Gender Disparities in Evidence-Based Statin Therapy in Patients With Cardiovascular Disease




Studies have shown gender disparities in cholesterol care in patients with cardiovascular disease (CVD), with women less likely than men to have low-density lipoprotein cholesterol levels <100 mg/dl. Whether this is related to a lower evidence-based statin or high-intensity statin use is not known. We used a national cohort of 972,532 patients with CVD (coronary heart disease, peripheral artery disease, and ischemic stroke) receiving care in 130 Veterans Health Administration facilities from October 1, 2010, to September 30, 2011, to identify the proportion of male and female patients with CVD receiving any statin and high-intensity statin. Women with CVD (n = 13,371) were less likely than men to receive statins (57.6% vs 64.8%, p <0.0001) or high-intensity statins (21.1% vs 23.6%, p <0.0001). Mean low-density lipoprotein cholesterol levels (99 vs 85 mg/dl) were higher in women compared with men (p <0.0001). In adjusted models, female gender was independently associated with a lower likelihood of receiving statins (odds ratio 0.68, 95% confidence interval 0.66 to 0.71) or high-intensity statins (odds ratio 0.76, 95% confidence interval 0.73 to 0.80). The median facility-level rate of statin and high-intensity statin use among female patients (57.3% [interquartile range = 8.93%] for statin, 20% [interquartile range = 7.7%] for high-intensity statin use) showed significant variation. In conclusion, women with CVD are less likely to receive evidence-based statin and high-intensity statins compared with men, although, their use remains low in both genders. There is a significant facility-level variation in evidence-based statin or high-intensity statin use in female patients with CVD. With the “statin dose-based approach” proposed by the recent cholesterol guidelines, these results highlight areas for quality improvement.


In patients with cardiovascular disease (CVD), the beneficial effects of statin therapy have not shown any gender-related heterogeneity with both female and male patients with CVD deriving the same magnitude of benefit. In these studies of secondary prevention, statin therapy compared with placebo and high-intensity statin therapy compared with low-to-moderate intensity statin therapy have shown more benefit. Although previous studies have shown gender-related disparities in care of patients with CVD, most have focused on low-density lipoprotein cholesterol (LDL-C) levels with few studies evaluating the differences in the receipt of statin therapy. Gender disparities in the use of high-intensity statin therapy are not known. This gender-related disparity in high-intensity statin therapy use is important to study as the recent American College of Cardiology (ACC)/American Heart Association (AHA) cholesterol management guideline recommends high-intensity statin therapy in most patients with CVD. Using data from a national cohort of patients with CVD, we determined the presence and the extent of gender disparities in the receipt of evidence-based statin and high-intensity statin therapy in patients with CVD. We also examined facility-level variation in the use of statin and high-intensity statin therapy in patients with CVD.


Methods


Using the Department of Veterans Affairs (VA) administrative data sources, we identified patients with CVD with primary care clinic visits in the VA health care system (130 facilities or their associated community-based outpatient clinics) from October 1, 2010, to September 30, 2011. Patients with CVD were those with a history of coronary heart disease or peripheral artery disease, including ischemic stroke. We identified patients as having coronary heart disease using International Classification of Diseases, Ninth Revision, Clinical Modification diagnoses and procedure codes for unstable angina or myocardial infarction, or current procedural terminology codes for percutaneous coronary intervention or coronary artery bypass grafting ( Supplementary Table A ). We also used International Classification of Diseases, Ninth Revision, Clinical Modification diagnoses codes ( Supplementary Table A ) to identify patients with peripheral artery disease. As patients with metastatic cancers and those receiving hospice care are not considered candidates for quality measurement, we excluded them from our cohort ( Figure 1 ). An index visit was defined as the most recent primary care visit for each patient from October 1, 2010, to September 30, 2011.




Figure 1


Flow chart of the study cohort identification and exclusions. Total adds up to >10,914 as some patients met >1 exclusion criteria. n for final analysis. CHD = coronary heart disease; PAD = peripheral arterial disease.


Using VA administrative pharmacy data sources, we evaluated whether these patients were prescribed a statin or a nonstatin LDL-C lowering medication within 100 days before or 14 days after their index visit. The nonstatin LDL-C lowering medications included bile acid-binding resins, niacin, and ezetimibe. Fibrates were not included as they only marginally lower LDL-C, and fish oil-based therapies were not included as they do not lower LDL-C.


Using VA’s administrative data sets, we assessed several patient characteristics including age, race, and history of diabetes or hypertension ( Supplementary Table A ). To assess the impact of patient’s illness burden on receipt of evidence-based statin therapy, we calculated a mean diagnostic cost group relative risk score (RRS) for each patient. Diagnostic cost group RRS is a ratio of the predicted cost to the mean cost and has been used as a measure of illness burden. For example, a patient with an RRS of 2 is expected to be twice as costly, with an illness burden twice as high as an “average” patient. We also assessed facility, provider, and system-of-care characteristics that could impact receipt of statin (or high-intensity statin) therapy. These included whether the facility was a teaching facility, the type of provider (physician or nonphysician primary care provider, such as a nurse practitioner or a physician assistant), and the number of primary care visits by a patient in the 12 months before the index visit. We first compared the patient, facility, provider, and system-of-care characteristics between female and male patients with CVD. We then compared the most recent levels of various lipid parameters (total cholesterol, LDL-C, high-density lipoprotein cholesterol [HDL-C], triglycerides, non-HDL-C) between male and female patients with CVD.


Our primary outcome was the receipt of statin therapy. We assessed the proportion of female and male patients receiving any statin. We then performed multivariate hierarchical logistic regression to determine whether gender is independently associated with receipt of statins. Covariates used for adjustment included patient, facility, provider, and system-of-care characteristics described previously. We also adjusted for clustering of patients at the facility-level in our regression models using generalized linear latent and mixed models in STATA (College Station, TX). We subsequently performed multivariate hierarchical logistic regression to determine whether gender is independently associated with the receipt of high-intensity statins among patients with CVD. Per the recent ACC/AHA guideline, high-intensity statin therapy was defined as the daily statin intensity associated with approximately ≥50% LDL-C reduction (atorvastatin dose of 40 to 80 mg/day, rosuvastatin 20 to 40 mg/day, or simvastatin >40 mg/day).


To evaluate the proportion of female patients with CVD at each facility receiving statin or high-intensity statin therapy, we calculated median facility-level rates for statin or high-intensity statin therapy with interquartile ranges in female patients with CVD. These analyses were restricted to facilities with at least 10 female patients with CVD (only 1 of the 130 facilities was excluded from these analyses).


As per the recent ACC/AHA guidelines, we also evaluated the proportion of female and male patients with CVD receiving at least a moderate-intensity statin therapy described as the daily dose of statin therapy associated with approximately 30% to <50% LDL-C reduction. We conducted the analyses with SAS version 9.1.3 (SAS Institute Inc, Cary, North Carolina) and STATA version 11 (College Station, Texas). The protocol was approved by the Institutional Review Boards at Baylor College of Medicine and the Michael E. DeBakey VA Medical Center.




Results


We excluded 10,941 (1.1%) patients with documented metastatic care or terminal illness from our initial cohort of 983,476 patients ( Figure 1 ). Our final analyses included 972,532 patients with 13,371 women (1.4%) and 959,161 (98.6%) men. Table 1 lists a comparison of the baseline characteristics between female and male patients with CVD. Female patients with CVD were on average younger, less often White, had a lower prevalence of diabetes and hypertension, and a higher prevalence of peripheral artery disease compared with male patients. Female patients with CVD had a higher overall illness burden (diagnostic cost group RRS) and were more likely to receive care at a teaching facility compared with male patients with CVD. On average, female patients with CVD received more primary care visits than male patients in the 12 months before their index visit. Female patients with CVD were less likely to receive care from a physician primary care provider (as opposed to a nurse practitioner or a physician assistant).



Table 1

Comparison of baseline characteristics between male and female patients with cardiovascular disease







































































Characteristic Females (n= 13,371) Males (n = 959,161) p
Age, mean/SD ( years) 65.99/14.05 71.24/10.55 < .0001
Whites 10131 (75.8%) 825666 (86.1%) < .0001
Blacks 2473 (18.5%) 83378 (8.7%)
Others 289 (2.2%) 16939 (1.8%)
Unknown 478 (3.6%) 33178 (3.5%)
Diabetes mellitus 5206 (38.9%) 412717 (43%) < .0001
Hypertension 10393 (77.7%) 767628 (80%) < .0001
History of CHD 12047 (90.1%) 910496 (94.9%) < .0001
History of PAD only 1324 (9.9%) 48665 (5.1%) < .0001
Diagnostic cost group relative risk score, mean/SD 2.54 /3.23 1.79/2.73 < .0001
Receiving primary care from a physician provider 9519 (73.9%) 717451 (77.2%) < .0001
Receiving care at a teaching facility 6751 (50.5%) 386785 (40.3%) < .0001
Number of primary care visit in the prior 12 months, mean/SD 5.96/ 5.32 4.54/ 3.89 < .0001

CHD = coronary heart disease; PAD = peripheral arterial disease; SD = standard deviation.

History of CHD with or without PAD.



As listed in Table 2 , a lower proportion of female patients with CVD (57.6%) were receiving statin therapy compared with male patients (64.8%). Furthermore, a lower proportion of female patients with CVD (21.1%) were on high-intensity statin therapy compared with male patients with CVD (23.6%). Total cholesterol, LDL-C, HDL-C, triglycerides, and non–HDL-C were on average 25 mg/dl, 14 mg/dl, 9 mg/dl, 6 mg/dl, and 15 mg/dl higher in female patients compared with male patients with CVD. In fully adjusted analyses ( Table 3 ), female gender was independently associated with 32% lesser likelihood of receipt of any statin therapy (odds ratio 0.68, 95% confidence interval 0.66 to 0.71) and a 24% lesser likelihood (odds ratio 0.76, 95% confidence interval 0.73 to 0.80) of receiving high-intensity statin therapy.



Table 2

Comparison of statin use and various lipid parameters between male and female cardiovascular disease patients












































Medication use or lipid parameter Female CVD patients
(n = 13,371)
Male CVD patients
(n = 959,161)
p
Any statin use 7696 (57.6%) 621309 (64.8%) <.0001
High dose statin use 2828 (21.1%) 226609 (23.6%) <.0001
Total cholesterol (mg/dL), mean/SD 178.6/45.2 153.9/37.2 <.0001
LDL-C (mg/dL), mean/SD 99.2/38 85/30.4 <.0001
HDL-C (mg/dL), mean/SD 51.3/16.8 42/12.4 <.0001
Triglycerides (mg/dL), mean/SD 153.5/123 147.5/106.7 <.0001
Non-HDL-C (mg/dL), mean/SD 128/44.2 112.5/35.8 <.001

CVD = cardiovascular disease; HDL-C = high density lipoprotein cholesterol; LDL-C = low density lipoprotein cholesterol; non-HDL-C = non-high density lipoprotein cholesterol; SD = standard deviation.

≥40 mg atorvastatin, ≥20 mg rosuvastatin, >40 mg simvastatin.


non-HDL-C = total cholesterol minus HDL-C.

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Nov 30, 2016 | Posted by in CARDIOLOGY | Comments Off on Gender Disparities in Evidence-Based Statin Therapy in Patients With Cardiovascular Disease

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