In the JournalsPerspective

Statin therapy reduces MACE, mortality in asymptomatic PAD

Patients with a low ankle-brachial index, but without clinically recognized CVD, may experience lower major adverse CV events and mortality rates while on statin therapy, according to study findings published in the Journal of the American College of Cardiology.

Rafel Ramos, MD, PhD, of the Jordi Gol Institute for Primary Care Research in Girona, Spain, and researchers categorized 5,480 patients from the Catalan primary care system’s clinical database into two groups: statins nonusers or new users (first prescription or re-prescribed after at least 6 months). All of the patients had an ankle-brachial index of 0.95 or lower and no diagnosis of CVD. The patients’ mean age was 67 years and 44% were women. Diabetes and hypertension were prevalent diagnoses in this population. The median follow-up was 3.6 years.

The primary outcomes were all-cause mortality and MACE, which included MI, cardiac revascularization and ischemic stroke. Angina and CHD were secondary outcomes.

The incidence of MACE was 19.7 events/1,000 person-years in new statin users and 24.7 events/1,000 person-years in nonusers. The rate of all-cause mortality was 24.8 in new users and 30.3 in nonusers. The HRs for MACE decreased by 20% and all-cause mortality by 19%.

According to the researchers, up to 85% of patients with asymptomatic peripheral artery disease could be identified with ankle-brachial screening. This suggests that an ankle-brachial index of 0.95 or lower may be useful in identifying good candidates for statin therapy, regardless of the lack of other risk factors, they wrote.

“Recent American College of Cardiology/American Heart Association guidelines on the treatment of blood cholesterol to reduce atherosclerotic [CV] risk in adults suggest that [ankle-brachial index] can be assessed as an additional factor to support statin therapy in patients at low 10-year [CHD] risk and with moderate LDL cholesterol blood level,” the researchers wrote.

Due to the observational design of the study, there may not be enough evidence to establish clinical recommendations, but the researchers called for randomized controlled trials to evaluate this further.

In a related editorial, Mary McGrae McDermott, MD, from Northwestern University Feinberg School of Medicine, and Michael H. Criqui, MD, MPH, from the University of California, San Diego School of Medicine, noted that “the AHA/ACC guidelines on cholesterol treatment already suggest that people with PAD should be treated with cholesterol-lowering therapy. This recommendation is not limited to people who have symptoms.”

“Widespread [ankle-brachial index] screening could be potentially useful if it identified a large number of individuals with a low [ankle-brachial index] who would otherwise not qualify for cholesterol-lowering therapy,” McDermott and Criqui wrote. “However, the results reported by Ramos et al suggest that most patients in their study qualified for statin therapy even before the [ankle-brachial index] measurement.”

Instead, McDermott and Criqui suggested the focus should be on patients with a low ankle-brachial index, but no other indications for statins. They wrote, however, that because this would be a small population, there was no justification for universal ankle-brachial index screening. – by Tracey Romero

Disclosure: Ramos reports collaborating (but not receiving a personal fee) in two projects of primary care for the Jordi Gol Institute for Primary Care Research that are funded by Amgen and AstraZeneca but unrelated to this study. Please see the full study for a list of all other authors’ relevant financial disclosures. McDermott and Criqui report no relevant disclosures.

Patients with a low ankle-brachial index, but without clinically recognized CVD, may experience lower major adverse CV events and mortality rates while on statin therapy, according to study findings published in the Journal of the American College of Cardiology.

Rafel Ramos, MD, PhD, of the Jordi Gol Institute for Primary Care Research in Girona, Spain, and researchers categorized 5,480 patients from the Catalan primary care system’s clinical database into two groups: statins nonusers or new users (first prescription or re-prescribed after at least 6 months). All of the patients had an ankle-brachial index of 0.95 or lower and no diagnosis of CVD. The patients’ mean age was 67 years and 44% were women. Diabetes and hypertension were prevalent diagnoses in this population. The median follow-up was 3.6 years.

The primary outcomes were all-cause mortality and MACE, which included MI, cardiac revascularization and ischemic stroke. Angina and CHD were secondary outcomes.

The incidence of MACE was 19.7 events/1,000 person-years in new statin users and 24.7 events/1,000 person-years in nonusers. The rate of all-cause mortality was 24.8 in new users and 30.3 in nonusers. The HRs for MACE decreased by 20% and all-cause mortality by 19%.

According to the researchers, up to 85% of patients with asymptomatic peripheral artery disease could be identified with ankle-brachial screening. This suggests that an ankle-brachial index of 0.95 or lower may be useful in identifying good candidates for statin therapy, regardless of the lack of other risk factors, they wrote.

“Recent American College of Cardiology/American Heart Association guidelines on the treatment of blood cholesterol to reduce atherosclerotic [CV] risk in adults suggest that [ankle-brachial index] can be assessed as an additional factor to support statin therapy in patients at low 10-year [CHD] risk and with moderate LDL cholesterol blood level,” the researchers wrote.

Due to the observational design of the study, there may not be enough evidence to establish clinical recommendations, but the researchers called for randomized controlled trials to evaluate this further.

In a related editorial, Mary McGrae McDermott, MD, from Northwestern University Feinberg School of Medicine, and Michael H. Criqui, MD, MPH, from the University of California, San Diego School of Medicine, noted that “the AHA/ACC guidelines on cholesterol treatment already suggest that people with PAD should be treated with cholesterol-lowering therapy. This recommendation is not limited to people who have symptoms.”

“Widespread [ankle-brachial index] screening could be potentially useful if it identified a large number of individuals with a low [ankle-brachial index] who would otherwise not qualify for cholesterol-lowering therapy,” McDermott and Criqui wrote. “However, the results reported by Ramos et al suggest that most patients in their study qualified for statin therapy even before the [ankle-brachial index] measurement.”

Instead, McDermott and Criqui suggested the focus should be on patients with a low ankle-brachial index, but no other indications for statins. They wrote, however, that because this would be a small population, there was no justification for universal ankle-brachial index screening. – by Tracey Romero

Disclosure: Ramos reports collaborating (but not receiving a personal fee) in two projects of primary care for the Jordi Gol Institute for Primary Care Research that are funded by Amgen and AstraZeneca but unrelated to this study. Please see the full study for a list of all other authors’ relevant financial disclosures. McDermott and Criqui report no relevant disclosures.

    Perspective
    Deepak L. Bhatt

    Deepak L. Bhatt

    Ankle-brachial index is easy and inexpensive and I find it has value in detecting PAD that may otherwise be overlooked in actual clinical practice. The fact that it is not typically reimbursed as a screening tool will likely limit its use. Even though these are observational data and not randomized, I believe the findings that statins reduce MACE in patients with asymptomatic PAD. In the REACH registry, we found a reduction in MACE associated with statin use and also a reduction in adverse limb events in patients with asymptomatic PAD. I think it is an excellent study. A limitation is its observational nature, though I am not sure anyone will fund a large randomized study of statins in PAD at this time, so these data may be the best we have on the topic. For the future, evaluation of PCSK9 inhibitors in PAD will be important. 

    • Deepak L. Bhatt, MD, MPH
    • CARDIOLOGY TODAY Editorial Board member CARDIOLOGY TODAY’s INTERVENTION Chief Medical Editor Harvard Medical School Brigham and Women’s Hospital

    Disclosures: Bhatt reports receiving research funding from Amarin, AstraZeneca, Bristol-Myers Squibb, Eisai, Ethicon, Forest Laboratories, Ischemix, Medtronic, Pfizer, Roche, Sanofi Aventis, The Medicines Company.