Information for Professionals

Predictive Diagnostics and Personalized Treatment: Dream or Reality

The EPMA Journal

PPPM in Cardiovascular Disorders

Tailored statin approach targeting baseline risk best for preventing CAD

January 18, 2010 | Michael O'Riordan

Ann Arbor, MI - A tailored approach to statin therapy, where a moderate- or high-dose statin is prescribed depending on the patient's overall cardiovascular risk, is more efficient than the traditional treat-to-target approach, preventing more coronary artery disease events and treating fewer patients with high-dose statins, new research shows [1].

"The idea is that instead of lumping people in large categories and making blanket decisions, we should take each person's risk/benefit and try to calculate it the best we can," said lead investigator Dr Rodney Hayward (University of Michigan, Ann Arbor). "Cholesterol is part of that, but the overall heart-attack risk is much more important."

Hayward said that in contrast to the standard strategy of treating LDL-cholesterol levels to target—the approach that is the basis of the National Cholesterol Education Program (NCEP) III guidelines—the tailored treatment approach incorporates the patient's overall risk of coronary artery disease when a physician is selecting either a moderate-dose or high-dose statin for treatment. In this way, LDL-cholesterol levels are used in conjunction with other risk factors to assess the patient's expected benefit from treatment.

"When we give one risk factor, like LDL cholesterol, so much more weight over the other risk factors, then we're not calculating the risk accurately," said Hayward. "We end up undertreating people with low LDL-cholesterol levels who might be at high cardiovascular risk and overtreating people with high LDL-cholesterol levels who don't necessarily have a high risk of cardiovascular disease."

The study is published in the January 19, 2010 issue of the Annals of Internal Medicine.

Tailored approach more efficient

In this simulated model of the population-level effects of treatment, the researchers compared the tailored treatment strategy with the standard and intensive NCEP III recommendations. Under the intensive NCEP III approach, statin therapy is intensified when listed as optional in the clinical guidelines. With the tailored treatment approach, all patients with a 5% to 15% risk of coronary artery disease received simvastatin 40 mg, considered a moderately potent statin, and those with a risk exceeding 15% were treated with atorvastatin 40 mg. Using data from National Health and Nutrition Examination Survey (NHANES, 1988-1994), the analysis was restricted to people 30 to 75 years old with no history of MI or stroke.

Compared with the standard NCEP recommendations, the intensive approach treated 15 million more people with statin therapy but resulted in 570 000 quality-adjusted life-years (QALY) saved. A strategy using the tailored approach treated approximately the same number of patients as the intensive NCEP strategy and saved more than half a million QALYs. Even under hypothetical base-case scenarios favoring the guideline-style approach to treatment, "tailored treatment was more efficient (with greater benefit per person treated) and produced more benefit across the American population than any of the variations of the NCEP III approaches," report the researchers.

Adults aged 30 to 75 years who received treatment

Outcomes prevented per five years of treatment

To heartwire, Hayward said that LDL cholesterol alone explains just 9% of an individual's risk of cardiovascular events, and that the guidelines, as well as the clinicians who follow them, do not pay sufficient attention to the remaining 91%. He added that LDL cholesterol is a multiplier of risk: not that important for individuals at low baseline risk, but critically important for those at higher risk for cardiovascular events.
"There are many people who benefit from high-dose, high-potency statins, but what should determine treatment is whether or not they are at very high risk at baseline," he said. "If the patient has a high overall risk, whether it's due to smoking, blood pressure, diabetes, family history, or low-HDL syndrome, then all of these things suggest benefit from a high-dose statin. If you just pay attention to LDL, then you're going to undertreat some of these individuals. Similarly, if a patient doesn't have any of those risk factors, then an LDL-cholesterol level of 160 [mg/dL] is a trivial risk factor."
In terms of practice, as well as the guidelines, Hayward said a shift in philosophy is needed to get doctors thinking more about baseline risk and less about single numbers, like LDL cholesterol. "Even though the evidence has accumulated over the past 15 years, we continue to go along with the old way of doing it," he said.

Source
1.        Hayward RA, Krumholz HM, Zulman DM, et al. Optimizing statin treatment for primary prevention of coronary artery disease. Ann Intern Med 2010; 152:69-77.