Expanding the horizons of suspected acute coronary syndrome management: insights from the RAPID-CTCA trial

Acute coronary syndrome (ACS) represents one of the most important cause of morbidity and mortality worldwide, requiring constant innovation in diagnostic and therapeutic strategies (1). Preventative treatment, including antithrombotic, lipid-lowering, and other modulation therapies, plays a crucial role in managing ACS (2), significantly reducing the risk of recurrent atherothrombotic events and improving survival. Current guidelines advocate for routine use of antiplatelet and statin therapies for all patients, with renin-angiotensin system blockers and beta-blockers recommended for those at higher risk (3). The diagnostic evaluation for suspected ACS involves electrocardiography, cardiac troponin testing, and clinical risk scoring. However, these methods cannot confirm the presence of coronary atherosclerosis, a key factor that would tailor preventative treatment more effectively.

Computed tomography coronary angiography (CTCA) offers a noninvasive modality to assess the extent of coronary artery disease, identifying even less severe but prognostically significant atherosclerosis (4). While CTCA has shown benefits in stable chest pain patients in the SCOT-HEART trial, its utility in guiding preventative treatment in ACS patients remains less clear (5). The secondary analysis of the RAPID-CTCA trial (6) explored the impact of early CTCA on treatment prescription in intermediate-risk ACS patients, finding similar overall treatment frequencies between early CTCA and standard care groups. This secondary analysis marks a significant step forward and has the purpose of assess how the early CTCA affects preventative treatment prescriptions and adjusts treatment based on the detected extent of coronary atherosclerosis.

The trial explored the impact of early CTCA on the prescription of preventative treatments in patients suspected of ACS, comparing outcomes against standard care. Among 1,743 patients, in those assigned to early CTCA, the modification of preventative treatments significantly differed based on CTCA outcomes. When compared to patients who either did not undergo CTCA by the time of discharge or whose scans were inconclusive, those identified with obstructive coronary artery disease exhibited an increased adjustment in preventative treatment. Conversely, patients with normal coronary arteries saw a higher tendency towards the reduction of antiplatelet and beta-blocker medications.

This confirms that anatomical assessment can refine preventative strategies by delineating the extent of coronary artery disease. Traditionally, the management of suspected ACS has been guided by clinical assessment, electrocardiograms, and biomarkers. The RAPID-CTCA trial introduces a paradigm shift, suggesting that the integration of early CTCA can enhance patient stratification and treatment individualization. This approach not only promises to improve patient outcomes through tailored therapy but also represents a judicious use of healthcare resources by preventing unnecessary interventions.

Current guidelines suggest the initial anatomical assessment of coronary arteries to guide the management of patients with non-ST-segment elevation ACS (7): this is particularly crucial for fine-tuning dual antiplatelet therapy to strike a balance between reducing ischemic risks and minimizing bleeding complications. The RAPID-CTCA trial shows that early CTCA not only improves the identification of patients with suspected ACS for further invasive coronary angiography and potential revascularization but also leads to a consistent increase in the use of P2Y₁₂ receptor antagonists, regardless of cardiac troponin levels.

Despite its significant findings, the RAPID-CTCA trial is not without limitations. The study was designed to focus on a specific group of patients at intermediate risk, characterized by either a history of coronary artery disease, electrocardiographic signs of myocardial ischemia, or elevated cardiac troponin levels. It excluded patients who did not survive until discharge, which may limit the broader applicability of the study’s findings. Moreover, the focus on immediate prescription changes post-CTCA did not extend to long-term adherence or clinical outcomes, leaving room for further exploration of CTCA impact on patient survival and quality of life. The SCOT-HEART trial demonstrated significant long-term cardiovascular benefit from the early and consistent use of antiplatelet and statin therapies guided by CTCA. The authors noted that, in comparison to the SCOT-HEART (5) and CATCH (8) trials, which both reported about a 10% increase in the use of these therapies, the RAPID-CTCA trial showed only a modest increase in their utilization. Consequently, the anticipated benefits from early CTCA in the RAPID-CTCA trial may take longer to materialize if these therapies were to be continued over time.

These limitations were already included in the original study, but two additional points should be noted. First, it is not recommended that patients with suspected ACS be treated without an anatomic diagnosis. This underscores the importance of imaging modalities like CTCA in providing a definitive diagnosis of coronary artery disease before initiating treatment. Without an anatomical assessment, there is a risk of either under-treating or over-treating patients, which could lead to suboptimal outcomes. In the context of the RAPID-CTCA trial, the reliance on early CTCA ensures that treatment decisions are based on precise anatomical data, thereby enhancing the accuracy of preventative treatment prescriptions.

Second, it should be clear how treatment was provided to patients with obstructive coronary artery disease versus those without. In the trial, patients identified with obstructive coronary artery disease through CTCA showed an increased adjustment in their preventative treatment regimens. Conversely, those with normal coronary arteries often experienced a reduction in antiplatelet and beta-blocker medications. This distinction is crucial as it highlights the tailored approach in managing ACS based on the anatomical findings. The presence or absence of significant coronary artery disease necessitates different therapeutic strategies to optimize patient outcomes and minimize unnecessary medication use. Therefore, a detailed understanding of how these treatment adjustments are made based on CTCA findings is essential for implementing similar strategies in clinical practice.

Furthermore, an extremely interesting aspect that remains open is related to the fact that the RAPID-CTCA trial studies anatomy (namely the degree of stenosis) but does not evaluate the structure of the plaque (composition and features of vulnerability) (9) and its potential effect in terms of risk and potential therapeutical strategy changes (10). Moreover, there is robust evidence demonstrating how the calcium score [easily obtainable when a computed tomography (CT) of the coronary arteries is performed] strongly stratifies risk (11). Additionally, once data related to the coronary tree are acquired by performing a CTCA with contrast, it becomes possible to evaluate the ultra-structure of the coronary plaques and, for example, identify whether all those characteristics defined as high risk of vulnerability are present (12). The intersection of these aspects in therapeutic strategies and how they may influence them remains an aspect of utmost importance.

Finally, it remains to be defined and understood the relationship between coronary treatment and its effects on other target areas of atherosclerotic disease, such as the carotids and the associated risk of stroke (13). Can a change in treatment guided by CTCA information open the possibility of benefits in other districts as well? Could there be, for example, a modification of the carotid plaque Reporting And Data System (RADS) score driven precisely by this type of therapeutic strategy change? (14).

The trial paves the way for several future research. Longitudinal studies assessing the long-term outcomes of patients treated based on early CTCA findings are essential to validate its clinical utility further. Additionally, cost-effectiveness analyses could elucidate the financial implications of widespread CTCA implementation in suspected ACS cases (15). Moreover, the trial findings advocate for updating clinical guidelines to incorporate CTCA as a standard diagnostic tool in specific patient populations.

In conclusion, the RAPID-CTCA trial represents a significant advancement in the management of suspected ACS, offering a compelling case for the routine use of early CTCA in guiding preventative treatment strategies. While acknowledging its limitations, the findings from this study emphasize the need for a more nuanced approach to ACS management, where anatomical assessment through CTCA plays a pivotal role. As we look to the future, embracing these insights and exploring their implications through further research will be crucial in our ongoing quest to optimize care for ACS patients.

Acknowledgments

Funding: None.

Footnote

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