTR. Toxicokinetic or pharmacokinetic data were available on 210 patients (including 32 for amlodipine, 20 for diltiazem, and 52 for verapamil). Regardless of the ECTR used, amlodipine, bepridil, diltiazem, felodipine, isradipine, mibefradil, nifedipine, nisoldipine, and verapamil were considered not dialyzable, with variable levels of evidence, while no dialyzability grading was possible for nicardipine and nitrendipine. Data were available for clinical analysis on 78 CCB poisoned patients (including 32 patients for amlodipine, 16 for diltiazem, and 23 for verapamil). Standard care (including high dose insulin euglycemic therapy) was not systematically administered. Clinical data did not suggest an improvement in outcomes with ECTR. Consequently, the EXTRIP workgroup recommends against using ECTR in addition to standard care for patients severely poisoned with either amlodipine, diltiazem or verapamil (strong recommendations, very low quality of the evidence (1D)). There were insufficient clinical data to draft recommendation for other CCBs, although the workgroup acknowledged the low dialyzability from, and lack of biological plausibility for, ECTR. Conclusion(s): Both dialyzability and clinical data do not support a clinical benefit from ECTRs

Item does not contain fulltext, AIMS: The aim of this study was to evaluate the impact of 23-month ticagrelor monotherapy following one-month dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI) on the rates of patient-oriented composite endpoints (POCE) and net adverse clinical events (NACE). METHODS AND RESULTS: The rates of site-reported Academic Research Consortium (ARC)-2 defined POCE (all-cause death, any stroke, any myocardial infarction or any revascularisation) and NACE (POCE or bleeding type 3 or 5 according to the Bleeding ARC [BARC]) were reported up to two years by intention-to-treat principle in the randomised, multicentre, open-label GLOBAL LEADERS study comparing two antiplatelet strategies in 15,991 patients undergoing PCI. The experimental strategy consisted of aspirin with ticagrelor for one month followed by ticagrelor monotherapy for 23 months, whereas the reference treatment consisted of 12-month DAPT followed by 12-month aspirin monotherapy. At two years, POCE occurred in 1,050 (13.2%) patients in the experimental group and in 1,131 (14.2%) in the reference group (HR 0.93, 95% CI: 0.85-1.01, p=0.085). NACE occurred in 1,145 (14.4%) patients in the experimental group and in 1,237 (15.5%) patients in the reference group (HR 0.92, 95% CI: 0.85-1.00, p=0.057). In pre-specified subgroup analyses, no significant treatment-by-subgroup interactions were found for either POCE or NACE at two years. CONCLUSIONS: The experimental treatment strategy of one-month DAPT followed by 23 months of ticagrelor alone did not result in a significant reduction in the rates of site-reported POCE or NACE, when compared to the reference treatment. ClinicalTrials.gov Identifier: NCT01813435.

Item does not contain fulltext, AIMS: The aim of the present study was to investigate the effects of successful PCI CTO on absolute myocardial blood flow (MBF) and functional recovery. METHODS AND RESULTS: Patients with a documented CTO were prospectively examined for ischaemia and viability with [15O]H2O positron emission tomography (PET) and late gadolinium enhancement cardiac magnetic resonance imaging (LGE-CMR). Sixty-nine consecutive patients, in whom PCI was successful, underwent follow-up PET and CMR after approximately 12 weeks to evaluate potential improvement of MBF as well as systolic function. After PCI, stress MBF in the CTO area increased from 1.22+/-0.36 to 2.40+/-0.90 mL.min-1.g-1 (p<0.001), whilst stress MBF in the remote area also increased significantly between baseline and follow-up PET (2.58+/-0.68 to 2.77+/-0.77 mL.min-1.g-1, p=0.01). The ratio of stress MBF between CTO and remote area was 0.49+/-0.13 at baseline and increased to 0.87+/-0.24 at follow-up (p<0.001). The MBF defect size of the CTO area decreased from 5.12+/-1.69 to 1.91+/-1.75 myocardial segments after PCI (p<0.001). Left ventricular ejection fraction (LVEF) increased significantly (46.4+/-11.0 vs. 47.5+/-11.4%, p=0.01) at follow-up. CONCLUSIONS: The vast majority of CTO patients with documented ischaemia and viability showed significant improvement in stress MBF and a reduction of ischaemic burden after successful percutaneous revascularisation with only minimal effect on LVEF.