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Ischaemic and bleeding risk assessment after myocardial infarction: combination is the key
  1. Arthur Darmon,
  2. Gregory Ducrocq
  1. FACT (French Alliance for Cardiovascular Trials), D.H.U FIRE, Department of Cardiology, Bichat-Claude Bernard Hospital, Paris, France
  1. Correspondence to Dr Gregory Ducrocq, FACT (French Alliance for Cardiovascular Trials), D.H.U FIRE Department of Cardiology, Bichat-Claude Bernard Hospital Paris France ; gregory.ducrocq{at}bch.aphp.fr

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Residual ischaemic risk after an acute coronary syndrome (ACS) remains high despite coronary revascularisation and current guideline-based secondary prevention. More potent antithrombotic strategies—such as prolonged dual antiplatelet therapy (DAPT),1 use of potent P2Y12 inhibitors,2 or combination of a low-dose anticoagulant and aspirin3—have recently been proposed. Each of these strategies not only reduces ischaemic risk, but also increases bleeding risk.

In parallel, knowledge on the impact of bleeding on prognosis in patients with coronary artery disease is increasing. As a consequence, maintaining a low bleeding risk is now of utmost importance in this population. This trend is attested by the fact that a growing number of randomised clinical trials have now bleeding rather than ischaemic events as primary endpoints.4

The selection of patients likely to derive benefit from potent antithrombotic strategies with acceptable bleeding risk therefore requires concomitant evaluation of ischaemic and bleeding risks.

In this issue of Heart, Lindholm et al 5 assessed the effects of combining key clinical risk factors on the recurrent ischaemic and bleeding risks after acute myocardial infarction (MI). To do this, they studied the SWEDEHEART registry, which included more than 100 000 patients admitted for MI. The key risk factors used in their model have been proven to be associated with worse outcomes in this population as they increase ischaemic and bleeding risks: age >65 years, multivessel disease, chronic kidney disease (with estimated glomerular filtration rate <60 mL/min/1.73 m2), diabetes, prior MI, and prior major bleeding. They observed that 20.6% of patients experienced cardiovascular death, MI, or stroke, and 5.9% major bleeding over a median follow-up of 3.6 years, highlighting that there is still much room for improvement in the management of this population. More than half of the population had more than one of the above-mentioned risk factors, which underlines the relevance of combining these risk factors. Taken separately, each of the risk factors was associated, after adjustment, with an increased risk of ischaemic events and all except ‘prior MI’ with an increased risk of major bleeding. ‘Prior bleeding’ had the highest association with increased bleeding risk. When combining risk factors, the authors observed a marked and gradual increase in ischaemic risk from one to six risk factors. This was also true for bleeding events, but to a lesser extent, and this was mainly driven by a history of prior bleeding. When analysing only patients without prior bleeding, an increasing number of risk factors was still associated with a substantial increased ischaemic risk while bleeding risk only minimally increased.

The fact that the risk of ischaemic events increased when patients had several risk factors is not surprising. However, the relatively small increase in bleeding risk is more unexpected and this differential increase has potential clinical implications.

The authors deserve to be congratulated for leading this important study, which offers a simple and pragmatic evaluation of the global risk of patients with previous MI. Tools to evaluate the risk of recurrent events were first developed for the acute phase of ACS.6 7 With improvements in the efficacy and safety of the acute phase of ACS management, the use of these tools has declined. The need for risk evaluation then moved to postpercutaneous coronary intervention (PCI) antiplatelet management.1 8 Owing to the constant improvement in PCI procedures, devices, and postprocedural management, the risk of a recurrent event is now more associated with an initially non-culprit lesion than with the stented segment. The need for risk evaluation has now, therefore, moved to overall secondary prevention.

Several risk scores in stable patients have been published and validated for the assessment of recurrent ischaemic9 and bleeding10 risks in stable patients. Looking in detail at the various parameters used for the calculation of these score, there is a significant overlap between ischaemic and bleeding risk scores. Thus, based on score evaluation, patients with a high ischaemic risk often also have a high bleeding risk, which precludes the use of these scores as clinical tools. The overlap in risk factors has been confirmed in the study by Lindholm et al.5 However, the novelty here is the different impact of the addition of risk factors on ischaemic and bleeding risks.

The DAPT score1 attempts to overcome the issue of overlapping risks, integrating ischaemic and bleeding risks in a single score. Its use is recommended in recent guidelines. It has, however, been designed to evaluate the risks and benefits of DAPT continuation after drug-eluting stent (DES) implantation (as attested by angiographic and procedural items in the score) and its use should be restricted to this indication.

Recent guidelines also recommend the use of the PREdicting bleeding Complications In patients undergoing Stent implantation and subsEquent Dual Anti Platelet Therapy (PRECISE-DAPT) score8 to evaluate bleeding risk after DES implantation in order to tailor DAPT duration. However, this score is mainly based on a history of prior bleeding since ‘prior bleeding’ has a fourfold impact on the score compared with other items. The findings of Lindholm et al 5 corroborate this as they also identified the pre-eminence of previous bleeding in the risk of bleeding occurrence. This item has such importance that they emphasise the need to assess bleeding history separately, rather than integrating it in a score.

Another limitation of risk scores is the complexity of using them in clinical practice (eg, the PRECISE-DAPT score requires a web calculator). An approach such as the one developed by Lindholm et al 5 can allow a semiquantitative evaluation of recurrent events based on a limited number of items without complex calculations.

Finally, whereas the most recently developed scores are based on randomised clinical trial1 8 recruiting highly selected patients, the model developed by Lindholm et al 5 is based on a contemporary large registry including non-selected patients. This could potentially improve its external validity in ‘real life’ populations.

In an era of very prolific new secondary prevention strategies after MI, clinicians need—more than ever— to compare ischaemic and bleeding risks to select the best strategy for a given patient. It is even more important when considering that preventing an ischaemic event with an optimised antithrombotic strategy would be underappreciated from the patient’s and physician’s point of view, while inducing a major bleed (or even repeated minor bleeding), would be entirely attributed to treatment. The approach developed by Lindholm et al 5 may help when evaluating the risk–benefit balance according to the patient’s risk profile.

References

Footnotes

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests None declared.

  • Provenance and peer review Commissioned; internally peer reviewed.

  • Patient consent for publication Not required.

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