High Dose Statins Should be Used in Most Acute Ischemic Stroke

High Dose Statins
Should be Used in
Most Acute Ischemic
Stroke Patients
Majaz Moonis MD,FRCP, DM
Department of Neurology
UMass Memorial Medical Center

Why Use Statins Before or After AIS
Reduce the risk of recurrent stroke
Reduce Mortality
Improve Outcome of Stroke
Primary and secondary prevention of MI,
since many patients have elevated LDL
and unrecognized CAD

Statins Reduce Infarct Size
Irrespective of the etiology of ischemic
stroke, use of statins has been associated
with reduced infarct size and a more
favorable outcome 1
Clinically, greater reperfusion and better
outcomes 2
Statins given within 4 weeks of stroke onset
improve stroke outcome at 90 days
compared to subjects not given statins 3
Cardiovasc Pharmacol Ther. 2008;13(1): 72, Stroke,2011;42, Stroke:2005:1298

Statin use and relative reperfusion.
Statin Use in Associated with Better
Reperfusion and better outcomes
Patients on statins had a greater
reperfusion
and a significantly better stroke outcome
∆NIHSS 8.8 vs 4.4(p=o.28)
The statin group had significantly greater
IHD compared to those not on statins
Reperfusion correlated with better outcome
Stroke,2011;42:1307
Copyright © American Heart Association
Ford A L et al. Stroke 2011;42:1307-1313

Biffi A et al. Stroke 2011;42:1314
Meta-analysis forest plot.

Statins: RIS or Incident Stroke
HPS: In patients with IHD, Simvastatin 40mg/d
reduced all cause mortality by 23%
This was evident in all groups except those with preexisting
stroke
IHD patients without preexisting stroke benefited in
prevention of incident stroke
SPARCL: In patients without known IHD,
Atorvastatin 80mg/d reduced
RIS 16% , TIA 27%, MI 33%
Trend towards reduced severity of Non-Fatal Stroke
HPSCG(2002), Lancet 360(9362):7-22::Goldstein LB et al. Stroke 2009;40: 3526

Type of Major Vascular
Event
Simvastatin Allocated
(N=10,269)
Placebo Allocated
(N=10,267)
Nonfatal MI 357 (3.5%) 574 (5.6%)
Coronary death 587 (5.7%) 707 (6.9%)
Subtotal: major
coronary event
898 (8.7%) 1212 (11.8%)
Nonfatal stroke 366 (3.6%) 499 (4.9%)
Fatal stoke 96 (0.9%) 119 (1.2%)
Subtotal: any stroke 444 (4.3%) 585 (5.7%)
Coronary revascular 513 (5.0%) 725 (7.1%)
Noncoronary
revascular
Subtotal: any
revascular
450 (4.4%) 532 (5.2%)
939 (9.1%) 1205 (11.7%)

Cardioembolic Stroke
207 patients with IS and LDL < 100 mg/dl
Stroke Distribution: CE 40%, AS 12% , SV 14%
Statins 100, No Statins: 107
31% discharged home with a good outcome
Patients on Statins had a better outcome
OR 1.91; p=0.033
These benefits were seen in all stroke sub-types
Stead et al: J Stroke and Cerebovasc. Dis. 2009; 18:124

Why High Dose Statins ?
12,689 patients with Ischemic Stroke
Included all stroke sub-types based on ICD-9
codes
Significant reduction in mortality in statin
pretreated and post-stroke statin patients
compared to no statin use
Statins >60mg/d had better outcomes than
those< 60 mg/d
Cholesterol (TC, LDL) were not predictors
Pleotropic effects were postulated to explain
these protective effects
Flint A C et al. Stroke 2012;43:147-154

Pleiotropic Effects of Statins
Pleiotropic effects of statins are dose dependent

High Dose Statin administration early in stroke hospitalization is associated with greater
poststroke survival.
Flint A C et al. Stroke 2012;43:147-154

The North Dublin Population Stroke
Study
448 patients with acute ischemic stroke were on
statins or begun on statins < 72 hours.
Statins before or early after stroke onset resulted
in
A highly significant prestroke statin survival advantage
(OR for death 0.12, 0.19, 0.26 at 7day,90days,1year; P<
0.006)
Highly significant poststroke statins use and survival (OR
0.04; P=0.003, 0.23; P

Statins are safe for long term use
Mataanalysis of 170,000 patients from 26 RCTs of intensive Lipid
lowering therapy
Death from non vascular causes or cancer did not defer from the statin naive group
Risk of ICH did not defer between high dose vs low dose statins
Metaanalysis:66,201 patients:
Outcome ICH did not defer between statin vs nonstatin groups, statins were protective and
ICH unrelated to TC or LDL
CTTC metaanalysis:>90,000 patients: similar results
SPARCL: increased incidence of hemorrhages, but no difference
in symptomatic hemorrhage or mortality.
Predictors of ICH: HTN, previous ICH, older age, microbleeds
Risk of DM: Older women (HPS)
No association with TC or LDL lowering with high dose statins
and outcomes or bleeds
Lancet 2010;378:1670, Arch. Neurol2012 ;69:46

Statins Should be Used in Most AIS
Reduce Risk of Recurrent or Incident
ischemic stroke
Reduce risk of MI
Reduce Mortality
Improve outcome of patients with or without
ischemic heart disease
Excellent safety profile at high doses over
long periods of 5-11 years

CONCLUSIONS
Use high dose statins in most AIS
Benificts:Reduce mortality, morbidity and
improve survival by reducing RIS and MI
Monitoring for DM in older women
Caution in patients with preexisting ICH
Better control of HTN may further reduce
risk of slight excess of ICH seen in
SPARCL
A randomized trial is needed to settle the question of IHD with
history of prior stroke