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Underutilization of Aspirin for Primary Prevention of Cardiovascular Disease among HIV-Infected Patients
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Clinical Infectious Diseases Advance Access published August 31, 2012
Greer A. Burkholder1, Ashutosh R. Tamhane1, Jorge L. Salinas1, Michael J. Mugavero1, James L. Raper1, Andrew O. Westfall2, Michael S. Saag1, James H. Willig1
1Department of Biostatistics, University of Alabama at Birmingham, Birmingham, AL, USA 2Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA
CONSULT WITH doctor/heart specialist before starting a regimen of aspirin for CVD
"Our study found ASA was markedly underprescribed among HIV-infected patients at risk for CVD events. Less than 20% of patients meeting the 2009 USPSTF criteria for ASA for primary prevention of CVD events were prescribed ASA. Even when the focus was narrowed to patients at intermediate to high risk for events (10-year risk ≥ 10%), which constituted 50% of the study sample, only 22% were on ASA......."
"Among 397 patients who qualified to receive ASA [aspirin] (mean age=52.2 years, 94% male, 36% African American), only 66 (17%) were prescribed ASA.......The 2009 United States Preventive Services Task Force (USPSTF) guidelines recommend use of ASA for primary prevention of MIs in men age 45 to 79 years and ischemic strokes in women age 55 to 79 years when the potential CVD benefit (events prevented) outweighs the risk of gastrointestinal hemorrhage [16]. Qualification for ASA is based on age-stratified 10-year coronary heart disease (CHD) risk score for men .......and 10-year stroke risk score for
women.......over half of HIV-infected patients in the U.S. are expected to be over 50 years of age by 2015 [2]. Recent large cohort studies of HIV-infected patients demonstrate morbidity and mortality due to non-AIDS- related events has surpassed that due to AIDS-related events in developed countries, with 6-15% of deaths attributed to cardiovascular disease (CVD)"
Abstract
Background. HIV-infected patients are at increased risk for cardiovascular disease (CVD) events compared to uninfected persons. However, little is known about HIV provider practices regarding aspirin (ASA) for primary prevention of CVD.
Methods. A cross-sectional study was conducted among patients attending the University of Alabama at Birmingham 1917 HIV Clinic during 2010 to determine the proportion receiving ASA for primary prevention of CVD and identify factors associated with ASA prescription. 10-year risk for CVD events was calculated for men age 45-79 and women age 55-79. The 2009 U.S. Preventive Services Task Force (USPSTF) guidelines were used to determine those qualifying for primary CVD prevention.
Results. Among 397 patients who qualified to receive ASA (mean age=52.2 years, 94% male, 36% African American), only 66 (17%) were prescribed ASA. In multivariable logistic regression analysis, diabetes mellitus (OR=2.60; 95% CI=1.28-5.27), hyperlipidemia (OR=3.42; 95% CI=1.55-7.56), and current smoking (OR=1.87; 95% CI=1.03-3.41) were significantly associated with ASA prescription. Odds of ASA prescription more than doubled for each additional CVD-related co-morbidity present among hypertension, diabetes, hyperlipdemia, and smoking (OR=2.13, 95% CI=1.51-2.99).
Conclusions. In this HIV-infected cohort, less than 1 in 5 patients in need received ASA for primary CVD prevention. Escalating likelihood of ASA prescription with increasing CVD-related co-morbidity count suggests providers may be influenced more by co-occurrence of these diagnoses than by USPSTF guidelines. In the absence of HIV-specific guidelines, interventions to improve HIV provider awareness of and adherence to existing general population guidelines on CVD risk reduction are needed.
Introduction
Due to widespread availability of potent combination antiretroviral therapy (ART), the life expectancy of HIV-infected patients has significantly improved in developed countries [1]. As a result, over half of HIV-infected patients in the U.S. are expected to be over 50 years of age by 2015 [2]. Recent large cohort studies of HIV-infected patients demonstrate morbidity and mortality due to non-AIDS- related events has surpassed that due to AIDS-related events in developed countries, with 6-15% of deaths attributed to cardiovascular disease (CVD) [3-7]. HIV-infected patients appear to have increased risk of coronary heart disease (CHD) and myocardial infarction (MI) compared to uninfected controls [8-11], and also have higher prevalence of subclinical atherosclerosis [12]. As age is an independent risk factor for CVD-related events (MI, ischemic stroke) [13, 14], we can expect temporal increases in incidence of these events as the HIV-infected population ages.
Despite heightened awareness regarding elevated CVD risk among HIV-infected patients [15], little is known about HIV provider practices regarding the use of aspirin (ASA) for primary prevention of CVD events (i.e. prevention of first MI or ischemic stroke). Due to the absence of HIV-specific guidelines, recommendations targeted toward the general population provide the only guidance regarding HIV-infected patients qualifying for ASA for primary prevention. The 2009 United States Preventive Services Task Force (USPSTF) guidelines recommend use of ASA for primary prevention of MIs in men age 45 to 79 years and ischemic strokes in women age 55 to 79 years when the potential CVD benefit (events prevented) outweighs the risk of gastrointestinal hemorrhage [16]. Qualification for ASA is based on age-stratified 10-year coronary heart disease (CHD) risk score for men (http://www.framinghamheartstudy.org/risk/coronary.html) and 10-year stroke risk score for
women (http://www.framinghamheartstudy.org/risk/stroke.html).
Due to the increasing importance of CVD risk assessment and prevention among HIV-infected patients successfully treated with ART, we conducted a cross-sectional study among patients attending a large university-based outpatient HIV clinic to assess the proportion of qualifying patients prescribed ASA for primary prevention per the USPSTF guidelines, and to examine associations of clinical, sociodemographic and psychosocial factors with ASA prescription.
Results
Framingham risk scores were calculated for 471 established patients meeting eligibility criteria. Of these, 402 (85%) met USPSTF criteria to receive ASA for primary prevention of CVD. Only 5 qualifying patients were of race/ethnicity other than African-American or white. They were excluded due to low numbers. The remaining 397 patients qualifying for ASA were included in the analyses.
Among the 397 qualifying study participants, the mean age (±SD) was 52.2 ± 5.9 years, 36% of the patients were African American, and 94% were male (Table 1). HIV risk group was men who have sex with men (MSM) in 66%, heterosexual transmission in 23%, and intravenous drug use (IVDU) in 11%. The majority of patients were insured (46% private insurance, 38% public insurance, 16% uninsured). Most patients (96%) were taking ARVs, HIV RNA was suppressed (<50 copies/mL) in 60%, and CD4+ cell count was >350 cells/mm3 in 70%.
Only 66 patients (17%) were prescribed ASA for primary CVD prevention. Notably, half of the 397 patients qualifying for ASA had intermediate to high risk for CVD-related events (10-year risk ≥10%); 39% were current smokers; 16% had DM, 62% HTN, 63% hyperlipidemia, and 20% were obese (BMI ≥30). Of the higher risk patients (10-year risk ≥10%), only 22% were prescribed ASA. No significant clustering of ASA prescription by individual primary HIV provider was observed.
Factors associated with ASA prescription
In univariate analysis, HTN, DM, hyperlipidemia, higher CVD-related co-morbidity count,higher 10-year risk for CVD events, and longer time in care were significantly associated with increased odds of ASA prescription, whereas CD4 count <200 cells/mm3 was associated with decreased odds of ASA prescription. Most recent HIV RNA was not significantly associated with ASA prescription. (Table 2) In multivariable logistic regression analysis, factors significantly associated with ASA prescription included: DM (OR=2.60; 95% CI=1.28-5.27), hyperlipidemia (OR=3.42; 95% CI=1.55-7.56), and current smoking (OR=1.87; 95% CI=1.03-3.41), while adjusted for age, sex, race/ethnicity, CD4 count, BMI, HTN, and length of time in care. FRS and CVD-related co-morbidity count were not included in this model due to collinearity with multiple included variables. In a separate multivariable model (not shown), 10-year CVD risk per FRS was included in place of characteristics impacting the score (age, sex, DM, HTN, hyperlipidemia, and current smoking). For every 5% increase in 10-year CVD risk per FRS, odds of ASA prescription increased by 35% (OR=1.35, 95% CI=1.12Ð1.62), after adjusting for race/ethnicity, CD4 count, BMI, and length of time in care. An additional multivariable analysis was performed with CVD-related co-morbidity count replacing individual co-morbidities (not shown). After adjusting for sex, race/ethnicity, CD4 count, BMI, and length of time in care, odds of ASA prescription more than doubled for each increase in co-morbidity count (OR=2.13, 95% CI=1.51-2.99)
Discussion
Our study found ASA was markedly underprescribed among HIV-infected patients at risk for CVD events. Less than 20% of patients meeting the 2009 USPSTF criteria for ASA for primary prevention of CVD events were prescribed ASA. Even when the focus was narrowed to patients at intermediate to high risk for events (10-year risk ≥ 10%), which constituted 50% of the study sample, only 22% were on ASA.
We evaluated clinical, sociodemographic, and psychosocial characteristics associated with ASA prescription in HIV-infected patients, which have not been addressed in the extant literature. As expected, traditional CVD risk factors (DM, hyperlipidemia, and current smoking) were associated with increased odds of ASA prescription. An interesting observation was the escalating likelihood of ASA prescription with increasing CVD-related co-morbidity count. This suggests provider ASA prescribing patterns may be influenced more by co-occurrence of these diagnoses rather than by FRS and USPSTF guidelines, given that all 397 patients qualified for ASA based on these guidelines yet <20% were receiving it.
A 2005 national survey of primary care physicians, cardiologists, and obstetrician/gynecologists found that physician perception of CVD risk predicted recommendations regarding preventive measures including ASA use, but frequently differed from calculated risk using the FRS [22]. Provider dependence on clinical assessment alone in the absence of a CVD risk score carries the dual hazard of failure to prescribe ASA for patients in whom it is indicated, and unnecessary prescription of ASA in low risk patients for whom risk of gastrointestinal bleeding outweighs potential CVD benefit.
The low rate of ASA prescription observed in our study is consistent with findings from the only two similar published studies regarding use of anti-platelet therapy for prevention of CVD-related events in HIV-infected patients. One was conducted at Hospital Gandia in Spain, where among 120 consecutive HIV-infected patients, 30.8% qualified for primary prevention of CVD with ASA by the 2009 USPSTF guidelines but only 2 were taking ASA [23]. Another study in Germany found that of HIV-infected patients with 10-year Framingham risk 10-20%, only 2.4% were receiving anti-platelet therapy, and of those with 10-year risk >20%, only 31.9% were receiving anti-platelet therapy (the authors did not distinguish between antiplatelet therapy for primary and secondary prevention) [24]. These two studies point to underprescribing of ASA in settings different than ours, highlighting a widespread need for greater attention among HIV providers on the role of ASA in CVD risk reduction.
Studies in the general population report racial disparities in ASA use, with whites more likely to use ASA for primary prevention of CVD-related events than African-Americans [25-27]. However, we noted no difference in ASA prescription between whites and African-Americans. We expected to see lower likelihood of ASA prescription in patients with more advanced HIV (CD4+ cell count <200 cells/mm3), presuming providers would be more focused on HIV management than general health maintenance issues like CVD risk reduction. While CD4+ cell count <200 cells/mm3 was significantly associated with lower odds of ASA prescription in univariate analysis, this association was not present in our multivariable model, potentially due to sample size. The absence of clustering of ASA prescribing by individual provider in our study suggests underutilization of ASA is a systemic problem, rather than a matter of deficiencies in the practice of select providers. The reasons behind low utilization of ASA for primary prevention of CVD by HIV providers is likely multifactorial. HIV providers may be unfamiliar with general population guidelines and recommendations. Of note, there is an absence of guidance in the HIV-specific literature [15, 28]. The relative impact of lack of clarity on the part of HIV providers regarding their role as primary care physicians, difficulty balancing the demands of caring for complex patients with myriad medical and social problems, patient-provider encounter time constraints, or some combination of these factors will require further study.
Results from this single-center study in the Southeastern, US may not be generalizable to other geographic regions or HIV clinical settings. The proportion of women was modest (6%), limiting our ability to draw broad inferences about this segment of the HIV-infected population. Due to the observational design, we can identify associations but cannot determine causality, and there may be unmeasured confounders for which we have not accounted. As this study is cross-sectional, we do not take account of the potential variability of the FRS over time, and we also note the FRS has not been validated in an HIV-infected population and may under-predict CVD risk in patients on ART [29]. However, in the absence of a more precise, validated HIV-specific scoring system, it is appropriate to use the FRS [15,30]
We used a single, non-standardized blood pressure measurement in our risk calculations, and fasting lipids were not routinely available. However, the purpose of this study was to evaluate provider practices regarding ASA prescription. We feel our methods are reflective of how our providers would likely calculate CVD risk scores in practice. In addition, there is literature suggesting fasting lipids may not be necessary for CVD risk prediction [31]. Data on co-morbidities and ASA prescription was extracted from the EHR, and underreporting by providers may have affected our estimates, although we note our system of 100% quality assurance reduced this potential limitation and bias.
We observed significant underutilization of ASA in the prevention of first CVD-related events among HIV-infected persons engaged in medical care. HIV-specific guidelines regarding the use of ASA are needed. In the short term, interventions to improve HIV provider knowledge of and adherence to existing recommendations governing CVD prevention and management for the general population would be beneficial. The development and implementation of computerized decision support systems to enhance provider awareness of patients who would benefit from ASA for primary prevention of CVD-related events would likely advance adherence to this important prevention strategy.
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