Right drug, wrong dosage: insights from the PAVE-AF antithrombotic study in older patients with atrial fibrillation.

Optimal antithrombotic treatment of older patients is usually impeded by several prevailing misconceptions. The aim of our study was to assess the type, dosage and predictors of antithrombotic therapy in older patients with non-valvular atrial fibrillation (NVAF). PAVE-AF was a prospective, cross-sectional study, including NVAF patients ≥ 80 years from 30 participating centers. Demographic data, comorbidities and treatment patterns were documented in a single visit. Patients treated with non-vitamin K oral anticoagulants (NOACs) were further classified into three dosing categories (recommended, underdosing and overdosing). Among 1018 patients (85.4±4.0 years), 88.4% received anticoagulants (AC), 8% antiplatelets (AP) and 3.6% no treatment. The primary reason for AP administration was physician concern of bleeding followed by patient denial. Patients ≥90 years had two times greater probability to receive AP therapy compared to patients < 90 years. Among patients treated with AC, one third received vitamin K antagonists, while two thirds received NOACs [34.6% apixaban, 9.5% dabigatran and 22.6% rivaroxaban]. Independent predictors of AC prescription over AP or no treatment were low HAS-BLED score, hypertension, labile INR, permanent AF, absence of uncontrolled hypertension, prior stroke/systemic embolism, age and male gender. In total, 37% of NOAC recipients received inappropriate dosage, while the number of patients receiving recommended dosing differed significantly among NOAC subgroups (p < 0.001). In our study, a minority of older NVAF patients received AP or no therapy for stroke prevention. Among patients treated with anticoagulants, two thirds were on NOAC treatment, though with a considerable proportion of inappropriate dosing.

Effect of Early-Onset Preeclampsia on Offspring's Blood Pressure during the First Month of Life.

OBJECTIVE: To explore the effect of early-onset preeclampsia on the blood pressure of offspring during the first month of life. STUDY DESIGN: This prospective case-control study included 106 neonates of mothers with early-onset preeclampsia (developing at <34 weeks of gestation) and 106 infants of normotensive mothers, matched 1-to-1 for sex and gestational age. Serial blood pressure measurements were obtained on admission, daily for the first postnatal week, and then weekly up to the fourth week of life. RESULTS: There were no differences in blood pressure values on admission and the first day of life between cases and controls. Conversely, infants exposed to preeclampsia had significantly higher systolic (SBP), diastolic (DBP), and mean blood pressure (MBP) on the subsequent days up to the fourth postnatal week (P <.001-.033). Multiple regression analyses with adjustment for sex, gestational age, antenatal corticosteroid use, and maternal antihypertensive medication use confirmed the foregoing findings (P <.001-.048). Repeated-measures ANOVA also identified preeclampsia as a significant determinant of trends in SBP, DBP, and MBP during the first month of life (F = 16.2, P < .001; F = 16.4, P < .001; and F = 17.7, P < .001, respectively). CONCLUSIONS: Infants of mothers with early-onset preeclampsia have elevated blood pressure values throughout the neonatal period compared with infants born to normotensive mothers.

Factors Affecting Platelet Reactivity 2 Hours After P2Y12 Receptor Antagonist Loading in Primary Percutaneous Coronary Intervention for ST-Elevation Myocardial Infarction - Impact of Pain-to-Loading Time.

BACKGROUND: Delay in the onset of antiplatelet action occurs in patients with ST-elevation myocardial infarction (STEMI) and is likely due to disturbed absorption. We hypothesized that patients presenting relatively late after the onset of symptoms would have faster antiplatelet action. METHODS AND RESULTS: We analyzed patient-level data from 5 studies of 207 P2Y12 receptor antagonist-naïve patients with STEMI undergoing primary percutaneous coronary intervention (PCI). All patients had available platelet reactivity (PR) assessment with the VerifyNow assay (in P2Y12 reaction units; PRU) prior to and 2 h after loading. High PR (HPR) was defined as ≥ 208 PRU. Pain-to-antiplatelet loading time independently predicted PR at 2 h after loading: every 1-h increase in pain-to-antiplatelet loading time produced a 7% decrease in PR (P=0.001). Pretreatment PR, body mass index, morphine and novel P2Y12 receptor antagonist also affected PR 2 h after loading. Novel P2Y12 receptor antagonist use and per hour increase in pain-to-antiplatelet loading time were independently associated with lower probability for HPR with an OR (95% CI) of 0.145 (0.095-0.220) and 0.776 (0.689-0.873), P<0.001 for both (C-statistic, 0.752; 95% CI: 0.685-0.819). CONCLUSIONS: In STEMI patients undergoing primary PCI, pain-to-antiplatelet loading interval is a newly described factor affecting PR shortly after P2Y12 receptor antagonist loading, according to patient-level data pooled analysis.

Ticagrelor vs clopidogrel followed by ticagrelor re-loading in patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention: A randomized, pharmacodynamic comparison.

Among patients allocated to ticagrelor in the primary percutaneous coronary intervention (PCI) cohort of Platelet Inhibition and Patient Outcomes (PLATO) trial, 40.7% had received pre-randomization 600 mg of clopidogrel. This scenario is frequently employed in real-world practice. In a prospective, three-center, single-blind, parallel design study, 74 P2Y12 inhibitor-naive patients undergoing primary PCI were randomized (Hour 0) to ticagrelor 180 mg loading dose (LD) vs clopidogrel 600 mg LD followed after 2 h by ticagrelor 180 mg re-LD. Platelet reactivity (VerifyNow, in PRU) was assessed at Hour 0, 2, 4, 6, and 24. The primary comparison was non-inferiority of ticagrelor to clopidogrel followed by ticagrelor re-LD regarding platelet reactivity at 24 h using a prespecified margin of <35 PRU for the upper bound of the one-sided 97.5% confidence interval (CI). Ticagrelor was proven non-inferior to clopidogrel followed by ticagrelor re-LD with a difference between arms of 13.5 PRU (28.8 upper 97.5% CI), p = 0.001. At Hour 2, platelet reactivity was lower in ticagrelor only vs clopidogrel followed by ticagrelor re-LD groups with least square estimate mean difference (95% CI) -105.7 (-140.6 to -70.8), p < 0.001, without significant difference thereafter. In conclusion, in patients undergoing primary PCI, a strategy of ticagrelor LD only was proven non-inferior to clopidogrel LD followed by ticagrelor re-LD, in terms of antiplatelet efficacy at 24 h post-randomization and provided an earlier onset of platelet inhibition.

Ticagrelor versus high dose clopidogrel in ST-segment elevation myocardial infarction patients with high platelet reactivity post fibrinolysis.

Limited data are available on high platelet reactivity (HPR) rate early post fibrinolysis, while no effective way to overcome it has been proposed. In this context, we aimed to compare ticagrelor versus high dose clopidogrel in patients with ST-segment elevation myocardial infarction (STEMI) who exhibit HPR post fibrinolysis. In a prospective, randomized, parallel design, 3-center study, 56 STEMI patients, out of 83 (67.5 %) screened, who presented with HPR (PRU ≥ 208 by VerifyNow) 3-48 h post fibrinolysis and prior to coronary angiography were allocated to ticagrelor 180 mg loading dose (LD)/90 mg bid maintenance dose (MD) or clopidogrel 600 mg LD/150 mg MD. Platelet reactivity was assessed at randomization (Hour 0), at Hour 2, Hour 24 and pre-discharge. The primary endpoint of platelet reactivity (in PRU) at Hour 2 was significantly lower for ticagrelor compared to clopidogrel with a least square mean difference (95 % confidence interval) of -141.7 (-173.4 to -109.9), p < 0.001. HPR rates at Hour 2 and 24 were significantly lower for ticagrelor versus clopidogrel (14.3 vs. 82.1 %, p < 0.001 and 0 vs. 25.0 %, p = 0.01 respectively), though not significantly different pre-discharge. In-hospital Bleeding Academic Research Consortium type ≥2 bleeding occurred in 1 and 2 clopidogrel and ticagrelor-treated patients, respectively. In STEMI patients, post fibrinolysis HPR is common. Ticagrelor treats HPR more effectively compared to high dose clopidogrel therapy. Although antiplatelet regimens tested in this study were well tolerated, this finding should be considered only exploratory.

Contraindications/special warnings and precautions for use of contemporary oral antiplatelet treatment in patients with acute coronary syndrome undergoing percutaneous coronary intervention.

BACKGROUND: The prevalence of contraindications/special warnings and precautions (CON/SWP) for clopidogrel, prasugrel and ticagrelor use is not adequately studied and might affect P2Y12 inhibitor choice in acute coronary syndrome (ACS) patients undergoing percutaneous coronary intervention (PCI). METHODS AND RESULTS: In the context of the GReek AntiPlatelet rEgistry (GRAPE) a detailed recording of CON/SWP for use of clopidogrel, prasugrel and ticagrelor was done for 1,280 consecutive, moderate-high-risk ACS patients undergoing PCI. At least 1 CON for use of clopidogrel, prasugrel and ticagrelor was present in 5 (0.4%), 49 (3.8%) and 12 patients (0.9%), respectively. Prevalence of at least 1 CON/SWP to clopidogrel (45.8%) was less frequent compared to prasugrel (49.1%) or ticagrelor (49.1%; P=0.02 and P=0.04, respectively), while 34% of patients had at least 1 CON/SWP to all the 3 P2Y12 inhibitors. At discharge, 482 (38.6%), 301 (24.1%) and 464 patients (37.2%) received clopidogrel, prasugrel and ticagrelor, respectively. Age ≥75 years, co-medication related to increased bleeding risk, and history of asthma/chronic obstructive pulmonary disease favored clopidogrel vs. prasugrel or ticagrelor use as discharge medication, while geographic region also affected this choice (C-statistic, 0.81; 95% CI: 0.78-0.83). CONCLUSIONS: In patients with ACS undergoing PCI the prevalence of CON to antiplatelet agents is low, whereas that of SWP is high. Certain SWP, along with regional trends may affect the choice of newer P2Y12 inhibitors vs. clopidogrel.

High-sensitivity cardiac troponin I for cardiovascular risk stratification in apparently healthy individuals.

Troponin I and T as cardiac-specific biomarkers are highly useful tools not only in the diagnosis of acute coronary syndromes but also as independent predictors of several other clinical conditions. High-sensitivity cardiac troponin (hs-cTn) assays allow the detection of considerably low concentrations of cardiac troponin in apparently healthy and asymptomatic individuals, being a candidate tool for cardiovascular risk stratification in the general population. A group of Greek experts summarized the bulk of evidence regarding the use of hs-cTnI as a predictor of cardiovascular events and mortality in apparently healthy individuals and its additive value on top of existing risk stratification methods. This document could serve as a guide for the incorporation of hs-cTnI as an additional risk stratification tool in cardiovascular prevention strategies in apparently healthy individuals.

Pharmacodynamic effect of prasugrel 5 mg vs clopidogrel 150 mg in elderly patients with high on-clopidogrel platelet reactivity.

BACKGROUND: Elderly patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI) frequently exhibit high platelet reactivity (HPR) while on clopidogrel. In the elderly cohort, either prasugrel is not recommended or, if used, halving of the dose has been suggested. We aimed to test the hypothesis that in elderly patients exhibiting HPR after standard treatment with clopidogrel, prasugrel-reduced dose (5 mg) could be more effective than high-dose (150 mg) clopidogrel. METHODS: Consecutive elderly (≥75 years old) patients with ACS undergoing PCI and loaded with clopidogrel were considered for platelet reactivity (PR) assessment at 24 hours after PCI with the VerifyNow assay (Accumetrics Inc, San Diego, CA), measured in P2Y12 reaction units (PRU). Of 63 screened patients, 30 (47.6%) were found with HPR (defined as PRU ≥230) and 27 of them participated in a prospective, randomized, single-center, single-blind, investigator-initiated, crossover study of platelet inhibition by prasugrel 5 mg/d vs clopidogrel 150 mg/d, with a 15-day treatment period. RESULTS: The primary end point of PR at the end of the 2 study periods was lower in patients receiving low-dose prasugrel than those receiving high-dose clopidogrel (least squares estimates 190.8 [95% CI 161.5-220.1] and 240.8 [95% CI 211.0-270.6], respectively; P = .008). The secondary end point of HPR rate at the end of treatment periods was lower for prasugrel (8/24; 33.3%) compared with clopidogrel (16/24; 66.7%), P = .02. CONCLUSIONS: In elderly patients with ACS undergoing PCI and exhibiting HPR after standard clopidogrel treatment, prasugrel 5 mg/d is significantly more efficacious than clopidogrel 150 mg/d in reducing PR and HPR rate.