New Guidelines Significantly Different from AHA/ACC Document

By Brenda L. Mooney

Patrick G. O'Malley, MD, MPH

Patrick G. O’Malley, MD, MPH

SAN ANTONIO — Nearly two years ago, new joint guidelines from the American Heart Association (AHA) and the American College of Cardiology (ACC) provoked controversy by essentially recommending high-intensity statin therapy for anyone with an LDL cholesterol level of at least 190 mg/dl or with a history of atherosclerotic cardiovascular disease.1

In their recent guideline revisions, the VA and DoD opted to take a very different approach, however. Clinicians working for those agencies are advised to prescribe a moderate strength statin for secondary prevention and then titrating to a higher dosage as necessary, according to analysis published recently in Annals of Internal Medicine.2

Review authors John R. Downs, MD, of University of Texas Health Science Center in San Antonio, and Patrick G. O’Malley, MD, MPH, of Uniformed Services University of the Health Science in Bethesda, MD, said “safety concerns influenced our pharmacologic treatment strategy that recommends starting with the more conservative and safer moderate-dose statin for both primary and secondary prevention, with upward titration in secondary prevention based on shared decision-making.”

And that isn’t the only difference between the two documents.

“Further, we support the use of risk calculators to estimate risk in primary prevention populations, call for a more nuanced shared-decision approach and suggest the use of additional tests for risk prediction in a more conservative manner than the ACC/AHA advocates,” Downs and O’Malley wrote. “Laboratory testing is based on clinical need for monitoring the results of liver function tests and non-fasting lipid profiles. Lastly, our guideline group contained members with no conflict of interest.”

The two authors, who championed approval of the guidelines released in December 2014, pointed out that high-dose statins haven’t been proven to reduce major cardiovascular events because only two of five original trials cited in the AHA/ACA recommendations demonstrated greater effectiveness from the higher dosage and those differences were limited to reducing nonfatal events.

While the risk for serious adverse events related to statins is low, they argued that symptoms such as myalgia occurs more often with higher-dose statins and may lower medication adherence.

Order to Chaos

“This guideline will undoubtedly provoke criticism,” Downs and O’Malley conceded. “However, as some have suggested, we hope to have brought some ‘order to the chaos’ of clinical guidelines by providing a rigorous, simple, transparent, and high-quality guideline that providers can use to efficiently care for their patients and improve patient-centered clinical outcomes.”

Their analysis summarizes key features of the guideline in five areas:

  • elimination of treatment targets;
  • additional tests for risk prediction;
  • primary and secondary prevention; and
  • laboratory testing.

While agreeing with the AHA/ACC that treatment targets should be eliminated, the VA/DoD guidelines extended the literature review through February 2014.

“Because of the lack of direct evidence about target cholesterol goals, which can lead to physicians prescribing escalating doses of statins and combinations of drugs with higher rates of adverse effects without known benefit in outcomes, the VA/DoD recommends against the use of cholesterol levels as treatment targets,” the authors noted. “However, clear evidence shows that moderate fixed-dose statin monotherapy improves total mortality and results in fewer CVD events.”

In addition, the VA/DoD guidelines are more conservative in terms of recommending additional tests to refine risk prediction; it advises those tests only should be used only when the rationale is clear. In general, the guideline working group found that evidence is insufficient to recommend for or against CVD risk prediction tests, such as new genetic, serologic, physiologic, anatomical and psychosocial risk markers, for any patients treated by the VA or DoD.

In line with efforts to create a more collaborative treatment environment, the document states that, once a patient’s 10-year risk has been calculated, shared decision-making should be employed to determine whether the potential benefits of medications outweigh the potential harms.

“Although the decision to start statins should always be shared with patients, the VA/DoD guideline panel concluded that, for patients with a risk of 12% or greater, the benefits in CVD risk reduction substantially outweigh the risks,” Downs and O’Malley wrote. “Thus, in such patients, the guideline strongly advocates offering treatment with a moderate-dose statin. In patients at intermediate risk (10-year CVD risk of 6% to 12%), the decision to initiate therapy should be based on an individual patient assessment and is nuanced; there is uncertainty about benefit because of the limited number of trials, the tendency for risk calculators to overestimate risk and the more tenuous balance between benefit and risk.”

They added that, while the absolute benefit of statin therapy depends on the patient risk for CVD, “the potential for harm is the same regardless of CVD risk.”

Finally, the VA/DoD call for non-fasting laboratory tests, but, once a statin is initiated, routine monitoring of lipids is not recommended. “Most patients do not come to clinic visits while fasting; thus, they are required to take time away from work or family and bear the expense and bother of a second visit after fasting,” according to the guideline review. “Some patients are unwilling to fast or to return and avoid lipid testing altogether. Laboratories can be burdened by the large number of patients who present early in the morning after an overnight fast. Thus, the small gain in accuracy of a fasting lipid profile over random measurement is outweighed by these burdens.”

In another note, while six of the 15 panel members developed the AHA/ACC guidelines disclosed relationships with pharmaceutical firms who market cholesterol drug, Downs and O’Malley emphasized that the work group creating the VA/DoD guideline members with no conflicts of interest.

1 Stone NJ, Robinson J, Lichtenstein AH, Bairey Merz CN, et al. 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation. Published online before print November 12, 2013, doi: 10.1161/01.cir.0000437738.63853.7a

2 Downs JR, O’Malley PG. Management of Dyslipidemia for Cardiovascular Disease Risk Reduction: Synopsis of the 2014 U.S. Department of Veterans Affairs and U.S. Department of Defense Clinical Practice Guideline. Ann Intern Med. Published online 23 June 2015 doi:10.7326/M15-0840