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Beatrice is now taking several steps to reduce her cardiovascular risk, but she is still worried about losing her leg or having a stroke. Is there more that can be done to protect Beatrice from major adverse cardiovascular and limb events?
Like Beatrice, many patients with PAD experience intermittent claudication or other leg symptoms.1 Co-morbid diabetes is also common in patients with PAD, and is estimated to occur in about 30–40% of patients.2,3 In fact, having diabetes approximately doubles the risk of developing PAD.4
Guidelines recommend a comprehensive risk factor management strategy that includes a healthy lifestyle and single antiplatelet therapy in all patients with symptomatic PAD, as well as statins, antihypertensive drugs and antidiabetic drugs where necessary.5,6
Beatrice and her physician are already following this advice, but is that enough to reduce her risk of major adverse cardiovascular and limb events?
Even patients with PAD who receive a high standard of risk factor management are at risk of major adverse cardiovascular and limb events, particularly when they also have diabetes. For example, one study estimated that patients who have PAD and diabetes, like Beatrice, have an approximately 1.5-fold increase in the risk of major cardiovascular events compared with those who only have PAD (hazard ratio [HR]=1.431; 95% confidence interval [CI] 1.276–1.605). The risk of major amputation was almost doubled in patients with PAD and co-morbid diabetes versus those with PAD alone (HR=1.863; 95% CI 1.372–2.531).7
A sub-analysis of patients with chronic PAD in the COMPASS trial showed that DPI with rivaroxaban vascular dose 2.5 mg twice daily (bid) plus low-dose aspirin significantly reduced the risk of major adverse cardiovascular events (MACE; cardiovascular death, stroke or myocardial infarction) by 28%, the risk of major adverse limb events (MALE) including major amputation by 46% and the risk of major amputation by 70% compared with aspirin alone. The reduction in the risk of the combined outcome of MACE and MALE including major amputation was consistent between subgroups of patients with and without diabetes. The risk of major bleeding based on a modified definition of the International Society on Thrombosis and Haemostasis (ISTH) criteria was significantly increased in patients with PAD receiving DPI compared with patients receiving aspirin alone; however, the risk of fatal or intracranial haemorrhage was not significantly different between treatment arms.8
Most patients in COMPASS received guideline-recommended therapies for the prevention of cardiovascular events. Therefore, the benefits of DPI versus aspirin alone were observed in addition to the standard cardiovascular risk management strategies.8
Although DPI reduced the risk of MACE and MALE versus aspirin alone in all patient subgroups in COMPASS, those with co-morbidities such as diabetes were shown to benefit particularly from DPI versus aspirin alone. These patients had a higher absolute risk of cardiovascular and limb events compared with patients without co-morbid diabetes. Therefore, patients with co-morbid diabetes had a particularly favourable benefit–risk profile with DPI versus aspirin alone.9,10
Dual pathway inhibition can reduce the risk of major adverse cardiovascular and limb events in patients with chronic PAD in the presence and absence of co-morbid diabetes8
Because of the potential of DPI to prevent serious atherothrombotic events, the 2019 European Society of Vascular Medicine (ESVM) guidelines on PAD recommended considering DPI in patients with PAD without a high risk of bleeding as part of an overall vascular protection strategy.5 The 2019 European Society of Cardiology (ESC) guidelines on diabetes, pre-diabetes and cardiovascular diseases also recommended considering DPI in patients like Beatrice who have chronic symptomatic lower-extremity PAD and comorbid diabetes, and without a high risk of bleeding.6
Rivaroxaban vascular dose 2.5 mg bid plus low-dose aspirin is a new treatment option that has been shown to reduce the risk of major adverse cardiovascular and limb events in patients with PAD. What could antithrombotic protection using DPI mean for patients like Beatrice? It could mean enhanced protection against potentially debilitating cardiovascular events and less fear about the possibility of a life-changing limb event such as an amputation. As Professor Sonia Anand explains in the video below,
“by showing that we can reduce both MACE or MALE events by 31%, patients with PAD stand to benefit significantly with this new therapy.”
High-risk subgroups in COMPASS, CAD Patients with PAD
Sonja Anand on Treatment Strategies