Publications by Year: 2021

IMPORTANCE: After a decline in cardiovascular mortality for nonelderly US adults, recent stagnation has occurred alongside rising income inequality. Whether this is associated with underlying economic trends is unclear.

OBJECTIVE: To assess the association between changes in economic prosperity and trends in cardiovascular mortality in middle-aged US adults.

DESIGN, SETTING, AND PARTICIPANTS: Retrospective analysis of the association between change in 7 markers of economic prosperity in 3123 US counties and county-level cardiovascular mortality among 40- to 64-year-old adults (102 660 852 individuals in 2010).

EXPOSURES: Mean rank for change in 7 markers of economic prosperity between 2 time periods (baseline: 2007-2011 and follow-up: 2012-2016). A higher mean rank indicates a greater relative increase or lower relative decrease in prosperity (range, 5 to 92; mean [SD], 50 [14]).

MAIN OUTCOMES AND MEASURES: Mean annual percentage change (APC) in age-adjusted cardiovascular mortality rates. Generalized linear mixed-effects models were used to estimate the additional APC associated with a change in prosperity.

RESULTS: Among 102 660 852 residents aged 40 to 64 years living in these counties in 2010 (51% women), 979 228 cardiovascular deaths occurred between 2010 and 2017. Age-adjusted cardiovascular mortality rates did not change significantly between 2010 and 2017 in counties in the lowest tertile for change in economic prosperity (mean [SD], 114.1 [47.9] to 116.1 [52.7] deaths per 100 000 individuals; APC, 0.2% [95% CI, -0.3% to 0.7%]). Mortality decreased significantly in the intermediate tertile (mean [SD], 104.7 [38.8] to 101.9 [41.5] deaths per 100 000 individuals; APC, -0.4% [95% CI, -0.8% to -0.1%]) and highest tertile for change in prosperity (100.0 [37.9] to 95.1 [39.1] deaths per 100 000 individuals; APC, -0.5% [95% CI, -0.9% to -0.1%]). After accounting for baseline prosperity and demographic and health care-related variables, a 10-point higher mean rank for change in economic prosperity was associated with 0.4% (95% CI, 0.2% to 0.6%) additional decrease in mortality per year.

CONCLUSIONS AND RELEVANCE: In this retrospective study of US county-level mortality data from 2010 to 2017, a relative increase in county-level economic prosperity was significantly associated with a small relative decrease in cardiovascular mortality among middle-aged adults. Individual-level inferences are limited by the ecological nature of the study.

BACKGROUND: Expanding statin use may help to alleviate the excess burden of atherosclerotic cardiovascular disease in people living with HIV (PLHIV). Pravastatin and pitavastatin are preferred agents due to their lack of substantial interaction with antiretroviral therapy. We aimed to evaluate the cost-effectiveness of pravastatin and pitavastatin for the primary prevention of atherosclerotic cardiovascular disease among PLHIV in the United States.

METHODS: We developed a microsimulation model that randomly selected (with replacement) individuals from the Data-collection on Adverse Effects of Anti-HIV Drugs study with follow-up between 2013 and 2016. Our study population was PLHIV aged 40 to 75 years, stable on antiretroviral therapy, and not currently using lipid-lowering therapy. Direct medical costs and quality-adjusted life-years (QALYs) were assigned in annual cycles and discounted at 3% per year. We assumed a willingness-to-pay threshold of $100,000/QALY gained. The interventions assessed were as follows: (1) treating no one with statins; (2) treating everyone with generic pravastatin 40 mg/day (drug cost $236/year) and (3) treating everyone with branded pitavastatin 4 mg/day (drug cost $2,828/year). The model simulated each individual's probability of experiencing atherosclerotic cardiovascular disease over 20 years.

RESULTS: Persons receiving pravastatin accrued 0.024 additional QALYs compared with those not receiving a statin, at an incremental cost of $1338, giving an incremental cost-effectiveness ratio of $56,000/QALY gained. Individuals receiving pitavastatin accumulated 0.013 additional QALYs compared with those using pravastatin, at an additional cost of $18,251, giving an incremental cost-effectiveness ratio of $1,444,000/QALY gained. These findings were most sensitive to the pill burden associated with daily statin administration, statin costs, statin efficacy and baseline atherosclerotic cardiovascular disease risk. In probabilistic sensitivity analysis, no statin was optimal in 5.2% of simulations, pravastatin was optimal in 94.8% of simulations and pitavastatin was never optimal.

CONCLUSIONS: Pravastatin was projected to be cost-effective compared with no statin. With substantial price reduction, pitavastatin may be cost-effective compared with pravastatin. These findings bode well for the expanded use of statins among PLHIV in the United States. To gain greater confidence in our conclusions it is important to generate strong, HIV-specific estimates on the efficacy of statins and the quality-of-life burden associated with taking an additional daily pill.

BACKGROUND: Costs can be a major barrier to medication adherence in low and middle-income countries and are an important target for policy-level interventions. The use of benzathine penicillin G (BPG) for secondary prevention of rheumatic heart disease (RHD) averts substantial morbidity and mortality, yet the total out-of-pocket costs for patients receiving this intervention are unknown.

OBJECTIVE: To estimate the total out-of-pocket costs for obtaining BPG prophylaxis among RHD patients in India.

METHODS: We prospectively collected self-reported drug-, transportation-, and provider-related costs for secondary prophylaxis among RHD patients presenting for follow-up to a tertiary care centre in New Delhi, India. Monthly costs were estimated by adjusting unit costs by frequency of drug administration.

RESULTS: The cost data provided by 420 patients [mean age (±SD) 11.6 (±2.9) years] was analysed. Majority of the patients were male (65.2%), hailed from rural areas (87.1%), and belonged to lower socioeconomic strata (73.3%). The median monthly total out-of-pocket costs (IQR) for obtaining BPG injections was Indian rupee (INR) 62.5 (42.5-117.0). The median costs for procuring the drug (IQR) was INR 34.0(30.0-39.0). Whereas median costs (IQR) for health care provider and transportation was INR 16.0 [0-32.0]) and INR 11 [0-31.0] respectively. When expressed as mean (SD), the costs for transportation constituted 50% of the total costs, whereas the mean cost for drug procurement and drug administration constituted 30% and 22% of the total costs respectively.

CONCLUSION: RHD patients receiving BPG prophylaxis incur substantial out-of-pocket costs, with transportation costs constituting nearly half of the total expenditures. National investments in RHD control must be strategically directed at improving health care access and drug supply in order to lower the total costs of secondary prophylaxis and improve adherence rates.

Background It is unknown whether clinical events identified with administrative claims have similar prognosis compared with trial-adjudicated events in cardiovascular clinical trials. We compared the prognostic significance of claims-based end points in context of trial-adjudicated end points in the DAPT (Dual Antiplatelet Therapy) study. Methods and Results We matched 1336 patients aged ≥65 years who received percutaneous coronary intervention in the DAPT study with the CathPCI registry linked to Medicare claims. We compared death at 21 months post-randomization using Cox proportional hazards models among patients with ischemic events (myocardial infarction or stroke) and bleeding events identified by: (1) both trial adjudication and claims; (2) trial adjudication only; and (3) claims only. A total of 47 patients (3.5%) had ischemic events identified by both trial adjudication and claims, 24 (1.8%) in trial adjudication only, 15 (1.1%) in claims only, and 1250 (93.6%) had no ischemic events, with annualized unadjusted mortality rates of 12.8, 5.5, 14.9, and 1.26 per 100 person-years, respectively. A total of 44 patients (3.3%) had bleeding events identified with both trial adjudication and claims, 13 (1.0%) in trial adjudication only, 65 (4.9%) in claims only, and 1214 (90.9%) had no bleeding events, with annualized unadjusted mortality rates of 11.0, 16.8, 10.7, and 0.95 per 100 person-years, respectively. Among patients with no trial-adjudicated events, patients with events in claims only had a high subsequent adjusted mortality risk (hazard ratio (HR) ischemic events: 31.5; 95% CI, 8.9‒111.9; HR bleeding events 23.9; 95% CI, 10.7‒53.2). Conclusions In addition to trial-adjudicated events, claims identified additional clinically meaningful ischemic and bleeding events that were prognostically significant for death.

Diabetes, Hypertension, Heart Disease, and Stroke Mortality Among Black and White Adults, 1999–2018

Background Only one third of patients recommended intensified treatment by the 2017 American College of Cardiology/American Heart Association (ACC/AHA) guideline for high blood pressure would have been eligible for the clinical trials on which recommendations were largely based. We sought to identify characteristics of adults who would have been trial-ineligible in order to inform clinical practice and research priorities. Methods and Results We examined the proportion of adults diagnosed with hypertension who met trial inclusion and exclusion criteria, stratified by age, diabetes mellitus status, and guideline recommendations in a cross-sectional study of the National Health and Nutrition Examination Survey, 2013-2016. Of the 107.7 million adults (95% CI, 99.3-116.0 million) classified as having hypertension by the ACC/AHA guideline, 23.1% (95% CI, 20.8%-25.5%) were below the target blood pressure of 130/80 mm Hg, 22.2% (95% CI, 20.1%-24.4%) would be recommended nonpharmacologic treatment, and 54.6% (95% CI, 52.5%-56.7%) would be recommended additional pharmacotherapy. Only 20.6% (95% CI, 18.8%-22.4%) of adults with hypertension would be trial-eligible. The majority of adults <50 years were excluded because of low cardiovascular risk and lack of access to primary care. The majority of adults aged ≥70 years were excluded because of multimorbidity and limited life expectancy. Reasons for trial exclusion were similar for patients with and without diabetes mellitus. Conclusions Intensive blood pressure treatment trials were not representative of many younger adults with low cardiovascular risk and older adults with multimorbidity who are now recommended more intensive blood pressure goals.

AIMS: Persons living with HIV (PLWH) have increased cardiovascular mortality, which may in part be due to differences in the management of acute coronary syndromes (ACS). The purpose of this study was to compare the in-hospital and post-discharge management and outcomes of ACS among persons with and without HIV.

METHODS AND RESULTS: This was a retrospective cohort study using data from Symphony Health, a data warehouse. All patients admitted between 1 January 2014 and 31 December 2016 with ACS were identified by International Classification of Diseases billing codes. Multivariate logistic regression models were used to examine in-hospital, 30-day and 12-month event rates between groups. A total of 1 125 126 individuals were included, 6612 (0.59%) with HIV. Persons living with HIV were younger (57.4 ± 10.5 vs. 67.4 ± 12.9 years, P< 0.0001) and had more medical comorbidities. Acute coronary syndrome type did not differ significantly with HIV status. Persons living with HIV were less likely to undergo coronary angiography (35.2% vs. 37.2%, adjusted OR 0.87, 95% CI 0.83-0.92, P < 0.0001), and those with both HIV and STEMI underwent fewer drug-eluting stents (60.1% vs. 68.5%, adjusted OR 0.81, 95% CI 0.68-0.96, P = 0.016). Persons living with HIV had higher adjusted rates of inpatient mortality (OR 1.29, 95% CI 1.15-1.44; P < 0.0001), 30-day readmission (OR 1.18, 95% CI 1.09-1.27; P < 0.0001) and 12-month mortality (OR 1.32, 95% CI 1.22-1.44; P < 0.0001). Twelve months following discharge, PLWH filled cardiac medications at lower rates.

CONCLUSION: In a contemporary cohort of persons hospitalized for ACS, PLWH received less guideline-supported interventional and medical therapies and had worse clinical outcomes. Strategies to optimize care are warranted in this unique population.

BACKGROUND: Marketing payments from the pharmaceutical industry to physicians have come under scrutiny due to their potential to influence clinical decision-making. Two proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) were approved by the US Food and Drug Administration in 2015 for reducing low-density lipoprotein cholesterol in high-risk patients, but their initial uptake was limited due to their high-cost and stringent prior authorization requirements. We sought to investigate the association between industry marketing and early adoption of PCSK9i among US physicians.

METHODS: We used nationwide databases of primary care physicians, cardiologists, and endocrinologists treating Medicare beneficiaries to examine the association between PCSK9i-related marketing payments in 2016 and the number of filled PCSK9i prescriptions in 2017, after adjusting for physician characteristics. In subgroup analyses, we stratified our analyses by physician specialty and prior experience with prescribing PCSK9i.

RESULTS: Among 209 840 physicians included in this analysis, 49 341 (24%) physicians received 292 941 PCSK9i-related marketing payments in 2016. The total value of these payments was $19 million, with a median payment of $61 per physician (interquartile range, $25-$132). Most payments (95%) were for meals, with a median of $14 per meal. The receipt of PCSK9i-related payments in 2016 was associated with increased PCSK9i prescription in 2017 (adjusted risk ratio, 3.18 [95% CI, 2.95-3.42]). This association was larger among primary care physicians (adjusted risk ratio, 6.67 [95% CI, 5.87-7.57]) than cardiologists (adjusted risk ratio, 2.00 [95% CI, 1.84-2.16]) and endocrinologists (adjusted risk ratio, 4.06 [95% CI, 2.95-5.59]). The association was observed across all types of payments.

CONCLUSIONS: At a time when few physicians had experience with prescribing PCSK9i under strict prior authorization requirements, industry marketing payments to physicians for PCSK9i, predominantly in the form of meals, were associated with increased PCSK9i prescription in the subsequent year.

INTRODUCTION: Low-dose rivaroxaban reduced major adverse cardiac and limb events among patients with stable atherosclerotic vascular disease (ASCVD) in the COMPASS trial. The objective of our study was to evaluate the eligibility and budgetary impact of the COMPASS trial in a real-world population.

METHODS: The VA administrative and clinical databases were utilized to conduct a cross-sectional study to identify patients eligible for low-dose rivaroxaban receiving care at all 141 facilities between October 1, 2014 and September 30, 2015. Proportion of patients with stable ASCVD eligible for low-dose rivaroxaban and prevalence of multiple risk enrichment criteria among eligible patients. Pharmaceutical budgetary impact using VA pharmacy pricing. Chi-squared and Student's t tests were used to compare patients eligible versus ineligible patients.

RESULTS: From an initial cohort of 1,248,214 patients with ASCVD, 488,495 patients (39.1%) met trial eligibility criteria. Eligible patients were older (74.2 vs 64.5 years) with higher proportion of hypertension (84.1% vs 82.1%) and diabetes (46.2% vs 32.9) compared with ineligible patients (p < 0.001 for all comparisons). A median of 38.7% (IQR 4.6%) of total ASCVD patients per facility were rivaroxaban eligible. Estimated annual VA pharmacy budgetary impact would range from $0.47 billion to $1.88 billion for 25% to 100% treatment penetration. Annual facility level pharmaceutical budgetary impact would be a median of $12.3 million (IQR $8.0-$16.3 million) for treatment of all eligible patients. Among eligible patients, age greater than 65 years was the most common risk enrichment factor (86.9%). Prevalence of eligible patients with multiple enrichment factors varied from 34.2% (one factor) to 6.2% (four or more).

CONCLUSION: Over one third of patients with stable ASCVD may qualify for low-dose rivaroxaban within the VA. Additional studies are needed to understand eligibility in other populations and a formal cost-effectiveness analysis is warranted.