Reduction of atherothrombotic burden before stent deployment in non-ST elevation acute coronary syndromes: Reduction of myocardial necrosis achieved with nose-dive manual thrombus aspiration (REMNANT) trial. A volumetric intravascular ultrasound study.

OBJECTIVES: To test whether thrombus aspiration (TA) reduces the atherosclerotic burden in culprit lesions and "facilitate" percutaneous coronary intervention with stent (S-PCI) among patients with non-ST elevation acute coronary syndromes (NSTE-ACS). BACKGROUND: Evidence on the effects of TA adjunctive to S-PCI in NSTE-ACS is limited and controversial. METHODS: TA was defined "aggressive" when using 7F devices or a catheter/artery ratio >0.6, "conservative" with 6F, and a catheter/artery ratio ≤0.6. Angiography and intravascular ultrasound (IVUS) were performed at baseline, after TA and after stent deployment. RESULTS: TA was accomplished in 61/76 patients (80%) with NSTE-ACS. The aspirated material was red thrombus in 23% and plaque fragments in 49% of cases. Compared with baseline, TA was associated with an 82% increase in minimal lumen diameter and a 15% reduction in diameter stenosis (P < 0.001 for both). After TA, IVUS documented a 24 and 16% increase in minimal lumen area and lumen volume, respectively (P < 0.001 for both), a 7% decrease in area stenosis through an 11% reduction of plaque + media volume (P < 0.001). When compared with "conservative", an "aggressive" TA was associated with a more pronounced reduction in percent area stenosis (P < 0.05) and an increase in percent stent expansion (P < 0.001). The plaque + media volume reduction after TA was correlated with stent expansion (r = 0.261, P = 0.046). CONCLUSIONS: Manual TA reduces atherothrombotic burden in culprit lesions of NSTE-ACS patients before S-PCI and, when deep plaque removal is obtained, TA optimizes subsequent stent expansion. © 2015 Wiley Periodicals, Inc.

Platelet function and long-term antiplatelet therapy in women: is there a gender-specificity? A 'state-of-the-art' paper.

Although the female gender is generally less represented in cardiovascular studies, observational and randomized investigations suggest that-compared with men-women may obtain different benefits from antiplatelet therapy. Multiple factors, including hormonal mechanisms and differences in platelet biology, might contribute to such apparent gender peculiarities. The thrombotic and bleeding risks, as well as outcomes after a cardiovascular event, appear to differ between genders, partly in relation to differences in age, comorbidities and body size. Equally, the benefits of antiplatelet therapy may differ in women compared with men in different vascular beds, during primary or secondary prevention and according to the type of an antiplatelet agent used. This document is an attempt to bring together current evidence, clinical practices and gaps of knowledge on gender-specific platelet function and antiplatelet therapy. On the basis of the available data, we provide suggestions on current indications of antiplatelet therapy for cardiovascular prevention in women with different clinical features; no strong recommendation may be given because the available data derive from observational studies or post hoc/subgroup analyses of randomized studies without systematic adjustments for baseline risk profiles.

Patient management and care after primary percutaneous coronary intervention: reinforcing a continuum of care after primary percutaneous coronary intervention.

Primary percutaneous coronary interventions (PPCIs) improve outcomes in patients with ST-elevation myocardial infarction and facilitate the hospitalization course. In most cases, the patient can be discharged within 3 to 5 days after the PPCI, provided that careful triage is applied. Bleeding--often associated with excessive antithrombotic drug dosing--is a major concern. Transfusion has been documented to be a strong and independent predictor of mortality; for this reason, recent guidelines recommend that bleeding be managed using a conservative strategy that limits transfusions and the discontinuation of antithrombotic drugs to major bleeding events and only when local hemostatic interventions are not effective. Primary percutaneous coronary intervention is often performed without previous assessment of renal function, and the amount of contrast medium should be kept to a minimum, because contrast-induced nephropathy occurs frequently and is associated with higher early and late mortality. The risk of major arrhythmias should also be addressed correctly. The prognostic implication of ventricular arrhythmias is extremely dependent on the timing of presentation: midterm mortality is much higher among subjects experiencing a new arrhythmic event after PPCI compared with patients with existing arrhythmias at PPCI or those without arrhythmias. The Zwolle risk score is useful for identifying subjects who may be safely discharged early. Secondary prevention starts at the end of PPCI. Hospital discharge and the planning of follow-up visits are critical for therapeutic recommendations. After an ST-elevation myocardial infarction, patients are at increased risk of recurrences, even when the PPCI is timely; a rehabilitation program and all measures that increase adherence to medications should be implemented, starting at discharge.

Inconsistency of different methods for assessing ex vivo platelet function: relevance for the detection of aspirin resistance.

BACKGROUND: Assays to evaluate platelet function are often interchangeably used to assess "resistance" to aspirin. We compared different platelet function assays in patients treated or untreated with aspirin. DESIGN AND METHODS: Platelet function was evaluated in 162 subjects, 85 of whom were not being treated with any antiplatelet drug and 77 of whom were receiving chronic therapy with low-dose aspirin. Platelet Function Analyzer collagen/ADP- and collagen/epinephrine closure times, as well as light transmittance aggregometry in response to ADP, collagen and arachidonic acid (this last in 47 aspirin-treated patients) were determined. In 43 aspirin-treated patients, serum thromboxane B(2) levels were also measured. RESULTS: In untreated patients, collagen/ADP- and collagen/epinephrine-closure times were correlated with each other (r=0.5, P=0.0001), but did not correlate with ADP- or collagen-induced aggregation. In patients treated with aspirin, collagen/ADP-closure time values were not different from those in untreated patients, while the collagen/epinephrine-closure time was prolonged. ADP-induced aggregation was unaffected by aspirin, while collagen-induced aggregation was reduced. Arachidonic acid-induced aggregation was almost completely suppressed (% maximum light transmittance aggregometry =5 ± 13%). There was, however, no correlation between the various platelet function tests. Serum thromboxane B(2), an index of platelet cyclooxygenase-1 activity, was almost completely suppressed (down to 8 ± 17 ng/mL) in treated patients, and was not correlated with arachidonic acid-, ADP- and collagen-induced aggregation or with collagen/ADP-closure time, but was inversely correlated with collagen/epinephrine-closure time. CONCLUSIONS: There is a high heterogeneity of results of tests evaluating inhibition of platelet function by aspirin, and the results of functional tests do not match biochemical measurement of cyclooxygenase-1 activity. Extreme caution should, therefore, be used in defining "resistance" to aspirin on the basis of the results of these tests.

Genetic determinants of cognitive responses to caffeine drinking identified from a double-blind, randomized, controlled trial.

The widely observed between-subject variability in cognitive responses to coffee may have a genetic basis. We evaluated cognitive responses to caffeine throughout three complex cognitive tasks assessing different subdomains of attention, namely Alerting and Orienting (Categorical Search Task) and Executive Control (Stroop Task and Eriksen Flanker Task). We explored whether they are influenced by gene variants affecting adenosine metabolism or catecholamine receptors. We recruited 106 healthy male subjects who were administered, in a double-blind design, 40mL of either a decaffeinated coffee preparation plus 3mg/kg caffeine (caf) or the corresponding vehicle (decaf). The protocol was repeated 24h later with the alternative preparation. Cognitive tasks were performed between 30min and 2h after caf or decaf administration. Each subject underwent ambulatory blood pressure monitoring for 2h. Blood samples were collected for genetic evaluations and for plasma caffeine and catecholamines measures. We found a significant reduction of reaction times in two of the cognitive tasks (Categorical Search Task and Stroop Task) after caf compared with decaf, indicating that caffeine, on average, improved the attention level in the domains under investigation. We also found, however, a great inter-individual variability in the cognitive performance responses to caffeine. In exploring genetic sources for such variability, we found a relation between polymorphisms of adenosine A2A and the caffeine effects on the attentional domains of Orienting and Executive control. In conclusion, variability in the attentional response to coffee may be partly explained by genetic polymorphisms of adenosine and adrenergic receptors.

Genetic determinants of blood pressure responses to caffeine drinking.

BACKGROUND: The widely observed between-subject variability in cardiovascular responses to coffee may have a genetic basis. OBJECTIVE: We evaluated acute blood pressure (BP) responses to caffeine and explored whether they are influenced by candidate gene variants affecting caffeine metabolism (for cytochrome P450 1A2), adenosine metabolism (for adenosine receptor and AMP deaminase), or catecholamine receptors. METHODS: We recruited 110 healthy male habitual moderate coffee drinkers who refrained from drinking coffee on the day preceding the study. Each subject underwent ambulatory BP monitoring at 6-min intervals for 2 h. Each participant was administered, in a double-blind design, 40 mL of either a decaffeinated coffee preparation plus 3 mg caffeine/kg (caf) or the corresponding vehicle (decaf). The protocol was repeated 24 h later with the alternative preparation. Blood samples were collected for genetic and plasma caffeine and catecholamine evaluations. RESULTS: Compared with decaf, caf was associated with a mean (± SD) significant increase in systolic BP of 4 ± 12 mm Hg and in diastolic BP of 3 ± 10 mm Hg (P < 0.001 for both). Plasma caffeine and adrenaline increased after caf, but not after decaf. Of 11 gene polymorphisms analyzed, a relation was observed between the ADORA2A TT variant and the change in SBP peak and between the ADRA2B I variant and the changes in both SBP mean and peak; mean peak change in SBP; these variants were associated with increased SBP responses to caf. CONCLUSIONS: Variability in the acute BP response to coffee may be partly explained by genetic polymorphisms of the adenosine A2A receptors and α(2)-adrenergic receptors. This trial is registered at clinicaltrials.gov as NCT01330680.