PAD plus diabetes ‘unique’ malignant phenotype; proper medical therapy essential
Click Here to Manage Email Alerts
Key takeaways:
- Peripheral artery disease often portends bad outcomes, especially when combined with diabetes or disease in another vascular bed.
- Numerous medical therapies have been shown to help patients with PAD.
PHILADELPHIA — Peripheral artery disease is often the first manifestation of CVD in patients with type 2 diabetes, and represents a “unique” malignant phenotype, a speaker said during the Heart in Diabetes CME Conference.
Approximately one in three patients with diabetes or current smoking aged 50 years or older have PAD, Marc P. Bonaca, MD, MPH, professor of medicine and director of vascular research at the University of Colorado School of Medicine, said during a presentation.
Image: Adobe Stock
“There is a lot of PAD out there that’s underdiagnosed, around 12 million [people] in the U.S. and 230 million worldwide,” he said. “When you look for it, it’s there.
“Identifying PAD is important for multiple prognostic reasons,” he said, noting that it is an independent predictor for HF and CVD, and in patients with ACS, “if you add [PAD and diabetes] together, you have a unique malignant phenotype where 50% are having a first cardiovascular event over 7 years, and the majority of that risk is after the first year.”
PAD also predicts poor renal outcomes in patients with diabetes, so “knowing whether your diabetes patient has an abnormal [ankle-brachial index] really matters if you want to understand what their risk is,” he said.
The goals of medical therapy in PAD are reducing risk for systemic atherosclerosis, improving and maintaining function and reducing risk for major adverse limb events, Bonaca said.
Lifestyle interventions, including healthy diet, exercise and smoking cessation, are essential in the PAD population, but medical therapy is often necessary to combat the pathways of risk for PAD, including lipids, diabetes, inflammation, smoking and thrombosis, he said.
Evidence from clinical trials
Because the burden of atherosclerosis predicts limb events, PCSK9 inhibitors, which can reverse plaque burden, have shown benefit in the PAD population, reducing risk for major adverse CV and limb events, Bonaca said.
In addition, icosapent ethyl (Vascepa, Amarin) has been shown to reduce risk for first and total CV events in statin-treated patients with elevated triglycerides, diabetes or equivalent CVD risk and PAD, he said.
Glucose-lowering agents, including SGLT2 inhibitors and GLP-1 receptor agonists, have also shown benefits in the PAD population, including reduced risk for CV death, HF and limb events, according to Bonaca.
He said one SGLT2 inhibitor trial, CANVAS, showed elevated risk for amputation with canagliflozin (Invokana, Janssen), but that has not been confirmed in other studies, so “you can’t deny the benefits of this class of therapy to patients with PAD. I don’t think there has been a consistent risk across the trials, and even if there were, it is mitigated by good foot hygiene.”
To combat thrombotic risk in PAD, a regimen of rivaroxaban (Xarelto, Janssen/Bayer) 2.5 mg per day plus aspirin lowered risk for CV death/MI/stroke/major adverse limb events/major vascular amputation compared with aspirin alone in the COMPASS trial, Bonaca said during the presentation.
In patients with PAD undergoing revascularization and already treated with aspirin and in some cases clopidogrel, rivaroxaban lowered risk for CV death/MI/stroke/major adverse limb events/major vascular amputation compared with placebo in the VOYAGER PAD trial, he said, noting that rivaroxaban prevented 181 thrombotic events per 10,000 patients treated at 1 year, while causing 29 TIMI major bleeding events per 10,000 patients treated at 1 year.
“This is a disease characterized by a high rate of recurrent events, more than any other cardiovascular disease,” Bonaca said. “If you don’t act early, this cycle of recurrent events remains uninterrupted. We have vast underutilization of the therapies that we have. We need systems of care that can address this gap.”
A personalized approach
Because “you can’t use every drug for every patient,” Bonaca said he determines therapy via a personalized approach:
- For patients with symptomatic PAD without prior revascularization or polyvascular disease: diet, exercise and smoking cessation as lifestyle measures; antiplatelet monotherapy to combat thrombotic risk; LDL target < 55 mg/dL; an ACE inhibitor if the patient has hypertension; an SGLT2 inhibitor or GLP-1 receptor agonist if the patient has diabetes; an SGLT2 inhibitor if the patient has HF or chronic kidney disease (CKD); and cilostazol for symptoms if necessary if the patient does not have HF.
- For patients with symptomatic PAD and prior revascularization or polyvascular disease: diet, exercise and smoking cessation as lifestyle measures; aspirin plus rivaroxaban to combat thrombotic risk if the patient is at low bleeding risk; LDL target < 55 mg/dL; an ACE inhibitor if the patient has hypertension; an SGLT2 inhibitor or GLP-1 receptor agonist if the patient has diabetes; an SGLT2 inhibitor if the patient has HF or CKD; and cilostazol for symptoms if necessary if the patient does not have HF.
- For patients with chronic limb-threatening ischemia or acute revascularization: diet, exercise and smoking cessation as lifestyle measures; aspirin plus rivaroxaban to combat thrombotic risk (if the patient is on dual antiplatelet therapy, keeping that to less than 30 days); LDL target < 55 mg/dL; avoidance of hypotension during the acute phase and treatment of BP to guideline-recommended levels once the acute phase is over; an SGLT2 inhibitor or GLP-1 receptor agonist if the patient has diabetes and is stable; an SGLT2 inhibitor if the patient has HF or CKD and is stable; and cilostazol for symptoms if necessary if the patient does not have HF.
References:
- Bhatt DL, et al. Circulation. 2020;doi:10.1161/CIRCULATIONAHA.120.046448.
- Bhatt DL, et al. Circulation. 2021;doi:10.1161/circ.144.suppl_1.10627.
- Bonaca MP, et al. N Engl J Med. 2020;doi:10.1056/NEJMoa2000052.
- Neal B, et al. N Engl J Med. 2017;doi:10.1056/NEJMoa1611925.
Collapse
Bonaca MP. Session 3 – Management of ASCVD Circa 2023. Presented at: Heart in Diabetes CME Conference; June 9-11, 2023; Philadelphia.
Click Here to Manage Email Alerts