Diana G. Mercurio, RPh, CDE, CDOE, CVDOE October 9, 2015

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1 Diana G. Mercurio, RPh, CDE, CDOE, CVDOE October 9, 2015

2 I do not have any significant financial relationships to disclose.

3 Primary prevention: treatment of individuals with no history of stroke Secondary prevention: treatment of individuals who have already had a stroke or TIA

4 Treatment of modifiable risk factors: HTN Diabetes Dysplipidemia Atrial fibrillation Depression Smoking cessation Weight/body fat reduction Sickle cell disease Postmenopausal HRT

A- antiaggregants (ASA, clopidogrel, extended-release dipyridamole, ticlopidine) and anticoagulation (warfarin, direct thrombin inhibitors and factor Xa inhibitors) B-Blood pressure-lowering

5 A- antiaggregants (ASA, clopidogrel, extended-release dipyridamole, ticlopidine) and anticoagulation (warfarin, direct thrombin inhibitors and factor Xa inhibitors) B-Blood pressure-lowering medications C-Cessation of cigarette smoking, cholesterol-lowering medications, carotid revascularization D-Diet E- Exercise Silver, Brian, MD, FRCPC, FAHA, FAAN Stroke Prevention overview

C-Cessation of cigarette smoking, cholesterol-lowering medications, carotid revascularization D-Diet E-

6 Define blood pressure control and choice of antihypertensive Identify advantages/disadvantages of novel anticoagulants vs. warfarin Review ACC/AHA guidelines for dysplipidemia treatment and treatment choices Identify blood glucose goals and describe new pharmacologic interventions Discuss pain after stroke and pharmacologic treatment options

warfarin Review ACC/AHA guidelines for dysplipidemia treatment and treatment choices

8 According to the AHA/ASA, which of the interventions do you think is most important for the secondary prevention of ischemic stroke? A. Treatment of atrial fibrillation B. Control of high blood pressure C. Lower cholesterol D. Carotid revascularization

ischemic stroke? A. Treatment of atrial fibrillation B.

9 AHA/ASA: Hypertension most important intervention for secondary prevention of ischemic stroke Present in approx 70% of ischemic stroke Defined as SBP >140 mm Hg or DBP > 90mm Hg 23% reduction in stroke risk found with pharmacologic therapy

70% of ischemic stroke Defined as SBP >140 mm Hg or DBP >

10 BP reduction more important than choice of agent; individualize therapy Three main classes for initial monotherapy: Thiazide diuretics (hydrochlorothiazide) ACE or ARB ( -pril, -arten) Long acting calcium channel blockers: amlodipine, felodipine, nifedipine

diuretics (hydrochlorothiazide) ACE or ARB ( -pril, -arten) Long

11 High blood pressure is asymptomatic Self-monitoring recommended Compliance with daily regimen necessary Take diuretics early in the morning Standing slowly risk of postural hypotension

12 Atrial Fibrillation 4-5 fold risk ischemic stroke Since 2010: 4 novel anticoagulants approved for stroke prevention in nonvalvular AF

13 Warfarin (Coumadin )-long history of benefit Gold Standard Effective stroke prevention in patients with AF Challenges: Food/drug interactions INR monitoring required Frequent dose changes confuse patients

with AF Challenges: Food/drug interactions INR

14 New or novel anticoagulants Direct thrombin inhibitor: dabigatran (Pradaxa ) Factor Xa inhibitors: rivaroxaban (Xarelto ) apixaban (Eliquis ) edoxaban (Savaysa )

15 Advantages: No regular monitoring No known food interactions Rates of ICH lower = or superior to warfarin in stroke prevention Disadvantages: Not recommended with prosthetic valves Effect fades rapidly after last dose No specific antidote currently Cost

prevention Disadvantages: Not recommended with prosthetic

16 Adherence!! OTC drugs and herbal supplements may affect anticoagulant activity All health care providers need to be informed

17 Adult ACC/AHA Guideline released 2013 No reliance on cholesterol measurement to select drug therapy (no LDL-C target) Guidelines identify 4 statin benefit groups

18 1. Clinical ASCVD Coronary heart disease (ACS, MI, angina, coronary revascularization) Cerebral vascular disease (ischemic stroke, TIA) Peripheral vascular disease (PAD due to atherosclerosis) 2. LDL > 190 mg/dl 3. Age with diabetes and LDL mg/dl 4. Age with LDL mg/dl and 10-year ASCVD risk > 7.5%

vascular disease (PAD due to atherosclerosis) 2. LDL > 190 mg/dl 3.

19 Statins and diabetes Can cause mild glucose elevation in predisposed individuals. Tend to unmask underlying diabetes Statins and memory Very little evidence that statins impair memory function. In fact, research suggests that statins may help preserve memory by warding off strokes. Statins and muscles Severe muscle damage is exceedingly rare. Minor aches and pains are common yet often benign.

20 DM risk for first ischemic stroke No major trials for secondary prevention of stroke specifically examined interventions for pre-diabetes or DM Treatment goals: A1c < 7% FBG mg/dl PPG <180 mg/dl

examined interventions for pre-diabetes or DM

22 DPP-4 Inhibitors Sitagliptin (Januvia ), saxagliptin (Onglyza ), linagliptin (Tradjenta ), alogliptin (Nesina ) Improve A1c without causing hypoglycemia Prevent breakdown of GLP-1 GLP-1 blood glucose No weight gain Neutral or + effect on cholesterol

23 GLP-1 Receptor agonists exenatide (Byetta, Bydureon ) albiglutide (Tanzeum ) dulaglutide (Trulicity ) liraglutide (Victoza ) Mimic action of glucagon-like peptide 1 (GLP-1) Stimulate insulin secretion in response to rising blood sugar levels after a meal Delay movement of food from stomach to small intestine

24 SGLT2 (sodium-glucose transporter 2) Inhibitors SGLT2 works in the kidney to reabsorb glucose; by blocking this action excess glucose eliminated in the urine Side effects: UTIs; postural hypotension Canaglifozin (Invokana ), dapagliflozin (Farxiga )

25 Concentrated insulins: U-300 glargine (Toujeo ) U-200 lispro (Humalog ) Inhaled insulin (Afrezza ) rapid acting used in conjunction with long-acting not recommended in smokers

26 Central Pain Syndrome (Dejerine Roussy Syndrome) Originates in brain; not in peripheral nerves Occurs in up to 12% of post stroke patients Spasticity and Contractures Shoulder pain Frozen shoulder Subluxation

27 No cure Older antidepressants ( amitriptyline) pain, but cause sleepiness, dry mouth, dizziness Cymbalta, a newer antidepressant: useful, less side effects Antiepileptic drugs affect transmission of sensory nerves most common: gabapentin and pregabalin

28 Botox Blocks action of nerves on muscle, reducing muscle contraction Reduces muscle tone Injection only useful in small muscles, e.g. hand Baclofen (Lioresal ) Blocks action of nerves on muscle, reducing muscle contraction Side effects: confusion, hallucinations, slight sedation, loss of muscle tone or coordination and weakness in unaffected muscles Tizanidine (Zanaflex ) Reduces spasticity by blocking nerve impulses Short duration of action Side effects : hypotension, dry mouth, sleepiness

29 Benzodiazepine (diazepam, clonazepam) Relax muscles and spasticity briefly Act on central nervous system Side effects: drowsiness, muscle weakness, mental impairment Dantrolene (Dantrium ) Block signals for muscle contraction, muscle tone Side effects: depression, weakness, drowsiness, N/V, dizziness, diarrhea, and rarely liver failure

30 Non-steroidal anti-inflammatory drug (NSAID) Simple analgesics (acetaminophen,hydrocodone) Steroid injection Antispasmodics Non-pharmacologic interventions

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