CAD in patients with renal impairment: Knowing how to address the risks

Patient case: understanding the impact of reduced renal function

How would you address CV risk in the following patient? Think about how their risk changes as diagnosis progresses.

Susan is a 70-year-old woman who was first diagnosed with CAD 2 years ago, after complaining of fatigue and shortness of breath
She was treated with a statin, an ACE inhibitor and a beta-blocker to address cardiovascular risk factors and a nitrate to manage acute symptoms of angina
However, Susan has recently presented to primary care with fatigue, swollen ankles and shortness of breath
Her creatinine clearance is measured and found to be 40 ml/min, confirming a diagnosis of stage III chronic kidney disease

Susan has stable angina

Susan is referred to a dietician for guidance on a low-protein and low-salt diet, and investigations show that her blood pressure and blood lipid levels are adequately managed with her current medication

Should any further action be taken to reduce Susan’s CV risk?

Reduced renal function, increased CV risk

Renal impairment in the REACH registry

Renal impairment is a widespread co-morbidity among patients with atherosclerotic disease. In the REACH registry, more than one-third of patients with stable atherosclerosis had a creatinine clearance lower than 60 ml/min, equivalent to moderate or severe renal impairment.1 For a physician treating a patient with CAD, a diagnosis of renal impairment should be a call to action because of the CV risks associated with this combination of conditions. Outcomes data from the same analysis of the REACH registry showed that increasing renal impairment was linked to a significantly higher risk of CV death and non-fatal MI.

CV outcomes in patients with renal impairment in the REACH registry

Increased benefit of dual pathway inhibition in patients with renal impairment

A large number of patients with renal impairment were included in the COMPASS trial of rivaroxaban 2.5 mg bid plus aspirin. Of 27,395 patients with chronic CAD or PAD, 22.9% had estimated glomerular filtration rate (eGFR) of <60 ml/min, although patients with eGFR <15 ml/min were excluded from the trial.2

Approximately 70% of patients in the COMPASS trial were receiving an ACE inhibitor or ARB, and approximately 90% were receiving a lipid-lowering drug, so the population can be considered well-managed at baseline. However, despite this widespread use of risk-factor management, 8.4% of patients with eGFR <60 ml/min receiving aspirin alone had a major adverse CV event (MACE; comprising MI, stroke or CV death) over the median trial follow-up period of 23 months. For comparison, the incidence of MACE was 4.5% in patients with eGFR ≥60 ml/min.2

Rivaroxaban 2.5 mg bid plus aspirin reduced the risk of MACE compared with aspirin alone

Compared with aspirin, treatment with rivaroxaban 2.5 mg bid plus aspirin reduced the risk of MACE by approximately 25% in patients regardless of renal function. However, the higher baseline risk in patients with eGFR <60 ml/min means that there was a higher absolute reduction in the risk of MACE in these patients compared with patients with eGFR ≥60 ml/min.2

Consistent with the use of an additional antithrombotic, rivaroxaban 2.5 mg bid plus aspirin was associated with an increase in the risk of modified ISTH major bleeding compared with aspirin alone. However, the relative increase in risk was unaffected by renal impairment and, because baseline risk of bleeding appeared to be similar in patients with and without renal impairment, the absolute increase in bleeding risk was similar too.2

Conclusion

Overall, the high risk of MACE in patients with eGFR <60 ml/min means these patients stand to benefit greatly from treatment with rivaroxaban 2.5 mg bid plus aspirin compared with aspirin alone. As Professor Keith Fox explains in the video below

“Patients with moderate renal dysfunction from COMPASS stand to benefit because we’ve shown that the benefits are just as much as the trial overall and there’s no excess in bleeding compared to the trial overall.”

High-risk Subgroups in COMPASS, CAD Patients with Renal Impairment
Keith Fox on Treatment Strategies
Approval Code PP-XAR-ALL-0783-1

References

Dumaine RL, Montalescot G, Steg PG et al. Renal function, atherothrombosis extent, and outcomes in high-risk patients. Am Heart J 2009;158:141–148 e141. Return to content
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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