CLINICAL PHARMACOLOGY
Mechanism Of Action
Angiotensin II [formed from angiotensin I in a reaction
catalyzed by angiotensin converting enzyme (ACE, kininase II)] is a potent
vasoconstrictor, the primary vasoactive hormone of the renin-angiotensin
system, and an important component in the pathophysiology of hypertension. It
also stimulates aldosterone secretion by the adrenal cortex. Losartan and its
principal active metabolite block the vasoconstrictor and aldosterone-secreting
effects of angiotensin II by selectively blocking the binding of angiotensin II
to the AT1 receptor found in many tissues, (e.g., vascular smooth muscle,
adrenal gland). There is also an AT2 receptor found in many tissues but it is
not known to be associated with cardiovascular homeostasis. Neither losartan
nor its principal active metabolite exhibits any partial agonist activity at
the AT1 receptor, and both have much greater affinity (about 1000-fold) for the
AT1 receptor than for the AT2 receptor. In vitro binding studies indicate that
losartan is a reversible, competitive inhibitor of the AT1 receptor. The active
metabolite is 10 to 40 times more potent by weight than losartan and appears to
be a reversible, non-competitive inhibitor of the AT1 receptor.
Neither losartan nor its active metabolite inhibits ACE
(kininase II, the enzyme that converts angiotensin I to angiotensin II and
degrades bradykinin), nor do they bind to or block other hormone receptors or
ion channels known to be important in cardiovascular regulation.
Pharmacodynamics
Losartan inhibits the pressor effect of angiotensin II
(as well as angiotensin I) infusions. A dose of 100 mg inhibits the pressor
effect by about 85% at peak with 25-40% inhibition persisting for 24 hours.
Removal of the negative feedback of angiotensin II causes a doubling to
tripling in plasma renin activity and consequent rise in angiotensin II plasma
concentration in hypertensive patients. Losartan does not affect the response
to bradykinin, whereas ACE inhibitors increase the response to bradykinin.
Aldosterone plasma concentrations fall following losartan administration. In
spite of the effect of losartan on aldosterone secretion, very little effect on
serum potassium was observed.
The effect of losartan is substantially present within
one week but in some studies the maximal effect occurred in 3-6 weeks. In
long-term follow-up studies (without placebo control) the effect of losartan appeared
to be maintained for up to a year. There is no apparent rebound effect after
abrupt withdrawal of losartan. There was essentially no change in average heart
rate in losartan-treated patients in controlled trials.
Pharmacokinetics
Absorption
Following oral administration, losartan is well absorbed
and undergoes substantial first-pass metabolism. The systemic bioavailability
of losartan is approximately 33%. Mean peak concentrations of losartan and its
active metabolite are reached in 1 hour and in 3-4 hours, respectively. While
maximum plasma concentrations of losartan and its active metabolite are
approximately equal, the AUC (area under the curve) of the metabolite is about
4 times as great as that of losartan. A meal slows absorption of losartan and
decreases its Cmax but has only minor effects on losartan AUC or on the AUC of
the metabolite (~10% decrease). The pharmacokinetics of losartan and its active
metabolite are linear with oral losartan doses up to 200 mg and do not change
over time.
Distribution
The volume of distribution of losartan and the active
metabolite is about 34 liters and 12 liters, respectively. Both losartan and
its active metabolite are highly bound to plasma proteins, primarily albumin,
with plasma free fractions of 1.3% and 0.2%, respectively. Plasma protein
binding is constant over the concentration range achieved with recommended
doses. Studies in rats indicate that losartan crosses the blood-brain barrier
poorly, if at all.
Metabolism
Losartan is an orally active agent that undergoes
substantial first-pass metabolism by cytochrome P450 enzymes. It is converted,
in part, to an active carboxylic acid metabolite that is responsible for most
of the angiotensin II receptor antagonism that follows losartan treatment.
About 14% of an orally-administered dose of losartan is converted to the active
metabolite. In addition to the active carboxylic acid metabolite, several
inactive metabolites are formed. In vitro studies indicate that cytochrome P450
2C9 and 3A4 are involved in the biotransformation of losartan to its
metabolites.
Elimination
Total plasma clearance of losartan and the active
metabolite is about 600 mL/min and 50 mL/min, respectively, with renal
clearance of about 75 mL/min and 25 mL/min, respectively. The terminal
half-life of losartan is about 2 hours and of the metabolite is about 6-9
hours. After single doses of losartan administered orally, about 4% of the dose
is excreted unchanged in the urine and about 6% is excreted in urine as active
metabolite. Biliary excretion contributes to the elimination of losartan and
its metabolites. Following oral 14C-labeled losartan, about 35% of
radioactivity is recovered in the urine and about 60% in the feces. Following
an intravenous dose of 14C-labeled losartan, about 45% of radioactivity is
recovered in the urine and 50% in the feces. Neither losartan nor its
metabolite accumulates in plasma upon repeated once-daily dosing.
Special Populations
Pediatric
Pharmacokinetic parameters after
multiple doses of losartan (average dose 0.7 mg/kg, range 0.36 to 0.97 mg/kg)
as a tablet to 25 hypertensive patients aged 6 to 16 years are shown in Table 4
below. Pharmacokinetics of losartan and its active metabolite were generally
similar across the studied age groups and similar to historical pharmacokinetic
data in adults. The principal pharmacokinetic parameters in adults and children
are shown in the table below.
Table 2: Pharmacokinetic Parameters in Hypertensive
Adults and Children Age 6-16 Following Multiple Dosing
|
Adults given 50 mg once daily for 7 days
N=12 |
Age 6-16 given 0.7 mg/kg once daily for 7 days
N=25 |
Parent |
Active Metabolite |
Parent |
Active Metabolite |
AUC0-24 (ng•hr/mL)* |
442 ± 173 |
1685 ± 452 |
368± 169 |
1866 ± 1076 |
Cmax (ng/mL)* |
224 ± 82 |
212 ± 73 |
141 ± 88 |
222 ± 127 |
T½(h)† |
2.1 ± 0.70 |
7.4 ± 2.4 |
2.3 ± 0.8 |
5.6 ± 1.2 |
TPEAK (h)‡ |
0.9 |
3.5 |
2.0 |
4.1 |
CLREN (mL/min)* |
56 ± 23 |
20 ± 3 |
53 ± 33 |
17 ± 8 |
* Mean ± standard deviation
† Harmonic mean and standard deviation
‡ Median |
The bioavailability of the suspension formulation was
compared with losartan tablets in healthy adults. The suspension and tablet are
similar in their bioavailability with respect to both losartan and the active metabolite
[see DOSAGE AND ADMINISTRATION].
Geriatric And Gender
Losartan pharmacokinetics have been investigated in the elderly (65-75 years) and in both genders. Plasma
concentrations of losartan and its active metabolite are similar in elderly and
young hypertensives. Plasma concentrations of losartan were about twice as high
in female hypertensives as male hypertensives, but concentrations of the active
metabolite were similar in males and females. No dosage adjustment is necessary
[see DOSAGE AND ADMINISTRATION].
Race
Pharmacokinetic differences due to race have
not been studied [see Use In Specific Populations].
Renal Insufficiency
Following oral administration, plasma concentrations and AUCs of losartan and its active
metabolite are increased by 50-90% in patients with mild (creatinine clearance
of 50 to 74 mL/min) or moderate (creatinine clearance 30 to 49 mL/min) renal
insufficiency. In this study, renal clearance was reduced by 55-85% for both
losartan and its active metabolite in patients with mild or moderate renal insufficiency.
Neither losartan nor its active metabolite can be removed by hemodialysis [see WARNINGS AND PRECAUTIONS and Use In Specific Populations].
Hepatic Insufficiency
Following oral administration in patients with mild to moderate alcoholic cirrhosis of the
liver, plasma concentrations of losartan and its active metabolite were,
respectively, 5-times and about 1.7-times those in young male volunteers.
Compared to normal subjects the total plasma clearance of losartan in patients
with hepatic insufficiency was about 50% lower and the oral bioavailability was
about doubled. Use a starting dose of 25 mg for patients with mild to moderate
hepatic impairment. COZAAR has not been studied in patients with severe hepatic
impairment [see DOSAGE AND ADMINISTRATION and Use In Specific Populations].
Drug Interactions
No clinically significant drug interactions have been
found in studies of losartan potassium with hydrochlorothiazide, digoxin,
warfarin, cimetidine and phenobarbital. However, rifampin has been shown to
decrease the AUC of losartan and its active metabolite by 30% and 40%,
respectively. Fluconazole, an inhibitor of cytochrome P450 2C9, decreased the
AUC of the active metabolite by approximately 40%, but increased the AUC of
losartan by approximately 70% following multiple doses. Conversion of losartan
to its active metabolite after intravenous administration is not affected by
ketoconazole, an inhibitor of P450 3A4. The AUC of active metabolite following
oral losartan was not affected by erythromycin, an inhibitor of P450 3A4, but
the AUC of losartan was increased by 30%.
The pharmacodynamic consequences of concomitant use of
losartan and inhibitors of P450 2C9 have not been examined. Subjects who do not
metabolize losartan to active metabolite have been shown to have a specific,
rare defect in cytochrome P450 2C9. These data suggest that the conversion of
losartan to its active metabolite is mediated primarily by P450 2C9 and not
P450 3A4.
Clinical Studies
Hypertension
Adult Hypertension
The antihypertensive effects of COZAAR were demonstrated
principally in 4 placebo-controlled, 6- to 12- week trials of dosages from 10
to 150 mg per day in patients with baseline diastolic blood pressures of 95-115.
The studies allowed comparisons of two doses (50-100 mg/day) as once-daily or
twice-daily regimens, comparisons of peak and trough effects, and comparisons
of response by gender, age, and race. Three additional studies examined the
antihypertensive effects of losartan and hydrochlorothiazide in combination.
The 4 studies of losartan monotherapy included a total of
1075 patients randomized to several doses of losartan and 334 to placebo. The
10- and 25-mg doses produced some effect at peak (6 hours after dosing) but
small and inconsistent trough (24 hour) responses. Doses of 50, 100 and 150 mg
once daily gave statistically significant systolic/diastolic mean decreases in
blood pressure, compared to placebo in the range of 5.5-10.5/3.5-7.5 mmHg, with
the 150-mg dose giving no greater effect than 50-100 mg. Twice-daily dosing at
50-100 mg/day gave consistently larger trough responses than once-daily dosing
at the same total dose. Peak (6 hour) effects were uniformly, but moderately,
larger than trough effects, with the trough-to-peak ratio for systolic and
diastolic responses 50-95% and 60-90%, respectively. Addition of a low dose of
hydrochlorothiazide (12.5 mg) to losartan 50 mg once daily resulted in
placeboadjusted blood pressure reductions of 15.5/9.2 mmHg.
Analysis of age, gender, and race subgroups of patients
showed that men and women, and patients over and under 65, had generally similar
responses. COZAAR was effective in reducing blood pressure regardless of race,
although the effect was somewhat less in Black patients (usually a low-renin population).
Pediatric Hypertension
The antihypertensive effect of losartan was studied in
one trial enrolling 177 hypertensive pediatric patients aged 6 to 16 years old.
Children who weighed <50 kg received 2.5, 25 or 50 mg of losartan daily and
patients who weighed ≥50 kg received 5, 50 or 100 mg of losartan daily.
Children in the lowest dose group were given losartan in a suspension
formulation [see DOSAGE AND ADMINISTRATION]. The majority of the
children had hypertension associated with renal and urogenital disease. The
sitting diastolic blood pressure (SiDBP) on entry into the study was higher
than the 95th percentile level for the patient's age, gender, and height. At
the end of three weeks, losartan reduced systolic and diastolic blood pressure,
measured at trough, in a dose-dependent manner. Overall, the two higher doses
(25 to 50 mg in patients <50 kg; 50 to 100 mg in patients ≥50 kg)
reduced diastolic blood pressure by 5 to 6 mmHg more than the lowest dose used
(2.5 mg in patients <50 kg; 5 mg in patients ≥50 kg). The lowest
dose, corresponding to an average daily dose of 0.07 mg/kg, did not appear to
offer consistent antihypertensive efficacy. When patients were randomized to
continue losartan at the two higher doses or to placebo after 3 weeks of
therapy, trough diastolic blood pressure rose in patients on placebo between 5
and 7 mmHg more than patients randomized to continuing losartan. When the low
dose of losartan was randomly withdrawn, the rise in trough diastolic blood
pressure was the same in patients receiving placebo and in those continuing
losartan, again suggesting that the lowest dose did not have significant
antihypertensive efficacy. Overall, no significant differences in the overall
antihypertensive effect of losartan were detected when the patients were
analyzed according to age (<, ≥12 years old) or gender. While blood
pressure was reduced in all racial subgroups examined, too few non-White
patients were enrolled to compare the dose-response of losartan in the
non-White subgroup.
Hypertensive Patients With Left Ventricular Hypertrophy
The LIFE study was a multinational, double-blind study
comparing COZAAR and atenolol in 9193 hypertensive patients with ECG-documented
left ventricular hypertrophy. Patients with myocardial infarction or stroke
within six months prior to randomization were excluded. Patients were randomized
to receive once daily COZAAR 50 mg or atenolol 50 mg. If goal blood pressure
(<140/90 mmHg) was not reached, hydrochlorothiazide (12.5 mg) was added
first and, if needed, the dose of COZAAR or atenolol was then increased to 100
mg once daily. If necessary, other antihypertensive treatments (e.g., increase in
dose of hydrochlorothiazide therapy to 25 mg or addition of other diuretic
therapy, calcium-channel blockers, alpha-blockers, or centrally acting agents,
but not ACE inhibitors, angiotensin II antagonists, or beta-blockers) were
added to the treatment regimen to reach the goal blood pressure. Of the
randomized patients, 4963 (54%) were female and 533 (6%) were Black. The mean
age was 67 with 5704 (62%) age ≥65. At baseline, 1195 (13%) had diabetes,
1326 (14%) had isolated systolic hypertension, 1469 (16%) had coronary heart
disease, and 728 (8%) had cerebrovascular disease. Baseline mean blood pressure
was 174/98 mmHg in both treatment groups. The mean length of follow-up was 4.8
years. At the end of study or at the last visit before a primary endpoint, 77%
of the group treated with COZAAR and 73% of the group treated with atenolol
were still taking study medication. Of the patients still taking study
medication, the mean doses of COZAAR and atenolol were both about 80 mg/day,
and 15% were taking atenolol or losartan as monotherapy, while 77% were also
receiving hydrochlorothiazide (at a mean dose of 20 mg/day in each group).
Blood pressure reduction measured at trough was similar for both treatment
groups but blood pressure was not measured at any other time of the day. At the
end of study or at the last visit before a primary endpoint, the mean blood
pressures were 144.1/81.3 mmHg for the group treated with COZAAR and 145.4/80.9
mmHg for the group treated with atenolol; the difference in systolic blood
pressure (SBP) of 1.3 mmHg was significant (p<0.001), while the difference
of 0.4 mmHg in diastolic blood pressure (DBP) was not significant (p=0.098).
The primary endpoint was the first occurrence of
cardiovascular death, nonfatal stroke, or nonfatal myocardial infarction.
Patients with nonfatal events remained in the trial, so that there was also an examination
of the first event of each type even if it was not the first event (e.g., a
stroke following an initial myocardial infarction would be counted in the
analysis of stroke). Treatment with COZAAR resulted in a 13% reduction
(p=0.021) in risk of the primary endpoint compared to the atenolol group (see
Figure 1 and Table 3); this difference was primarily the result of an effect on
fatal and nonfatal stroke. Treatment with COZAAR reduced the risk of stroke by
25% relative to atenolol (p=0.001) (see Figure 2 and Table 3).
Figure 1: Kaplan-Meier estimates of the primary
endpoint of time to cardiovascular death, nonfatal stroke, or nonfatal
myocardial infarction in the groups treated with COZAAR and atenolol. The Risk
Reduction is adjusted for baseline Framingham risk score and level of
electrocardiographic left ventricular hypertrophy.
Figure 2: Kaplan-Meier estimates of the time to
fatal/nonfatal stroke in the groups treated with COZAAR and atenolol. The Risk Reduction
is adjusted for baseline Framingham risk score and level of
electrocardiographic left ventricular hypertrophy.
Table 3 shows the results for the primary composite
endpoint and the individual endpoints. The primary endpoint was the first
occurrence of stroke, myocardial infarction or cardiovascular death, analyzed
using an ITT approach. The table shows the number of events for each component
in two different ways. The Components of Primary Endpoint (as a first event)
counts only the events that define the primary endpoint, while the Secondary
Endpoints count all first events of a particular type, whether or not they were
preceded by a different type of event.
Table 3: Incidence of Primary Endpoint Events
|
COZAAR |
Atenolol |
Risk Reduction† |
95% CI |
p-Value |
N (%) |
Rate* |
N (%) |
Rate* |
Primary Composite Endpoint |
508 (11) |
23.8 |
588 (13) |
27.9 |
13% |
2% to 23% |
0.021 |
Components of Primary Composite Endpoint (as a first event) |
Stroke (nonfatal) |
209 (5) |
|
286 (6) |
|
|
|
|
Myocardial infarction (nonfatal) |
174 (4) |
|
168 (4) |
|
|
|
|
Cardiovascular mortality |
125 (3) |
|
134 (3) |
|
|
|
|
Secondary Endpoints (any time in study) |
|
Stroke (fatal/nonfatal) |
232 (5) |
10.8 |
309 (7) |
14.5 |
25% |
11% to 37% |
0.001 |
Myocardial infarction (fatal/nonfatal) |
198 (4) |
9.2 |
188 (4) |
8.7 |
-7% |
-13% to 12% |
0.491 |
Cardiovascular mortality |
204 (4) |
9.2 |
234 (5) |
10.6 |
11% |
-7% to 27% |
0.206 |
Due to CHD |
125 (3) |
5.6 |
124 (3) |
5.6 |
-3% |
-32% to 20% |
0.839 |
Due to Stroke |
40 (1) |
1.8 |
62 (1) |
2.8 |
35% |
4% to 67% |
0.032 |
Other‡ |
39 (1) |
1.8 |
48 (1) |
2.2 |
16% |
-28% to 45% |
0.411 |
* Rate per 1000 patient-years of follow-up
† Adjusted for baseline Framingham risk score and level of electrocardiographic
left ventricular hypertrophy
‡ Death due to heart failure, non-coronary vascular disease, pulmonary
embolism, or a cardiovascular cause other than stroke or coronary heart disease |
Although the LIFE study favored COZAAR over atenolol with
respect to the primary endpoint (p=0.021), this result is from a single study
and, therefore, is less compelling than the difference between COZAAR and
placebo. Although not measured directly, the difference between COZAAR and
placebo is compelling because there is evidence that atenolol is itself
effective (vs. placebo) in reducing cardiovascular events, including stroke, in
hypertensive patients.
Other clinical endpoints of the LIFE study were: total
mortality, hospitalization for heart failure or angina pectoris, coronary or
peripheral revascularization procedures, and resuscitated cardiac arrest. There
were no significant differences in the rates of these endpoints between the
COZAAR and atenolol groups.
For the primary endpoint and stroke, the effects of
COZAAR in patient subgroups defined by age, gender, race and presence or
absence of isolated systolic hypertension (ISH), diabetes, and history of cardiovascular
disease (CVD) are shown in Figure 3 below. Subgroup analyses can be difficult
to interpret and it is not known whether these represent true differences or
chance effects.
Figure 3: Primary Endpoint Events† within Demographic
Subgroups
Nephropathy In Type 2 Diabetic Patients
The RENAAL study was a randomized, placebo-controlled,
double-blind, multicenter study conducted worldwide in 1513 patients with type
2 diabetes with nephropathy (defined as serum creatinine 1.3 to 3.0 mg/dL in
females or males ≤60 kg and 1.5 to 3.0 mg/dL in males >60 kg and
proteinuria [urinary albumin to creatinine ratio ≥300 mg/g]).
Patients were randomized to receive COZAAR 50 mg once
daily or placebo on a background of conventional antihypertensive therapy
excluding ACE inhibitors and angiotensin II antagonists. After one month,
investigators were instructed to titrate study drug to 100 mg once daily if the
trough blood pressure goal (140/90 mmHg) was not achieved. Overall, 72% of
patients received the 100-mg daily dose more than 50% of the time they were on
study drug. Because the study was designed to achieve equal blood pressure
control in both groups, other antihypertensive agents (diuretics,
calcium-channel blockers, alpha- or beta-blockers, and centrally acting agents)
could be added as needed in both groups. Patients were followed for a mean
duration of 3.4 years.
The study population was diverse with regard to race
(Asian 16.7%, Black 15.2%, Hispanic 18.3%, White 48.6%). Overall, 63.2% of the
patients were men, and 66.4% were under the age of 65 years. Almost all of the
patients (96.6%) had a history of hypertension, and the patients entered the
trial with a mean serum creatinine of 1.9 mg/dL and mean proteinuria (urinary
albumin/creatinine) of 1808 mg/g at baseline.
The primary endpoint of the study was the time to first
occurrence of any one of the following events: doubling of serum creatinine,
end-stage renal disease (ESRD) (need for dialysis or transplantation), or death.
Treatment with COZAAR resulted in a 16% risk reduction in this endpoint (see
Figure 4 and Table 4). Treatment with COZAAR also reduced the occurrence of
sustained doubling of serum creatinine by 25% and ESRD by 29% as separate
endpoints, but had no effect on overall mortality (see Table 4).
The mean baseline blood pressures were 152/82 mmHg for
COZAAR plus conventional antihypertensive therapy and 153/82 mmHg for placebo
plus conventional antihypertensive therapy. At the end of the study, the mean
blood pressures were 143/76 mmHg for the group treated with COZAAR and 146/77
mmHg for the group treated with placebo.
Figure 4: Kaplan-Meier curve for the primary composite
endpoint of doubling of serum creatinine, end stage renal disease (need for dialysis
or transplantation) or death.
Table 4: Incidence of Primary Endpoint Events
|
Incidence |
Risk Reduction |
95% C.I. |
p- Value |
Losartan |
Placebo |
Primary Composite Endpoint |
43.5% |
47.1% |
16.1% |
2.3% to 27.9% |
0.022 |
Doubling of Serum Creatinine, ESRD and Death Occurringas a First Event |
Doubling of Serum Creatinine |
21.6% |
26.0% |
|
|
|
ESRD |
8.5% |
8.5% |
|
|
|
Death |
13.4% |
12.6% |
|
|
|
Overall Incidence of Doubling of Serum Creatinine, ESRD and Death |
Doubling of Serum Creatinine |
21.6% |
26.0% |
25.3% |
7.8% to 39.4% |
0.006 |
ESRD |
19.6% |
25.5% |
28.6% |
11.5% to 42.4% |
0.002 |
Death |
21.0% |
20.3% |
-1.7% |
-26.9% to 18.6% |
0.884 |
The secondary endpoints of the study were change in
proteinuria, change in the rate of progression of renal disease, and the
composite of morbidity and mortality from cardiovascular causes
(hospitalization for heart failure, myocardial infarction, revascularization,
stroke, hospitalization for unstable angina, or cardiovascular death). Compared
with placebo, COZAAR significantly reduced proteinuria by an average of 34%, an
effect that was evident within 3 months of starting therapy, and significantly
reduced the rate of decline in glomerular filtration rate during the study by
13%, as measured by the reciprocal of the serum creatinine concentration. There
was no significant difference in the incidence of the composite endpoint of
cardiovascular morbidity and mortality.
The favorable effects of COZAAR were seen in patients
also taking other anti-hypertensive medications (angiotensin II receptor
antagonists and angiotensin converting enzyme inhibitors were not allowed),
oral hypoglycemic agents and lipid-lowering agents.
For the primary endpoint and ESRD, the effects of COZAAR
in patient subgroups defined by age, gender and race are shown in Table 5
below. Subgroup analyses can be difficult to interpret and it is not known whether
these represent true differences or chance effects.
Table 5: Efficacy Outcomes within Demographic
Subgroups
|
No. of Patients |
Primary Composite Endpoint |
ESRD |
COZAAR Event Rate % |
Placebo Event Rate % |
Hazard Ratio
(95% CI) |
COZAAR Event Rate % |
Placebo Event Rate % |
Hazard Ratio
(95% CI) |
Overall Results |
1513 |
43.5 |
47.1 |
0.84 (0.72, 0.98) |
19.6 |
25.5 |
0.71 (0.58, 0.89) |
Age |
<65 years |
1005 |
44.1 |
49.0 |
0.78 (0.65, 0.94) |
21.1 |
28.5 |
0.67 (0.52, 0.86) |
≥65 years |
508 |
42.3 |
43.5 |
0.98 (0.75, 1.28) |
16.5 |
19.6 |
0.85 (0.56, 1.28) |
Gender |
Female |
557 |
47.8 |
54.1 |
0.76 (0.60, 0.96) |
22.8 |
32.8 |
0.60 (0.44, 0.83) |
Male |
956 |
40.9 |
43.3 |
0.89 (0.73, 1.09) |
17.5 |
21.5 |
0.81 (0.60, 1.08) |
Race |
Asian |
252 |
41.9 |
54.8 |
0.66 (0.45, 0.95) |
18.8 |
27.4 |
0.63 (0.37, 1.07) |
Black |
230 |
40.0 |
39.0 |
0.98 (0.65, 1.50) |
17.6 |
21.0 |
0.83 (0.46, 1.52) |
Hispanic |
277 |
55.0 |
54.0 |
1.00 (0.73, 1.38) |
30.0 |
28.5 |
1.02 (0.66, 1.59) |
|
|
|
|
|
|
|
|
White |
735 |
40.5 |
43.2 |
0.81 (0.65, 1.01) |
16.2 |
23.9 |
0.60 (0.43, 0.83) |