From the Journals

Poor response to statins hikes risk of cardiovascular events

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Guidelines are only as good as their implementation

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.



About half of patients taking statins for hyperlipidemia don’t adequately respond, leaving them at a 22% increased risk of cardiovascular disease, compared with optimal responders.

Blister pack of generic statins RogerAshford/Thinkstock

Over 6 years, there were about 2,000 more cardiovascular events among those who failed to experience the national treatment target of at least a 40% reduction in LDL cholesterol, according to Stephen F. Weng, MD, and his colleagues. The report is in Heart.

Physicians’ choice of initial statin weighed heavily in the outcomes. Patients who ended up with an optimal response were more likely to get a more potent statin right off, while those with a poorer response were more likely to get a less-potent statin.

“This study provides ‘real world evidence’ that 50% of patients started on statins do not derive the intended therapeutic benefit from them, significantly increasing their risk of future cardiovascular disease,” wrote Dr. Weng of the University of Nottingham, England, and his colleagues. “These findings contribute to the debate on the effectiveness of statin therapy and highlight the need for personalized medicine in lipid management for patients.”

The study comprised 165,411 primary care patients who had hypercholesterolemia but were free of cardiovascular disease at baseline. Statins were prescribed with the goal of at least a 40% reduction in baseline LDL within 24 months of the start of therapy.

Patients had a mean age of 62 years, with a mean baseline LDL of 4.1 mmol/L (158 mg/dL). About 49% were women.

The primary endpoints were the number of patients who did not achieve the 40% or higher reduction in baseline LDL and the between-group risk differences in cardiovascular events (coronary heart disease, stroke or transient ischemic attack, peripheral vascular disease, cardiovascular death).

After 24 months, 51.2% of patients experienced a suboptimal LDL response, with a mean reduction of 2.1 mmol/L (81 mg/dL) compared with 3.1 mmol/L (120 mg/dL). Compared with optimal responders, these patients were significantly more likely to have received a low-potency statin (29% vs. 18%).

Incident cardiovascular events occurred in 14% of the overall group (coronary artery disease, 8%; stroke/TIA, 3%; peripheral vascular disease 1.9%; cardiovascular death, 1%). All of these outcomes were significantly more common among suboptimal responders than optimal responders.

During a mean of 6 years of follow-up, there were 22,798 cardiovascular disease events overall, with significantly more occurring in suboptimal than optimal responders (12,142 vs. 10,656). This translated to a cardiovascular disease rate of 22.6 and 19.7 per 1,000 person-years, respectively.

In a multivariate analysis controlling for age and baseline LDL level, suboptimal responders were 22% more likely to have a cardiovascular disease incident than were optimal responders.

Among suboptimal responders, every unit decrease of 1 mmol/L (39 mg/dL) conferred a significant 6% risk reduction in cardiovascular disease (odds ratio, 0.94).

The benefit was not universal, the authors pointed out. “In this group, the decreased risk remained significant for only stroke/TIA and was not significant for other constituent cardiovascular disease outcomes. However, in patients with an optimal response, an even greater protective effect of LDL reduction and future cardiovascular disease was seen [13%; OR, 0.87],” and this reduction was significant for all of the individual outcomes.

“The study also highlights the benefit of reducing LDL to optimal values, which would lead to better cardiovascular disease outcomes for patients currently on statins,” the authors concluded.

None of the authors had any relevant financial disclosures.

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

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