A roundup of breaking cardiology news

Cardiology Review® Online, February 2006, Volume 23, Issue 2

New AHA/ACC guidelines promote early detection, treatment of PAD

New guidelines for the management of patients with peripheral arterial disease (PAD) emphasize early detection and treatment to optimize outcomes. Comprehensive risk assessment in­cludes the use of ankle-brachial index (ABI), magnetic resonance angiography (MRA), and computed tomography angiography (CTA). Depending on the findings of these tests, some of the recommended treatments include statins, antiplatelet therapy, and cilostazol.

The guidelines were released by the American College of Cardiology (ACC) and the American Heart Association (AHA) and were developed in collaboration with and approved by the American Association for Vascular Surgery/Society for Vascular Sur­gery, the Society for Cardiovascular Angiography and Interventions, the Society of In­terventional Radiology, the Society for Vascular Medicine and Biology, and the ACC/AHA Task Force on Practice Guidelines.

The full text of the PAD guidelines will be published online at

and

An executive summary of the guidelines will be published in the Journal of the American College of Cardiology and Circulation.

www.acc.orgwww.heart.org.

“We’re saying to physicians for the first time, ‘Don’t wait for the patient to complain to you about symptoms that they may not appreciate as hallmark signs of poor health,” Alan T. Hirsh, MD, chairman of the writing committee, said in a prepared statement. “Ask specific questions to define high-risk groups, and initiate early therapy to maintain functional independence and decrease the risk of heart attack, stroke, and death.”

A driving force behind the guidelines was recognition that a wide range of physicians treat PAD, and each brings a different set of tools and knowledge to the task, depending on background and training, according to Dr Hirsh, associate professor of epidemiology, medicine, and radiology at the University of Min­nesota, and director of Abbott North­western’s Vascular Center in Minneapolis.

The guidelines have been developed not just for specialists but also for primary care physicians, nurse practitioners, and physician assistants.

Among the primary recommendations in the guidelines:

• Patients at risk of lower extremity PAD should undergo a vascular review of symptoms to assess walking impairment, claudication, ischemic rest pain, and nonhealing wounds.

• Measurement of ABI should be used to identify patients with asymptomatic lower extremity PAD. Patients with symptoms of intermittent claudication should undergo a vascular physical examination, including ABI measurement.

• Antiplatelet therapy is indicated for patients with asymptomatic PAD to reduce the risk of adverse cardiovascular events.

• In patients with atherosclerotic lower extremity PAD, aspirin (75 to 325 mg/day) is recommended, with clopidogrel (75 mg/day) considered an effective alternative to reduce the risk of myocardial infarction, stroke, or vascular death.

• Treatment with statins is indicated for all patients with PAD to achieve a low-density lipoprotein cholesterol <100 mg/dL.

• Patients who undergo infrainguinal bypass grafts should be followed with resting ABIs, physical examination, and a duplex ultrasound if a venous conduit has been used.

• MRA or CTA are useful in selecting patients with lower extremity PAD as candidates for endovascular intervention or surgery.

• A program of supervised exercise training is recommended as an initial treatment for patients with intermittent claudication.

• Cilostazol (100 mg twice daily) is an effective therapy to improve symptoms and increase walking distance in pa&shy;tients with lower extremity PAD and intermittent claudication.

• In patients with claudication, endovascular procedures are indicated when disability is lifestyle-limiting and the likelihood of symptomatic improvement is reasonable. Sur&shy;gery is indicated when functional disability is significant and the patient is unresponsive to exercise or pharmacotherapy.

Mixed results with fibrate in patients with type 2 diabetes

The fibric acid derivative fenofibrate did not lower the incidence of total coronary events compared with placebo in patients with type 2 diabetes but did significantly reduce the incidence of total cardiovascular events in a study known as FIELD (Fenofibrate Intervention and Event Lowering in Diabetes), the results of which were presented at the American Heart Association’s 2005 Scientific Sessions in Dallas.

According to Anthony Keech, MD, lead investigator of FIELD, the role of fenofibrate in patients with type 2 diabetes will probably be in combination with a statin.

FIELD, which was conducted at 63 centers in Australia, New Zealand, and Finland, was the largest study to assess the effect of intervention on the risk of cardiovascular disease in patients with type 2 diabetes. It included 9795 patients with type 2 diabetes with well-controlled glucose levels who were randomized to once-daily treatment with micronized fenofibrate, 200 mg, or placebo for 5 to 7 years. None of the patients enrolled had a clear indication for lipid-modifying therapy. The vast majority of patients enrolled (n = 7664) were without prior cardiovascular disease and 2131 had at least 1 manifestation of cardiovascular disease.

Fenofibrate reduced the risk of total coronary events (a composite of myo&shy;cardial infarction and coronary death) by 11% compared with placebo, but this difference did not achieve statistical significance (P = .16).

Confounding the interpretation, the investigators discovered that significantly more patients randomized to placebo had begun statin therapy than patients allocated to fenofibrate (P = .16). After adjustment for this new lipid-lowering therapy, fenofibrate reduced the risk of coronary heart disease events by 19% (P = .01) and of total cardiovascular disease events by 15% (P = .004).

Other secondary endpoints favored the use of fenofibrate, including an 11% reduction in total cardiovascular events (cardiovascular death, heart attack, stroke, coronary and carotid revascularization) (P = .035), and a 21% reduction in coronary revascularization (P = .003).

There was a beneficial treatment ef&shy;fect on microvascular endpoints, specifically on progression of albuminuria and the need for laser treatments for retinopathy. Progression to albuminuria occurred in 466 (10%) patients as&shy;signed to fenofibrate and 539 (11%) as&shy;signed to placebo (P = .002). Twenty-one placebo patients and 16 fenofibrate pa&shy;tients required dialysis during the study.

One or more retinal laser treatments were necessary in 3.6% of the fenofibrate group and 5.2% of the placebo group (P < .001), representing a 30% risk reduction.

FIELD is the first large-scale clinical study to show that a lipid-modifying agent can reduce the risk of macrovascular and microvascular events in pa&shy;tients with type 2 diabetes.

The favorable effects of fenofibrate were observed predominantly among patients in the primary prevention group, in whom fenofibrate reduced the risk of total cardiovascular events by 19% (P < .004). “We found a clear signal of ben&shy;efit in the primary prevention group, which constituted 78% of the study group,” said Dr Keech.

The reduced risks did not translate into an improvement in survival: 7.3% of the fenofibrate group and 6.6% of the placebo group died, a nonsignificant difference.

“These results wouldn’t support choosing fenofibrate against a statin, given that statins are so well established in the setting of diabetes,” said Dr Keech, professor of medicine at the University of Sydney, Australia. “The role of the drug is likely to be additive to statin therapy.”