Data Support Treating Patient Risk, Not LDL Cholesterol Targets, Paper Argues
The emergence of new data from clinical trials and the availability of an exciting new drug class should in no way change the current approach to lipid management, according to 3 physicians who published their opinion this week in the Annals of Internal Medicine.
The 2013 American College of Cardiology/American Heart Association recommendations to focus on overall cardiovascular risk rather than treat to an LDL cholesterol target should remain the current approach to care given that medication is most appropriately suited for patients at high cardiovascular risk, say the physicians.
Speaking with TCTMD, lead author Timothy Hofer, MD, of the Veterans Affairs Center for Clinical Management Research (Ann Arbor, MI), said the publication of the IMPROVE-IT trial and the approval of the new drug class of PCSK9 inhibitors led many to call for a return to treating patients to cholesterol targets, such as to less than 100 mg/dL or to less than 70 mg/dL in very high-risk patients. In contrast, the 2013 lipid guidelines did away with those targets and recommend a moderate- or high-intensity statin based a patient’s baseline 10-year risk of atherosclerotic cardiovascular disease.
“We felt it was important to point that these 2 things are not necessary connected,” said Hofer. “The fact that the lipid trials gave some evidence for the LDL hypothesis—that LDL is the causal pathway through which these medications work, which is still uncertain, but was even more uncertain before these trials—doesn’t at all change the reasoning for why you would move to a risk-based approach. It seems like that was being conflated.”
Senior author Rodney Hayward, MD, of the University of Michigan in Ann Arbor, agreed, telling TCTMD that IMPROVE-IT provides good evidence that lowering LDL cholesterol is the major pathway for reducing cardiovascular risk in patients treated with statins, ezetimibe, and possibly the PCSK9 inhibitors. However, knowing the causal pathway of any medication is “not necessarily important in determining who should be treated,” he said. Instead, when deciding on therapy, physicians should ask how much treatment reduces cardiovascular risk and what the likelihood of a clinical event is if the patient is not treated. LDL cholesterol is only important to the degree that it helps you estimate that risk, he added.
Cost of PCSK9 Inhibitors Amplified Talk About Lipid Targets
IMPROVE-IT, a large cardiovascular outcomes trial, showed that adding ezetimibe (Zetia, Merck/Schering Plough) to statin therapy in post-ACS patients reduced the risk of cardiovascular events 6.4% compared with statins alone. The new PCSK9 inhibitors alirocumab (Praluent, Sanofi/Regeneron) and evolocumab (Repatha, Amgen)—both of which were approved by the Food and Drug Administration this past summer—significantly lower LDL cholesterol levels but there is hope they might also reduce the risk of cardiovascular events, as has been hinted at in the preliminary studies.
In August, CVS Health, a large pharmacy benefits manager, made headlines when employees of the company published a perspective in the Journal of the American Medical Association calling for the return of goal-based cholesterol targets to limit the large costs of the new PCSK9 inhibitors. Alirocumab is listed at $14,600 per year, and evolocumab costs $14,100. Other physicians have also called for a return to goal-based treatment for clinical reasons.
In response, Hofer said cost is not the best argument for why you would switch back to a goal-based approach. Like Hayward, he said that if a physician is faced with deciding on one of these expensive drugs, LDL cholesterol is just one piece of the puzzle. “You’re much better focusing on the overall risk rather than just the LDL cholesterol,” said Hofer. Clinically speaking, he noted, some patients might have high LDL cholesterol levels but be at relatively low cardiovascular risk. Other patients might have very low cholesterol levels yet be at a significantly increased risk of clinical events and would benefit from treatment.
Hayward made a similar point, telling TCTMD that LDL cholesterol provides “very little” information in identifying which patients benefit from medication. The IMPROVE-IT study, he argued, actually supports the premise of treating based on patient risk as the patients in the trial were very-high-risk patients who benefited from additional LDL lowering. For these very-high-risk patients, the “degree of LDL cholesterol elevation has little importance,” according to the authors.
Hofer TP, Sussman JB, Hayward RA. New studies do not challenge the American College of Cardiology/American Heart Association lipid guidelines. Ann Intern Med. 2016;Epub ahead of print.
- IMPROVE-IT Published: Hotly Debated Ezetimibe Helpful When Added to Statin Therapy
- ACC, AHA Risk-Based Approach Remains Best Method for Statin Allocation in Primary Prevention
- USPSTF Issues Preliminary Recommendations on Statin Use in Primary Prevention
- Hofer reports no conflicts of interest.
- Sussman reports receiving grants from US Department of Veterans Affairs.
- Hayward reports receiving grants from the National Institutes of Health and Veterans Affairs.