Platelet Function Monitoring in Patients With Coronary Artery Disease

Studies focused on patient responsiveness to antiplatelet therapies, particularly aspirin and clopidogrel, have increased in recent years. However, the relations of in vivo platelet function and adverse clinical events to results of ex vivo platelet function tests remain largely unknown. This article describes current methods of measuring platelet function in various clinical and research situations and their advantages and disadvantages, reviews evidence for antiplatelet response variability and resistance, discusses the potential pitfalls of monitoring platelet function, and demonstrates emerging data supporting the positive clinical and treatment implications of platelet function testing

The duration of pretreatment with ticlopidine prior to stenting is associated with the risk of procedure-related non–Q-wave myocardial infarctions

AbstractObjectives. This study sought to determine whether the duration of pretreatment with the adenosine diphosphate receptor antagonist ticlopidine prior to intracoronary stenting is associated with the incidence of procedure-related non–Q-wave myocardial infarctions (MIs).Background. Dual antiplatelet therapy with ticlopidine and aspirin is routinely used with stenting, although ticlopidine is commonly not begun until the day of the procedure. Periprocedural MIs are at least partially platelet-dependent events. As the maximal platelet inhibitory effects of this drug take 2 to 3 days to be realized, we hypothesized that longer treatment prior to stenting would be associated with lower rates of procedure-related MIs.Methods. We reviewed outcomes in 175 consecutive patients treated with ticlopidine prior to stenting at the Cleveland Clinic Foundation. Those patients with an elevation in creatine kinase above our laboratory normal (>210 IU/L) with ≥4% MB fraction on routine evaluation were defined as having a non–Q-wave MI.Results. There were 28 patients (16%) who had a non–Q-wave MI. Longer duration of ticlopidine pretreatment was strongly associated with a lower incidence of procedure-related non–Q-wave MIs (duration of pretreatment <1 day, 29% had MI; 1 to 2 days, 14%; ≥3 days, 5%; chi-square for trend = 9.6; p = 0.002). Ticlopidine pretreatment of ≥3 days was associated with a significant reduction in the risk of non–Q-wave MI (unadjusted odds ratio 0.18, 95% confidence interval = 0.04 to 0.78, p = 0.01) compared with pretreatment of <3 days.Conclusions. Among patients undergoing intracoronary stenting, beginning ticlopidine therapy several days prior to the procedure is associated with a reduced risk of procedural non–Q-wave MIs

Rapid platelet-function assay. An automated and quantitative cartridge-based method

Background-The platelet glycoprotein (GP) IIb/IIIa receptor is important in mediating platelet thrombus formation, and the GP IIb/IIIa antagonist abciximab (c7E3 Fab; ReoPro) is effective in preventing thrombotic ischemic cardiovascular complications of unstable angina and percutaneous coronary interventions. Small-molecule antagonists of GP IIb/IIIa based on the Arg-Gly-Asp (RGD) sequence show similar benefit, and some of these agents are orally active. However, there may be significant interindividual variation in response to such antagonists, especially with chronic oral therapy. It will be essential to balance the beneficial antithrombotic effect of these drugs with their potential for causing bleeding. In response to this need, we have developed a rapid platelet-function assay (RPFA), a point-of-care system that provides a quantitative measure of the competence of the GP IIb/IIIa receptor as reflected in the ability of platelets to agglutinate fibrinogen-coated beads. Methods and Results-Polystyrene beads were coated with fibrinogen and placed in a cartridge along with a lyophilized peptide that activates the thrombin receptor. Anticoagulated whole blood was added to the cartridge, and then a microprocessor-controlled operation mixed the reagents and detected agglutination between platelets and coated beads. Quantitative digital results were displayed within 3 minutes. Because there is no dilution of the blood, the assay can be used to measure platelet activity in samples that have been treated with GP IIb/IIIa antagonists with high dissociation rates. RPFA results of whole-blood samples treated with different GP IIb/IIIa antagonists correlated well with both conventional turbidimetric platelet aggregation (r 2 ϭ0.95) and the percentage of free GP IIb/IIIa molecules in the sample (r 2 ϭ0.96). The mean difference in measurements between RPFA and aggregometry was -4% (Ϯ4% SD), and the mean difference in measurements between RPFA and free GP IIb/IIIa receptors was -2% (Ϯ6% SD). Conclusions-Th

Clinical outcomes according to permanent discontinuation of clopidogrel or placebo in the CHARISMA trial

SummaryBackgroundLate discontinuation of clopidogrel after an acute coronary syndrome or stent placement may be associated with a clinical rebound effect.AimsTo describe the characteristics and evolution of patients non-compliant to study drug in the prospective, randomized, double-blind CHARISMA trial.MethodsOf 15,603 patients aged 45 or older years with established atherothrombotic disease (coronary artery disease, stroke, peripheral arterial disease) or multiple cardiovascular risk factors, 2999 permanently interrupted (withdrawers) study drug (clopidogrel or placebo) during follow-up. The primary endpoint was first occurrence since randomization of myocardial infarction, stroke or cardiovascular death.ResultsWithdrawers displayed a higher risk profile and rates of death/myocardial infarction/stroke (13.5% versus 5.6%; hazard ratio [HR]: 3.18; 95% confidence interval [CI]: 3.05–3.32; p<0.001) and severe bleeding (4.9% versus 0.7%; odds ratio [OR]: 7.42; 95% CI: 5.67–9.70; p<0.001) versus non-withdrawers. Death/myocardial infarction/stroke occurred after an average of 228 days (95% CI: 197–258) and was less frequent in patients assigned to clopidogrel versus placebo (9.7% versus 11.9%; HR: 0.80; 95% CI: 0.64–1.00; p=0.051); the rate of severe bleeding was the same (4.0% versus 4.3%; OR: 0.92; 95% CI: 0.65–1.32; p=0.66). Among withdrawers, initial clopidogrel treatment was an independent correlate of survival (HR: 0.74, 95% CI: 0.59–0.93; p=0.011), but not severe bleeding (OR: 0.94; 95% CI: 0.65–1.35; p=0.74). Kaplan-Meier curves for the primary endpoint suggested no rebound effect or disease reactivation after discontinuation of clopidogrel compared with placebo.ConclusionsPatients who stopped medication had increased rates of ischaemic and bleeding events and mortality. Patients initially on clopidogrel had fewer ischaemic events than those on placebo; discontinuation was not associated with any clinically detectable rebound effect

A Systematic Review of Fitness Apps and Their Potential Clinical and Sports Utility for Objective and Remote Assessment of Cardiorespiratory Fitness

Key Points The validity and reliability of existing and/or underdevelopment fitness apps should be further investigated. Physiological signals should be incorporated into fitness apps, such as heart rate measures using a smartphone camera, during or after exercise testing. There is a need to develop interoperable fitness apps (e.g., different languages, apps integrated into both app markets, data that is device-independent). Fitness apps should incorporate evidence-based cutpoints of CRF, allowing interpretation of fitness testing resultsWe are grateful to Ms Carmen Sainz-Quinn for assistance with the English language.Background Cardiorespiratory fitness (CRF) assessment provides key information regarding general health status that has high clinical utility. In addition, in the sports setting, CRF testing is needed to establish a baseline level, prescribe an individualized training program and monitor improvement in athletic performance. As such, the assessment of CRF has both clinical and sports utility. Technological advancements have led to increased digitization within healthcare and athletics. Nevertheless, further investigation is needed to enhance the validity and reliability of existing fitness apps for CRF assessment in both contexts. Objectives The present review aimed to (1) systematically review the scientific literature, examining the validity and reliability of apps designed for CRF assessment; and (2) systematically review and qualitatively score available fitness apps in the two main app markets. Lastly, this systematic review outlines evidence-based practical recommendations for developing future apps that measure CRF. Data Sources The following sources were searched for relevant studies: PubMed, Web of Science®, ScopusTM, and SPORTDiscus, and data was also found within app markets (Google Play and the App Store). Study Eligibility Criteria Eligible scientific studies examined the validity and/or reliability of apps for assessing CRF through a field-based fitness test. Criteria for the app markets involved apps that estimated CRF. Study Appraisal and Synthesis Methods The scientific literature search included four major electronic databases and the timeframe was set between 01 January 2000 and 31 October 2018. A total of 2796 articles were identified using a set of fitness-related terms, of which five articles were finally selected and included in this review. The app market search was undertaken by introducing keywords into the search engine of each app market without specified search categories. A total of 691 apps were identified using a set of fitness-related terms, of which 88 apps were finally included in the quantitative and qualitative synthesis. Results Five studies focused on the scientific validity of fitness tests with apps, while only two of these focused on reliability. Four studies used a sub-maximal fitness test via apps. Out of the scientific apps reviewed, the SA-6MWTapp showed the best validity against a criterion measure (r = 0.88), whilst the InterWalk app showed the highest test–retest reliability (ICC range 0.85–0.86). Limitations Levels of evidence based on scientific validity/reliability of apps and on commercial apps could not be robustly determined due to the limited number of studies identified in the literature and the low-to-moderate quality of commercial apps. Conclusions The results from this scientific review showed that few apps have been empirically tested, and among those that have, not all were valid or reliable. In addition, commercial apps were of low-to-moderate quality, suggesting that their potential for assessing CRF has yet to be realized. Lastly, this manuscript has identified evidence-based practical recommendations that apps might potentially offer to objectively and remotely assess CRF as a complementary tool to traditional methods in the clinical and sports settings

Evacetrapib and Cardiovascular Outcomes in High-Risk Vascular Disease

BACKGROUND: The cholesteryl ester transfer protein inhibitor evacetrapib substantially raises the high-density lipoprotein (HDL) cholesterol level, reduces the low-density lipoprotein (LDL) cholesterol level, and enhances cellular cholesterol efflux capacity. We sought to determine the effect of evacetrapib on major adverse cardiovascular outcomes in patients with high-risk vascular disease. METHODS: In a multicenter, randomized, double-blind, placebo-controlled phase 3 trial, we enrolled 12,092 patients who had at least one of the following conditions: an acute coronary syndrome within the previous 30 to 365 days, cerebrovascular atherosclerotic disease, peripheral vascular arterial disease, or diabetes mellitus with coronary artery disease. Patients were randomly assigned to receive either evacetrapib at a dose of 130 mg or matching placebo, administered daily, in addition to standard medical therapy. The primary efficacy end point was the first occurrence of any component of the composite of death from cardiovascular causes, myocardial infarction, stroke, coronary revascularization, or hospitalization for unstable angina. RESULTS: At 3 months, a 31.1% decrease in the mean LDL cholesterol level was observed with evacetrapib versus a 6.0% increase with placebo, and a 133.2% increase in the mean HDL cholesterol level was seen with evacetrapib versus a 1.6% increase with placebo. After 1363 of the planned 1670 primary end-point events had occurred, the data and safety monitoring board recommended that the trial be terminated early because of a lack of efficacy. After a median of 26 months of evacetrapib or placebo, a primary end-point event occurred in 12.9% of the patients in the evacetrapib group and in 12.8% of those in the placebo group (hazard ratio, 1.01; 95% confidence interval, 0.91 to 1.11; P=0.91). CONCLUSIONS: Although the cholesteryl ester transfer protein inhibitor evacetrapib had favorable effects on established lipid biomarkers, treatment with evacetrapib did not result in a lower rate of cardiovascular events than placebo among patients with high-risk vascular disease. (Funded by Eli Lilly; ACCELERATE ClinicalTrials.gov number, NCT01687998 .)