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Suboptimal LDL-C response with statins common, leads to high CVD risk

Jairia Dela Cruz
16 May 2019

About half of the patients who initiate statin therapy for primary prevention of cardiovascular disease (CVD) fail to achieve optimal reduction in their low-density lipoprotein cholesterol (LDL-C) levels within 2 years, as reported in a recent study. At the heart of this is that a suboptimal response further raises the risk of developing future CVD.

“This study provides real world evidence that 50 percent of patients started on statins do not derive the intended therapeutic benefit from them, significantly increasing their risk of future CVD,” according to lead study author Ralph Kwame Akyea, a doctoral student and research associate at the University of Nottingham in UK.

Akyea and colleagues examined a large population of primary care patients (n=165,411; mean age, 62.4 years; 48.6 percent female) who were initiating statin therapy and were free of CVD at baseline. Of these, 84,609 patients (51.2 percent) showed suboptimal treatment response, defined as <40-percent reduction in baseline LDL-C levels within 24 months of initiation. [Heart 2019;doi:10.1136/heartjnl-2018-314253]

CVD events occurred in a total of 22,798 patients (13.8 percent) over a median follow-up of 6.2 years. Specifically, 8.0 percent of patients had coronary artery disease, 2.9 percent stroke/transient ischaemic attack, 1.9 percent peripheral vascular disease and 1.0 percent CVD-related death.

Compared with the group of patients who had optimal statin response, the group with suboptimal response had a higher incidence of CVD events (12,142 vs 10,656 patients). A less-than-optimal response contributed to a 22-percent increase in the risk of developing CVD (hazard ratio [HR], 1.22; 95 percent CI, 1.19–1.25; p<0.001). 

The present data highlight the cardioprotective benefit of reducing LDL-C to optimal values in addition to the fact that statins elicit varied cholesterol responses, Akyea pointed out.

“Based on evidence from clinical trial settings, the response of patients to statins varies widely, with reductions in LDL-C values ... ranging from 5–70 percent,” he added. “Currently, there is no management strategy in clinical practice which takes into account patient variations in LDL-C response, and no guidelines for predictive screening before commencement of statin therapy.” [Lipid Insights 2016;9:13-29]

Akyea underscored a need for validated clinical decision tools that can predict cholesterol response to statins, or to other drugs, with interventions to help clinicians tailor and optimize treatments for individual patients.

Strict guideline implementation needed

In a linked editorial, Drs Márcio Bittencourt and Fernando Cesena from Sao Paulo, Brazil, opined that suboptimal LDL-C response to statins may involve both physician- and patient-related issues. [Heart 2019;doi:10.1136/heartjnl-2019-314723]

On the one hand, physicians may prefer to prescribe low-dose statins due mainly to unawareness of guideline recommendation, uncertainty regarding attainment of better outcomes with higher doses, and fear of adverse reactions or drug interactions. There is also the possibility of the so-called therapeutic inertia or the reluctance to uptitrate drugs when treatment goals are not achieved.

On the other, lack of adherence or persistence to the treatment by patients yields, unsurprisingly, suboptimal results, although an interindividual response to statins may also occur according to the genetic background.

“Both physicians and patients should [therefore] be targets for approaches aiming at improving adherence to guidelines. For clinicians, these strategies should include serious programmes of continuing medical education and the development of in-house protocols,” said Bittencourt and Cesena.

“[Meanwhile], 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,” they added.

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Most Read Articles
Stephen Padilla, 04 Sep 2019
Use of sodium glucose cotransporter 2 (SGLT2), as compared with dipeptidyl peptidase 4 (DPP4), inhibitors appears to reduce the risk of heart failure and any-cause death without major cardiovascular events in the primary intention-to-treat analysis, according to a study.
Pearl Toh, 04 Sep 2019
More intensive LDL-lowering by adding ezetimibe to simvastatin in elderly individuals aged ≥75 years significantly reduced recurrent cardiovascular (CV) events without raising safety issues compared with simvastatin alone, a secondary analysis of the IMPROVE-IT* has shown.
27 Aug 2019
A once-weekly regimen of 25 mg trelagliptin is effective and safe for type 2 diabetes mellitus (T2DM) patients with severe renal impairment or end-stage renal disease, reports a new study.
Elvira Manzano, Yesterday

The US Preventive Services Task Force (USPSTF), in an update of its 2013 recommendations, called on clinicians to offer risk-reducing medications to women who are at increased risk for breast cancer but at low risk for adverse effects.