Cardiovascular considerations on recreational scuba diving. SEC-Clinical Cardiology Association/SEC-Working Group on Sports Cardiology consensus document.

The practice of recreational scuba diving has increased worldwide, with millions of people taking part each year. The aquatic environment is a hostile setting that requires human physiology to adapt by undergoing a series of changes that stress the body. Therefore, physical fitness and control of cardiovascular risk factors are essential for practicing this sport. Medical assessment is not mandatory before participating in this sport and is only required when recommended by a health questionnaire designed for this purpose. However, due to the significance of cardiovascular disease, cardiology consultations are becoming more frequent. The aim of the present consensus document is to describe the cardiovascular physiological changes that occur during diving, focusing on related cardiovascular diseases, their management, and follow-up recommendations. The assessment and follow-up of individuals who practice diving with previous cardiovascular disease are also discussed. This document, endorsed by the Clinical Cardiology Association of the Spanish Society of Cardiology (SEC) and the SEC Working Group on Sports Cardiology of the Association of Preventive Cardiology, aims to assist both cardiologists in evaluating patients, as well as other specialists responsible for assessing individuals' fitness for diving practice.

Impact of renal function on Ticagrelor-induced antiplatelet effects in coronary artery disease patients.

Background: Chronic renal failure (CKD) is associated with the presence of increased platelet reactivity and lower clinical benefit of clopidogrel. Ticagrelor has a more favorable pharmacodynamic and pharmacokinetic profile compared to clopidogrel, which has translated into better clinical outcomes in patients with acute coronary syndrome (ACS). We conducted a prospective mechanistic cohort study in order to investigate the impact of renal failure on the pharmacokinetics and pharmacodynamics of ticagrelor in patients with acute ACS. Methods: Patients were divided into two groups based on their estimated renal clearances (eGFR ≥ 60 mL/min and eGFR < 60 mL/min). Platelet function was determined using the VerifyNow system at baseline, after the ticagrelor loading dose and at discharge. In addition, levels of ticagrelor and its active metabolite (AR-C124910XX) were determined in the first hour after loading dose. Results: 48 patients were recruited (eGFR ≥ 60 mL/min: 35 and eGFR < 60 mL/min: 13). There were no significant differences between the groups in terms of platelet inhibition after the loading or after 7 days of treatment (p = 0.219). However, the levels of ticagrelor and its active metabolite were lower in subjects with normal renal function than in CKD, especially at 4 (p = 0.02 and 0.04 respectively) and 6 h of loading (p = 0.042 and 0.08 respectively). Conclusion: No differences in platelet inhibition were observed after treatment with ticagrelor in patients with different renal function, although patients with renal impairment showed higher levels of ticagrelor and AR-C124910XX after 4 h of the loading dose.

Simplified Geleijnse score for identifying chest pain features associated with coronary ischemia.

BACKGROUND: The Geleijnse score, which was proposed to assess for coronary ischemia, has practical limitations. OBJECTIVES: Our aim was to design and evaluate a simplified version of the Geleijnse score. METHODS: We enrolled patients with suspected coronary heart disease but negative troponin T or absence of enzymatic curve, and a non-diagnostic 12-lead ECG. The initial study was performed in a retrospective derivation cohort and the results were subsequently validated in a prospective cohort. RESULTS: From 109 patients included in the derivation cohort, 33 (30.3%) received a diagnosis of coronary heart disease. Chest pain with both arms radiation (OR 3.54), severe intensity (OR 2.41), improvement by nitroglycerin (OR 1.61), associated dyspnea (OR 1.97) and prior exertional angina history (OR 2.91) were independently associated with an ischemic origin on multivariate logistic regression analysis. ROC curves comparison demonstrated both the original and simplified scores presented modest predictive ability with significant difference when analyzed using dichotomous cut-offs (0.647 [simplified] vs. 0.544 [original], p = 0.042) but not as a continuous variable (0.670 [simplified] vs. 0.621 [original], p = 0.396). In 305 patients from the validation cohort, the simplified score presented extensively increased predictive accuracy than the Geleijnse, in the continuous (c-indexes = 0.735 vs. 0.685, p = 0.040) and the dichotomic (c-indexes = 0.682 vs. 0.514, p<0.001) forms. CONCLUSIONS: A simplified version of the Geleijnse score, including some routine clinical manifestations associated with coronary heart disease, presented significantly better predictive ability compared to the original score.

Effect of cocoa (Theobroma cacao L.) on platelet function testing profiles in patients with coronary artery disease: ECLAIR pilot study.

INTRODUCTION: This prospective pharmacodynamic nutraceutical study assessed the effect of a 1-week trial of 30 g/day of 65% cocoa (dark chocolate) (Theobroma cacao L.) consumption intervention on platelet reactivity. METHODS: Patients with stable coronary artery disease (CAD) (n=20) who were on maintenance dual antiplatelet therapy of aspirin (ASA) 81 mg/day and clopidogrel 75 mg/day were recruited. Platelet function was evaluated with the VerifyNow P2Y12 reaction unit (PRU) and aspirin reaction unit (ARU) assays (Werfen, Bedford, Massachusetts, USA) and assessed prior to initiation of and after a 1-week trial of 30 g/day of 65% cocoa consumption intervention. Results were compared with a paired t-test. RESULTS: Cocoa augmented the inhibitory effect of clopidogrel, demonstrated by a reduction of 11.9% (95% CI 5.7% to 18.0%, p value 0.001), significantly decreasing the PRU by 26.85 (95% CI 12.22 to 41.48, p value 0.001). The inhibitory effect of ASA was not impacted by cocoa, reflected by a non-significant reduction in ARU of 17.65 (95% CI 21.00 to 56.3, p value 0.351). No patients experienced any serious adverse events. CONCLUSIONS: Cocoa augmented the inhibitory effect of clopidogrel but not ASA. This nutraceutical study could be potentially informative and applicable for patients with stable CAD. Further long-term studies are required to confirm these exploratory findings. TRIAL REGISTRATION NUMBER: NCT04554901.

Global longitudinal strain assessment of cardiac function and extravascular lung water formation after diving using semi-closed circuit rebreather.

PURPOSE: The aim of the present investigation is to study the relationship of ventricular global longitudinal strain (GLS) and ultrasound lung comets (ULC) formation to establish a link between extravascular pulmonary water formation and cardiac contractile dysfunction. METHODS: This is a prospective observational study including 14 active military divers. The subjects performed two sea dives of 120 min each with a semi-closed SCUBA circuit at 10 m depth. Divers were examined at baseline, 15 min (D1) and 60 min (D2) after diving. The evaluation included pulmonary and cardiac echography (including speckle tracking techniques). Blood samples were drawn at baseline and after diving, assessing hs-TnT and Endothelin-1. RESULTS: ULC were detected in 9 (64.2%) and 8 (57.1%) of the subjects after D1 and D2 respectively. No differences were found in right and left ventricular GLS after both immersions (RV: Baseline: - 17.9 4.9 vs. D1: - 17.2 6.5 and D2: - 16.7 5.8 s-1; p = 0.757 and p = 0.529; LV: Baseline: - 17.0 2.3 vs. D1: - 17.4 2.1 and D2: - 16.9 2.2 s-1; p = 0.546 and p = 0.783). However, a decrease in atrial longitudinal strain parameters have been detected after diving (RA: Baseline: 35.5 9.2 vs. D1: 30.3 12.8 and D2: 30.7 13.0 s-1; p = 0.088 and p = 0.063; LA: Baseline: 39.0 10.0 vs. D1: 31.6 6.1 and D2: 32.4 10.6 s-1; p = 0.019 and p = 0.054). CONCLUSION: In the present study, no ventricular contractile dysfunction was observed. However, increase pulmonary vasoconstriction markers were present after diving.

The Effect of Dapagliflozin on Platelet Function Testing Profiles in Diabetic Patients: The EDGE Pilot Study.

INTRODUCTION: This prospective pharmacodynamic (PD) study assessed the effect of the sodium-glucose co-transporter-2 inhibitor (SGLT2i), dapagliflozin, on platelet reactivity. METHODS: Patients with stable coronary artery disease (CAD) and type 2 diabetes mellitus (T2DM) (n = 27) who were on maintenance dual antiplatelet therapy (DAPT) of aspirin 81 mg daily, and clopidogrel 75 mg daily were recruited. Platelet function was evaluated with the VerifyNow™ P2Y12 assay (Werfen, Bedford, MA, USA) and assessed prior to initiation of and after 10 days of treatment with dapagliflozin 10 mg once-daily dose regimen. Results were compared with a paired t test. RESULTS: Treatment with dapagliflozin significantly decreased P2Y12 reaction units (PRU) by 20%, (95% confidence interval (CI) 8.5-32.6%, p value 0.002). The mean difference in PRU was 36.70 (95% CI 16.66-56.75). No patients experienced any serious adverse events (SAEs). CONCLUSIONS: Significantly diminished platelet reactivity was observed on dapagliflozin as compared to without dapagliflozin. This dedicated pharmacodynamic study could be potentially informative and applicable for Trinidadian stable CAD patients with T2DM on DAPT. Further studies are required to confirm these exploratory findings. CLINICAL TRIAL REGISTRATION: EDGE ClinicalTrials.gov number NCT04400760.

Antithrombotic Therapy in Patients with Peripheral Artery Disease: A Focused Review on Oral Anticoagulation.

Peripheral artery disease (PAD) is a major cause of morbidity and mortality but it is usually underdiagnosed and undertreated. Patients with PAD present dysregulated procoagulant, anticoagulant, and fibrinolytic pathways leading to arterial and venous thrombosis. The risk of several ischemic-related complications could be mitigated with appropriate antithrombotic therapy, which plays a central role in all types of PAD. For years, antiplatelets have been indicated in patients with symptomatic PAD or those who have undergone revascularization. Unfortunately, a non-negligible proportion of patients with PAD will suffer from adverse events during the follow-up, even despite proper medical therapies for the prevention of PAD complications. Thus, there is room for improving clinical outcomes in these patients. Given the implication of both, primary and secondary hemostasis in arterial thrombosis and the pathophysiology of PAD, the combination of antiplatelets and anticoagulants has emerged as a potential antithrombotic alternative to antiplatelets alone. In this narrative review article, we have highlighted the most recent evidence about antithrombotic therapy in PAD patients, with a special focus on oral anticoagulation. Certainly, COMPASS and VOYAGER PAD trials have shown promising results. Thus, rivaroxaban in combination with aspirin seem to reduce cardiovascular outcomes with a similar bleeding risk compared to aspirin alone. Nevertheless, results from real-world studies are needed to confirm these observations, and other trials will provide novel evidence about the safety and efficacy of emerging anticoagulant agents.

Impact of Comorbidities and Antiplatelet Regimen on Platelet Reactivity Levels in Patients Undergoing Transcatheter Aortic Valve Implantation.

ABSTRACT: The aim of our study is to assess the impact of anemia, chronic kidney disease, and diabetes mellitus on platelet reactivity (PR) in patients with severe aortic stenosis, both at baseline and after transcatheter aortic valve implantation (TAVI). This study is a prespecified subanalysis of the REAC-TAVI prospective, multicenter trial that included patients pretreated with aspirin + clopidogrel before TAVI. PR was measured at baseline and at 5 different time points after TAVI with the VerifyNow assay (Accriva Diagnostics, San Diego, CA), over a 3-month follow-up period. Patients with high PR (HPR) at baseline, before TAVI (n = 48) were randomized to aspirin + clopidogrel or aspirin + ticagrelor for 3 months, whereas those with normal PR (NPR) (n = 20) were continued on aspirin + clopidogrel. A "raiser response" in PR was defined as an increase in PR units >20% of baseline after TAVI. Patients with HPR before TAVI presented concomitant anemia and chronic kidney disease more frequently than their counterparts with NPR. Anemia and higher body mass index were independently associated with HPR to clopidogrel at baseline. Moreover, anemic patients with baseline HPR who were continued on clopidogrel presented higher PR after TAVI than patients with HPR switched to ticagrelor. All patients with baseline NPR presented a "raiser response" after TAVI, which was nonexistent among patients with HPR managed with ticagrelor. In summary, anemia seems as a relevant factor associated with baseline HPR and higher PR after TAVI in patients with baseline HPR randomized to clopidogrel, whereas ticagrelor proved more effective than clopidogrel at attaining sustained reductions in PR during follow-up, regardless of baseline comorbidities.

The Effect of Empagliflozin on Platelet Function Profiles in Patients with Stable Coronary Artery Disease in Trinidad: The EFFECT Pilot Study.

INTRODUCTION: This prospective pharmacodynamic (PD) study aimed to assess the effect of the sodium-glucose cotransporter 2 inhibitor (SGLT2i) empagliflozin on platelet reactivity. METHODS: Patients with stable coronary artery disease (CAD) and type 2 diabetes mellitus (T2DM) (n = 20) who were actively treated with dual antiplatelet therapy (DAPT) of aspirin 81 mg daily and clopidogrel 75 mg daily were recruited. Platelet function was measured with the VerifyNow™ P2Y12 assay (Instrumentation Laboratory, Massachusetts, USA) and assessed before the initiation of and after 10 days of treatment with empagliflozin 25 mg once daily maintenance dose regimen. Results were compared with a paired t test. RESULTS: The mean P2Y12 reaction units (PRU) on empagliflozin was significantly less than without empagliflozin at baseline (187.35, 95% confidence interval (CI) 155.38-219.32 vs. 217.25, CI 180.60-253.90; p < 0.030). The mean difference in PRU was 29.90 (95% CI 3.17-56.63). No patients experienced any serious adverse events (SAEs). CONCLUSIONS: Significantly attenuated platelet reactivity was observed on empagliflozin as compared to without empagliflozin. This dedicated pharmacodynamic study could be clinically pertinent for Trinidadian patients with stable CAD and T2DM on DAPT. Further studies are required to confirm these exploratory findings. (Funded by the University of the West Indies, St. Augustine; EFFECT). CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov number NCT04342819.

The Effect of Low-Dose Ticagrelor on Platelet Function Profiles in Patients With Stable Coronary Artery Disease in Trinidad: The TWIST Pilot Study.

INTRODUCTION: This prospective, pharmacodynamic study aimed to explore the potential applicability of a low-dose ticagrelor regimen in a heterogeneous Trinidadian subpopulation. METHODS: Patients with stable coronary artery disease (n = 25) who were actively treated with dual antiplatelet therapy of aspirin 81 mg daily and clopidogrel 75 mg daily were recruited. Platelet function was measured with the VerifyNow P2Y12 assay (Accriva Diagnostics, San Diego, CA, USA) and assessed before initiation of and after 14 days of treatment with a low-dose ticagrelor 45 mg twice daily maintenance dose regimen. Results were compared with a paired t test. RESULTS: The mean P2Y12 reaction units (PRU) score on ticagrelor was significantly less compared to that of clopidogrel (50.4, 95% confidence interval (CI) 29-73.9; vs. 149.6, 95% CI 129.4-169.9; p value < 0.001). Of the patients, 4% experienced Medical Research Council class 1 dyspnea, and Bleeding Academic Research Consortium class 1 bleeding on the ticagrelor regimen (one patient each). CONCLUSIONS: Significantly attenuated platelet reactivity was seen on the low ticagrelor maintenance dose as compared to clopidogrel. This dedicated pharmacodynamic study could be applicable and informative for Trinidadian stable coronary artery disease patients. Further studies are required to confirm these exploratory findings.(Funded by the University of the West Indies, St. Augustine). TRIAL REGISTRATION: ClinicalTrials.gov number NCT04206176.

Influence of Valve Type and Antiplatelet Regimen on Platelet Reactivity After TAVI: Subanalysis of the REAC-TAVI Trial.

OBJECTIVES: Ticagrelor has proven more effective than clopidogrel at attaining a maintained suppression of high platelet reactivity (HPR) in aortic stenosis patients undergoing transcatheter aortic valve implantation (TAVI). This study aims to assess the influence of implanted valve type on the degree of platelet reactivity (PR) after TAVI. METHODS: This study is a prespecified analysis of REAC-TAVI, a prospective, multicenter study that included patients on dual-antiplatelet therapy with aspirin and clopidogrel before TAVI. Patients with HPR (n = 48) were randomized to aspirin and clopidogrel or aspirin and ticagrelor for 3 months, while those without HPR (n = 20) were continued on aspirin and clopidogrel. PR was measured 6 hours, 24 hours, 5 days, 30 days, and 90 days after TAVI with VerifyNow assay. Bioprosthetic valves were classified as balloon-expandable valve (BEV), self-expandable valve (SEV), or other. RESULTS: Sixty-eight patients comprising 32 BEVs, 28 SEVs, and 8 other valves were included. Devices were larger and postdilation was more frequent in the SEV group. Follow-up PR was lower in patients treated with ticagrelor vs those treated with clopidogrel at all time points after TAVI, including patients without baseline HPR (P<.001). PR after TAVI was similar in the three groups. Major cardiovascular adverse events, stroke, and hemorrhagic complications were comparable across the different bioprosthesis groups at 4-month follow-up. CONCLUSIONS: The effect of valve type on PR after TAVI is similar across the spectrum of most transcatheter valves. In our sample, ticagrelor achieved a faster and more effective reduction in PR than clopidogrel in patients with HPR undergoing TAVI, irrespective of valve type.

Recommendations on antithrombotic treatment during the COVID-19 pandemic. Position statement of the Working Group on Cardiovascular Thrombosis of the Spanish Society of Cardiology.

The new coronavirus SARS-CoV-2, which gives rise to the highly contagious COVID-19 disease, has caused a pandemic that is overwhelming health care systems worldwide. Affected patients have been reported to have a heightened inflammatory state that increases their thrombotic risk. However, there is very scarce information on the management of thrombotic risk, coagulation disorders, and anticoagulant therapy. In addition, the situation has also greatly influenced usual care in patients not infected with COVID-19. This article by the Working Group on Cardiovascular Thrombosis of the Spanish Society of Cardiology aims to summarize the available information and to provide a practical approach to the management of antithrombotic therapy.

[Recommendations on antithrombotic treatment during the COVID-19 pandemic. Position statement of the Working Group on Cardiovascular Thrombosis of the Spanish Society of Cardiology]. / Recomendaciones sobre el tratamiento antitrombótico durante la pandemia COVID-19. Posicionamiento del Grupo de Trabajo de Trombosis Cardiovascular de la Sociedad Española de Cardiología.

The new coronavirus SARS-CoV-2, which gives rise to the highly contagious COVID-19 disease, has caused a pandemic that is overwhelming health care systems worldwide. Affected patients have been reported to have a heightened inflammatory state that increases their thrombotic risk. However, there is very scarce information on the management of thrombotic risk, coagulation disorders, and anticoagulant therapy. In addition, the situation has also greatly influenced usual care in patients not infected with COVID-19. This article by the Working Group on Cardiovascular Thrombosis of the Spanish Society of Cardiology aims to summarize the available information and to provide a practical approach to the management of antithrombotic therapy.

One-year efficacy and safety of prasugrel and ticagrelor in patients with acute coronary syndromes: Results from a prospective and multicentre ACHILLES registry.

BACKGROUND: Prasugrel and ticagrelor have demonstrated higher efficacy than clopidogrel in their main clinical trials for patients with acute coronary syndrome (ACS). However, the long-term prognosis and different clinical characteristics related to the type of antiplatelet prescription in current clinical practice ACS patients have not been analysed in depth. The objective of this study was to analyse the clinical profile of ACS and the efficacy and safety of novel oral P2Y12 inhibitors in current clinical practice patients discharged afterACS. METHODS: We collected data from the ACHILLES registry, and an observational, prospective and multicentre registry of patients discharged after ACS. We analysed baseline characteristics, clinical profile and therapy during ACS admission and compared with the different treatments at discharge. After 1 year of follow-up, ischaemic and major bleeding events were analysed. Multivariate Cox regression analysis and Kaplan Meier curves were also plotted. RESULTS: Of 1717 consecutive patients, 1294 (75.4%) were discharged with a P2Y12 inhibitor without oral anticoagulation. Novel oral P2Y12 inhibitors were indicated in 47%. Patients treated with clopidogrel were elderly (69.1 ± 13.4 vs 60.4 ± 11.5 years; P < .001) and had a higher prevalence of cardiovascular risk factors. GRACE and CRUSADE scores were higher in the clopidogrel than in novel oral P2Y12 inhibitors group (P < .001). After 1 year of follow-up, 64(5.0%/year) patients had a new myocardial infarction, 127(10.0%/year) had a major adverse cardiovascular event (MACE) and 78(6.1%/year) died. Patients treated with clopidogrel had a significantly higher annual rate of cardiovascular mortality, MACE and all-cause mortality (allP < .001) without differences in major bleeding (P = .587) compared with novel oral P2Y12 inhibitors. After multivariate adjustment for the main clinical variables related to adverse prognosis in ACS patients, the discharge with novel oral P2Y12 inhibitors therapy was independently associated with lower risk of all-cause mortality (HR0.49, 95% CI [0.24-0.98], P = .044) and lower risk of MACE (HR0.64, 95% CI [0.41-0.98], P = .044). CONCLUSIONS: In this prospective, observational and current clinical practice ACS registry, the use of novel oral P2Y12 inhibitors was associated with a reduction in adverse events compared with clopidogrel in patients with ACS. Novel oral P2Y12 inhibitors prescription at discharge was independently associated with lower all-cause mortality and MACE without differences in bleeding events. However, clopidogrel remained the most common P2Y12 inhibitor employed for ACS, especially in older and high-risk patients.

TRimetazidine as an Agent to affeCt clopidogrEl Response: The TRACER Study.

INTRODUCTION: This prospective study aimed to determine whether trimetazidine (TMZ) alters the pharmacodynamic (PD) effects of clopidogrel. METHODS: Patients with stable coronary artery disease (SCAD) (n = 24) who were actively treated with dual antiplatelet therapy (DAPT) of aspirin 81 mg daily and clopidogrel 75 mg daily were recruited. Platelet function was measured with the VerifyNow P2Y12 assay (Accriva Diagnostics, San Diego, CA, USA) and assessed before the initiation of and after 14 days of treatment with TMZ. Results were compared using a paired t test. RESULTS: Almost 80% of the study population were of South Asian descent and had diabetes mellitus (DM). P2Y12 reaction units (PRUs) were higher in patients on TMZ (204 ± 56 compared with 174 ± 71 before TMZ, p = 0.005). The average increase in PRU score was 29 (95% confidence interval 8.8-49.7). Before TMZ, the proportion of patients with high on-treatment platelet reactivity (PRU > 208 units) was 25%, which increased to 42% for patients on TMZ. CONCLUSION: Higher platelet reactivity was seen in patients on TMZ, suggesting that TMZ attenuated the PD effects of clopidogrel in this study of a predominantly South Asian diabetic subpopulation. Alternative therapies should be considered and further research is warranted. TRIAL REGISTRATION: ClinicalTrials.gov number, NCT03603249.

Under-prescription of novel antiplatelet drugs in patients with acute coronary syndrome and previous cardiovascular disease.

BACKGROUND: Patients with acute coronary syndrome (ACS) and previous cardiovascular disease (CVD) (stroke, peripheral arterial disease [PAD] or coronary artery disease [CAD]) are at high risk of serious events and mortality. Current clinical guidelines recommend new antiplatelet drugs (NADs) for high cardiovascular risk patients with ACS; however, these drugs are underused in different scenarios. METHODS: This study included 1717 ACS patients from 3 tertiary hospitals. Of them, 641 (37.33%) suffered from previous CVD: 149 patients with stroke, 154 patients with PAD and 541 patients with CAD. Bleeding, mortality and major adverse cardiac events (MACE) at 1 year of follow-up after hospital discharge were analyzed. RESULTS: NADs administration during hospital stay and at discharge was less frequent in patients with previous CVDs (P<0.001, for both). Cox analysis in this cohort of patients showed that clopidogrel prescription at discharge was independently associated with MACEs (HR: 1.59 [95% CI: 1.03-2.45]; P=0.036) and with death (HR: 1.99 [95% CI: 1.00-3.98]; P=0.049) in multivariate analysis. More specifically, when ticagrelor prescription at discharge was compared with clopidogrel, a significant death reduction was found in both, the univariate and the multivariate Cox analysis (HR: 4.54 [95% CI: 2.26-9.13]; P<0.001 and HR: 2.61 [95% CI: 1.16-5.90]; P=0.021, respectively). CONCLUSIONS: New antiplatelet drugs, especially ticagrelor, showed lower rates of mortality in patients with CVD without differences for bleeding. Despite the recommendations of current clinical guidelines for high risk patients with ACS, the use of NADs is very low in "real-life" patients with previous CVD.

Prevalence of clOpidogrel 'resIstaNce' in a selected population of patients undergoing elective percutaneous coronary intervention at a tertiary cardiovascular centre in Trinidad: the POINT pilot study.

Objectives: This novel, pilot study aimed to assess the estimated prevalence of high on-treatment platelet reactivity (HPR) in Trinidad and Tobago. Methods: Patients (n=40) who were awaiting elective percutaneous coronary intervention on maintenance dual antiplatelet therapy (DAPT) with aspirin 81 mg daily and clopidogrel 75 mg or loaded at least 48 hours prior were recruited. Platelet reactivity with the VerifyNow P2Y12 assay (Accriva Diagnostics, San Diego, California, USA) was assessed prior to cardiac catheterisation. Results: 60.7% (17/28) of the South Asian (Indo-Trinidadians) patients had HPR, whereas 14.3% (1/7) of Africans and 40% (2/5) of mixed ethnicity had HPR. There was a significant association between HPR (P2Y12 reaction units >208) and ethnicity with South Asians (Indo-Trinidadians) (OR 5.4; 95% CI 1.18 to 24.66, p=0.029). Conclusions: This pilot study serves to introduce the preliminary observation that the estimated prevalence of HPR is considerably higher within the heterogeneous population in Trinidad at 50% as compared with predominantly Caucasian studies. Furthermore, the HPR is significantly higher in South Asians (Indo-Trinidadians) (>60% of patients) which has severe clinical repercussions considering the cardiovascular disease pandemic. Clopidogrel may not be a satisfactory or optimal antiplatelet agent in this subgroup, and therefore, another more potent antiplatelet such as ticagrelor should be used instead. Further large-scale studies are imperative to confirm these findings. (Funded by the University of the West Indies, St. Augustine; POINT ClinicalTrials.gov number, NCT03667066.).

High and low on-treatment platelet reactivity to P2Y12 inhibitors in a contemporary cohort of acute coronary syndrome patients undergoing percutaneous coronary intervention.

INTRODUCTION: There is compelling evidence supporting the association between high on-treatment platelet reactivity (HPR) and low on-treatment platelet reactivity (LPR) to clopidogrel with atherothrombotic and bleeding events, respectively. However, it is uncertain if current cutoff values should be used in prasugrel- or ticagrelor-treated subjects. The objective of this analysis was to evaluate the pharmacodynamic (PD) efficacy of P2Y12 antagonists in a contemporary real-world population. MATERIALS AND METHODS: This PD study included 988 patients with acute coronary syndromes (ACS) undergoing percutaneous coronary intervention (PCI) and receiving dual therapy with aspirin and a P2Y12 inhibitor (clopidogrel, prasugrel or ticagrelor). Platelet function was assessed at day 1 and day 30 post-PCI by VerifyNow P2Y12 assay, multiple electrode aggregometry and vasodilator-stimulated phosphoprotein (VASP) assay. RESULTS: Clopidogrel-treated patients (n = 324) had greater platelet reactivity than those receiving ticagrelor (n = 469) or prasugrel (n = 195) at both time points (p < 0.001 for all comparisons). No difference between ticagrelor and prasugrel was observed at day 1 with the VerifyNow P2Y12 assay (51.5 ±â€¯2.8 vs. 42.7 ±â€¯3.5 PRUs; p = 0.298), whereas ticagrelor achieved greater platelet inhibition at day 30 (48.1 ±â€¯2.5 vs. 89.2 ±â€¯4.2 PRUs; p < 0.001). Similar results were obtained with the VASP assay. Both prasugrel and ticagrelor had markedly lower HPR rates than clopidogrel and very high rates of LPR at both time points. CONCLUSIONS: Prasugrel and ticagrelor displayed more potent and consistent PD effects than clopidogrel in ACS patients undergoing PCI, with a trend towards greater platelet inhibition with ticagrelor during the maintenance phase of therapy compared to prasugrel.