ABSTRACT
ABSTRACT: Although recent studies described platelet reactivity (PR) changes in days after transcatheter aortic valve implantation (TAVI), precise time course and duration of these changes have not been fully investigated. The aim of this study was to investigate PR pattern during and after TAVI in multiple time points. Study included 40 consecutive patients undergoing TAVI. All patients underwent the procedure on dual antiplatelet therapy. PR was measured in 7 time points: before induction of anesthesia (T1), after heparin administration (T2), 10 minutes after initial valve implantation (T3), at the end of procedure (T4), and on 3rd, 6th, and 30th postoperative day (T5-T7). PR was measured using impedance aggregometer using 3 different platelet aggregation agonists (arachidonic acid in ASPItest, adenosine diphosphate in ADPtest and thrombin receptor activating peptide 6 in TRAPtest). All patients underwent successful TAVI procedure. Mean PR on T1 was 22.9 ± 23.0 U for ASPItest, 40.5 ± 23.7 U for ADPtest and 91.7 ± 32.5 U for TRAPtest. There was no significant difference in PR on T2. On T3, significant reduction of PR in all 3 tests was observed [ASPI 10.4 ± 11.6 U (P = 0.001), ADP 24.2 ± 14.1 U (P < 0.001) and TRAP 69.3 ± 26.6 U (P < 0.001)]. PR nadir for all tests was reached on T5, with subsequent PR incline. PR values in all tests returned to baseline levels on T7. Our results show that successful TAVI procedure induces transient decrease in PR regardless of the platelet activation pathway.
Subject(s)
Aortic Valve Stenosis/surgery , Blood Platelets/drug effects , Platelet Activation/drug effects , Platelet Aggregation Inhibitors/administration & dosage , Transcatheter Aortic Valve Replacement/adverse effects , Aged , Aged, 80 and over , Aortic Valve Stenosis/blood , Aortic Valve Stenosis/physiopathology , Blood Platelets/metabolism , Croatia , Dual Anti-Platelet Therapy , Female , Hemodynamics , Humans , Male , Platelet Aggregation Inhibitors/adverse effects , Platelet Function Tests , Prospective Studies , Stress, Mechanical , Time Factors , Treatment OutcomeABSTRACT
Clopidogrel is still widely used in acute coronary syndrome despite the development of more potent P2Y12 inhibitors. Previously, we conducted a trial that evaluated serial clopidogrel dose adjustment based on platelet function testing in acute coronary syndrome patients with initial high on-treatment platelet reactivity (HTPR). In this substudy, we performed post hoc analysis of the effect of ABCB1 genetic variants C3435T and G2677T/A on platelet inhibition and outcomes. There were no differences in the proportion of HTPR patients among C3435T carriers and noncarriers in both interventional and control group. G2677T carriers expressed significantly higher proportion of HTPR pattern throughout 12-month follow-up in the control group with no difference in the interventional group. There was no difference in ischemic outcomes between C3435T and G2677T carriers and noncarriers in both groups of patients. The results indicate that ABCB1 genotyping is not useful to guide clopidogrel therapy tailoring to improve high-risk patient management.
Subject(s)
Acute Coronary Syndrome/drug therapy , Blood Platelets/drug effects , Clopidogrel/administration & dosage , Gastrointestinal Absorption/genetics , Pharmacogenomic Variants , Platelet Aggregation Inhibitors/administration & dosage , Platelet Aggregation/drug effects , Purinergic P2Y Receptor Antagonists/administration & dosage , Receptors, Purinergic P2Y12/drug effects , ATP Binding Cassette Transporter, Subfamily B/genetics , ATP Binding Cassette Transporter, Subfamily B/metabolism , Acute Coronary Syndrome/blood , Acute Coronary Syndrome/diagnosis , Aged , Blood Platelets/metabolism , Clopidogrel/metabolism , Drug Monitoring , Female , Humans , Male , Middle Aged , Platelet Aggregation Inhibitors/metabolism , Purinergic P2Y Receptor Antagonists/metabolism , Randomized Controlled Trials as Topic , Receptors, Purinergic P2Y12/blood , Treatment OutcomeABSTRACT
Heart failure (HF) is a common cause of morbimortality with different etiopathogenesis and prognosis between men and women. This review provides a brief overview of gender-based differences in response to pharmacological therapies of heart failure with or without reduced ejection fraction (EF). It focuses on the differences in therapy outcomes with angiotensin-converting enzyme inhibitors (ACEi), angiotensin receptor blockers (ARBs), angiotensin neprilysin inhibitors (ARNI), beta-adrenergic blockers, mineralocorticoid/ aldosterone receptor antagonists, diuretics, ivabradine and digoxin. The baseline data originate from randomised controlled trials (RCTs) and large registries. We conclude that current guidelines recommending similar therapeutic approaches for both men and women are appropriate, while additional consideration should be given to different approaches regarding the use of ARBs, ACEi, and digoxin. Based on the available data, the ARBs might be considered a first-line therapy of HR for women instead of ACEi. Moreover, female patients should have stricter digoxin monitoring due to higher sensitivity and increased risk of complications. Finally, women are underrepresented in current clinical trials, and therefore future trials should aim to balance the gender recruitment disparity allowing sub-group analysis and comparisons between genders to guide individualised therapeutic strategies and appropriately targeted preventative steps.
Subject(s)
Angiotensin Receptor Antagonists , Heart Failure , Adrenergic beta-Antagonists/pharmacology , Angiotensin Receptor Antagonists/pharmacology , Angiotensin Receptor Antagonists/therapeutic use , Angiotensin-Converting Enzyme Inhibitors/pharmacology , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Digoxin/pharmacology , Digoxin/therapeutic use , Female , Heart Failure/drug therapy , Humans , Male , Mineralocorticoid Receptor Antagonists/therapeutic use , Sex Characteristics , Stroke VolumeABSTRACT
BACKGROUND: Controversy exists as to whether low-dose aspirin use may give benefit in primary prevention of cardiovascular (CV) events. We hypothesized that the benefits of aspirin are underevaluated. METHODS: We investigated 12,123 Caucasian patients presenting to hospital with acute coronary syndromes as first manifestation of CV disease from 2010 to 2019 in the ISACS-TC multicenter registry (ClinicalTrials.gov, NCT01218776). Individual risk of ST segment elevation myocardial infarction (STEMI) and its association with 30-day mortality was quantified using inverse probability of treatment weighting models matching for concomitant medications. Estimates were compared by test of interaction on the log scale. FINDINGS: The risk of STEMI was lower in the aspirin users (absolute reduction: 6·8%; OR: 0·73; 95%CI: 0·65-0·82) regardless of sex (p for interaction=0·1962) or age (p for interaction=0·1209). Benefits of aspirin were seen in patients with hypertension, hypercholesterolemia, and in smokers. In contrast, aspirin failed to demonstrate a significant risk reduction in STEMI among diabetic patients (OR:1·10;95%CI:0·89-1·35) with a significant interaction (p: <0·0001) when compared with controls (OR:0·64,95%CI:0·56-0·73). Stratification of diabetes in risk categories revealed benefits (p interaction=0·0864) only in patients with concomitant hypertension and hypercholesterolemia (OR:0·87, 95% CI:0·65-1·15), but not in smokers. STEMI was strongly related to 30-day mortality (OR:1·93; 95%CI:1·59-2·35). INTERPRETATION: Low-dose aspirin reduces the risk of STEMI as initial manifestation of CV disease with potential benefit in mortality. Patients with diabetes derive substantial benefit from aspirin only in the presence of multiple risk factors. In the era of precision medicine, a more tailored strategy is required. FUNDING: None.