Focus on optimizing treatment of coronary heart disease

European Heart Journal—Cardiovascular Pharmacotherapy received its first impact factor 3 years ago. Recently, Clarivate released the 2021 Impact Factor Scores and the impact factor of the journal has now increased to 11 177. The journal remains the number one in the world of journals dedicated to cardiovascular pharmacology and number 15 of all journals within cardiac and cardiovascular systems. We are so grateful to our authors, editors, board members, and reviewers! In this issue of the journal, we focus on different aspects of coronary heart disease.1–3 Myocardial infarction (MI) in the absence of obstructive coronary artery disease is found in ≈5–6% of all patients with acute infarction who are referred for coronary angiography. There are a variety of causes that can result in this clinical condition, entitled myocardial infarction with non-obstructive coronary arteries.4 In a Danish study, Warnakula Olesen et al. examined the effectiveness of aspirin and statin treatment on cardiovascular and bleeding incidence in patients with diabetes and absent obstructive coronary artery disease (CAD). They concluded that among patients with diabetes and no obstructive CAD, aspirin neither reduced major adverse cardiac events (MACE) nor increased bleeding. In contrast, statin treatment was associated with a major reduction in the risk of MACE. Primary percutaneous coronary intervention (pPCI) is the preferred reperfusion strategy in patients with ST-segment elevation myocardial infarction (STEMI) provided it can be performed within 120 min from diagnosis.5 However, it is unclear whether pPCI or a pharmaco-invasive (P-I) strategy is the best choice in patients who cannot receive timely pPCI. The aim of a study by Dr Jortveit et al. from Norway was to compare outcomes after delayed and late pPCI vs. a P-I strategy in STEMI patients who did not receive timely pPCI. They registered 21 121patients with ≤12 h from symptom onset to first medical contact. Among patients who met the inclusion criteria, 54% patients underwent timely pPCI, 11% delayed pPCI 121–180 min, 7% late pPCI (>180 min), and 17% patients were treated with a P-I strategy. After a median follow-up time of 2.5 years, mortality was higher in the delayed pPCI and in the late pPCI groups compared with the P-I strategy group, but bleeding complications were more frequent after the P-I strategy. The authors concluded that in STEMI patients who did not receive timely PCI, a P-I strategy seemed to be associated with better long-term survival compared with delayed/late pPCI. Patients having both diabetes mellitus (DM) and chronic kidney disease (CKD) are at an increased risk of atherothrombotic events. Personalized antiplatelet therapy might be considered among these patients.6,7 Dr Angiolilli et al. from the USA have in a randomized, cross-over study examined how CKD status affects the pharmacodynamic (PD) and pharmacokinetic (PK) profiles of different ticagrelor maintenance dose regimens in patients with DM. PD assessments included VASP-PRI, VerifyNow P2Y12, and LTA. A total of 92 patients with DM were randomized. They concluded that in patients with DM, although ticagrelor maintenance dose regimens (60 and 90 mg) yield potent P2Y 12 inhibition, non-CKD patients are characterized by higher interpatient variability than CKD patients. Levels of platelet reactivity tended to be lower in CKD patients compared with non-CKD patients. In patients with coronary or peripheral arterial disease, adding low-dose rivaroxaban to aspirin may reduce cardiovascular events and mortality.8–10 Polypharmacy and multimorbidity are frequent in such patients. Dr Vanassche et al. aimed to analyse whether the benefits and risks of rivaroxaban plus aspirin vary in patients with comorbidities and receiving multiple drugs in the randomized, double-blind COMPASS study.9,10 The authors report that adding low-dose rivaroxaban to aspirin resulted in benefits irrespective of the number of concomitant drugs or comorbidities. Multiple comorbidities and/or polypharmacy should not dissuade the addition of rivaroxaban to aspirin in otherwise eligible patients. The use of digitalis has been plagued by controversy since its initial use.11,12 Dr Bugiardini et al. aimed to determine the relationship between digoxin use and outcomes in hospitalized patients with acute coronary syndromes (ACSs) complicated by heart failure (HF). The authors concluded that digoxin therapy was associated with an increased risk of early death among women and men with ACS complicated by HF. This finding highlights the need for reexamination of digoxin use in the clinical setting of ACS. In patients with acute MI, upper gastrointestinal bleeding (UGIB) is relatively common and of specific interest, since it could be prevented by several prophylactic measures. Dr Simonsson et al. from Sweden aimed to determine the incidence, associated outcomes, and predictors of UGIB following acute MI. They included 149 477 patients with acute MI enrolled in the SWEDEHEART registry, discharged alive on any antithrombotic therapy (n = 149 477). The study group concluded that after acute MI, readmission because of UGIB is common and significantly associated with a poor prognosis. By using machine learning in addition to traditional logistic regression, new predictors of UGIB, such as blood glucose and smoking status, were identified. Optimal dual antiplatelet therapy (DAPT) in patients undergoing percutaneous coronary intervention (PCI) for ACS intends to balance ischaemic and bleeding risks. Various DAPT de-escalation strategies,13,14 defined as switching from a full-dose potent to a reduced dose or less potent P2Y12 inhibitor, have been evaluated in several ACS-PCI trials. Dr Dangas et al. aimed to compare DAPT de-escalation to standard DAPT with full-dose potent P2Y12 inhibitors in ACS patients who underwent PCI. The used five randomized trials (n = 10 779 patients) that assigned DAPT de-escalation (genetically guided to clopidogrel n = 1242; platelet function guided to clopidogrel n = 1304; unguided to clopidogrel n = 1672; and unguided to lower dose n = 1170) vs. standard DAPT (control group n = 5391). They found that de-escalation of DAPT after PCI for ACS, both unguided and guided by genetic or platelet function testing, was associated with lower rates of clinically relevant bleeding and ischaemic events as compared with standard DAPT with potent P2Y12 inhibitors. Following STEMI, an intense inflammatory response occurs. The anti-inflammatory, Canakinumab Anti-inflammatory Thrombosis Outcome trial showed prevention of recurrent atherothrombotic events.15 Dr Abate et al. from the USA aimed to evaluate the effect of anakinra, a recombinant interleukin-1 receptor antagonist, on the incidence of HF. They analysed 139 patients with STEMI from three separate trials. The study group concluded that IL-1 blockade with anakinra for 14 days in patients with STEMI reduces the incidence of new-onset HF or hospitalization for HF at 1 year following STEMI. The PRECISE-DAPT score16 appears to identify patients at high risk of bleeding complications following PCI. International guidelines recommend the PRECISE-DAPT to identify patients at high risk for bleeding, who may benefit from shortened DAPT. The association of the PRECISE-DAPT score to ischaemic outcomes remains unclear. Dr Clifford et al. from Canada performed a meta-analysis investigating the association between a high PRECISEDAPT score and ischaemic outcomes. From 12 included studies, there were 39 459 patients with PRECISE-DAPT. The authors reported that patients with a PRECISE-DAPT score ≥25 are at increased risk for ischaemic events, bleeding, and all-cause mortality. Low-dose direct oral anticoagulants (DOACs) in adjunct to antiplatelet therapy, known as dual pathway inhibition (DPI), have been tested to prevent ischaemic events in patients with cardiovascular disease (CVD). Dr Angiolillo et al. have conducted a systematic review and meta-analysis to determine the overall safety and efficacy of low-dose DOACs vs. placebo on a background of antiplatelet therapy. A total of 55 782 patients from seven RCTs were included. Low-dose DOACs vs. placebo were associated with significant reductions in MACE and MI and significant increases in major or all bleeding. Thus, the authors concluded that in patients with CVD, a low-dose DOAC regimen vs. placebo, on a background of antiplatelet therapy, is effective in reducing ischaemic events at the expense of increased major and all bleeding, but without significantly increasing intracranial or fatal bleeds, while the benefit is of borderline significance in regard to cardiovascular and total mortality. A DPI with very low-dose DOAC (i.e. rivaroxaban 2.5 mg twice daily) appears particularly advantageous, especially when combined with a single antiplatelet agent, and used among patients at high ischaemic and low bleeding risk. Long-term outcome after coronary artery bypass grafting (CABG) is dependent on the prevention of progressive native artery disease and maintained graft patency. Beta-blockers have been shown to improve outcomes for patients with reduced left ventricular function.17 However, there may be a gradient of the benefit of beta-blockers in ACS patients: from severely depressed ejection fraction up to the normal level.18–20 The evidence for treatment with beta-blockers after CABG is sparse and primarily based on studies of patients with reduced LVEF and a recent MI who had not had CABG.21 Dr Martinsson et al. from Sweden assessed the long-term utilization of beta-blockers after CABG and its association with outcome. A total of 35 184 patients who underwent first-time isolated CABG were included in a nationwide population-based observational study. The authors found that ongoing treatment with selective beta-blockers after CABG was associated with a reduction in MACE, mainly due to an association with reduced long-term risk for MI. The association between selective beta-blockers and MI was consistent in patients with and without previous MI, HF, or reduced left ventricular ejection fraction.