BETHESDA, MD 13 Jan 2014—The recent release of new prevention guidelines for the treatment of hypercholesterolemia in adults heralds major changes in how clinicians manage drug therapy for their patients.
Within weeks of the November 12 online publication of the guidelines, Clinical Pharmacist Tracy A. Martinez of the John D. Dingell Veterans Affairs Medical Center in Detroit was implementing the new recommendations while simultaneously working to update patient care templates.
"I had a patient that I saw yesterday in my lipid clinic who came in on fenofibrate, Zetia, Crestor, and niacin," Martinez said in mid-December. "When I saw him, I stopped the niacin, the fenofibrate, and the Zetia and I said, 'Let's try the Crestor all by itself and see how we do.'"
The guidelines, developed by the American College of Cardiology and the American Heart Association in collaboration with the National Heart, Lung, and Blood Institute (NHLBI), emphasize statin therapy over other lipid-lowering treatments and eliminate past recommendations to treat patients to specific low-density-lipoprotein (LDL) cholesterol target levels.
The guidelines also replace the Framingham risk-assessment calculator, which focused on coronary heart disease, with a new tool to assess atherosclerotic cardiovascular disease (ASCVD) risk among a diverse patient population.
Martinez said most of the patients who visit her lipid clinic are considered hard to manage and are already taking a statin.
Although she doesn't expect the new recommendations to boost her caseload, she said many of her patients could see their drug regimens simplified under the new guidelines.
Deniz Yavas, a postgraduate year 2 ambulatory care pharmacy resident who has worked with Martinez, said he thinks that the new guidelines will result in more widespread statin use overall.
"In order to improve outcomes, a lot more patients need to be on statins," he said. "The benefits of preventing atherosclerosis clearly outweigh any possible side effects."
No targets. Under guidelines released in 2002 by NHLBI's Adult Treatment Panel III (ATP III), patients at high risk for cardiovascular events were generally treated with the goal of reducing their LDL cholesterol level to <100 mg/dL. The ATP III guidelines made specific recommendations for supplementing statin therapy with bile acid sequestrants, nicotinic acid, and fibric acids to achieve LDL targets.
But according to the new guidelines, there is no evidence that targeted therapy reduces the risk of ASCVD. The guidelines also state that the potential for nonstatin therapies to cause adverse events exceeds the drugs' potential risk-reduction benefits.
The guidelines identify four patient populations for whom statin therapy has been shown to reduce the risk of ASCVD: men and women with clinical ASCVD, those with an LDL cholesterol level of ≥190 mg/dL, people 40–75 years of age with diabetes and an LDL cholesterol level of 70–189 mg/dL, and people 40–75 years of age with an LDL cholesterol level of 70–189 mg/dL who do not have clinical ASCVD or diabetes but whose estimated 10-year risk of ASCVD is 7.5% or higher.
Martinez said she was initially skeptical about the new guidelines.
"But when I sat down and read them, they are very evidence based," she said. "We've all been so used to treat to target, treat to target, but when you look at the studies, there's not a single study that has treated to a target. Every study has either been either a fixed-dose statin versus placebo or a high-intensity statin versus a moderate-intensity statin."
Intensity of therapy. For most men and women with clinical ASCVD who are not currently taking a statin, the new guidelines recommend that clinicians initiate high-intensity statin therapy, meaning a drug and dosage that reduce LDL cholesterol by at least 50% from untreated baseline levels.
Patients with ASCVD who are over age 75, are intolerant to statins, or have conditions or take medications that increase the risk for statin-related adverse events should receive moderate-intensity statin therapy that reduces LDL cholesterol levels by 30–50%, according to the guidelines.
Men and women without ASCVD who are candidates for a statin should be assessed to determine whether high- or moderate-intensity therapy is the more appropriate treatment to prevent cardiovascular events.
"The data is really supportive of getting the patient on the right dose of a statin," Martinez said.
The guidelines strongly emphasize that patients should adopt a heart-healthy lifestyle and be assessed regularly for adherence to lifestyle and medication recommendations. Within 4–12 weeks after a patient starts taking a statin, a lipid panel should be ordered to assess adherence, and follow-up testing should occur every 3–12 months as clinically indicated.
For patients whose lipid levels do not fall as expected, the guidelines recommend intensifying statin therapy or considering nonstatin therapy and, in some cases, excluding secondary causes of hypercholesterolemia.
Routine monitoring of liver function is not recommended unless liver toxicity is suspected, according to the guidelines.
Redefining goals. Martinez noted that some of her patients are on high-intensity statin therapy, but their LDL cholesterol level has bottomed out at, say, 110 mg/dL.
"So I'm titrating niacin, and the patients are having side effects, and we're giving them aspirin to manage those side effects. I might put them on bile acid sequestrants, which they have to take [separately] from their other medications. It's a lot more complicated when you start adding on the additional therapies."
By eliminating the LDL cholesterol goals and nonstatin therapies, the new guidelines eliminate such complications. And simpler drug regimens, coupled with the lack of specific targets, could reduce the need for laboratory tests and eliminate some follow-up visits.
But Martinez noted that some of her patients tell her that to stay motivated, they need to visit the clinic regularly.
"So I'm just trying to say I'm going to be still checking your labs, but maybe not as often," she said. "What I want to see is that you're taking that statin, and it is lowering your LDL."
Yavas likened the elimination of LDL cholesterol goals to what happens when patients treated with warfarin are switched to an anticoagulant that does not require International Normalized Ratio assessment.
"When there's no routine monitoring, the patients have a sense of uncertainty about how they're doing," he said.
Martinez said she's exploring ways to keep her patients motivated without the hard LDL cholesterol goals.
"But I am a little worried about that, because a lot of the patients that end up in my clinic have compliance issues," she said.