Nikolaos Spinthakis

Morphine Analgesia Pre-PPCI Is Associated with Prothrombotic State, Reduced Spontaneous Reperfusion and Greater Infarct Size

The emergency management of ST-elevation myocardial infarction (STEMI) involves treatment with dual-antiplatelet therapy (DAPT) and primary percutaneous coronary intervention (PPCI). Pain is generally treated with opiates, which may delay gastric transit and reduce DAPT absorption. We sought to assess the effect of morphine on reperfusion, infarct size and thrombotic status in 300 patients presenting for PPCI. Morphine was given in a non-randomized fashion as required by emergency teams en route to the heart attack centre. All patients received DAPT and PPCI according to standard care, with optional glycoprotein IIb/IIIa inhibitor (GPI) use. Patients were assessed for ST-segment resolution, coronary flow, thrombotic status and peak troponin. Patients receiving morphine (n = 218; 72.7%) experienced less spontaneous ST-segment resolution pre-PPCI, lower rate of TIMI 2/3 flow in the infarct-related artery pre-PPCI and higher peak troponin level post-PPCI (median [interquartile range]; 1,906 [1,002-4,398] vs. 1,268 [249-2,920] ng/L; p = 0.016) than those who did not. Patients receiving morphine exhibited significantly enhanced platelet reactivity and impaired endogenous fibrinolysis on arrival, compared with no-morphine patients. Morphine administration was an independent predictor of failure of spontaneous ST-segment resolution after adjustment for other variables (odds ratio: 0.26; confidence interval: 0.08-0.84; p = 0.025). Among patients receiving GPI, there was no difference in pre-PPCI flow or peak troponin according to morphine use, suggesting that the adverse effects of morphine relate to delayed DAPT absorption, which may be overcome by GPI. Our hypothesis-generating data suggest that morphine use in STEMI is associated with enhanced platelet reactivity, reduced spontaneous myocardial reperfusion (pre-PPCI) and larger infarct size, and these adverse effects may be influenced by GPI use. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT02562690.

Use of bioresorbable vascular scaffold: a meta-analysis of patients with coronary artery disease

Background Differences in outcomes between bioresorbable vascular scaffold (BVS) systems and drug-eluting metal stents (DES) have not been fully evaluated. We aimed to compare clinical and angiographic outcomes in randomised studies of patients with coronary artery disease (CAD), with a secondary analysis performed among registry studies. Methods A meta-analysis comparing outcomes between BVS and DES in patients with CAD. Overall estimates of treatment effect were calculated with random-effects model and fixed-effects model. Results In 6 randomised trials (3818 patients), BVS increased the risk of subacute stent thrombosis (ST) over and above DES (OR 2.14; CI 1.01 to 4.53; p=0.05), with a trend towards an increase in the risk of myocardial infarction (MI) (125 events in those assigned to BVS and 50 to DES; OR 1.36; CI 0.97 to 1.91; p=0.07). The risk of in-device late lumen loss (LLL) was higher with BVS than DES (mean difference 0.08 mm; CI 0.03 to 0.13; p=0.004). There was no difference in the risk of death or target vessel revascularisation (TVR) between the two devices. In 6 registry studies (1845 patients), there was no difference in the risk of death, MI, TVR or subacute ST between the two stents. Final BVS dilation pressures were higher in registry than in randomised studies (18.7±4.6 vs 15.2±3.3 atm; p<0.001). Conclusions Patients treated with BVS had an increased risk of subacute ST and slightly higher LLL compared with those with DES, but this might be related to inadequate implantation techniques, in particular device underexpansion.

Should STEMI Patients Receive Opiate Analgesia? The Morphine Paradox

BACKGROUND The very significant benefit of P2Y12 receptor inhibitor administration in patients with ST-elevation myocardial infarction (STEMI), in reducing future ischaemic events and stent thrombosis, is undisputed. Morphine analgesia is very frequently co-administered to these patients for pain relief, along with antiplatelet therapy, at the time of presentation, and prior to reperfusion with primary percutaneous coronary intervention. METHODS Research and online content related to opiates use in STEMI was reviewed. Bibliographies of retrieved studies were searched manually for additional studies and reviews. RESULTS There is sufficient data from pharmacokinetic and pharmacodynamic studies showing that the co-administration of morphine with oral P2Y12 receptor inhibitor results in delayed antiplatelet effects. However, whether this results in adverse outcomes remains unclear. Data from studies reporting the effect of morphine on clinical outcomes in STEMI are inconsistent, although they tend to be underpowered to show an effect on hard clinical outcomes, but some clearly show a relationship between morphine use and infarct size. Strategies to overcome the potentially significant negative impact of morphine on platelet reactivity in STEMI are discussed. CONCLUSION Whilst clearly definitive, adequately powered, randomised controlled trials are lacking, we would recommend avoiding the combination of morphine with oral P2Y12 receptor inhibitors and recommend alternative strategies including intravenous platelet inhibitor strategies, in high risk patients.

Is there a Role for Oral Triple Therapy in Patients with Acute Coronary Syndromes Without Atrial Fibrillation

BACKGROUND Acute Coronary Syndrome (ACS) patients, despite treatment with Dual Anti- Platelet Therapy (DAPT), have up to 10% risk of recurrent Major Adverse Cardiac Events (MACE) in the short term. METHODS Here we review studies using more potent antithrombotic agent combinations to reduce this risk, namely Triple Therapy (TT) with the addition of an oral anticoagulant, PAR-1 antagonist, or cilostazol to DAPT (mainly aspirin and clopidogrel), and discuss the limitations of trials to date. RESULTS Generally speaking, TT leads to an increase in bleeding. Vorapaxar showed a signal for reducing ischaemic events, but increased intracranial haemorrhage 3-fold in the subacute phase of ACS, although remains an option for secondary prevention beyond the immediate subacute phase, particularly if prasugrel or ticagrelor are not available. Non-Vitamin K Oral Anticoagulants (NOACs) all increased bleeding, with only modest reduction in MACE noted with low dose rivaroxaban. Rivaroxaban can be considered combined with aspirin and clopidogrel in ACS patients at high ischaemic and low bleeding risk, without prior stroke/TIA. The combination of P2Y12 inhibitor and NOAC, without aspirin, looks promising. DAPT may be replaced, not by TT, but by dual therapy comprising a NOAC with a P2Y12 inhibitor. CONCLUSION More potent antithrombotic regimens increase bleeding and should only be considered on an individual basis, after careful risk stratification. Accurate risk stratification of ACS patients, for both ischaemic and bleeding risk, is essential to allow individualised treatment.

Percutaneous coronary intervention with drug-eluting stent versus coronary artery bypass grafting: A meta-analysis of patients with left main coronary artery disease

BACKGROUND The relative efficacy and safety of percutaneous coronary intervention (PCI) with drug-eluting stents (DES), in comparison to coronary artery bypass grafting (CABG) for left main coronary artery disease (LMCAD) remains controversial. METHODS We performed a meta-analysis of randomised studies comparing patients with LMCAD treated with PCI with DES versus those treated with CABG, with respect to clinical outcomes at 1, 3 and 5years. A secondary meta-analysis was performed according to low (<32), or high (≥33) SYNTAX score. RESULTS Five studies comprising 4595 patients were included. There was no significant difference in all-cause death at all time points or when stratified with respect to SYNTAX score. The need for repeat revascularization was significantly higher with PCI at all time-points, and regardless of SYNTAX score. There was significant association between need for repeat revascularization with PCI and diabetics (p=0.04). At 5years, non-fatal MI was higher with PCI owing to increased non-procedural events (OR 3.00; CI 1.45-6.21; p=0.003). CABG showed higher rate of stroke at 1year (OR 0.21; CI 0.07-0.63; p=0.005). There was no difference in non-fatal MI or stroke at other time points, nor according to SYNTAX score. CONCLUSIONS PCI with DES or CABG are equivalent strategies for LMCAD up to 5years with respect to death, regardless of SYNTAX score. PCI increases the rate of non-procedural MI at 5years. CABG avoids the need for repeat revascularization, especially in diabetics, but this benefit is offset by higher rate of stroke in the first year of follow up.

CHA2DS2VASC SCORE DOES NOT CORRELATE WITH THROMBOTIC STATUS IN ATRIAL FIBRILLATION

The CHA2DS2VASc score is established and recommended for the risk stratification of stroke in patients with atrial fibrillation (AF) based on clinical parameters. How this relates to haematological characteristics, in particular global thrombotic status is unknown. We assessed the thrombotic status

59 Does CHA²DS²VASc Score Correlate with Point-of-Care Global Thrombotic Status in Atrial Fibrillation Patients?

Background The CHA²DS²VASc score is established and recommended for the risk stratification of stroke in patients with atrial fibrillation (AF) based on clinical parameters. How this relates to haematological characteristics, in particular global thrombotic status is unknown. Methods We assessed the thrombotic status of 80 patients with newly diagnosed AF (61% male, 72 ± 12 yrs), who were divided into 3 groups according to CHA²DS²VASc score (Group I: 0–1, Group II: 2–3, Group III: ≥4). Assessment of thrombotic status was performed using the Global Thrombosis Test (GTT), an automated, point-of-care test that assesses both platelet reactivity and endogenous thrombolysis from a native, non-anticoagulated blood sample. The time taken to form an occlusive thrombus under high shear stress (occlusion time, OT), and the time required to restore flow through endogenous thrombolysis (lysis time, LT) were measured at baseline and after being established on stable anticoagulation. Results Overall CHA²DS²VASc score was 2.9 ± 1.7. There were 21 patients in Group I, 29 in Group II, and 30 in Group III. Anticoagulation prolonged OT (419 ± 122s vs. 584 ± 153s; p = 0.00001), and reduced LT (1939 ± 829s vs. 1625 ± 934s; p = 0.03). At baseline, there was no difference between the 3 groups with respect to OT (Group I: 412 ± 98s, Group II: 434 ± 149s, Group III: 408 ± 110s; p = 0.7), or LT (Group I: 1778 ± 537s, Group II: 1879 ± 747s, Group III: 2108 ± 1038s; p = 0.3). Following anticoagulation, OT was similar in the 3 groups (Group I: 561 ± 148s, Group II: 582 ± 155s, Group III: 602 ± 157s; p = 0.7), and LT was also similar (Group I: 1265 ± 846s, Group II: 1734 ± 817s, Group III: 1775 ± 1050s; p = 0.1). There was no difference in the relative change (∆) in OT (Group I: 149 ± 169s, Group II: 148 ± 129s, Group III: 193 ± 126s; p = 0.4) or LT (Group I: -514 ± 1002s, Group II: -117 ± 928s, Group III: -333 ± 1229s; p = 0.4) between the 3 groups in response to anticoagulation. Conclusions The CHA²DS²VASc score does not appear to reflect global thrombotic status either before or after anticoagulation. Whilst the CHA²DS²VASc score is incredibly useful in assessing populations at risk, it may not be an accurate reflection of the underlying thrombotic status of an individual.