Clinical Edge

Summaries of Must-Read Clinical Literature, Guidelines, and FDA Actions

Poor Response to Statins Increases Risk of CV Events

Key clinical point: Suboptimal statin response within 2 years increased risk of cardiovascular events by 6 years.

Major finding: Suboptimal responders faced a 22% increased risk of cardiovascular events.

Study details: The prospective study comprised 165,411 primary care patients followed for a mean of 6 years.

Disclosures: The authors had no relevant financial disclosures.


Weng S. et al. Heart 2019 Apr. doi: 10.1136/heartjnl-2018-314253.


Guidelines always look good on paper, but they’re only as good as their implementation, Márcio S. Bittencourt, MD, wrote in an accompanying editorial.

In the United Kingdom, the National Institute for Health and Care Excellence (NICE) guideline pinned effective statin therapy as a lowering of LDL cholesterol by at least 40%. This target aligns well with data accumulated in randomized controlled studies, but it doesn’t benefit patients unless it can be put into practice.

“An important step after a guideline publication is the assessment of its uptake among health practitioners and patients in the real world, as well as of the impact of its adherence on clinical outcomes. These analyses may not only verify its appropriateness, providing feedback for continuous improvement of recommendations, but also identify targets to optimize delivery of health to the society.”

To understand suboptimal statin response, we must understand the many possible reasons behind it – on the part of both physicians and patients.

Physicians may prefer to prescribe low-potency statins for several reasons, including unawareness of guideline recommendations, doubtfulness of better outcomes with higher potent statins or when a lower LDL is attained, and fear of adverse reactions or drug interactions, Dr. Bittencourt noted. “Moreover, doctors may be reluctant to up-titrate drugs when the treatment goals are not achieved, the so-called therapeutic inertia.”

In this study, for example, optimal responders were more likely to initially receive moderately potent statins. Suboptimal responders, on the other hand, were more likely to receive low-potency statins.

“This probably explains why baseline LDL was higher in optimal responders, indicating that higher LDL motivates the physician to be more aggressive upfront.”

Patients bring their own issues to the treatment table.

“Although an inter-individual response to statins may occur according to the genetic background, most cases where LDL response is less than expected are probably due to lack of adherence or persistence to the treatment. ... Of note, poor adherence to lipid-lowering therapy, together with low-intensity therapy, as opposed to high-intensity treatment, is associated with higher cardiovascular risk.”

Effective implementation of guidelines “has been a challenge for a long time. Both physicians and patients should be targets for approaches aiming at improving adherence to guidelines.”

For clinicians, these could include continuing medical education and simplified treatment algorithms. Patients, too, would benefit from some teaching.

“Patients and society should be educated on the scientific evidence documenting the benefits of lipid-lowering therapy, and antistatin propaganda based on pseudoscience should be strongly disavowed and demystified by health authorities.”

Dr. Bittencourt is an internist at the University Hospital San Paolo, Brazil.