Importance
Even with currently available therapies and lifestyle
modifications following an ischemic stroke, there remains a substantial
residual lifetime risk of stroke recurrence and cardiovascular
morbidity. This review summarizes emerging novel therapeutic approaches
that have demonstrated signals of efficacy for prevention of
noncardioembolic stroke from phase II and phase III randomized clinical
trials (RCTs) and provides an overview of drug regimens that have had
promising results in primary stroke prevention and could be considered
for further evaluation.
Observations
After a minor acute ischemic stroke or transient ischemic
attack,
patients bear a high cardiovascular risk that is insufficiently
addressed by long-term antiplatelet treatment. The potent combination of
low-dose rivaroxaban with aspirin as an antithrombotic option for the
secondary prevention in patients with clinical atherosclerosis and a
history of previous stroke warrants further study. Two international
RCTs are currently evaluating the utility of oral factor XI inhibitors
combined with antiplatelets for secondary, noncardioembolic ischemic
stroke prevention. Aggressive lipid management with statins has been
shown to ameliorate ischemic stroke recurrence and total cardiovascular
risk. Proprotein convertase subtilisin/kexin type 9 inhibitors are drug
regimens that researchers have suggested confer additional protection
against stroke recurrence, while antisense oligonucleotide therapies
targeting lipoprotein(a) have been reported to hold great promise as a
future therapeutic strategy to decrease the residual cardiovascular risk
mediated through lipoprotein(a). Glucagon-like peptide-1 receptor
agonists are newer antidiabetic medications, recently highlighted
because of their consistently greater benefit on stroke reduction
compared with other cardiovascular outcomes.
Conclusions and Relevance
There are currently several exciting emerging opportunities in
secondary stroke prevention, with RCTs investigating novel
antithrombotic, hypolipidemic, anti-inflammatory, and antidiabetic
agents with novel mechanisms that are likely to reduce the future burden
of recurrent stroke.
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