Meeting News

Medical therapies provide options for PAD treatment

Marc P. Bonaca
Marc P. Bonaca

LAS VEGAS — In recent years, data have emerged showing a variety of medical therapies can improve outcomes of patients with peripheral artery disease, according to a session dedicated to pharmacotherapy at VIVA 18.

In addition, according to experts here, following all relevant guidelines on medical therapy seems to benefit those with PAD and other CVDs.

Role of antiplatelet therapy

Antiplatelet therapy — including agents such as aspirin, clopidogrel, ticagrelor (Brilinta, AstraZeneca) and prasugrel (Effient, Daiichi Sankyo/Eli Lilly) — appears to benefit patients with PAD.

However, while it is common practice to prescribe dual antiplatelet therapy after lower-extremity endovascular revascularization as is done after PCI, there are little data to support this, according to Mark F. Conrad, MD, director of clinical research and assistant program director in the division of vascular and endovascular surgery at Massachusetts General Hospital.

“No prior systematic reviews have focused solely on this subject,” Conrad said during a presentation. “Despite this, prescription of DAPT following such procedures is common, with data from survey studies and regional registries suggesting greater than 70% of providers routinely prescribe DAPT, especially following stent placement and after intervention in the more distal arteries.”

Society for Vascular Surgery guidelines released in 2015 recommend DAPT for 30 days in these patients, while American College of Cardiology/American Heart Association guidelines released in 2016 state it may be reasonable, and 2012 American College of Chest Physicians guidelines recommend monotherapy, he said.

Role of rivaroxaban

The COMPASS trial “changed how we pay attention to” medical therapy in patients with PAD, Joshua Beckman, MD, director of vascular medicine and professor of medicine at Vanderbilt University Medical Center, said during a presentation.

In COMPASS, among patients with stable PAD, rivaroxaban (Xarelto, Janssen/Bayer) 2.5 mg plus aspirin conferred lower risk for MACE and major adverse limb events (MALE) compared with aspirin alone.

In contrast, Beckman said, while clopidogrel has been associated with reduction of MACE risk in this population, unlike rivaroxaban, it has not been linked to reduction of risk for all-cause mortality or MALE.

“Because of that, I’m not sure where [clopidogrel] fits in anymore,” he said.

Role of vorapaxar

In the TRA2P-TIMI 50 trial, vorapaxar (Zontivity, Aralez) was shown to reduce risk for MACE, hospitalization for acute limb ischemia and peripheral revascularization in patients with PAD, regardless of whether they were symptomatic, Marc P. Bonaca, MD, MPH, executive director of CPC Clinical Research and director of vascular research and William R. Hiatt Endowed Chair for Cardiovascular Research at the University of Colorado, said here.

Bonaca noted that the treatment effect of vorapaxar in the PAD cohort of TRA2P-TIMI 50 was similar to the treatment effect of rivaroxaban in the PAD cohort of COMPASS in CV death and major adverse limb events, and that bleeding risks appeared to be similar, but there were several important differences between the trials.

In COMPASS, the background therapy was aspirin, whereas in TRA2P-TIMI 50, it could be aspirin, clopidogrel or DAPT, he said. And, he noted, COMPASS showed a 28% relative reduction of risk for MACE from rivaroxaban, while TRA2P-TIMI 50 showed a 15% relative reduction of risk for MACE from vorapaxar.

Therefore, he said, vorapaxar is an option in patients with PAD at low bleeding risk and high risk for MACE and MALE, but in most cases, rivaroxaban is likely be preferred.

“Reasons to consider vorapaxar include when there is use of a P2Y12 inhibitor either as monotherapy or DAPT; when there are renal concerns because it is not cleared by the kidneys; when there are adherence concerns because it is taken once daily, is well-tolerated and has a long half-life; and when the patient is unable to tolerate rivaroxaban,” he said.

Role of PCSK9 inhibitors

While PCSK9 inhibitors are traditionally considered as a treatment for patients with CAD, analyses of the FOURIER trial showed that evolocumab (Repatha, Amgen) also benefited patients with PAD, Matthew T. Menard, MD, co-director of vascular and endovascular surgery and program director of the vascular and endovascular surgical fellowship at Brigham and Women’s Hospital and assistant professor of medicine at Harvard Medical School, said during a presentation.

Among the 1,505 patients with PAD but no prior MI or stroke in FOURIER, evolocumab was associated with a 42% relative risk reduction and an absolute risk reduction of 4.8% for CV death/MI/stroke (number needed to treat = 21), he said.

In the same cohort, evolocumab conferred a 57% relative risk reduction and a 1.3% absolute risk reduction for major adverse limb events, he said.

Evolocumab also showed a benefit in MACE and major adverse limb events when the cohort was expanded to include all patients with PAD, according to Menard.

“FOURIER highlights significant potential to impact CV health in the PAD and CLI population through reduction of LDL down to very low levels,” he said. “However, there are cost limitations, though the recently announced price reduction for evolocumab may help address those.”

Role of cilostazol

Cilostazol has been used as a treatment for intermittent claudication since 1999 and has been shown to improve walking distance, J. Michael Bacharach, MD, MPH, section head of vascular medicine and peripheral vascular intervention at North Central Heart Institute and Avera Heart Hospital, Sioux Falls, South Dakota, said here.

“[Cilostazol] has been effective in some patients for intermittent claudication coupled with an exercise program,” he said. However, “there has been some controversy about how much improvement is from the drug itself and how much is from the exercise program. There is a trend showing that it may prevent restenosis in patients with below-the-knee critical limb ischemia. There is clearly a role for the drug, it is readily available and, for the most part, it has a good safety profile.” – by Erik Swain

References:

Bacharach JM. What is the Role of Cilostazol in Modern PAD Therapy? PharmacoRx: Pharmacotherapy in PAD.

Beckman J. What is the Role for P2Y12 Therapy in PAD After COMPASS? PharmacoRx: Pharmacotherapy in PAD.

Bonaca MP. Vorapaxar: Why, When, and in Whom? PharmacoRx: Pharmacotherapy in PAD.

Conrad MF. Is There a Role for Aspirin Monotherapy in PAD? PharmacoRx: Pharmacotherapy in PAD.

Menard MT. Do the FOURIER Results Mandate Usage in PAD? PharmacoRx: Pharmacotherapy in PAD. All presented at: VIVA 18; Nov. 5-8, 2018; Las Vegas.

Bonaca MP, et al. Circulation. 2017;doi:10.1161/CIRCULATIONAHA.117.032235.

Eikelboom JW, et al. N Engl J Med. 2017;doi:10.1056/NEJMoa1709118.

Morrow DA, et al. N Engl J Med. 2012;doi:10.1056/NEJMoa1200933.

Disclosures: Bacharach reports he received honoraria from Boston Scientific, Bristol-Myers Squibb, Cook Medical and W.L. Gore and Associates, has consulted for W.L. Gore and Associates and has received research funding from AstraZeneca, Bayer, Bolton Medical, Endologix, St. Jude Medical, TriVascular, Veryan/Novate and W.L. Gore and Associates. Beckman reports he has consulted for AstraZeneca, Antidote Therapeutics, Bayer, Bristol-Myers Squibb, Janssen, Merck, Novartis and Sanofi Aventis and holds equity in EMX and Janacare. Bonaca reports he has consulted for Amgen, Aralez, AstraZeneca, Bayer, Janssen, Merck and Sanofi Aventis and has received research funding from Amgen, AstraZeneca, Merck, Medimmune and Pfizer. Conrad reports he has consulted for Bard Peripheral Vascular, Endologix and Medtronic. Menard reports he has consulted for Janssen.

Marc P. Bonaca
Marc P. Bonaca

LAS VEGAS — In recent years, data have emerged showing a variety of medical therapies can improve outcomes of patients with peripheral artery disease, according to a session dedicated to pharmacotherapy at VIVA 18.

In addition, according to experts here, following all relevant guidelines on medical therapy seems to benefit those with PAD and other CVDs.

Role of antiplatelet therapy

Antiplatelet therapy — including agents such as aspirin, clopidogrel, ticagrelor (Brilinta, AstraZeneca) and prasugrel (Effient, Daiichi Sankyo/Eli Lilly) — appears to benefit patients with PAD.

However, while it is common practice to prescribe dual antiplatelet therapy after lower-extremity endovascular revascularization as is done after PCI, there are little data to support this, according to Mark F. Conrad, MD, director of clinical research and assistant program director in the division of vascular and endovascular surgery at Massachusetts General Hospital.

“No prior systematic reviews have focused solely on this subject,” Conrad said during a presentation. “Despite this, prescription of DAPT following such procedures is common, with data from survey studies and regional registries suggesting greater than 70% of providers routinely prescribe DAPT, especially following stent placement and after intervention in the more distal arteries.”

Society for Vascular Surgery guidelines released in 2015 recommend DAPT for 30 days in these patients, while American College of Cardiology/American Heart Association guidelines released in 2016 state it may be reasonable, and 2012 American College of Chest Physicians guidelines recommend monotherapy, he said.

Role of rivaroxaban

The COMPASS trial “changed how we pay attention to” medical therapy in patients with PAD, Joshua Beckman, MD, director of vascular medicine and professor of medicine at Vanderbilt University Medical Center, said during a presentation.

In COMPASS, among patients with stable PAD, rivaroxaban (Xarelto, Janssen/Bayer) 2.5 mg plus aspirin conferred lower risk for MACE and major adverse limb events (MALE) compared with aspirin alone.

In contrast, Beckman said, while clopidogrel has been associated with reduction of MACE risk in this population, unlike rivaroxaban, it has not been linked to reduction of risk for all-cause mortality or MALE.

“Because of that, I’m not sure where [clopidogrel] fits in anymore,” he said.

Role of vorapaxar

In the TRA2P-TIMI 50 trial, vorapaxar (Zontivity, Aralez) was shown to reduce risk for MACE, hospitalization for acute limb ischemia and peripheral revascularization in patients with PAD, regardless of whether they were symptomatic, Marc P. Bonaca, MD, MPH, executive director of CPC Clinical Research and director of vascular research and William R. Hiatt Endowed Chair for Cardiovascular Research at the University of Colorado, said here.

PAGE BREAK

Bonaca noted that the treatment effect of vorapaxar in the PAD cohort of TRA2P-TIMI 50 was similar to the treatment effect of rivaroxaban in the PAD cohort of COMPASS in CV death and major adverse limb events, and that bleeding risks appeared to be similar, but there were several important differences between the trials.

In COMPASS, the background therapy was aspirin, whereas in TRA2P-TIMI 50, it could be aspirin, clopidogrel or DAPT, he said. And, he noted, COMPASS showed a 28% relative reduction of risk for MACE from rivaroxaban, while TRA2P-TIMI 50 showed a 15% relative reduction of risk for MACE from vorapaxar.

Therefore, he said, vorapaxar is an option in patients with PAD at low bleeding risk and high risk for MACE and MALE, but in most cases, rivaroxaban is likely be preferred.

“Reasons to consider vorapaxar include when there is use of a P2Y12 inhibitor either as monotherapy or DAPT; when there are renal concerns because it is not cleared by the kidneys; when there are adherence concerns because it is taken once daily, is well-tolerated and has a long half-life; and when the patient is unable to tolerate rivaroxaban,” he said.

Role of PCSK9 inhibitors

While PCSK9 inhibitors are traditionally considered as a treatment for patients with CAD, analyses of the FOURIER trial showed that evolocumab (Repatha, Amgen) also benefited patients with PAD, Matthew T. Menard, MD, co-director of vascular and endovascular surgery and program director of the vascular and endovascular surgical fellowship at Brigham and Women’s Hospital and assistant professor of medicine at Harvard Medical School, said during a presentation.

Among the 1,505 patients with PAD but no prior MI or stroke in FOURIER, evolocumab was associated with a 42% relative risk reduction and an absolute risk reduction of 4.8% for CV death/MI/stroke (number needed to treat = 21), he said.

In the same cohort, evolocumab conferred a 57% relative risk reduction and a 1.3% absolute risk reduction for major adverse limb events, he said.

Evolocumab also showed a benefit in MACE and major adverse limb events when the cohort was expanded to include all patients with PAD, according to Menard.

“FOURIER highlights significant potential to impact CV health in the PAD and CLI population through reduction of LDL down to very low levels,” he said. “However, there are cost limitations, though the recently announced price reduction for evolocumab may help address those.”

PAGE BREAK

Role of cilostazol

Cilostazol has been used as a treatment for intermittent claudication since 1999 and has been shown to improve walking distance, J. Michael Bacharach, MD, MPH, section head of vascular medicine and peripheral vascular intervention at North Central Heart Institute and Avera Heart Hospital, Sioux Falls, South Dakota, said here.

“[Cilostazol] has been effective in some patients for intermittent claudication coupled with an exercise program,” he said. However, “there has been some controversy about how much improvement is from the drug itself and how much is from the exercise program. There is a trend showing that it may prevent restenosis in patients with below-the-knee critical limb ischemia. There is clearly a role for the drug, it is readily available and, for the most part, it has a good safety profile.” – by Erik Swain

References:

Bacharach JM. What is the Role of Cilostazol in Modern PAD Therapy? PharmacoRx: Pharmacotherapy in PAD.

Beckman J. What is the Role for P2Y12 Therapy in PAD After COMPASS? PharmacoRx: Pharmacotherapy in PAD.

Bonaca MP. Vorapaxar: Why, When, and in Whom? PharmacoRx: Pharmacotherapy in PAD.

Conrad MF. Is There a Role for Aspirin Monotherapy in PAD? PharmacoRx: Pharmacotherapy in PAD.

Menard MT. Do the FOURIER Results Mandate Usage in PAD? PharmacoRx: Pharmacotherapy in PAD. All presented at: VIVA 18; Nov. 5-8, 2018; Las Vegas.

Bonaca MP, et al. Circulation. 2017;doi:10.1161/CIRCULATIONAHA.117.032235.

Eikelboom JW, et al. N Engl J Med. 2017;doi:10.1056/NEJMoa1709118.

Morrow DA, et al. N Engl J Med. 2012;doi:10.1056/NEJMoa1200933.

Disclosures: Bacharach reports he received honoraria from Boston Scientific, Bristol-Myers Squibb, Cook Medical and W.L. Gore and Associates, has consulted for W.L. Gore and Associates and has received research funding from AstraZeneca, Bayer, Bolton Medical, Endologix, St. Jude Medical, TriVascular, Veryan/Novate and W.L. Gore and Associates. Beckman reports he has consulted for AstraZeneca, Antidote Therapeutics, Bayer, Bristol-Myers Squibb, Janssen, Merck, Novartis and Sanofi Aventis and holds equity in EMX and Janacare. Bonaca reports he has consulted for Amgen, Aralez, AstraZeneca, Bayer, Janssen, Merck and Sanofi Aventis and has received research funding from Amgen, AstraZeneca, Merck, Medimmune and Pfizer. Conrad reports he has consulted for Bard Peripheral Vascular, Endologix and Medtronic. Menard reports he has consulted for Janssen.

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