Download Antihypertensive Medications Prescribed at Discharge After

Antihypertensive Medications Prescribed at Discharge After
an Acute Ischemic Cerebrovascular Event
Bruce Ovbiagele, MD; Nancy K. Hills, PhD, MBA; Jeffrey L. Saver, MD;
S. Claiborne Johnston, MD, PhD; for the CASPR Investigators
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Background and Purpose—Hypertension is poorly controlled in stroke survivors, thereby placing them at increased risk
for recurrent events. Clinical trial evidence suggests that antihypertensive treatment may be beneficial for stroke
prevention in hypertensive and normotensive stroke patients. We aimed to evaluate the discharge antihypertensive
prescription patterns in patients hospitalized for an ischemic cerebrovascular event and to determine factors associated
with treatment utilization.
Methods—We analyzed patients diagnosed with ischemic stroke or transient ischemic attack (TIA) in the California Acute
Stroke Prototype Registry (CASPR). We used generalized estimating equations to identify factors independently
associated with receiving antihypertensives at the time of hospital discharge.
Results—Data were collected on 764 consecutive patients with ischemic stroke or TIA encountered at 11 hospitals
representative of facilities in the state of California. Overall, the rate of discharge with a prescription for any
antihypertensive in the CASPR cohort was 69.4%. Hospital-specific rates were heterogeneous (P⫽0.04), varying from
55% to 100%. In multivariate analysis, independent predictors of prescription for antihypertensive medication at
discharge were a history of hypertension (P⬍0.0001), diabetes (P⫽0.0009), and older age.
Conclusions—About two-thirds of patients hospitalized with acute ischemic cerebrovascular events are discharged from
the hospital on ⱖ1 antihypertensive medication. However, there is great variability in prescription rates between
hospitals and considerable room for improvement. (Stroke. 2005;36:1944-1947.)
Key Words: hypertension 䡲 secondary prevention 䡲 stroke
H
ypertension is a potent yet modifiable risk factor for
recurrent stroke,1 and the use of antihypertensive treatment has been shown to reduce this risk substantially.2– 4
Nonetheless, blood pressure is poorly controlled among
individuals who have experienced a previous stroke.5 Indeed,
with recent community-based data revealing a high early risk
of secondary stroke6,7 and evidence indicating the presence of
hypertension at the time of hospital discharge as a predictor of
such risk,8 there is a need to improve antihypertensive
treatment rates in stroke survivors, including those who are
normotensive.4
A potential bridge for the antihypertensive knowledge–
treatment divide could be the systematic and appropriate
prescription of antihypertensives before the patient leaves the
hospital or after admission for an acute ischemic stroke or
transient ischemic attack (TIA).9 This strategy is attractive
because it can be safe,10 studies suggest that in-hospital
behavior strongly influences postdischarge community practice,11 and moderate reductions in blood pressure during the
first week after hospital admission have been associated with
improved short-term functional outcome in patients with
acute ischemic stroke.12 However, no previous study has
analyzed the frequency and patterns of discharge prescription
for antihypertensives in patients with ischemic stroke or TIA.
In a cohort study derived from representative Californian
hospitals, we evaluated the frequency and patterns of discharge antihypertensive utilization in a large, multicenter
cohort of hospitalized stroke and TIA patients and assessed
the impact of recent national hypertensive guidelines and
clinical trial evidence on discharge prescription behavior.
Patients and Methods
Data from the California Acute Stroke Prototype Registry (CASPR)
were analyzed. CASPR collected data prospectively on acute stroke
care in individuals with a diagnosis of suspected stroke or TIA in 11
hospitals in 5 major population regions of California from November
1, 2002, through January 31, 2003, and from November 1, 2003,
through January 31, 2004. The CASPR study methods have been
described previously.13 Human subject review boards at each participating center approved CASPR.
For these analyses, we included all patients with a discharge
diagnosis of ischemic stroke or TIA who were admitted during either
time period. We first examined rates of antihypertensive use among
hospitals to determine whether intrahospital variability existed at a
Received April 16, 2005; accepted May 30, 2005.
From the Stroke Center and Department of Neurology (B.O., J.L.S.), UCLA Medical Center, Los Angeles, Calif; Department of Neurology (B.O.,
J.L.S.), Olive View—UCLA Medical Center, Los Angeles, Calif; and Department of Neurology (N.K.H., S.C.J.), University of California, San Francisco.
Correspondence to Bruce Ovbiagele, MD, Stroke Center and Department of Neurology, University of California at Los Angeles, 710 Westwood Plaza,
Los Angeles, CA 90095. E-mail [email protected]
© 2005 American Heart Association, Inc.
Stroke is available at http://www.strokeaha.org
DOI: 10.1161/01.STR.0000177522.80092.b7
1944
Ovbiagele et al
Antihypertensive Prescription After Ischemic Stroke
significant level. We identified the rates of use of different classes of
medication categorizing antihypertensives into the following groups:
angiotensin-converting enzyme inhibitors (ACEIs), ␤-adrenergic
blocking agents, calcium channel blockers, angiotensin receptor
blockers, diuretics, and “other” antihypertensives, including centrally acting adrenergics, peripherally acting antiadrenergics, and
vasodilators. We then examined characteristics potentially associated
with receipt of any antihypertensive medication at discharge in the
overall cohort. Because this analysis could potentially reflect risk
factors for hypertension as well as predictors of treatment with
antihypertensive medications, we also analyzed patients with and
without a history of hypertension separately.
Statistical Analysis
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The ␹2 test for homogeneity was used to evaluate whether or not the
hospitals were homogeneous with respect to the proportion of
patients treated with antihypertensive medications. Because a significant difference in treatment rates was observed, generalized estimating equations were used for univariate and multivariate analyses
to account for within-hospital and between-hospital variances. Variables significant at the ␣⫽0.05 level in univariate analysis were
included in multivariate analysis. SAS (version 8e; SAS Institute)
was used for all statistical analysis.
Results
Overall, 764 patients were diagnosed with either ischemic
stroke or TIA at the 11 CASPR hospitals. Subjects in the
overall cohort were 53.4% women, 55.4% white, 9.9% black,
with an average age of 70.4 (⫾15.4) years.
Among these, 530 patients (69.4%) received a discharge
prescription for any antihypertensive. However, rates among
hospitals were heterogeneous (P⫽0.04), ranging from a low
of 55% to a high of 100%. Across the entire cohort, 17 (2.2%)
were discharged on ⱖ4 antihypertensive agents, 60 (7.9%) on
3, 177 (23.2%) on 2, and 276 (36.1%) on 1.
Factors associated in univariate analysis with receipt of
antihypertensives at discharge included older age, diagnosis
of ischemic stroke (versus TIA), history of coronary artery
disease, history of congestive heart failure, history of hypertension, history of diabetes, and history of atrial fibrillation
(Table). Patients who received tissue plasminogen activator
who were ambulatory at discharge or who were discharged
home were less likely to receive antihypertensives (Table). In
multivariate analysis, history of hypertension, history of
diabetes, and older age (those who were 73 years of age
compared with those who were ⱕ60 years of age) remained
significantly associated with receiving antihypertensives at
discharge (Table).
In separate analyses of patients without a history of
hypertension (n⫽242), 39% received antihypertensive medication at discharge. Older age and a history of atrial fibrillation were significantly associated with higher rates of antihypertensive usage at discharge among those with no
previous history of hypertension, whereas those patients with
independent ambulation were less likely to receive treatment.
Patients with a documented history of hypertension were
more likely to receive antihypertensives at discharge if they
had a history of dyslipidemia or diabetes (multivariate analysis; results not shown).
ACEIs were the most prescribed class of antihypertensives
in 303 patients (39.7% of the cohort), as seen in the Figure.
Among the 254 patients in the entire cohort taking 2 or more
antihypertensives, the most common combination regimen
1945
was ACEI and a ␤-blocker, which was used in 59 patients
(23%).
Discussion
This study shows that at representative hospitals in California, a substantial majority of individuals discharged from the
hospital after an ischemic stroke or TIA are prescribed ⱖ1
antihypertensive agents, but 1 of every 3 patients is discharged on no antihypertensive therapy. Strengths of our
study are the inclusion of multiple hospitals in different
healthcare settings and the examination of characteristics
associated with receipt of antihypertensive treatment at discharge. We found that older individuals and those with a
history of hypertension or diabetes were more likely to
receive a prescription for an antihypertensive at the time of
hospital discharge.
At first glance, the fact that a majority of hospitalized
ischemic stroke and TIA patients are discharged on ⱖ1
antihypertensive drug may seem encouraging. However, the
evidence that large numbers of stroke survivors with hypertension remain poorly controlled5,14 suggests there is either
ineffective implementation or suboptimal long-term maintenance of these therapies. Studies have shown that strategies
such as low-dose combination therapy, for instance, increase
antihypertensive treatment efficacy and reduce adverse effects, and current national guidelines specifically call for
combination therapy in stroke survivors.15–17 However, only
33.2% of patients in our study were discharged on combination antihypertensive regimens. It should also be noted that in
our study, a history of a previous stroke or TIA was not
independently associated with antihypertensive prescription.
This is despite current guidelines16 and a large secondary
stroke prevention trial,4 indicating the benefit of antihypertensive treatment for secondary stroke prevention among
those with relatively normal blood pressures. Such omission
after ⱖ2 cerebrovascular events is cause for concern because
it is inappropriate to assume that therapy will be initiated in
a timely fashion, if at all, after hospitalization for a vascular
event.11 Another finding from our study, was that although
national guidelines recommend that thiazide-type diuretics be
used in drug treatment for most hypertensive patients either
alone or combined with drugs from other classes,16 we found
a lower prescription of these medications compared with
ACEIs and ␤-blockers among our patients.
A wide variation in discharge antihypertensive treatment
rates existed among CASPR hospitals. This is perhaps not
surprising given the paucity of data and guidelines pertaining
to the appropriate timing for systematic, safe, and appropriate
antihypertensive drug initiation after an ischemic stroke or
TIA. Supporting an early rather than delayed approach to
antihypertensive agent initiation, a recent study showed that
systematic in-hospital initiation of antihypertensives before
hospital discharge after an ischemic stroke or TIA was
associated with high treatment adherence rates 3 months after
hospitalization.18 The results of the ACCESS trial, in which
improved outcomes were observed in patients receiving an
antihypertensive agent early after stroke onset, lends further
credence to the potential safety and effectiveness of this
strategy.10 The first few weeks and months after initial TIA or
1946
Stroke
September 2005
Discharge Prescription of Antihypertensive Medication After Ischemic Stroke/TIA Hospitalization
Antihypertensive at
Discharge (n⫽522)
Characteristics
n
No (%)
Univariate†
OR (95% CI)
P Value
Adjusted†
OR (95% CI)
P Value
Age in quartiles
⬍60 years
183
102 (55.7)
Reference
60–73 years
180
128 (71.1)
2.17 (1.25, 3.77)
⬍0.006
1.50 (0.85, 2.61)
0.16
73–82 years
188
144 (76.6)
2.98 (2.13, 4.16)
⬍0.0001
2.08 (1.54, 2.83)
⬍0.0001
⬎82 years
213
156 (73.2)
2.45 (1.72, 3.48)
⬍0.0001
1.46 (1.06, 2.01)
0.02
Female
408
290 (71.1)
Reference
Male
356
240 (67.4)
0.83 (0.62, 1.09)
Reference
Gender
0.18
Ethnicity
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Black
76
54 (71.1)
Reference
Other
688
476 (69.2)
1.09 (0.58, 2.04)
TIA
172
108 (63)
Reference
Ischemic stroke
592
422 (71)
1.45 (1.05, 2.00)
Year 1
516
355 (68.8)
Reference
Year 2
248
175 (70.6)
1.16 (0.70, 1.92)
0.57
Hypertension
516
431 (83.5)
8.03 (6.08, 10.6)
⬍0.0001
Stroke/TIA
277
203 (73.3)
1.36 (0.97, 1.90)
0.07
Myocardial infarction or coronary
artery disease
160
126 (78.8)
1.84 (1.31, 2.57)
0.0004
0.79
Event type
Reference
0.02
1.25 (0.74, 2.11)
0.39
7.25 (5.16, 10.2)
⬍0.0001
Treatment year
History of*
Heart failure
1.35 (0.85, 2.14)
0.2
83
67 (80.7)
2.00 (1.24, 3.23)
0.005
1.13 (0.65, 1.97)
0.67
Diabetes
199
160 (80.4)
2.17 (1.70, 2.77)
⬍0.0001
1.58 (1.21, 2.07)
0.0009
Dyslipidemia
243
188 (77.4)
1.80 (1.40, 2.30)
⬍0.0001
1.11 (0.89, 1.38)
0.38
Atrial fibrillation
125
102 (81.6)
2.19 (1.30, 3.69)
0.003
2.10 (0.97, 4.56)
0.06
No
748
523 (69.9)
Yes
16
7 (43.8)
0.35 (0.17, 0.72)
0.005
0.36 (0.11, 1.17)
0.09
Ambulation status**
400
257 (64.3)
0.60 (0.50, 0.71)
⬍0.0001
0.80 (0.50, 1.29)
0.36
Discharged home
501
333 (66.5)
0.67 (0.50, 0.91)
0.009
1.04 (0.58, 1.88)
0.89
Received tissue plasminogen activator
Reference
Reference
†All analyses performed using generalized estimating equations; *reference category consists of all patients without a history of
the given characteristic; **at discharge.
ischemic stroke is the period of highest risk for recurrence,6
making early implementation of optimal secondary prevention therapies highly desirable. Interestingly, we observed
that a substantial proportion of individuals with no history of
hypertension were discharged on antihypertensive agents.
However, this finding may reflect the influence of clinical
trial results that suggest stroke survivors with normal blood
pressures may reap benefit from antihypertensive treatment,5
or these agents may have been prescribed for other therapeutic reasons such as ␤-blocker use for cardiac rate control or
ACEIs for heart failure.
Although we collected data on history of hypertension
among CASPR subjects, we did not collect data on the
premorbid use of antihypertensive agents. We are also limited
by a paucity of information on the potential contraindications
or adverse reactions that might have prevented the use of
certain antihypertensive medications. CASPR investigators
also did not collect information on stroke/TIA mechanisms,
which could have influenced the decision to initiate antihypertensive therapies, particularly in patients with nonatherosclerotic mechanisms such as hypercoagulable states, vasculitis, etc, for their event. Finally, we have no information on
actual blood pressure measurements during hospitalization;
and although these may have impacted treatment decisions, it
has been shown that blood pressures in the majority of acute
stroke patients may not return fully to baseline levels for
several days to weeks after the index event,19 and so stroke
hospitalization blood pressures may not be the best parameter
by which to judge the treatment needs of an individual stroke
patient. Furthermore, the approach of using blood pressure
measurement as the sole determinant in the decision whether
to initiate antihypertensives for the majority of ischemic
Ovbiagele et al
Antihypertensive Prescription After Ischemic Stroke
Percentage of total patients with ischemic stroke or TIA who
were treated with each specific class of antihypertensive medication at discharge. Percentages for each group do not total to
100% because some patients received ⬎1 antihypertensive
medication.
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stroke/TIA patients may not be as relevant as thought
previously because the key to the efficacy of antihypertensive
treatment in stroke prevention may lie in blood pressure
reduction4 and perhaps additional mechanisms,20 –22 not just
treatment of diagnosed hypertension.
Acknowledgments
This study was supported by the Centers for Disease Control
(U50 CCU920271).
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Antihypertensive Medications Prescribed at Discharge After an Acute Ischemic
Cerebrovascular Event
Bruce Ovbiagele, Nancy K. Hills, Jeffrey L. Saver and S. Claiborne Johnston
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Stroke. 2005;36:1944-1947; originally published online July 28, 2005;
doi: 10.1161/01.STR.0000177522.80092.b7
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