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Assistant Professor Department of Pharmacy Practice University of Nebraska Medical Center Omaha, Nebraska Assistant Professor Department of Pharmacy University of Southern California School of Pharmacy 1985 Zonal Avenue Los Angeles, California 90089-9121 fax 323/442-1681 tienng{at}usc.edu
Assistant Professor Department of Preventative and Societal Medicine University of Nebraska Medical Center
Associate Professor Department of Internal Medicine University of Nebraska Medical Center
Published Online, December 28, 2004. www.theannals.com, DOI 10.1345/aph.1E395
Methods. In a retrospective, cohort design, consecutive charts of
patients with HF at the university were screened for prescribing data.
Inclusion criteria were HF diagnosis after January 1, 1996, left-ventricular
ejection fraction (LVEF) 
40%, and age 
40 years. Male (n = 38) and
female (n = 21) cohorts were of similar age (mean ± SD, 64 ± 12
y), race (85% white), HF etiology (76% ischemic), New York Heart Association
(NYHA) functional classification (78% II or III), and LVEF (21% ± 7%).
Doses of angiotensin (AT) antagonists (ACE inhibitors and AT receptor
blockers) and ß-blockers were standardized to enalapril and metoprolol
equivalents, respectively.
Univariate comparisons included the Wilcoxon rank-sum test (age, weight,
height, years since HF diagnosis, LVEF) and Fisher's exact test (race, HF
etiology, NYHA functional class, comorbid illnesses, concomitant medications,
primary care service subspecialty). Multivariate comparisons were based on
linear (a natural log transformed response used, where appropriate, to account
for skewed distributions) and logistic regression. The multivariate
regressions utilized a model that included gender and all other covariates
significantly (
< 0.1) associated with the response upon univariate
analyses.
Discussion. Based on the multivariate analysis, a history of cerebrovascular event, height, female gender, and final diastolic blood pressure were significantly associated with an increased median number of days for an upward titration of AT antagonists. After adjustment for these confounding factors, gender was independently associated with the number of days between dosage titrations (p = 0.004). The median number of days between uptitrations was 2.5 times (95% CI 1.4 to 4.7) longer in female than in male patients. Gender was also significantly associated with the odds of requiring more than one visit to uptitrate the dose (p = 0.01). The odds of requiring more than one visit on average to uptitrate for women were 34.0 times the odds for men (95% CI 2.0 to 565.2). There were no differences in final mean systolic blood pressure and mean heart rate between genders. There was no significant difference in the final mean maintenance dose of AT antagonists. No differences in uptitration or maintenance doses achieved with ß-blockers were observed based on gender.
The results suggest that female gender was associated with less aggressive uptitration of AT antagonists as reflected in a longer median time interval before dosage uptitration and higher odds of requiring more than one clinic visit before dose uptitration when compared with male patients. Despite less aggressive uptitration, maintenance doses achieved were not significantly different for men and women. The reason for slower upward titration of dosage does not appear to be related to hemodynamic tolerability. To our knowledge, as of December 2, 2004, this is the first attempt to characterize the influence of gender on the aggressiveness of dose titration in chronic HF. Although the study results do not provide reasons why women's doses were increased more slowly, the importance of this study lies in the potential to increase awareness over issues related to the management of female cardiovascular patients.
Footnotes
Abstract presented at the American College of Clinical Pharmacy Annual Meeting, Atlanta, GA, November 2–5, 2003.
References
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