Optimal management of myocardial infarction: from invasive treatment to secondary prevention and rehabilitation

For the podcast associated with this article, please visit https://academic.oup.com/eurheartj/pages/Podcasts. This issue contains two contributions from our ‘Top 10’ article series. In ‘The year in cardiovascular medicine 2022: the top 10 papers in acute cardiac care and ischaemic heart disease’, Susanna Price from the Imperial College in London, UK, and colleagues discuss contributions published last year that may influence the management of ischaemic heart disease (IHD) patients and of those requiring acute cardiac care.1 In ‘The year in cardiovascular medicine 2022: the top 10 papers in diabetes and metabolic disorders’, EHJ Editors Francesco Cosentino, Nikolaus Marx, and Subodh Verma do the same thing for diabetes and metabolic disorders. 2 The issue continues with a focus on IHD. In a meta-analysis article entitled ‘Exercise-based cardiac rehabilitation for coronary heart disease: a meta-analysis’, Grace Dibben from the University of Glasgow in the UK, and colleagues note that coronary heart disease (CHD) is the most common reason for referral to exercise-based cardiac rehabilitation (CR) globally.3 However, the generalizability of previous meta-analyses of randomized controlled trials (RCTs) is questioned. Therefore, a contemporary updated meta-analysis was undertaken. Database and trial registry searches were conducted up to September 2020, seeking RCTs of exercise-based interventions with ≥6 months’ follow-up, compared with no exercise control for adults with myocardial infarction (MI), angina pectoris, or following coronary artery bypass graft (CABG) or percutaneous coronary intervention (PCI). The outcomes were pooled using random-effects meta-analysis. A total of 85 RCTs in >23 000 participants with a median of 12 months follow-up were included. Overall, exercise-based CR was associated with significant risk reductions (RRs) in cardiovascular mortality [RR: 0.74, number needed to treat (NNT): 37], hospitalizations (RR: 0.77, NNT: 37), and MI (RR: 0.82, NNT: 100). There was no significant impact on overall mortality, CABG, or PCI. No significant difference in effects were found across different patient subsets. Dibben et al. conclude that their meta-analysis confirms that participation in exercise-based CR of patients with CHD receiving contemporary medical management reduces cardiovascular mortality, recurrent cardiac events, and hospitalizations. The contribution is accompanied by an Editorial by Sherry Grace from York University in Toronto, ON, Canada.4 Grace notes that we more greatly resource and implement all other clinical guideline recommendations for cardiovascular disease patients when compared with the CR referral recommendation, although implementation of optimal medication therapy is also suboptimal. While more trials in under-represented groups, readily accessibly models, as well as implementation trials are needed, it is hoped policymakers will turn to implementation of CR. Indeed, the World Health Organization has almost completed their Package of Interventions for Rehabilitation for IHD which, should it be ratified by member states, will support implementation of CR in Europe and beyond. Although findings of previous randomized trials suggest a complete revascularization strategy is more beneficial than infarct-related artery (IRA)-only PCI, it is still unclarified regarding which non-IRA lesions should be revascularized. The FRAME-AMI trial showed that fractional flow reserve (FFR)-guided PCI reduced a composite of death, MI, or repeat revascularization at a median follow-up of 3.5 years compared with angiography-guided PCI for the treatment of non-IRA lesions in patients with acute MI and multivessel disease. This reduction was driven mainly by a significantly lower risk of death and MI in the FFR-guided PCI group. Moreover, fewer stents and fewer contrast media were used with FFR-guided PCI than with angiography-guided PCI. The findings shed light on the efficacy and safety of performing selective PCI of non-IRA lesions using FFR-guided decision-making and show that that this would mean that fewer stents and less contrast media use would be needed, and that there would be a significantly lower risk of adverse clinical events after PCI, compared with a strategy of routine PCI based on angiographic diameter stenosis in non-IRA.10 In patients with acute MI (AMI) the treatment of choice is PCI of the infarct-related artery.5–9 In patients with MI and multivessel coronary artery disease, additional PCI of the non-infarct-related artery further reduces death or MI. However, whether selective PCI guided by fractional flow reserve (FFR) is superior to routine PCI guided by angiography alone is unclear. In a Fast Track Clinical Research article entitled ‘Fractional flow reserve versus angiography-guided strategy in acute myocardial infarction with multivessel disease: a randomized trial’, Joo Myung Lee from the University School of Medicine in Seoul, South Korea and colleagues sought to compare FFR-guided PCI with angiography-guided PCI for non-infarct-related artery lesions among patients with AMI and multivessel disease.10 Patients with AMI and multivessel coronary artery disease who had undergone successful PCI of the infarct-related artery were randomly assigned to either FFR-guided PCI (FFR ≤0.80) or angiography-guided PCI (diameter stenosis of >50%) for non-infarct-related artery lesions. The primary endpoint was a composite of time to death, MI, or repeat revascularization. A total of 562 patients underwent randomization. PCI was performed for the non-infarct-related artery in 64.1% in the FFR-guided PCI group and in 97.1% in the angiography-guided PCI group, and resulted in significantly fewer stents used in the FFR-guided PCI group. At a median follow-up of 3.5 years, the primary endpoint occurred less frequently in the FFR-guided PCI group than in the angiography-guided PCI group (7.4% vs. 19.7%; P = 0.003) (Figure 1). The authors conclude that in patients with AMI and multivessel coronary artery disease, a strategy of selective PCI using FFR-guided decision-making is superior to a strategy of routine PCI based on angiographic diameter stenosis for treatment of non-infarct-related artery lesions regarding the risk of death, MI, or repeat revascularization. The manuscript is accompanied by an Editorial by Shamir Mehta and Brian P. McGrath from the Population Health Research Institute, McMaster University in Ontario, Canada.11 The authors conclude that it is possible, perhaps even likely, that intravascular imaging assessing plaque morphology is complementary to a physiology-guided strategy. However, until the results of COMPLETE-2 are known and based on the results of the current randomized trials, either a physiology-guided or angiography-guided strategy complete revascularization strategy is appropriate for the management of non-culprit lesions in patients with MI. Outcomes of IHD improved during recent decades alongside better risk factor management and implementation of guideline-recommended treatments.12–16 In a Clinical Research article entitled ‘Long-term mortality, cardiovascular events, and bleeding in stable patients 1 year after myocardial infarction: a Danish nationwide study’, Daniel Mølager Christensen from the Danish Heart Foundation in Copenhagen, Denmark, and colleagues note that it is unknown whether this applies to stable patients who are event free 1 year after MI.17 Using nationwide Danish registries, the authors included all patients with first-time MI during 2000–2017 who survived 1 year free from bleeding and cardiovascular events (n = 82 108, median age 64 years, 68% male). Follow-up started 1 year after MI and continued through January 2022. Crude risks of mortality, cardiovascular events, and bleeding were estimated in consecutive 3-year periods. Standardized risks were calculated with respect to the distribution of age, sex, comorbidities, and treatments in the latter period. Guideline-recommended treatment use increased during the study period, e.g. statins (69–92%) and PCI (24–68%). The crude 5-year risks of outcomes decreased (all P-trend <0.001): mortality 18.6%; recurrent MI 7.5%; bleeding, 3.9%. Crude 5-year risk of mortality in 2015–2017 was as low as 2.6% for patients aged <60 years. Use of guideline-recommended treatments was associated with improved outcomes. The authors conclude that for patients who were event free 1 year after MI, the long-term risks of mortality, cardiovascular events, and bleeding decreased significantly, along with an improved use of guideline-recommended treatments between 2000 and 2017. In the most recent period, 1 year after MI, the risk of additional events is lower than previously reported. This manuscript is accompanied by an Editorial by Nicolas Danchin from the Hôpital Saint Joseph in Paris, France.18 Danchin concludes that whatever the potential limitations of the Danish data, the results presented here are particularly encouraging, and the observed decline in long-term mortality is indisputable. While cardiovascular diseases still are the number one killer worldwide, it seems that, provided treatment can be given as appropriate and with optimal healthcare coverage, the time is soon to come where patients hospitalized for an MI will have a life expectancy nearly the same as that of the general population. High-sensitivity troponin-T (hsTnT) plays a key role in the assessment of patients with or without suspected MI in several clinical settings.19–21 In a Clinical Research article entitled ‘Serial troponin-T and long-term outcomes in suspected acute coronary syndrome’, Manan Pareek from the Copenhagen University Hospital in Denmark, and colleagues point out that the long-term prognostic implications of serial high-sensitivity troponin concentrations in subjects with suspected acute coronary syndrome (ACS) are unknown.22 Individuals with a first diagnosis of MI, unstable angina, observation for suspected MI, or chest pain from 2012 through 2019 who underwent two hsTnT measurements 1–7 h apart were identified through Danish national registries. Absolute and relative risks for death at days 0–30 and 31–365, stratified for whether subjects had normal or elevated hsTnT concentrations, and whether these concentrations changed by <20%, > 20% to 50%, or >50% in either direction from first to second measurement, were calculated through multivariable logistic regression with average treatment effect modelling. Of the almost 29 000 individuals included, 2.8% had died at 30 days, whereas 4.9% of those who had survived the first 30 days died between days 31 and 365. The standardized risk of death was highest among subjects with two elevated hsTnT concentrations (0–30 days, 4.3%; 31–365 days, 7.2%). In this group, mortality was significantly higher in those with a > 20% to 50% or >50% rise from first to second measurement, though only at 30 days. The risk of death was very low in subjects with two normal hsTnT concentrations and did not depend on relative or absolute changes between measurements. Pareek et al. conclude that individuals with suspected ACS and two consecutively elevated hsTnT concentrations consistently have the highest risk of death. Mortality is very low in subjects with two normal hsTnT concentrations, irrespective of changes between measurements. The contribution is accompanied by an Editorial by David Morrow from Harvard Medical School in Boston, MA, USA.23 Morrow highlights that the robustly sized study of Pareek et al. of serial hsTnT in patients with suspected ACS lends additional reassurance for clinicians of the low mortality risk out to 1 year of patients with serial values in the normal range and underscores the adverse prognosis in patients with serial elevation, whether dynamic or not. Interpretation of mortality risk in this setting, however, also should consider the magnitude of hsTn elevation and the starting value when considering changing concentration. Moreover, taking the totality of available evidence, patients presenting with suspected ACS who have a rising or falling pattern and only one hsTn above the 99th percentile URL may be a shrinking population with the introduction of high-sensitivity assays and may also be at lower mortality risk with medical management, but should not be classified as ‘low risk’ when considering other cardiovascular outcomes. Such patients probably warrant additional diagnostic evaluation in most cases. A propensity-matched comparison of late outcomes amongst patients who underwent timely primary PCI, late primary PCI, or a pharmaco-invasive strategy; STEMI, ST-elevation myocardial infaction; PCI, percutaneous coronary intervention; pPCI, primary percutaneous coronary intervention.26 Primary PCI (pPCI) is the preferred treatment of patients with ST-elevation MI (STEMI).24,25 Pharmaco-invasive PCI (PI-PCI) is recommended for patients with STEMI who are unable to undergo timely pPCI. In a Clinical Research article entitled ‘Late outcomes of ST-elevation myocardial infarction treated by pharmaco-invasive or primary percutaneous coronary intervention’, Javeria Jamal from Western Sydney University in Australia, and colleagues examined late outcomes after PI-PCI (successful reperfusion followed by scheduled PCI or failed reperfusion and rescue PCI) compared with timely and late pPCI (>120 min from first medical contact).26 All patients with STEMI presenting within 12 h of symptom onset who underwent PCI during their initial hospitalization from October 2003 to March 2014 were included. Amongst 2091 STEMI patients (80% male), 52% underwent pPCI (68% timely, 32% late), and 48% received PI-PCI (33% rescue, 67% scheduled). Mortality at 3 years was 11.1% after pPCI (6.7% timely, 20.2% late) and 6.2% after PI-PCI (9.4% rescue, 4.8% scheduled); P < 0.01 (Figure 2). Jamal et al. conclude that patients who undergo late pPCI have higher mortality rates than those undergoing a pharmaco-invasive strategy. Despite rescue PCI being required in a third of patients, a pharmaco-invasive approach should be considered when delays to PCI are anticipated, as it achieves better outcomes than late pPCI. The manuscript is accompanied by an Editorial by J.J. Coughlan from the Technische Universität München in Germany, and Borja Ibanez from the IIS-Fundación Jiménez Díaz University Hospital in Madrid, Spain.27 The authors conclude that overall, the data presented by Jamal et al. should not be interpreted as challenging the primacy of timely pPCI for patients with STEMI. Rather, they remind us that the pharmaco-invasive approach still has a role in the treatment of STEMI and that the basic tenet of treatment for patients presenting with an occluded artery is to open the artery and restore perfusion as soon as possible. The old adage ‘time is muscle’ remains as relevant today as when it was first coined by Eugene Braunwald over 50 years ago. For patients with an acutely occluded artery, timely reperfusion is the goal, and this can be achieved via fibrinolysis if timely pPCI is not feasible. The upcoming randomized STREAM-2 trial, comparing a pharmaco-invasive and primary PCI strategy in patients >60 years old with acute STEMI should provide further important information regarding the relative benefits and risks of these approaches in the modern setting. In the interim, we should all remember that ‘delays have dangerous ends’ and strive to increase the proportion of STEMI patients achieving timely reperfusion, by any means possible. The issue is also complemented by two Discussion Forum contributions. In a commentary entitled ‘Does plaque morphology truly not matter?’, Wen Wu and Dai-Min Zhang from the Nanjing Medical University in China comment on the recent publication ‘Plaque histology and myocardial disease in sudden coronary death: the Fingesture study’ by Lauri Holmström from the University of Oulu and Oulu University Hospital in Finland.28,29 Holmström et al. respond in a separate comment.30 The editors hope that this issue of the European Heart Journal will be of interest to its readers. Dr. Crea reports speaker fees from Abbott, Amgen, Astra Zeneca, Chiesi, Daiichi Sankyo, Menarini outside the submitted work. With thanks to Amelia Meier-Batschelet, Johanna Huggler, and Martin Meyer for help with compilation of this article.