Low-dose ticagrelor with or without acetylsalicylic acid in patients with acute coronary syndrome: Rationale and design of the ELECTRA-SIRIO 2 trial

© 2022 Via Medica. This article is available in open access under Creative Common Attribution-Non-Commercial-No Derivatives 4.0 International (CC BY-NC-ND 4.0). https://creativecommons.org/licenses/by-nc-nd/2.0/Peer reviewedFinal Published versio

Guidelines on the management of valvular heart disease: The Task Force on the Management of Valvular Heart Disease of the European Society of Cardiology.

80These guidelines focus on valvular heart disease in adults and adolescents, are oriented towards management, and will not deal with endocarditis and congenital valve diseases in adults and adolescents, since recent guidelines have been produced by the ESC on these topics. Although valvular heart disease is less common in industrialized countries than coronary disease, heart failure, or hypertension, guidelines are needed in this field for several reasons: valvular heart disease is common and often requires intervention; substantial advances have been made in the understanding of its pathophysiology; the patient population has changed with a continuous decline of acute rheumatic fever and an increased incidence of degenerative valvular diseases in industrialized countries. The incidence of endocarditis remains stable and other causes of valve disease are rare. Because of the predominance of degenerative valve disease, the two most frequent valve diseases are now calcific aortic stenosis and mitral regurgitation. Aortic regurgitation and mitral stenosis have become less common. Diagnosis is now dominated by echocardiography, which has become the standard to evaluate valve structure and function. Treatment has not only developed through the continuing progress in prosthetic valve technology, but has also been reoriented by the development of conservative surgical approaches and the introduction of percutaneous interventional techniques.openopenVahanian, A; Baumgartner, ; H, ; Bax, ; J, ; Butchart, ; E, ; Dion, ; R, ; Filippatos, ; G, ; Flachskampf, ; F, ; Hall, ; R, ; Iung, ; B, ; Kasprzak, ; J, ; Nataf, ; P, ; Tornos, ; P, ; Torracca, ; L, ; Wenink, ; A, ; Silvia, ; Priori, G.; Blanc, Jean-Jacques; Andrzej, ; Budaj, ; John, ; Camm, ; Veronica, ; Dean, ; Jaap, ; Deckers, ; Kenneth, ; Dickstein, ; John, ; Lekakis, ; Keith, ; Mcgregor, ; Marco, ; Metra, ; João, ; Morais, ; Ady, ; Osterspey, ; Juan, ; Tamargo, ; Luis, José; Zamorano, ; Annalisa, ; Angelini, ; Manuel, ; Antunes, ; Angel, Miguel; Fernandez, Garcia; Christa, ; Gohlke-Baerwolf, ; Gilbert, ; Habib, ; John, ; Mcmurray, ; Catherine, ; Otto, ; Luc, ; Pierard, ; Josè, ; Pomar, L.; Bernard, ; Prendergast, ; Raphael, ; Rosenhek, ; Sousa, Miguel; Uva, ; Juan, ; Tamargo,Vahanian, A; Baumgartner, ; H, ; Bax, ; J, ; Butchart, ; E, ; Dion, ; R, ; Filippatos, ; G, ; Flachskampf, ; F, ; Hall, ; R, ; Iung, ; B, ; Kasprzak, ; J, ; Nataf, ; P, ; Tornos, ; P, ; Torracca, ; L, ; Wenink, ; A, ; Silvia, ; Priori, G.; Blanc, Jean Jacques; Andrzej, ; Budaj, ; John, ; Camm, ; Veronica, ; Dean, ; Jaap, ; Deckers, ; Kenneth, ; Dickstein, ; John, ; Lekakis, ; Keith, ; Mcgregor, ; Marco, ; Metra, Marco; João, ; Morais, ; Ady, ; Osterspey, ; Juan, ; Tamargo, ; Luis, José; Zamorano, ; Annalisa, ; Angelini, ; Manuel, ; Antunes, ; Angel, Miguel; Fernandez, Garcia; Christa, ; Gohlke, Baerwolf; Gilbert, ; Habib, ; John, ; Mcmurray, ; Catherine, ; Otto, ; Luc, ; Pierard, ; Josè, ; Pomar, L.; Bernard, ; Prendergast, ; Raphael, ; Rosenhek, ; Sousa, Miguel; Uva, ; Juan, ; Tamargo

Lipoprotein‐Associated Phospholipase A2 Activity Is a Marker of Risk But Not a Useful Target for Treatment in Patients With Stable Coronary Heart Disease

Background: We evaluated lipoprotein‐associated phospholipase A2 (Lp‐PLA2) activity in patients with stable coronary heart disease before and during treatment with darapladib, a selective Lp‐PLA2 inhibitor, in relation to outcomes and the effects of darapladib in the STABILITY trial. Methods and Results: Plasma Lp‐PLA2 activity was determined at baseline (n=14 500); at 1 month (n=13 709); serially (n=100) at 3, 6, and 18 months; and at the end of treatment. Adjusted Cox regression models evaluated associations between Lp‐PLA2 activity levels and outcomes. At baseline, the median Lp‐PLA2 level was 172.4 μmol/min per liter (interquartile range 143.1–204.2 μmol/min per liter). Comparing the highest and lowest Lp‐PLA2 quartile groups, the hazard ratios were 1.50 (95% CI 1.23–1.82) for the primary composite end point (cardiovascular death, myocardial infarction, or stroke), 1.95 (95% CI 1.29–2.93) for hospitalization for heart failure, 1.42 (1.07–1.89) for cardiovascular death, and 1.37 (1.03–1.81) for myocardial infarction after adjustment for baseline characteristics, standard laboratory variables, and other prognostic biomarkers. Treatment with darapladib led to a ≈65% persistent reduction in median Lp‐PLA2 activity. There were no associations between on‐treatment Lp‐PLA2 activity or changes of Lp‐PLA2 activity and outcomes, and there were no significant interactions between baseline and on‐treatment Lp‐PLA2 activity or changes in Lp‐PLA2 activity levels and the effects of darapladib on outcomes. Conclusions: Although high Lp‐PLA2 activity was associated with increased risk of cardiovascular events, pharmacological lowering of Lp‐PLA2 activity by ≈65% did not significantly reduce cardiovascular events in patients with stable coronary heart disease, regardless of the baseline level or the magnitude of change of Lp‐PLA2 activity

Prolonged antithrombotic therapy in patients after acute coronary syndrome: A critical appraisal of current European Society of Cardiology guidelines

The increased risk of non-cardiovascular death in patients receiving clopidogrel or prasugrel in comparison with the placebo group in the Dual Antiplatelet Therapy (DAPT) trial in contrast to the decreased risk of cardiovascular death and all-cause death seen in patients treated with low-dose ticagrelor in the EU label population of the PEGASUS-TIMI 54 trial, resulted in inclusion in the 2020 ESC NSTE-ACS guidelines the recommendation for use of clopidogrel or prasugrel only if the patient is not eligible for treatment with ticagrelor.The prevalence of the primary outcome composed of cardiovascular death, stroke, or myocardial infarction was lower in the low-dose rivaroxaban and acetylsalicylic acid (ASA) group than in the ASA-alone group in the COMPASS trial. Moreover, all-cause mortality and cardiovascular mortality rates were lower in the rivaroxaban-plus-ASA group.Comparison of the PEGASUS-TIMI 54 and COMPASS trial patient characteristics clearly shows that each of these treatment strategies should be addressed at different groups of patients. A greater benefit in post-acute coronary syndrome (ACS) patients with a high risk of ischemic events and without high bleeding risk may be expected with ASA and ticagrelor 60 mg b.i.d. when the therapy is continued without interruption or with short interruption only after ACS. On the other hand, ASA and rivaroxaban 2.5 mg b.i.d. seems to be a better option when indications for dual antithrombotic therapy (DATT) appear after a longer time from ACS (more than 2 years) and/or from cessation of DAPT (more than 1 year) and in patients with multiple vascular bed atherosclerosis. Thus, both options of DATTs complement each other rather than compete, as can be presumed from the recommendations. However, a direct comparison between these strategies should be tested in future clinical trials

Prolonged antithrombotic therapy in patients after acute coronary syndrome: A critical appraisal of current European Society of Cardiology guidelines

The increased risk of non-cardiovascular death in patients receiving clopidogrel or prasugrel in comparison with the placebo group in the dual antiplatelet therapy (DAPT) trial in contrast to the decreased risk of cardiovascular death and all-cause death seen in patients treated with low-dose ticagrelor in the EU label population of the PEGASUS-TIMI 54 trial, resulted in inclusion in the 2020 ESC NSTE-ACS guidelines the recommendation for use of clopidogrel or prasugrel only if the patient is not eligible for treatment with ticagrelor. The prevalence of the primary outcome composed of cardiovascular death, stroke, or myocardial infarction was lower in the low-dose rivaroxaban and acetylsalicylic acid (ASA) group than in the ASA-alone group in the COMPASS trial. Moreover, all-cause mortality and cardiovascular mortality rates were lower in the rivaroxaban-plus-ASA group. Comparison of the PEGASUS-TIMI 54 and COMPASS trial patient characteristics clearly shows that each of these treatment strategies should be addressed at different groups of patients. A greater benefit in postacute coronary syndrome (ACS) patients with a high risk of ischemic events and without high bleeding risk may be expected with ASA and ticagrelor 60 mg b.i.d. when the therapy is continued without interruption or with short interruption only after ACS. On the other hand, ASA and rivaroxaban 2.5 mg b.i.d. seems to be a better option when indications for dual antithrombotic treatment (DATT) appear after a longer time from ACS (more than two years) and/or from cessation of DAPT (more than one year) and in patients with multiple vascular bed atherosclerosis. Thus, both options of DATTs complement each other rather than compete, as can be presumed from the recommendations. However, a direct comparison between these strategies should be tested in future clinical trials