1. Jim Hoehns, Pharm.D.

2. Lancet 2013;382:507-15

3. Albers G et al. Chest. 2001; 119 (suppl): 300S. Ischemic stroke 85% Hemorrhagic stroke 15% Other 5% Cryptogenic 30% Cardiogenic embolism 20% Small vessel disease “lacunes” 25% Atherosclerotic cerebrovascular disease 20%

4.  Randomized, open-label, multi-center trial  3,020 patients; mean follow-up: 3.4 years  North America, Latin America, Spain; 81 centers  Funding: NINDS  Treatment  High SBP: 130-149 mm Hg  Low SBP: <130 mm Hg  Randomization ▪ Stratified by baseline hypertensive status  Inclusion criteria:  Age ≥30 yrs  Symptomatic lacunar stroke within past 180 days ▪ MRI criteria: lesion ≤ 2.0 cm; corresponded to clinical syndrome ▪ TIAs allowed only if MRI evidence present  No surgically correctable carotid artery disease  No major risk factors for cardioembolic stroke N Engl J Med 2012;367:817-25. Starting at least 2 weeks after stroke

5.  Exclusion criteria:  History of intracerebral bleeding  Disabling stroke (modified Rankin score ≥4)  Primary outcome:  Stroke recurrence (any ischemic stroke or ICH, including subdural hematomas)  Power analysis:  Estimated 3 yr rate of recurrent stroke: 21% ▪ 90% power to detect 25% RRR with combination  Blood pressure  Managed by site PI

6. Median time from qualifying stroke until randomization: 62 days

7. 138 127 At 1 year: 75% of high BP group at goal, 65% of low BP group at goal

14.  Rate of recurrent stroke much lower than anticipated  Frequent use of statins, high adherence to antiplatelets, good BP control in both groups  Unblinded; however endpoints were adjudicated in blind fashion  Approximately 5% in either group did not attain BP goal

15.  Authors  Findings consistent with those of previous studies…support a treatment target of <130 for most patients with recent lacunar stroke  Intervention well tolerated  BP meds permanently discontinued in 17% in both groups  Patient disposition  3% lost to follow-up  15% prematurely discontinued study