Is it Time for Single-Pill Combinations in Dyslipidemia?
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Abstract
Despite the availability of lipid-lowering therapies (LLTs) that are
safe and effective, the overall rate of low-density lipoprotein
cholesterol (LDL-C) control at a population level in real-life studies
is low. Higher-intensity treatment, earlier intervention, and
longer-term treatment have all been shown to improve outcomes. However,
in clinical practice, actual exposure to LLT is a product of the
duration and intensity of, and adherence to, the treatment. To increase
exposure to LLTs, the European Society of Cardiology guidelines
recommended a stepwise optimization of LLTs by increasing statin
intensity to the maximally tolerated dose, with subsequent addition of
ezetimibe and proprotein convertase subtilisin/kexin type 9 (PCSK9)
inhibitors. Evidence from randomized controlled trials performed in a
range of patients suggested that adding ezetimibe to statins rather than
doubling the statin dose resulted in significantly more patients at
LDL-C goal and significantly fewer patients discontinuing treatment
because of adverse events. In addition, data showed that combination
treatments effectively increased exposure to LLT. Despite these data and
recommendations, optimization of LLT is often limited to increasing
statin dose. Therapeutic inertia and poor treatment adherence are
significant and prevalent barriers to increasing treatment exposure.
They are known to be influenced by pill burden and complexity of
treatment. Single-pill combinations provide a strategic approach that
supports the intensification of treatment without increasing pill burden
or treatment complexity. Single-pill combinations, compared with free
associations, have been shown to increase the adherence to LLT and the
percentage of patients at LDL-C goal