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Risk stratification of patients with stable atherosclerosis: Who needs extra protection?

Is my patient likely to be better off with or without this treatment?

This familiar question underpins treatment decisions in clinical practice. In preventative medicine, benefit–risk assessment is especially important, because a patient may not see any perceivable benefit in terms of symptom relief – most of the benefit comes from the prevention of events.

 

In this series of Vascular Advisor articles, we have looked at risk assessment in a wide range of patients with CAD, including:

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Helen, who was diagnosed with diabetes

VA risk stratification

Peter, who is at risk of reinfarction

VA risk stratification

Susan, who had to adjust her lifestyle when her renal function declined

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Henry, who, as is typical of many patients who have CAD, progressed to polyvascular disease

What is it that connects these patients? They all have an especially high residual risk of CV events and are likely to derive a particularly high benefit from rivaroxaban 2.5 mg bid plus aspirin. There is now a lot of data on the benefits associated with dual pathway inhibition…

 

…but what are the clinical implications?

Why is the risk stratification analysis important?

In clinical practice, benefit–risk assessment is fundamental to decision-making; the availability of clear, supporting data is invaluable for informing such decisions.

 

The COMPASS study showed that treatment with rivaroxaban 2.5 mg bid plus aspirin had an overall net benefit in patients with chronic CAD and/or PAD, reducing the risk of major adverse CV events (MACE; comprising MI, stroke or CV death) by 24% compared with aspirin alone.1 Further analysis showed a consistent relative reduction in risk across the majority of subgroups assessed, suggesting that this regimen may benefit a wide range of patients. Although this is encouraging, it may leave you asking

 

“How do I know which of my patients stand to gain the greatest absolute benefit?”

VA CAD HF

In the overall COMPASS population, rivaroxaban 2.5 mg bid plus aspirin reduced the relative risk of MACE by 24% compared with aspirin alone

The COMPASS risk stratification analysis aimed to answer this question by identifying key patient characteristics associated with the highest ischaemic event risk. Such information is invaluable for better recognizing the CAD and/or PAD patients likely to benefit most from the COMPASS regimen, aiding benefit–risk assessment in clinical practice.

 

How were high-risk features identified?

Two independent methods were used to identify high-risk features in COMPASS patients:
1. A modified REACH (mREACH) score was calculated for each patient and used to find the study median (median score = 12); features that individually conferred a risk of MACE, ALI or amputation above this value (i.e. 13+) were considered high risk
2. A CART survival analysis, which used algorithms to identify independent groups of high-risk individuals, was used to divide the COMPASS population into subgroups based on incidence risk over time

 

Using these two methods, the following four high-risk/high-benefit subgroups were identified:

  • Patients with a history of vascular disease affecting ≥2 beds
  • Patients with a history of heart failure
  • Patients with renal insufficiency (estimated glomerular filtration rate [eGFR]
  • Patients with a history of diabetes

 

VA CAD HF

High-risk features for ischaemic events identified in the COMPASS risk stratification analysis

Data suggest patients at highest absolute risk gain the greatest absolute benefit

Overall, the addition of rivaroxaban 2.5 mg bid to aspirin would prevent 23 more ischaemic events (composite of CV death, MI, stroke, ALI and total vascular amputation) per 1000 COMPASS-like patients over 30 months compared with aspirin alone, corresponding to a 25% relative risk reduction (RRR).

 

This effect was amplified in patients with ≥1 of the four identified high-risk features, with the relative number of ischaemic events that would be prevented per 1000 patients over 30 months rising to:

  • 31 in patients with a history of diabetes (26% RRR)
  • 36 in patients with an eGFR <60 ml/min (26% RRR)
  • 44 in patients with a history of heart failure (35% RRR)
  • 60 in patients with ≥2 vascular beds (36% RRR)

 

VA CAD HF

Ischaemic events prevented and bleeding events caused per 1000 patients over 30 months with addition of rivaroxaban 2.5 mg bid to aspirin in high-risk groups

There were no significant increases in the risk of severe bleeding (composite of fatal bleeding and bleeding into a critical organ) observed with the addition of rivaroxaban 2.5 mg bid to aspirin across any of the high-risk subgroups

 

What does this mean in clinical practice?

The overall protective benefit of rivaroxaban 2.5 mg bid plus aspirin against ischaemic events has been demonstrated across patients with CAD and/or PAD, regardless of risk level.1 As such, the regimen can be considered for use across a wide range of patients. However, the risk stratification analysis identified polyvascular disease, history of heart failure, renal insufficiency and a history of diabetes as characteristics that could be used to identify patients who stand to gain the greatest absolute benefit from this regimen. Given the lack of increased risk of the most severe bleeding events, the addition of rivaroxaban 2.5 mg bid to aspirin should be strongly considered in patients with ≥1 of these four high-risk features in order to improve ischaemic event protection in clinical practice.

 

Conclusion

Most patients in COMPASS gained net clinical benefit with rivaroxaban 2.5 mg bid plus aspirin compared to aspirin alone.1 However, as explained in the risk stratification manuscript,

 

“a substantial number of clinical events including CV death, MI, stroke, and vascular limb events can be prevented by use of low-dose rivaroxaban and aspirin in the highest-risk groups.”

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References
  • Eikelboom JW, Connolly SJ, Bosch J et al. Rivaroxaban with or without aspirin in stable cardiovascular disease. N Engl J Med 2017;377:1319–1330. Return to content

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