Impact of Preadmission Morphine on Reinfarction in Patients With ST-Elevation Myocardial Infarction Treated With Percutaneous Coronary Intervention: A Meta-Analysis.

Opiates are the traditional analgesics used in patients with ST-elevation myocardial infarction (STEMI). Pharmacodynamic studies indicate that opiates delay the absorption of orally administered P2Y12 inhibitors and the onset of platelet inhibition. Whether these negative effects on platelet inhibition have an impact on clinical outcomes is unclear. A systematic review and meta-analysis was performed searching PubMed, MEDLINE, and Cochrane Central Register of Controlled Trials to identify studies comparing morphine and no-morphine treatment in STEMI patients undergoing primary percutaneous coronary intervention. The primary end point was the occurrence of in-hospital myocardial infarction, and secondary end points were in-hospital stroke and death. Four observational studies were identified, including 3,220 patients with STEMI. Morphine-treated patients had a higher unadjusted rate of reinfarction compared with patients not receiving morphine (1.5% vs. 0.67%, odds ratio (OR) 2.41; 95% confidence interval (CI), 1.11-5.21; P = 0.03). Unadjusted mortality rate was lower in morphine-treated patients (1.7% vs. 4.2%, OR 0.43, 95% CI, 0.23-0.81; P = 0.009). Exclusion of the study with baseline differences between groups showed more frequent reinfarction in the morphine group, but this was no longer statistically significant (1.3% vs. 0.5%, OR 2.02; 95% CI, 0.39-10.43; P = 0.40). There was no difference in stroke according to morphine treatment. Patients pretreated with morphine appear to have a higher rate of reinfarction than patients not receiving morphine. This may be attributable to opiate-related delay in P2Y12 inhibitor absorption and resultant delay in onset of platelet inhibition. These concerning findings indicate the need for prospective, randomized trials to assess the impact of opiates on clinical outcomes in STEMI.

Rationale and design of "Can Very Low Dose Rivaroxaban (VLDR) in addition to dual antiplatelet therapy improve thrombotic status in acute coronary syndrome (VaLiDate-R)" study : A randomised trial modulating endogenous fibrinolysis in patients with acute coronary syndrome.

Impaired endogenous fibrinolysis is novel biomarker that can identify patients with ACS at increased cardiovascular risk. The addition of Very Low Dose Rivaroxaban (VLDR) to dual antiplatelet therapy has been shown to reduce cardiovascular events but at a cost of increased bleeding and is therefore not suitable for all-comers. Targeted additional pharmacotherapy with VLDR to improve endogenous fibrinolysis may improve outcomes in high-risk patients, whilst avoiding unnecessary bleeding in low-risk individuals. The VaLiDate-R study (ClinicalTrials.gov Identifier: NCT03775746, EudraCT: 2018-003299-11) is an investigator-initiated, randomised, open-label, single centre trial comparing the effect of 3 antithrombotic regimens on endogenous fibrinolysis in 150 patients with ACS. Subjects whose screening blood test shows impaired fibrinolytic status (lysis time > 2000s), will be randomised to one of 3 treatment arms in a 1:1:1 ratio: clopidogrel 75 mg daily (Group 1); clopidogrel 75 mg daily plus rivaroxaban 2.5 mg twice daily (Group 2); ticagrelor 90 mg twice daily (Group 3), in addition to aspirin 75 mg daily. Rivaroxaban will be given for 30 days. Fibrinolytic status will be assessed during admission and at 2, 4 and 8 weeks. The primary outcome measure is the change in fibrinolysis time from admission to 4 weeks follow-up, using the Global Thrombosis Test. If VLDR can improve endogenous fibrinolysis in ACS, future large-scale studies would be required to assess whether targeted use of VLDR in patients with ACS and impaired fibrinolysis can translate into improved clinical outcomes, with reduction in major adverse cardiovascular events in this high-risk cohort.

Apixaban enhances endogenous fibrinolysis in patients with atrial fibrillation.

AIMS: Approximately 20% of ischaemic stroke patients exhibit spontaneous arterial recanalization, attributable to endogenous fibrinolysis, which strongly relates to improved functional outcome. The impact of oral anticoagulants on endogenous fibrinolysis is unknown. Our aim was to test the hypothesis that apixaban enhances endogenous fibrinolysis in non-valvular atrial fibrillation (NVAF). METHODS AND RESULTS: In a prospective cross-sectional analysis, we compared endogenous fibrinolysis in NVAF patients (n = 180) taking aspirin, warfarin, or apixaban. In a prospective longitudinal study, patients were tested before and after apixaban (n = 80). Endogenous fibrinolysis was assessed using the Global Thrombosis Test (GTT) and thromboelastography (TEG). Endogenous fibrinolysis [measured by GTT lysis time (LT)] was shorter on apixaban compared with warfarin or aspirin [median 1850 (IQR 1591-2300) vs. 2758 (2014-3502) vs. 2135 (1752-2463) s, P < 0.0001]. Among TEG indices, a small but significant difference in clot lysis time (CLT) was observed [apixaban 60.0 (45.0-61.0) vs. warfarin 61.0 (57.0-62.0) vs. aspirin 61.0 (59.0-61.0) min, P = 0.036]. Apixaban improved endogenous fibrinolysis measured using the GTT [LT pre-treatment 2204 (1779-2738) vs. on-treatment 1882 (1607-2374) s, P = 0.0003], but not by using TEG. Change in LT (ΔLT) with apixaban correlated with baseline LT (r = 0.77, P < 0.0001). There was weak correlation between ΔLT and ΔCLT in response to apixaban (r = 0.28, P = 0.02) and between on-apixaban LT and CLT (r = 0.25, P = 0.022). CONCLUSION: Apixaban enhances endogenous fibrinolysis, with maximal effect in those with impaired fibrinolysis pre-treatment. Apixaban-treated patients exhibit more favourable fibrinolysis profiles than those taking warfarin or aspirin. Whether apixaban may confer additional thrombotic risk reduction in NVAF patients with impaired fibrinolysis, compared to warfarin, merits further study.

Relationship of Platelet Reactivity and Inflammatory Markers to Recurrent Adverse Events in Patients with ST-Elevation Myocardial Infarction.

BACKGROUND: Patients with ST-elevation myocardial infarction (STEMI) exhibit pro-thrombotic and pro-inflammatory states. Markers of enhanced platelet reactivity and inflammation are predictive of adverse outcome. However, the relationship between these biomarkers, and their combined usefulness for risk stratification, is not clear. METHODS: In a prospective study of 541 patients presenting with STEMI, blood samples were taken on arrival to measure high-sensitivity C-reactive protein (hs-CRP), neutrophil/lymphocyte ratio (NLR) and platelet reactivity using the point-of-care Global Thrombosis Test. These biomarkers, alone and in combination, were related to the occurrence of major adverse cardiovascular events (MACE, defined as composite of cardiovascular death, myocardial infarction and cerebrovascular accident) at 30 days and 12 months. RESULTS: Platelet reactivity and hs-CRP, but not NLR, were weakly predictive of MACE at 30 days and 12 months. The combination of enhanced platelet reactivity and raised hs-CRP was strongly predictive of MACE at 30 days (hazard ratio [HR] 3.46 [95% confidence interval [CI] 1.81-6.62], p < 0.001) and 12 months (HR 3.46 [95% CI 1.81-6.63], p < 0.001). Combination of all three biomarkers (NLR, hs-CRP and platelet reactivity) provided the best prediction of MACE at 30 days (HR 3.73 [95% CI 1.69-8.27], p < 0.001) and 12 months (HR 3.85 [95% CI 1.72-8.60], p < 0.001), and improved the prediction of MACE when added to Thrombolysis In Myocardial Infarction score (net reclassification index 0.296, p < 0.001). CONCLUSION: A combination of three easy to measure biomarkers on arrival, namely hs-CRP, NLR and platelet reactivity, can help identify STEMI patients at high risk of recurrent adverse events over the subsequent year.

Impaired endogenous fibrinolysis at high shear using a point-of-care test in STEMI is associated with alterations in clot architecture.

Impaired endogenous fibrinolysis is an adverse prognostic biomarker in acute coronary syndrome (ACS). Abnormally dense in vitro fibrin thrombi have been demonstrated in ACS patients and related to hypofibrinolysis using cumbersome, laboratory-based methods. We aimed to assess endogenous fibrinolysis using a point-of-care technique and relate this to clot architecture. From patients with ST-segment elevation myocardial infarction (STEMI), venous blood was drawn immediately on arrival to assess thrombotic status. Blood was assessed using the point-of-care Global Thrombosis Test which measures occlusive thrombus formation under high shear and subsequently endogenous fibrinolysis (lysis time, LT). Two samples per patient were run in parallel. In one channel, the measurement was allowed to proceed as normal. In the other, after occlusion, thrombus was extracted, washed, fixed in glutaraldehyde, dried, sputter-coated, and assessed using scanning electron microscope. Endogenous fibrinolysis was strongly associated fibrin fibre thickness (p = 0.0001). As LT increased (less efficient fibrinolysis), the fibrin network of the thrombus was significantly more compact and dense, with thinner fibrin fibres and smaller gaps. Fibrin fibre thickness correlated inversely with LT (r = - 0.89, p = 0.001). Adverse clot architecture in vitro is directly related to impaired endogenous fibrinolysis using a relatively new point-of-care technique in patients with STEMI. This may transform the relevance of fibrin clot architecture from an off-line laboratory association to being directly relevant to endogenous fibrinolysis at the patient bedside, which could be used as a near-patient test to guide prognosis and assess the effect of treatment.

Effect of P2Y12 inhibitors on thrombus stability and endogenous fibrinolysis.

Although used routinely to reduce thrombotic events in patients with coronary disease, the effects of P2Y12 inhibitors on thrombus stability and endogenous fibrinolysis are largely unknown. Blood taken from patients pre- and post-aspirin (n = 20) and on aspirin alone and on dual antiplatelet therapy comprising aspirin plus clopidogrel (n = 20), ticagrelor (n = 20) or cangrelor (n = 20), was tested using the Global Thrombosis Test. The number of "rebleeds" or drops (D) after early platelet-rich thrombus formation (occlusion time, OT), and before final lasting occlusion, was used as an inverse measure of thrombus stability. Whilst clopidogrel had no effect, ticagrelor and cangrelor both increased D significantly, reflecting increased thrombus instability [D pre- and post-clopidogrel 4.3 ±â€¯1.6 vs. 4.5 ±â€¯1.4, p = 0.833; pre- and post-ticagrelor 4.1 ±â€¯2.4 vs. 6.8 ±â€¯5.1, p = 0.048; pre- and post-cangrelor 3.6 ±â€¯2.0 vs. 7.9 ±â€¯8.9, p = 0.046]. Platelet reactivity was reduced by all P2Y12 inhibitors, demonstrated by OT prolongation (clopidogrel 378 ±â€¯87 s vs. 491 ±â€¯93 s, p < 0.001; ticagrelor 416 ±â€¯122 s vs. 549 ±â€¯121 s, p < 0.001; cangrelor 381 ±â€¯146 s vs. 613 ±â€¯210 s, p < 0.001). The magnitude of OT prolongation compared to baseline (ΔOT) was significantly greater for cangrelor compared to clopidogrel and ticagrelor. Cangrelor was the only agent to enhance fibrinolysis (lysis time pre- and post-cangrelor 1622[1240-2048]s vs. 1388[960-1634]s, p = 0.005). We demonstrate the ability to assess the effect of pharmacotherapy on thrombus stability in vitro and show that P2Y12 inhibitors potentiate thrombus instability at high shear. Cangrelor, and to a lesser extent ticagrelor, de-stabilised thrombus formation and cangrelor also enhanced fibrinolysis. Potentiation of thrombus instability could become a new pharmacological target, that may be particularly important in acute coronary syndromes.

Impaired endogenous fibrinolysis in ST-segment elevation myocardial infarction patients undergoing primary percutaneous coronary intervention is a predictor of recurrent cardiovascular events: the RISK PPCI study.

Aims: The endogenous fibrinolytic system serves to prevent lasting thrombotic occlusion and infarction following initiation of coronary thrombosis. We aimed to determine whether impaired endogenous fibrinolysis can identify patients with ST-segment elevation myocardial infarction (STEMI) who remain at high cardiovascular risk despite dual antiplatelet therapy (DAPT). Methods and results: A prospective, observational study was conducted in 496 patients presenting with STEMI for primary percutaneous coronary intervention (PPCI). Blood was tested on arrival pre-PPCI, at discharge and at 30 days to assess thrombotic status using the automated point-of-care global thrombosis test and patients followed for 1 year for major adverse cardiovascular events (MACEs). Endogenous fibrinolysis was significantly impaired [baseline lysis time (LT) ≥2500 s] in 14% of patients and was highly predictive of recurrent MACE [hazard ratio (HR) 9.1, 95% confidence interval (CI) 5.29-15.75; P < 0.001], driven by cardiovascular death (HR 18.5, 95% CI 7.69-44.31; P < 0.001) and myocardial infarction (HR 6.2, 95% CI 2.64-14.73; P < 0.001), particularly within 30 days. Fibrinolysis remained strongly predictive of MACE after adjustment for conventional risk factors (HR 8.03, 95% CI 4.28-15.03; P < 0.001). Net reclassification showed that adding impaired fibrinolysis improved the prediction of recurrent MACE by >50% (P < 0.001). Patients with spontaneous ST-segment resolution pre-PPCI had more rapid, effective fibrinolysis [LT 1050 (1004-1125) s vs. 1501 (1239-1997) s, P < 0.001] than those without. Lysis time was not altered by standard of care STEMI treatment including DAPT and was unchanged at 30 days. Conclusion: Endogenous fibrinolysis assessment can identify patients with STEMI who remain at very high cardiovascular risk despite PPCI and DAPT. Further studies are needed to assess whether these patients may benefit from additional, personalized antithrombotic/anticoagulant medication to reduce future cardiovascular risk. Clinical trial registration: http://www.clinicaltrials.gov. Unique identifier: NCT02562690.

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.

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.

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.

"Mind the gap" acute coronary syndrome in women: A contemporary review of current clinical evidence.

The incidence and prevalence of coronary artery disease in women has exceeded that in men over the past four decades, and although a significant decline in mortality has occurred in the past two decades, there is a growing body of evidence suggesting that there are gender differences between the clinical manifestations and course of coronary artery disease, as well as differences in treatment and treatment response. This review article considers the current literature regarding the gender-specific manifestation of acute coronary syndromes. Through the review of basic science articles, subsets of trial data, and meta-analyses, the gender-specific differences in within acute coronary syndromes are considered in terms of diagnostic dilemmas, pathophysiology, and treatment options (including pharmacological, percutaneous and surgical methods). Finally, acute coronary syndromes and their management in the special circumstance of pregnancy are also reviewed.

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.

Relative effects of different non-vitamin K antagonist oral anticoagulants on global thrombotic status in atrial fibrillation.

Non-vitamin K antagonist oral anticoagulants (NOACs) reduce the risk of thromboembolism in patients with atrial fibrillation (AF). There has been no head-to-head comparison of the effect of these agents on ex vivo thrombotic and thrombolytic status. Enhanced platelet reactivity and impaired endogenous thrombolysis are risk factors for recurrent thrombotic events. We aimed to assess the comparative effect of NOACs and warfarin using an ex vivo test of thrombosis and thrombolysis. Eighty patients with newly diagnosed non-valvular AF were tested before, and after being established on apixaban (n = 20), dabigatran (n = 20), rivaroxaban (n = 20), or warfarin (n = 20). Thrombotic status was assessed with the automated, point-of-care Global Thrombosis Test (GTT) that assesses both platelet reactivity and endogenous thrombolysis from native blood. The time taken to form an occlusive thrombus (occlusion time, OT) and the time required to restore flow through endogenous thrombolysis (lysis time, LT) were measured. All anticoagulants caused OT prolongation compared to baseline (apixaban 403 ± 102s vs. 496 ± 125s, p = 0.006; dabigatran 471 ± 106s vs. 656 ± 165s, p < 0.00001; rivaroxaban 381 ± 119s vs. 579 ± 158, p < 0.00001; warfarin 420 ± 145s vs. 604 ± 124s, p < 0.00001). Apixaban reduced LT from baseline (1895[1702-2167]s vs. 1435[347-1990]s; p = 0.006). A trend for LT reduction was seen with other NOACs (dabigatran 1594[1226-2069]s vs. 1539[561-2316]s, p = 0.499; rivaroxaban 2085[1366-2428]s vs. 1885[724-2420]s, p = 0.295) but not with warfarin (1490[1206-1960]s vs. 1776[1545-2334], p = 0.601). Our results suggest that NOACs and warfarin have a similar favorable effect on reducing platelet reactivity. All NOACs exhibited a trend toward enhancing endogenous thrombolytic status, although this was significant only for apixaban. This raises the possibility of using NOACs to enhance impaired endogenous fibrinolysis in patients at high-thrombotic risk.

Treatment of calcified coronary artery lesions.

Heavily calcified coronary plaques represent a complex lesion subset and a challenge to the interventional cardiologist, as they are often resistant to simple plaque modification with conventional balloon angioplasty. Inadequate plaque modification can lead to stent underdeployment, which itself predisposes to in-stent restenosis and stent thrombosis. Over the years, a number of mechanical devices ranging from modified angioplasty balloons to atherectomy devices have become available in order to tackle such lesions. Here we review these devices concentrating on the evidence behind their use.

Bivalirudin versus unfractionated heparin: a meta-analysis of patients receiving percutaneous coronary intervention for acute coronary syndromes.

OBJECTIVE: Acute coronary syndrome (ACS) encompasses ST segment elevation myocardial infarction (STEMI), with generally high thrombus burden and non-ST segment elevation ACS (NSTE-ACS), with lower thrombus burden. In the setting of percutaneous coronary intervention (PCI) for ACS, bivalirudin appears superior to unfractionated heparin (UFH), driven by reduced major bleeding. Recent trials suggest that the benefit of bivalirudin may be reduced with use of transradial access and evolution in antiplatelet therapy. Moreover, a differential role of bivalirudin in ACS cohorts is unknown. METHODS: A meta-analysis of randomised trials comparing bivalirudin and UFH in patients with ACS receiving PCI, with separate analyses in STEMI and NSTE-ACS groups. Overall estimates of treatment effect were calculated with random-effects model. RESULTS: In 5 trials of STEMI (10 358 patients), bivalirudin increased the risk of acute stent thrombosis (ST) (OR 3.62; CI 1.95 to 6.74; p<0.0001) compared with UFH. Bivalirudin reduced the risk of major bleeding only when compared with UFH plus planned glycoprotein IIb/IIIa inhibitors (GPI) (OR 0.49; CI 0.36 to 0.67; p<0.00001). In 14 NSTE-ACS trials (25 238 patients), there was no difference between bivalirudin and UFH in death, myocardial infarction or ST. However, bivalirudin reduced the risk of major bleeding compared with UFH plus planned GPI (OR 0.52; CI 0.43 to 0.62; p<0.00001), or UFH plus provisional GPI (OR 0.68; CI 0.46 to 1.01; p=0.05). The reduction in major bleeding with bivalirudin was not related to vascular access site. CONCLUSIONS: Bivalirudin increases the risk of acute ST in STEMI, but may confer an advantage over UFH in NSTE-ACS while undergoing PCI, reducing major bleeding without an increase in ST.

Age and outcomes of primary percutaneous intervention for ST elevation myocardial infarction in a tertiary center-are we there yet?

BACKGROUND: Primary percutaneous intervention (PPCI) is the treatment of choice for ST elevation myocardial infarction (STEMI) but robust evidence in the very elderly is lacking. We compared PPCI outcomes between different age quartiles (quartile 1 < 60 years, quartile 2 ≥ 60 to < 70 years, quartile 3 ≥ 70 to < 80 years, quartile 4 ≥ 80 years). METHODS: Retrospective observational analysis of our Morriston Tertiary Cardiac Center (Abertawe Bro Morgannwg University Health Board) patients from 2005 to 2010 with STEMI who underwent PPCI. RESULTS: Of 434 patients, 57 (13%) were in quartile 4 (≥ 80 years). In older age quartiles, patients were less likely to receive a drug eluting stent (DES, P = 0.001) or glycoprotein IIb/IIIa inhibitor (GPI, P < 0.0001). Increase in age was associated with reduced time to survival (ß-coefficient: -0.192, t: -3.70, 95%CI: -4.91 to -1.50, P < 0.0001) as was the presence of cardiogenic shock (ß-coefficient: -0.194, t = 3.77, 95%CI: -5.26 to -1.65, P < 0.0001). Use of GPI was associated with increased time to survival (ß-coefficient: 0.138, t = 2.82, 95%CI: 1.58-8.58, P = 0.005) but older age quartiles were less likely to receive GPI (P < 0.0001). In-hospital mortality (1.8% quartile 1, 3.6% quartile 2, 10.9% quartile 3 and 12.3% quartile 4, P = 0.002) and 1-year mortality (5.4% quartile 1, 5.5% quartile 2, 16.8% quartile 3 and 24.6% quartile 4, P < 0.0001, respectively) was significantly higher in older age quartiles. CONCLUSIONS: Increased short term and intermediate term mortality is seen in the very elderly after PPCI. Age and cardiogenic shock were prognostic factors. Intervention should not be based on age alone and awareness regarding prognostic factors can help improve management.

Incidence and angiographic characteristics of patients with apical ballooning syndrome (takotsubo/stress cardiomyopathy) in the HORIZONS-AMI trial: an analysis from a multicenter, international study of ST-elevation myocardial infarction.

OBJECTIVES: To determine the incidence, clinical characteristics, and the coronary angiographic features of patients with apical ballooning syndrome (ABS) among those recruited into a large, prospective, international, multicenter trial. BACKGROUND: ABS is an important entity in the differential diagnosis of ST-elevation myocardial infarction (STEMI). Current data regarding ABS are limited to single center registries. METHODS: Patients with ABS were identified, based on the Mayo Clinic diagnostic criteria, from those enrolled into the HORIZONS-AMI trial. Quantitative angiography was performed by a core laboratory to identify the frequency and severity of coronary artery disease. RESULTS: Among the 2,648 patients who had left ventriculography in addition to coronary angiography, 12 patients were identified with ABS. All patients were female and they were compared to the remaining 571 female patients with STEMI. Compared with patients with STEMI (97.9% of our cohort), patients with ABS (2.1%) had a lower prevalence (42% vs. 100%, P < 0.05) and severity (number of plaques measuring >30% diameter stenosis per patient: 0.58 ± 0.90 vs. 4.13 ± 2.68, P < 0.0001) of coronary artery disease. There were no in-hospital deaths or major adverse cardiovascular events (MACE) in the ABS group vs. 2.1% and 3.7% respectively in the STEMI group, nor at 2-year follow up (death: 0% vs. 5.5%, MACE: 0% vs. 19.4%), but these differences were not statistically significant. CONCLUSIONS: In HORIZONS-AMI, ABS was identified exclusively in women (2.1% of female patients, 0.5% of all patients) and MACE were absent in this uncommon but important group of patients. Coronary artery disease was often present in patients with ABS, but its prevalence and severity was significantly less compared with STEMI patients.

Stress cardiomyopathy: case series and the review of literature.

BACKGROUND: Apical ballooning syndrome (ABS) or stress cardiomyopathy is increasingly recognized as a cause of acute coronary syndrome with unobstructed coronaries, but remains underdiagnosed. OBJECTIVES: Retrospective review of the angiographic database (between January 2006 and December 2010) to obtain incidence and clinical presentation of ABS at our center. ABS was defined according to the modified Mayo Clinic criteria. CASE RESULTS: Normal or unobstructed coronaries on angiography were observed in 1780 (25.4%) of a total of 6983 patients who underwent urgent or emergency coronary angiography. Twelve patients (0.17%) fulfilled the modified Mayo Clinic criteria for ABS. Eleven patients (92%) were aged ≥ 50 years (median 68 years, range 27-86 years), and 10 were female (83%). Four patients (31%) presented with ST-elevation myocardial infarction, and 1 patient presented with cardiogenic shock and acute coronary syndrome. Emotional stress was the precipitant in 4 patients (33%). Unusual precipitants like cold-water immersion and intravenous chemotherapy were observed. All 12 patients had the typical appearance of ABS on left ventriculogram (75%) or echocardiography (25%). Follow-up imaging with either echocardiography or magnetic resonance imaging (done in all 12 patients) up to 16 weeks after discharge showed that left ventricular function had normalized. CONCLUSIONS: The incidence and clinical features of ABS in our tertiary center are similar to those reported in other settings. Unusual precipitants were observed, but left ventriculograms were performed less frequently and could be contributory to the under-diagnosis of ABS.

Metal fatigue in myocardial bridges: stent fracture limits the efficacy of drug-eluting stents.

Myocardial bridging (MB) is a common anatomical varient in which a segment of coronary artery takes an intramural path. Occasionally, it can result in symptomatic ischemia. We present four cases in which MB was treated with drug-eluting stents that subsequently fractured, leading to recurrent symptoms.