NEW HAVEN, CT — Inconsistent guideline recommendations for cardiovascular prevention and in particular LDL cholesterol may leave clinicians and patients scratching their heads over how best to treat high cholesterol.
In one of two viewpoint articles on the topic in the Journal of the American Medical Association August 1, 2017, Dr John Ioannidis (Stanford University, CA) notes that the emergence of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors that can dramatically lower LDL-C levels has led to debate about whether LDL-C should be a main target of treatment and about how low to drive LDL-C levels[1].
Available data, he points out, suggest the possibility that the greater the LDL-C lowering, the greater the reduction of composite cardiovascular outcomes.
"If so, should LDL-C not only be considered a risk factor to be zeroed in on but also have its levels driven toward zero? This would be equivalent to considering LDL-C analogous to smoking, whereby any smoking is deleterious and its total elimination is a worthy goal," writes Ioannidis.
On the flip side, however, this approach would differ from other risk factors such as blood glucose or blood-pressure levels, for which thresholds exist below which harms outweigh the benefits. There is no evidence regarding what it could mean to lower LDL-C toward almost undetectable levels, and there is some suggestion of an increased risk of neurocognitive harms, Ioannidis points out.
Cost is also a factor, with the current licensed PCSK9 inhibitors costing about $14,000 a year. This means that treatment of fewer than 20 million US adults with evolocumab (Repatha, Amgen) would reach $280 billion annually, which matches the entire cost for all other prescription drugs for all diseases in the US combined, Ioannidis notes.
In his view, "multiplying the cost of pharmaceutical care without any evidence for saving lives cannot be justified at this point.
"Having new agents with powerful effects on a single surrogate marker (LDL-C) and on composite end points is good news. Although these therapies may be indicated for selected subgroups of patients (for instance, as an adjunct to maximally tolerated statin therapy for patients with familial hypercholesterolemia), more evidence is needed to determine whether using this armamentarium in large-scale patient populations is worthwhile," concludes Ioannidis.
"In the meanwhile, while debate on whether zeroing in on and zeroing LDL-C levels will continue, there are other important targets, like smoking, hypertension, poor diet, or lack of exercise, for which clinicians and patients can feel fully confident about the need to intensify efforts to address them," he adds.
Shared Decision-making Key
In the companion viewpoint[2], Dr Harlan Krumholz (Yale University, New Haven, CT) says when the risks and costs of an intervention are immediate and the benefits are in the future, as is the case with lipid-lowering therapy, shared decision-making is especially important. And patients will have wide-ranging views about what amount of benefit from a prevention drug is meaningful enough to merit taking a pill every day.
Yet, despite the importance of shared decision-making, few effective tools exist to accomplish this, notes Krumholz. "In particular, there remains a need for better point-of-care algorithms that individualize estimates of risks and benefits and that could be presented in a way that would enable patients to participate actively in the decision if that were their choice," he says.
So how should clinicians address cholesterol in 2017? "Except for extreme phenotypes, the decision is about risk reduction, not cholesterol levels. The evidence-based lipid-lowering drugs seem to lower risk even if a patient's initial LDL is low; they are risk-reduction medications. Two people may choose different strategies, and both be right based on their preferences," Krumholz notes.
It's important, therefore, that clinicians not dictate treatments but help inform choices. "Different people may choose differently, and all be correct for what is important to them." Krumholz offers the following specific advice:
Orient the patient to atherosclerotic cardiovascular disease (ASCVD) risks and determine risk based on prior ASCVD events, risk calculator, or coronary calcium score.
Promote a healthful lifestyle for everyone, with attention to smoking cessation, healthful diet, regular physical activity, and optimal weight.
Discuss benefits, risks, and costs of evidence-based lipid-lowering therapy, helping patients understand what they stand to gain and what it will take to get there.
For people at highest risk, including those who have already experienced an ASCVD event, treatment with high-dose, high-intensity statins (eg, atorvastatin 80 mg/day) can best reduce risk with minimal adverse effects and cost.
For lower-risk individuals, treatment with statins provides a smaller benefit, but many will find the benefits to outweigh risks. In this case, it is prudent to begin with a lower dosage of statins (eg, atorvastatin 20 mg/day) and intensify depending on the patient's preference for greater risk reduction.
For those who have experienced an event and desire even more risk reduction, nonstatin treatment may be considered using ezetimibe first, and then, possibly, evolocumab.
For those who have a mild or moderate intolerance to statins, another statin may be tried before progressing to the evidence-based nonstatin therapies. For those with a severe reaction, the use of evidence-based nonstatins would be preferred.
In all cases, the use of medications without outcomes evidence should be avoided, especially those with safety concerns.
Physicians can consider lipid-level testing as a tool to evaluate adherence, in partnership with patients.
Best practice should involve regular reassessment of the patient's preference, medication approach, and tolerance to the medication.
The overarching goal, Krumholz concludes, is to get maximum benefit from clinical care while maintaining alignment with each patient's preferences and goals.
"The strongest treatment recommendations should be where the risk is highest, the evidence is robust, and the cost is affordable. The use of statins for higher-risk patients and the judicious use of other evidence-based options, partnership in decision-making with patients, and wise reliance on healthful lifestyles provide the best hope of success in preventing the morbidity and mortality caused by cardiovascular disease," he writes.
Ioannidis has disclosed no relevant financial relationships. Krumholz has received research grants through his institution from Medtronic, Johnson & Johnson (Janssen), and the US FDA; works under contract with the Centers for Medicare & Medicaid Services; chairs a cardiac scientific advisory board for UnitedHealth; is a participant and participant representative of the IBM Watson Health Life Sciences Board; is a member of the advisory board for Element Science and the physician advisory board for Aetna; and is the founder of Hugo, a personal health information platform.
For more from theheart.org, follow us on Twitter and Facebook.
Medscape Medical News © 2017
Cite this: Heavyweights Weigh In on Inconsistent Cholesterol Advice - Medscape - Aug 14, 2017.
Comments