The year in cardiology 2016: acute coronary syndromes

The year 2016 brought us several studies on the pathophysiology of acute coronary syndrome (ACS), in particular, on the role of basophils and eosinophils in the mechanism of disease. New puzzling data have also emerged on the pathomechanisms of very late stent thrombosis and the role of neutrophils in ventricular remodelling. New information has also been published on the early diagnosis of ACS by high sensitivity troponin (hsTn) and the role of new exciting biomarkers and clinical scores on risk stratification. With regards to antithrombotic treatment, the year 2016 has brought important new data on the duration of dual antiplatelet therapy (DAPT) and on the management of the growing population of very elderly. Finally, new interesting information has been published on the outcome of specific patient subsets. The studies reported in this review are summarized in Table 1. Summary of the main studies Allergic immunity is altered in ACS VLST is frequently associated to suboptimal stent implantation In experimental models neutrophil depletion is associated to worse remodelling Niccoli1 Taniwaki2 Horckmans3 The best hsTn algorithm to rule out ACS remains controversial Potential role of micro-RNA The role of coronary computed tomography angiography in the emergency department in patients with suspected ACS is limited Pickering5, Shah4 Coskunpinar7 Dedic8 GDF-15 predicts both bleeding and ischemic risk New clinical risk scores to predict in-hospital mortality and medium-term risk of sudden cardiac death in patients admitted with ACS Hagstrom11 Hess10 The efficacy of Cangrelor compared to clopidogrel previously found in the CHAMPION PHOENIX trial is independent of the puncture site The pharmacodynamic effects of Ticagrelor are impaired by morphine Data from SWEDEHEART database confirm the better efficacy of Ticagrelor as compared to Clopidogrel in ACS in the real world The pharmacodynamic effects of crushed Prasugrel tablets are better than those of intact tablets A meta-analysis suggests that dual antiplatelet therapy beyond one year after ACS reduces subsequent ischemic events The addition of ezetimibe to simvastatin reduced first and subsequent cardiovascular events in ACS patients in the IMPROVE-IT trial A sub-study of the LEADERS FREE trial confirms that Biolimus-A9 polymer-free coated stent is superior to bare metal stent in ACS patients with high-bleeding risk on one-month double antiplatelet treatment A real-world analysis fails to show superiority of bivaluridin as compared to other anti-thrombotic treatments The efficacy of early beta-blockers in STEMI remains controversial In early STEMI admitted to non-capable PCI centres, transfer for primary PCI is better than fibrinolysis if the delay is less than 140 min In NSTEMI a single-staged compared with a multi-staged PCI is associated with a lower rate of target vessel revascularization during follow-up In the very elderly with ACS, an invasive approach is associated to a better outcome as compared to a conservative approach PCI in unprotected left main stenosis is associated with comparable clinical outcomes to those observed with coronary artery grafting at long-term follow-up The outcome of left ventricular assist device implanted in patients with ACS is similar to that observed in stable patients Gutierrez13 Kubica16 Sahlen17 Rollini19 Udell20 Murphy31 Naber22 Sirker28 Garcia-Ruiz29 Carrillo32 Sardella33 Tegn36 Pyxaras34 Acharya38 Women: a statement from the American Heart Association on ACS in women summarizes the main differences between men and women in this setting. Smokers: smoking is independently associated to better left ventricular remodelling Rheumatoid arthritis: among patients with ACS rheumatoid arthritis is associated to a worse outcome Vasospastic angina: among patients with vasospastic angina those who present with aborted sudden cardiac death have a worse outcome during follow up Takotsubo syndrome: the outcome of the “happy heart syndrome” is similar to that of the “broken heart syndrome” Mehta39 Symons40 Mantel41 Ahn42 Ghadri44 Allergic immunity is altered in ACS VLST is frequently associated to suboptimal stent implantation In experimental models neutrophil depletion is associated to worse remodelling Niccoli1 Taniwaki2 Horckmans3 The best hsTn algorithm to rule out ACS remains controversial Potential role of micro-RNA The role of coronary computed tomography angiography in the emergency department in patients with suspected ACS is limited Pickering5, Shah4 Coskunpinar7 Dedic8 GDF-15 predicts both bleeding and ischemic risk New clinical risk scores to predict in-hospital mortality and medium-term risk of sudden cardiac death in patients admitted with ACS Hagstrom11 Hess10 The efficacy of Cangrelor compared to clopidogrel previously found in the CHAMPION PHOENIX trial is independent of the puncture site The pharmacodynamic effects of Ticagrelor are impaired by morphine Data from SWEDEHEART database confirm the better efficacy of Ticagrelor as compared to Clopidogrel in ACS in the real world The pharmacodynamic effects of crushed Prasugrel tablets are better than those of intact tablets A meta-analysis suggests that dual antiplatelet therapy beyond one year after ACS reduces subsequent ischemic events The addition of ezetimibe to simvastatin reduced first and subsequent cardiovascular events in ACS patients in the IMPROVE-IT trial A sub-study of the LEADERS FREE trial confirms that Biolimus-A9 polymer-free coated stent is superior to bare metal stent in ACS patients with high-bleeding risk on one-month double antiplatelet treatment A real-world analysis fails to show superiority of bivaluridin as compared to other anti-thrombotic treatments The efficacy of early beta-blockers in STEMI remains controversial In early STEMI admitted to non-capable PCI centres, transfer for primary PCI is better than fibrinolysis if the delay is less than 140 min In NSTEMI a single-staged compared with a multi-staged PCI is associated with a lower rate of target vessel revascularization during follow-up In the very elderly with ACS, an invasive approach is associated to a better outcome as compared to a conservative approach PCI in unprotected left main stenosis is associated with comparable clinical outcomes to those observed with coronary artery grafting at long-term follow-up The outcome of left ventricular assist device implanted in patients with ACS is similar to that observed in stable patients Gutierrez13 Kubica16 Sahlen17 Rollini19 Udell20 Murphy31 Naber22 Sirker28 Garcia-Ruiz29 Carrillo32 Sardella33 Tegn36 Pyxaras34 Acharya38 Women: a statement from the American Heart Association on ACS in women summarizes the main differences between men and women in this setting. Smokers: smoking is independently associated to better left ventricular remodelling Rheumatoid arthritis: among patients with ACS rheumatoid arthritis is associated to a worse outcome Vasospastic angina: among patients with vasospastic angina those who present with aborted sudden cardiac death have a worse outcome during follow up Takotsubo syndrome: the outcome of the “happy heart syndrome” is similar to that of the “broken heart syndrome” Mehta39 Symons40 Mantel41 Ahn42 Ghadri44 ACS, acute coronary syndrome; NSTEMI, non-ST elevation myocardial infarction; PCI, percutaneous coronary intervention; STEMI, ST elevation myocardial infarction; VLST, very late stent thrombosis. Summary of the main studies Allergic immunity is altered in ACS VLST is frequently associated to suboptimal stent implantation In experimental models neutrophil depletion is associated to worse remodelling Niccoli1 Taniwaki2 Horckmans3 The best hsTn algorithm to rule out ACS remains controversial Potential role of micro-RNA The role of coronary computed tomography angiography in the emergency department in patients with suspected ACS is limited Pickering5, Shah4 Coskunpinar7 Dedic8 GDF-15 predicts both bleeding and ischemic risk New clinical risk scores to predict in-hospital mortality and medium-term risk of sudden cardiac death in patients admitted with ACS Hagstrom11 Hess10 The efficacy of Cangrelor compared to clopidogrel previously found in the CHAMPION PHOENIX trial is independent of the puncture site The pharmacodynamic effects of Ticagrelor are impaired by morphine Data from SWEDEHEART database confirm the better efficacy of Ticagrelor as compared to Clopidogrel in ACS in the real world The pharmacodynamic effects of crushed Prasugrel tablets are better than those of intact tablets A meta-analysis suggests that dual antiplatelet therapy beyond one year after ACS reduces subsequent ischemic events The addition of ezetimibe to simvastatin reduced first and subsequent cardiovascular events in ACS patients in the IMPROVE-IT trial A sub-study of the LEADERS FREE trial confirms that Biolimus-A9 polymer-free coated stent is superior to bare metal stent in ACS patients with high-bleeding risk on one-month double antiplatelet treatment A real-world analysis fails to show superiority of bivaluridin as compared to other anti-thrombotic treatments The efficacy of early beta-blockers in STEMI remains controversial In early STEMI admitted to non-capable PCI centres, transfer for primary PCI is better than fibrinolysis if the delay is less than 140 min In NSTEMI a single-staged compared with a multi-staged PCI is associated with a lower rate of target vessel revascularization during follow-up In the very elderly with ACS, an invasive approach is associated to a better outcome as compared to a conservative approach PCI in unprotected left main stenosis is associated with comparable clinical outcomes to those observed with coronary artery grafting at long-term follow-up The outcome of left ventricular assist device implanted in patients with ACS is similar to that observed in stable patients Gutierrez13 Kubica16 Sahlen17 Rollini19 Udell20 Murphy31 Naber22 Sirker28 Garcia-Ruiz29 Carrillo32 Sardella33 Tegn36 Pyxaras34 Acharya38 Women: a statement from the American Heart Association on ACS in women summarizes the main differences between men and women in this setting. Smokers: smoking is independently associated to better left ventricular remodelling Rheumatoid arthritis: among patients with ACS rheumatoid arthritis is associated to a worse outcome Vasospastic angina: among patients with vasospastic angina those who present with aborted sudden cardiac death have a worse outcome during follow up Takotsubo syndrome: the outcome of the “happy heart syndrome” is similar to that of the “broken heart syndrome” Mehta39 Symons40 Mantel41 Ahn42 Ghadri44 Allergic immunity is altered in ACS VLST is frequently associated to suboptimal stent implantation In experimental models neutrophil depletion is associated to worse remodelling Niccoli1 Taniwaki2 Horckmans3 The best hsTn algorithm to rule out ACS remains controversial Potential role of micro-RNA The role of coronary computed tomography angiography in the emergency department in patients with suspected ACS is limited Pickering5, Shah4 Coskunpinar7 Dedic8 GDF-15 predicts both bleeding and ischemic risk New clinical risk scores to predict in-hospital mortality and medium-term risk of sudden cardiac death in patients admitted with ACS Hagstrom11 Hess10 The efficacy of Cangrelor compared to clopidogrel previously found in the CHAMPION PHOENIX trial is independent of the puncture site The pharmacodynamic effects of Ticagrelor are impaired by morphine Data from SWEDEHEART database confirm the better efficacy of Ticagrelor as compared to Clopidogrel in ACS in the real world The pharmacodynamic effects of crushed Prasugrel tablets are better than those of intact tablets A meta-analysis suggests that dual antiplatelet therapy beyond one year after ACS reduces subsequent ischemic events The addition of ezetimibe to simvastatin reduced first and subsequent cardiovascular events in ACS patients in the IMPROVE-IT trial A sub-study of the LEADERS FREE trial confirms that Biolimus-A9 polymer-free coated stent is superior to bare metal stent in ACS patients with high-bleeding risk on one-month double antiplatelet treatment A real-world analysis fails to show superiority of bivaluridin as compared to other anti-thrombotic treatments The efficacy of early beta-blockers in STEMI remains controversial In early STEMI admitted to non-capable PCI centres, transfer for primary PCI is better than fibrinolysis if the delay is less than 140 min In NSTEMI a single-staged compared with a multi-staged PCI is associated with a lower rate of target vessel revascularization during follow-up In the very elderly with ACS, an invasive approach is associated to a better outcome as compared to a conservative approach PCI in unprotected left main stenosis is associated with comparable clinical outcomes to those observed with coronary artery grafting at long-term follow-up The outcome of left ventricular assist device implanted in patients with ACS is similar to that observed in stable patients Gutierrez13 Kubica16 Sahlen17 Rollini19 Udell20 Murphy31 Naber22 Sirker28 Garcia-Ruiz29 Carrillo32 Sardella33 Tegn36 Pyxaras34 Acharya38 Women: a statement from the American Heart Association on ACS in women summarizes the main differences between men and women in this setting. Smokers: smoking is independently associated to better left ventricular remodelling Rheumatoid arthritis: among patients with ACS rheumatoid arthritis is associated to a worse outcome Vasospastic angina: among patients with vasospastic angina those who present with aborted sudden cardiac death have a worse outcome during follow up Takotsubo syndrome: the outcome of the “happy heart syndrome” is similar to that of the “broken heart syndrome” Mehta39 Symons40 Mantel41 Ahn42 Ghadri44 ACS, acute coronary syndrome; NSTEMI, non-ST elevation myocardial infarction; PCI, percutaneous coronary intervention; STEMI, ST elevation myocardial infarction; VLST, very late stent thrombosis. Spontaneous ACS can be caused by plaque fissure, plaque erosion, or functional alterations of epicardial coronary arteries or by vasoconstriction of the microcirculation. Activation of inflammatory cells plays a key role in both plaque fissure and erosion although the mechanisms leading to plaque instability are substantially different in these two conditions. Indeed, while monocyte and lymphocyte activation is the key alteration in plaque fissure, neutrophil activation is a crucial player in plaque erosion. The role of eosinophil and basophil activation is still largely unknown. Niccoli et al.1 found a higher degree of both eosinophil and basophil activation, as assessed by flow cytometry, in patients with ACS than in those with stable angina. Furthermore, in a prospective cohort study they found that higher levels of eosinophil cationic protein (ECP) were associated with a worse outcome during follow-up. This suggests that novel therapies targeting eosinophils should be tested in ACS patients exhibiting raised ECP levels. It is well known that very late stent thrombosis is a possible cause of ACS. The pathomechanisms underlying very late stent thrombosis after implantation of drug-eluting stents (DES) are incompletely understood. Using optical coherence tomography (OCT), Taniwaki et al.2 investigated potential causes of this adverse event. They found that the leading associated findings in very late stent thrombosis were in descending order: (i) stent malapposition, (ii) neoatherosclerosis, (iii) uncovered stent struts, and (iv) stent underexpansion. The longitudinal extension of malapposed and uncovered struts was the most important correlate of thrombus formation. These findings might further expand the clinical utilization of OCT in optimizing the results of stent implantation. Another important issue in ACS are the mechanisms responsible for left ventricular remodelling after myocardial infarction (MI). In an elegant experimental study in a mice model of MI, Horckmans et al.3 found that neutrophil-depleted animals had worsened cardiac function, increased fibrosis, and progressively developed heart failure. Thus, while high neutrophil counts are considered as predictor of adverse clinical outcomes and mortality in patients with ACS and their contribution in the acute inflammatory phase after MI is generally considered detrimental, these data suggest that neutrophils participate in MI repair skewing macrophages towards a resolving phenotype, which mediates efficient clearance of cell debris. This novel role for neutrophils should be taken in account when designing and applying ‘aggressive’ anti-neutrophil treatments in the setting of MI. The evaluation of patients presenting at the emergency department (ED) with suspected ACS remains a clinical challenge. The traditional assessment includes clinical risk assessment based on symptoms, cardiovascular (CV) risk factors with serial electrocardiograms and hsTn measurements, often followed by advanced cardiac testing as inpatients or outpatients. With regards to hsTn, several cohort studies have shown that patients with undetectable plasma hsTn concentrations at presentation are at low risk of MI. However, the optimal approach and threshold of hsTn for the identification of low-risk patients suitable for immediate discharge is still debated. Shah et al.4 did a prospective cohort study of 6304 consecutively enrolled patients with suspected ACS presenting to 4 secondary and tertiary care hospitals in Scotland. They measured plasma Tn concentrations at presentation using a hsTnI assay and evaluated the negative predictive value of a range of hsTnI concentrations for the primary outcome of index MI, or subsequent MI or cardiac death at 30 days in derivation and validation cohorts. The median time from arrival in the ED to blood sampling for measurement of hsTn was 54 min. They found that a hsTn concentration of less than 5 ng/L at presentation met their pre-specified criteria for a negative predictive value of at least 99.5%. At this threshold, almost two-thirds of patients with suspected ACS could have been discharged with very few cardiac events. Indeed, implementation of this threshold could double the number of patients discharged directly from the ED. In one study, et tested the rule out algorithm by the on for the management of ACS in patients presenting in patients with serial and hsTnI The algorithm out patients with a sensitivity of The hsTnI algorithm out patients with a sensitivity of They that the sensitivity of the of assessment algorithm to with troponin be for ED to patients Thus, the identification of the optimal hsTn algorithm in patients with suspected ACS admitted to ED remains as well as the optimal controversial is the utilization of a With regards to new biomarkers in the early diagnosis of ACS, in a of study et assessed the potential role of in patients with ACS. They found that was with Tn and and with left ventricular They that be a for early of ACS. It is a by early coronary computed tomography angiography is superior to optimal care hsTn for patients suspected of ACS in the ED. In a et enrolled patients presenting with of an ACS at the ED of 5 and hospitals in the The primary was the number of patients with coronary artery revascularization 30 was in the primary from the ED was after and of was The that in the of patients with coronary or for discharge from the ED. et using the and With the database developed a model in-hospital The population patients from was a for model with the for model A risk was to prospective risk in clinical heart blood presentation after cardiac presentation in presentation in heart presentation with elevation MI, and Tn were independently associated with in-hospital mortality substantially risk from in the risk to in the risk This and mortality risk models developed for patients with for the at the time of their in patient and management The new risk might this In a cohort analysis which data from in 4 et found that sudden cardiac death for of during follow-up and that reduced left ventricular lower higher heart MI, artery and high were associated with They also developed an from this which a from to This might in the identification of for and beyond the assessment of although prospective assessment of device therapy is sudden death is and in from other causes as MI or cardiac of artery bleeding and cardiovascular death by of assessed in patients admitted with acute coronary coronary artery with from et of the artery by percutaneous coronary and management antithrombotic therapy the of ACS In the CHAMPION PHOENIX et among patients the or approach for PCI with the efficacy and of for the primary efficacy in the for the primary efficacy in the with from et The and of antiplatelet be by and first Furthermore, a between morphine and when has been In a et investigated the and of when with or morphine in ACS In morphine the to and by and this the clinical remains to be for the primary outcome of myocardial or in ACS patients from the SWEDEHEART show the of the primary as well as the primary bleeding outcome of with bleeding with clopidogrel is shown in and in with from et In STEMI patients primary PCI antiplatelet effects of have been et investigated the of crushed tablets The study that compared with crushed to reduced by 30 min which at and 4 Thus, in STEMI patients primary PCI, crushed to and and antiplatelet effects compared with this be associated with clinical acute stent to be in cohorts. The optimal duration of after PCI in the setting of ACS is as patients considered at high risk of bleeding from a In subsequent ischemic events in stable ACS patients be reduced by beyond as was in a However, bleeding often In a trial a Biolimus-A9 coated stent better outcomes with dual antiplatelet therapy compared to a bare metal in patients at high-bleeding This sub-study on patients with ACS was with the The of the coated stent the bare metal stent was ACS, acute coronary syndrome; bare metal coated NSTEMI, myocardial infarction; stent STEMI, myocardial infarction; target with from et In primary PCI for elevation MI the had previously shown a mortality for with with other anti-thrombotic a real-world analysis of patients from the PCI from to in or medium-term mortality between STEMI patients with and at primary be to the role of in primary The of beta-blockers primary PCI on clinical outcomes and is well A analysis from the that the is in the of an STEMI, the the However, the did show between STEMI patients to early or In this study, reduced the of in the acute phase was associated with a in the and the that reduces has shown for in patients with coronary artery disease. In an analysis of the IMPROVE-IT the addition of ezetimibe to simvastatin reduced the rate of first primary also reduced the rate of subsequent adverse in ACS a new of which are for the treatment of are in ACS patients The for ACS patients presenting with STEMI is primary However, fibrinolysis is still in STEMI patients in hospitals if transfer for primary PCI to In a prospective STEMI et compared the of in fibrinolysis PCI transfer on mortality in a cohort of STEMI The study that patients in the transfer from first to device time was 140 min were associated with lower mortality for and for and In with fibrinolysis was an independent mortality predictive These results that transfer to a should be if delay is less than 140 min. A to of ACS patients present with disease. The best treatment and the optimal for PCI in ACS is a of In the patients with ST elevation MI with were to revascularization during the in the of cardiac death and MI was found between although target vessel was higher in the However, was of multi-staged the of an ACS is in an unprotected left main coronary artery the optimal revascularization is a of In the the long-term outcomes of ACS patients with with coronary artery grafting or PCI was In ACS differences emerged for the of and patients in this study stents a lower rate of target vessel be with et the of therapies and in-hospital outcomes of ACS patients enrolled in the prospective in cohort to and first and PCI increased as well as of At the in-hospital mortality of the population from in the first to in the and in-hospital adverse cardiac and events from to This study that of therapies is in the elderly. It remains to this is also for in the very elderly population was investigated by et They patients or presenting with an ACS elevation from an early invasive compared to an conservative a median follow-up of the primary a of MI, for and in of patients to the invasive and 140 of patients to the conservative The two did in of bleeding In in with the an invasive in patients or presenting with non-ST elevation MI was superior to a conservative who present with acute heart or to and In the patients who a ventricular assist device in the setting of an ACS were compared to those who a for In an analysis the ACS had higher early phase reduced of death than the ACS patients had similar outcomes compared to implantation is a in ACS patients with or heart to interesting statement from the American Heart Association on ACS in summarizes the main differences between men and women in this setting. In particular, is that of a year of a first women than men 5 of a first women than men have heart or from a although the higher mortality for women compared with men is by differences in risk clinical and Indeed, the of heart and is higher in women compared with with women present with NSTEMI and coronary artery disease. are also to have mechanisms of ACS as coronary artery or coronary artery et assessed the of smoking in STEMI patients by cardiac was associated with at after for other factors associated with smoking was an independent predictor adverse left ventricular remodelling with the although the of at this effects of It remains to mediates these effects of smoking in STEMI in to new a of studies an increased of ACS in rheumatoid arthritis less is known the clinical and their with outcome of ACS. et compared the clinical presentation of ACS in a cohort of with and in a cohort of population frequently with STEMI, had higher levels of hsTn and higher of in-hospital compared with the population Furthermore, the mortality was higher among ACS. The higher risk of ACS is with the important role of in the of ACS and should further for the identification of of et compared the outcomes of patients with vasospastic angina and aborted and patients with vasospastic angina aborted enrolled from heart in The had a higher risk of death than the of of and left descending artery It remains to which mechanisms the to in these presentation of elevation myocardial infarction Takotsubo and angina. with from and and in patients with elevation myocardial infarction Takotsubo syndrome and with from and has been in the of ACS. In particular, novel data that both basophils and eosinophils a role in ACS new potential are also in the early diagnosis of ACS when remains after optimal Tn The that GDF-15 predicts both ischemic and bleeding risk is exciting although role in remains to be With regards to antithrombotic treatment, remains to duration to Finally, the worse outcome of patients with as compared to those that the of treatment to be in of has from and has from is for and for has from and as well as from and from