Statin Prescribing Practices in the Comprehensive Care for HIV-Infected Patients

To the Editors: INTRODUCTION HIV infection is associated with an increased risk for cardiovascular disease (CVD), even in the setting of virologic suppression.1–4 However, HIV infection is not factored into the current 2013 American College of Cardiology (ACC)/American Heart Association (AHA) guidelines for assessing cardiovascular risk and for determining lipid-lowering therapies to reduce atherosclerotic CVD (ASCVD) risk.5,6 Details on statin use in HIV infection are also lacking in other international cardiovascular guidelines given the continued dearth of large-scale trial data on ASCVD-preventive therapies in HIV. Statins may nonetheless be particularly beneficial in reducing ASCVD risk for HIV+ persons because they can reduce the volume and rupture the potential of high-risk, noncalcified plaque, which is associated with HIV infection.7–10 Although current cardiovascular guidelines are not validated for the HIV+ population, recent retrospective studies have demonstrated a concerning statin gap among HIV+ patients who may benefit from a statin and those actually prescribed one.11,12 These studies, however, used pre-2013 data; the clinical application of more recent guidelines to the HIV+ populations has been sparsely assessed. We performed a single-center, retrospective study of HIV+ patients at an HIV clinic and evaluated cardiovascular care practices of HIV providers in accordance with 2013 ACC/AHA guidelines. METHODS A sample of 460 consecutive HIV+ patients receiving care at the Infectious Diseases Center of Northwestern University between June 1, 2015, and May 31, 2016, was selected. Inclusion criteria were age ≥21 years and an available cholesterol panel. Factors pertaining to statin recommendations [clinical ASCVD, age, race, gender, cholesterol, blood pressure, hypertension, diabetes mellitus (DM), and smoking] were obtained by chart abstraction. ASCVD was defined as documented diagnosis of coronary heart disease, ischemic stroke, or peripheral arterial disease based on administrative codes. DM was defined as documented diagnosis of DM as per the primary medical provider, hemoglobin-A1c ≥6.5%, or use of diabetic medication (only individuals with DM aged 40–75 years were considered eligible for statins). Smoking was defined as documented history of current smoking by case manager, social worker, or primary medical provider. Documented medication lists were reviewed. Ten-year ASCVD risk scores were calculated for each patient who is at least 40 years old. Univariate and multivariate analyses were performed using logistic regression to determine clinical and demographic factors associated with statin prescription. Statistical analysis was executed by SAS version 9.4 (SAS Institute, Cary, NC) and SPSS version 23 (SPSS; IBM, New York, NY). This study was conducted for quality improvement. The Northwestern University Institutional Review Board determined that it did not involve human subjects and required no further institutional review board review or approval. RESULTS Among all HIV+ patients who had received care at the Northwestern University Infectious Disease Center in Chicago, IL, between June 1, 2015, and May 31, 2016, 460 consecutive patients were selected. The majority (81%) were male with a median age of 52 years. The common statins used were atorvastatin (60%), pravastatin (24%), and rosuvastatin (9%). Of the 194 patients eligible for statins based on 2013 ACC/AHA guidelines, 95 (49%) were prescribed a statin (Fig. 1). Patients were significantly more likely to be prescribed a statin if they had clinical ASCVD (46.5; confidence interval, 14 to 154; P < 0.0001) or DM (6.2; confidence interval, 3.4 to 11.4; P < 0.0001); the majority of patients with clinical ASCVD (26/28; 93%), DM (23/40; 58%), or both (13/14; 93%) were prescribed a statin. However, patients with ASCVD 10-year risk score ≥7.5% [without clinical ASCVD, DM, low-density lipoprotein cholesterol (LDL-C) ≥190 mg/d] were not significantly more likely to be prescribed a statin (P = 0.29); only 32/109 (29%) who were eligible for statins as primary prevention were prescribed one (Fig. 1). Overall, white patients were more likely to have been prescribed a statin than black patients (P = 0.0015). There was no significant gender difference in statin receipt (P = 0.059). We also observed no significant difference in statin receipt among patients with or without a detectable HIV viral load (P = 0.42).FIGURE 1.: Statin eligibility and statin use. ASCVD, atherosclerotic cardiovascular disease; CVD, cardiovascular disease; DM, diabetes mellitus; HDL, high-density lipoprotein; LDL, low-density lipoprotein; N/A, not applicable; SBP, systolic blood pressure. *Peripheral arterial disease, ischemic stroke. **In the absence of CVD, DM, and LDL ≥ 190 mg/dL.DISCUSSION Among the 460 HIV+ patients evaluated in this academic, single-center HIV clinic, less than half of those for whom statins are recommended by the 2013 ACC/AHA guidelines were prescribed a statin, and less than one-third for whom statins were recommended as primary prevention were prescribed a statin. Although we acknowledge that current cardiovascular guidelines have not been validated for the HIV+ population, this study highlights potentially suboptimal CVD prevention and management among HIV+ patients. Despite of the deficiency of HIV-specific statin trial data, available evidence strongly supports statin use in HIV+ patients. HIV+ persons are exceptionally vulnerable to ASCVD compared with the general population due to an increased burden of high-risk, noncalcified plaque and higher prevalence of other ASCVD risk factors.1,7,13–15 Additionally, actual ASCVD event rates of HIV+ subjects may exceed those predicted by the ASCVD 10-year risk score.16 Statins have been shown to reduce the volume and high-risk features of plaque in HIV infection.17–19 Furthermore, because statins have been associated with reduction in several markers of immune activation in HIV infection, they may be particularly beneficial in mitigating other detrimental cardiovascular complications of chronic inflammation.20 The low compliance with 2013 ACC/AHA guidelines found among our cohort may be partly explained by the recency of the guidelines and their stricter recommendations compared with the Adult Treatment Panel III guidelines, which were the last endorsed by the Infectious Diseases Society of America.19 Nonetheless, several other cardiovascular guidelines have been introduced in recent years with discordant recommendations: the US Preventive Service Task Force recommends statins for patients with a 10-year ASCVD risk score ≥10% plus ≥1 CVD risk factor21; the European Society of Cardiology/European Atherosclerosis Society (ESC/EAS) 2016 guidelines recommend statins targeting specific LDL-C goals without Pooled Cohort Equation use22; the 2016 Canadian Cardiovascular Society recommends statins based on LDL-C level, CVD risk factors, and 10-year CVD event risk (based on the Framingham Risk Score) generally ≥10%23; the 2014 UK National Institute for Health and Care Excellence recommends statins for patients with a 10-year CVD event risk ≥10% (based on QRISK2 Assessment Tool)24; the 2014 National Lipid Association Recommendations for Dyslipidemia Management recommends statins based on LDL-C level and ASCVD risk factors assessment, with supplemental use of the Framingham risk calculator or the ACC/AHA Pooled Cohort Equation.25 The 2013 ACC/AHA guidelines demonstrate rigorous application of statins, more so than several of the above guidelines, including the US Preventive Service Task Force and ESC/EAS guidelines.26 Given the greater burden and risk of CVD in HIV+ patients and the 2013 ACC/AHA guidelines' comprehensive recommendations for statins, we opine that these guidelines and their 10-year ASCVD Pooled Cohort Equation should be a standard in the cardiovascular care for HIV+ patients until data-driven guidelines validated in HIV infection are available. The ongoing REPRIEVE study (NCT02344290) is expected to enrich the evidence base for statin use in HIV+ patients. A comprehensive cardiovascular care strategy in HIV patients should begin with encouraging modifiable risk reduction (such as smoking cessation and diet/exercise optimization) and include appropriate lipid-lowering therapy for patients with continual appraisal of compliance with guidelines. Barriers to statin use need to be addressed, such as pill burden, which may lead to nonadherence. Adverse interactions between statins and antiretroviral therapy may reduce another barrier to statin use as the field moves away from older regimens containing boosted protease inhibitors for initial therapy. Concern for such interactions has potentially shifted provider preference from high-intensity statins in HIV infection. Indeed, available data suggest that submaximal dosing for certain statins should be used in the setting of HIV infection, which represents a significant barrier to maximizing statin intensity per the 2013 ACC/AHA guidelines.27 Nonetheless, with fewer drug–drug interactions in newer antiretroviral therapy regimens, use of higher intensity statins, which have been demonstrated to yield persistently favorable lipid profiles in HIV+ patients with ASCVD than lower intensity statins, may be more fastidiously used.28 The cross-sectional, retrospective nature and lack of an HIV-negative control arm are significant limitations in this study. We also were unable to examine reasons for which statins may have been deferred if not clearly documented in the medical record. For attribution of diagnoses of hypertension and diabetes, diagnosis-specific medication use was included as diagnostic criteria; such a method may mischaracterize participants taking such medication for different indications. Finally, we evaluated providers at a large, urban, academic hospital, and our patient population consisted primarily of men living in a large urban center; thus, this study may not be generalizable to all HIV providers and their patients. Even so, it is possible other HIV clinics experience a similar deficit in cardiovascular care based on this study and those evaluating pre-2013 data.11,12 HIV+ persons carry a disproportionate risk of ASCVD. Many HIV+ persons receive all primary care through HIV specialists, relying on them for the management and prevention of chronic, noninfectious diseases, including CVD. Two years after the introduction of the ACC/AHA guidelines on statin use, uptake of the recommendations was low at our clinical site. The growing evidence of increased CVD risk in HIV+ patients, likely even higher than predicted by the ACC/AHA guidelines, underscores the need for corrective measures. Further studies are needed to evaluate 2013 ACC/AHA guidelines uptake in broader HIV+ patient populations, and strategies are needed to optimize compliance with best practices for cardiovascular health in HIV+ patients.

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