PracticeUpdate Neurology February 2019

EDITOR’S PICKS 11

Stroke Outcomes and Anticoagulation Strategies Circulation Take-home message • This is an analysis of data from the COMPASS trial that looked at stroke outcomes in 27,395 patients with peripheral artery disease or stable coronary artery disease. The COMPASS participants were randomized to one of three anticoagulation strategies; follow-up was a mean of 23 months. The treatment groups were: aspirin 100 mg daily; rivaroxaban 5 mg twice daily; or low-dose rivaroxaban 2.5 mg twice daily and aspirin. Patients who received rivaroxaban and aspirin had significantly fewer strokes than those who received aspirin alone. The number of ischemic strokes was also significantly reduced. The number of strokes was similar in the rivaroxaban-only and aspirin-only groups. Prior stroke, systolic blood pressure at baseline, hypertension, diabetes, age, and Asian ethnicity were all independent predictors of stroke. • These findings support the use of rivaroxaban plus aspirin to reduce stroke risk in patients with stable vascular disease.

Abstract BACKGROUND Strokes were significantly reduced by the combination of rivaroxaban plus aspirin compared with aspirin in the COMPASS Trial. We present detailed analyses of stroke by type, predictors, and antithrombotic effects in key subgroups. METHODS Participants had stable coronary artery or peripheral artery disease and were randomly assigned to receive aspirin 100 mg once daily (n=9126), rivaroxaban 5 mg twice daily (n=9117) or rivaroxaban 2.5 mg twice daily plus aspirin (n=9152). Patients requiring anticoagulation, stroke within 1 month, previous lacunar stroke or intracerebral hemorrhage were excluded. RESULTS During a mean follow-up of 23 months, fewer patients had strokes in the rivaroxaban plus aspirin group than in the aspirin group (83 Take-home message • This review discusses the recent evidence in the diagnosis and man- agement of statin-associated muscle symptoms (SAMS). • The authors concluded that better management of SAMS may increase the number of patients able to ben- efit from statin therapy. Future trials are warranted to more accurately assess SAMS via a rigorous dechal- lenge–rechallenge protocol or a double-blind, placebo-controlled statin run-in study.

[0.9% per year] vs. 142 [1.6% per year], HR 0.58, 95% CI 0.44-0.76, p<0.0001). Ischemic/uncer- tain strokes were reduced by nearly half (68 [0.7% per year] vs. 132 [1.4% per year] HR 0.51, 95% CI 0.38-0.68, p<0.0001) by the combination compared with aspirin. No significant difference was noted in the occurrence of stroke in the rivaroxaban alone group compared with aspi- rin: annualized rate of 0.7% (HR 0.82, 95% CI 0.65-1.05). The occurrence of fatal and disabling stroke (mRS 3-6) was decreased by the combi- nation (32 [0.3% per year] vs. 55 [0.6% per year], HR 0.58, 95% CI 0.37-0.89, p=0.01). Independent predictors of stroke were prior stroke, hyper- tension, systolic blood pressure at baseline, age, diabetes, and Asian ethnicity. Prior stroke was the strongest predictor of incident stroke Abstract Since the first approval of lovastatin in 1987, hydroxy-methyl-glutaryl CoA (HMG CoA) reduc- tase inhibitors, or statins, have been effective and widely popular cholesterol-lowering agents with substantial benefits for the prevention and treat- ment of cardiovascular disease. Not all patients can tolerate these drugs, however, and statin intolerance is most frequently associated with a range of side effects directed toward skeletal muscle, termed statin-associated muscle symp- toms or SAMS. SAMS are particularly difficult to treat because there are no validated biomark- ers or tests that can be used to confirm patient self-reports of SAMS, and a number of patients who report SAMS have non-specific muscle pain not attributable to statin therapy. This review sum- marizes the most recent evidence related to diagnosis and management of SAMS. First, the range of skeletal muscle side effects associated

(HR 3.63, 95% CI 2.65-4.97, p<0.0001) and was associated with a 3.4% per year rate of stroke recurrence on aspirin. The effect of the com- bination compared with aspirin was consistent across subgroups with high stroke risk, includ- ing those with prior stroke. CONCLUSIONS Low-dose rivaroxaban plus aspi- rin is an important new antithrombotic option for primary and secondary stroke prevention in patients with clinical atherosclerosis. Stroke Outcomes in the Cardiovascular Out- coMes for People Using Anticoagulation StrategieS (COMPASS) Trial. Circulation 2019 Jan 22;[EPub Ahead of Print], M Sharma, RG Hart, SJ Connolly, et al. www.practiceupdate.com/c/79091

Statin-Associated Muscle Disease Neurotherapeutics

with statin therapy is described. Second, data regarding the incidence and prevalence of SAMS, the most frequently experienced muscle side effect, are presented. Third, themost promis- ing new techniques to confirmdiagnosis of SAMS are explored. Finally, themost effective strategies for the clinical management of SAMS are summa- rized. Better diagnostic and treatment strategies for SAMS will increase the number of patients using these life-saving statins, thereby increas- ing statin adherence and reducing the costs of avoidable cardiovascular events. Statin-Associated Muscle Disease: Advances in Diagnosis and Management. Neurotherapeutics 2018 Sep 24;[EPub Ahead of Print], BA Taylor, PD Thompson. www.practiceupdate.com/c/74615

VOL. 4 • NO. 1 • 2019