Evaluating alternative methods of comparing antihypertensive treatment intensity.

OBJECTIVES: To change blood pressure treatment, clinicians can modify medication count or dose. However, existing studies have measured count modification, which may miss clinically important dose change in the absence of count change. This research demonstrates how dose modification captures more information about management than medication count alone. STUDY DESIGN: Retrospective cohort study. METHODS: We included patients 65 years and older with established primary care at the Veterans Health Administration (July 2011-June 2013). We captured medication count and standardized dose change over 90 to 120 days using a validated pharmacy fill algorithm. We determined frequency of dose change without count change (and vice versa), no change in either, change in same direction ("concordant"), and change in opposite direction ("discordant"). We compared change according to systolic blood pressure (SBP) and compared concordance using a minimum threshold definition of dose change of at least 50% (instead of any change) of baseline dose modification. RESULTS: Among 440,801 patients, 64.2% had dose change; 22.0%, count change; 35.6%, no change in either; 42.4%, dose change without count modification; and 0.2%, count change without dose modification. Discordance occurred in 2.1% of observations. Using the minimum threshold definition of change, 68.7% had no change in either dose or count. Treatment was more frequently changed at SBP greater than 140 mm Hg. CONCLUSIONS: Measuring change in antihypertensive treatment using medication count frequently missed an isolated dose change in treatment modification and less often misclassified regimen modifications where there was no modification in total dose. In future research, measuring dose modification using our new algorithm would capture change in hypertension treatment intensity more precisely than current methods.

Adding a New Medication Versus Maximizing Dose to Intensify Hypertension Treatment in Older Adults : A Retrospective Observational Study.

BACKGROUND: There are 2 approaches to intensifying antihypertensive treatment when target blood pressure is not reached, adding a new medication and maximizing dose. Which strategy is better is unknown. OBJECTIVE: To assess the frequency of intensification by adding a new medication versus maximizing dose, as well as the association of each method with intensification sustainability and follow-up systolic blood pressure (SBP). DESIGN: Large-scale, population-based, retrospective cohort study. Observational data were used to emulate a target trial with 2 groups, new medication and maximizing dose, who underwent intensification of their drug regimen. SETTING: Veterans Health Administration (2011 to 2013). PATIENTS: Veterans aged 65 years or older with hypertension, an SBP of 130 mm Hg or higher, and at least 1 antihypertensive medication at less than the maximum dose. MEASUREMENTS: The following 2 intensification approaches were emulated: adding a new medication, defined as a total dose increase with new medication, and maximizing dose, defined as a total dose increase without new medication. Inverse probability weighting was used to assess the observational effectiveness of the intensification approach on sustainability of intensified treatment and follow-up SBP at 3 and 12 months. RESULTS: Among 178 562 patients, 45 575 (25.5%) had intensification by adding a new medication and 132 987 (74.5%) by maximizing dose. Compared with maximizing dose, adding a new medication was associated with less intensification sustainability (average treatment effect, -15.2% [95% CI, -15.7% to -14.6%] at 3 months and -15.1% [CI, -15.6% to -14.5%] at 12 months) but a slightly larger reduction in mean SBP (-0.8 mm Hg [CI, -1.2 to -0.4 mm Hg] at 3 months and -1.1 mm Hg [CI, -1.6 to -0.6 mm Hg] at 12 months). LIMITATION: Observational data; largely male population. CONCLUSION: Adding a new antihypertensive medication was less frequent and was associated with less intensification sustainability but slightly larger reductions in SBP. Trials would provide the most definitive support for our findings. PRIMARY FUNDING SOURCE: National Institute on Aging and Veterans Health Administration.

Factors associated with antihypertensive treatment intensification and deintensification in older outpatients.

BACKGROUND: New hypertension performance measures encourage more intensive treatment in older adults. Treatment intensification includes starting new medications and increasing the dose of old ones. Medication dose is particularly important to older adults, given their vulnerability to dose-related side effects. We previously validated a standardized measure of beneficial doses tested in hypertension trials, Hypertension Daily Dose (HDD). AIM OF THE STUDY: To test whether changes in treatment intensity using HDD was associated with systolic blood pressure (SBP) and patient characteristics. METHODS: Longitudinal study of all Veterans aged ≥65 years with a diagnosis of hypertension. We defined 3 groups of risk: 1) cardiovascular risk; 2) geriatric/frail; 3) low-risk (comparator). Using multinomial regression, we assessed the probability of deintensification, intensification, vs. stable treatment, according to SBP and group. RESULTS: Among 1,331,111 Veterans, 19.9% had deintensification, and 29.6% intensification. Deintensification decreased, while intensification increased, with SBP. Compared to low-risk patients, cardiovascular risk patients had 1.11 (95% CI 1.10-1.13) times the odds of intensifying, and geriatric/frail patients 1.45 (95%CI 1.43-1.47) times the odds of deintensifying. DISCUSSION: Patient-level HDD change was consistent with an expected association with cardiovascular risk and geriatric/frail conditions, suggesting that HDD can be used longitudinally to assess hypertension treatment modification in large health systems.

Clinical outcomes of modifying hypertension treatment intensity in older adults treated to low blood pressure.

BACKGROUND/OBJECTIVES: Hypertension treatment reduces cardiovascular events. However, uncertainty remains about benefits and harms of deintensification or further intensification of antihypertensive medication when systolic blood pressure (SBP) is tightly controlled in older multimorbid patients, because of their frequent exclusion in trials. We assessed the association of hypertension treatment deintensification or intensification with clinical outcomes in older adults with tightly controlled SBP. DESIGN: Longitudinal cohort study (2011-2013) with 9-month follow-up. SETTING: U.S.-nationwide primary care Veterans Health Administration healthcare system. PARTICIPANTS: Veterans aged 65 and older with baseline SBP <130 mmHg and ≥1 antihypertensive medication during ≥2 consecutive visits (N = 228,753). EXPOSURE: Deintensification or intensification, compared with stable treatment. MAIN OUTCOMES AND MEASURES: Cardiovascular events, syncope, or fall injury, as composite and distinct outcomes, within 9 months after exposure. Adjusted logistic regression and inverse probability of treatment weighting (IPTW, sensitivity analysis). RESULTS: Among 228,753 patients (mean age 75 [SD 7.5] years), the composite outcome occurred in 11,982/93,793 (12.8%) patients with stable treatment, 14,768/72,672 (20.3%) with deintensification, and 11,821/62,288 (19.0%) with intensification. Adjusted absolute outcome risk (95% confidence interval) was higher for deintensification (18.3% [18.1%-18.6%]) and intensification (18.7% [18.4%-19.0%]), compared with stable treatment (14.8% [14.6%-15.0%]), p < 0.001 for both effects in the multivariable model). Deintensification was associated with fewer cardiovascular events than intensification. At baseline SBP <95 mmHg, cardiovascular event risk was similar for deintensification and stable treatment, and fall risk lower for deintensification than intensification. IPTW yielded similar results. Mean follow-up SBP was 124.1 mmHg for stable treatment, 125.1 mmHg after deintensification (p < 0.001), and 124.0 mmHg after intensification (p < 0.001). CONCLUSION: Antihypertensive treatment deintensification in older patients with tightly controlled SBP was associated with worse outcomes than continuing same treatment intensity. Given higher mortality among patients with treatment modification, confounding by indication may not have been fully corrected by advanced statistical methods for observational data analysis.

A Method to Quantify Mean Hypertension Treatment Daily Dose Intensity Using Health Care System Data.

Importance: Simple measures of hypertension treatment, such as achievement of blood pressure (BP) targets, ignore the intensity of treatment once the BP target is met. High-intensity treatment involves increased treatment burden and can be associated with potential adverse effects in older adults. A method was previously developed to identify older patients receiving intense hypertension treatment by low BP and number of BP medications using national Veterans Health Administration and Medicare Part D administrative pharmacy data to evaluate which BP medications a patient is likely taking on any given day. Objective: To further develop and validate a method to more precisely quantify dose intensity of hypertension treatment using only health system administrative pharmacy fill data. Design, Setting, and Participants: Observational, cross-sectional study of 319 randomly selected older veterans in the national Veterans Health Administration health care system who were taking multiple BP-lowering medications and had a total of 3625 ambulatory care visits from July 1, 2011, to June 30, 2013. Measure development and medical record review occurred January 1, 2017, through November 30, 2018, and data analysis was conducted from December 1, 2019, to August 31, 2020. Main Outcomes and Measures: For each BP-lowering medication, a moderate hypertension daily dose (HDD) was defined as half the maximum dose above which no further clinical benefit has been demonstrated by that medication in hypertension trials. Patients' total HDD was calculated using pharmacy data (pharmacy HDDs), accounting for substantial delays in refills (>30 days) when a patient's pill supply was stretched (eg, cutting existing pills in half). As an external comparison, the pharmacy HDDs were correlated with doses manually extracted from clinicians' visit notes (clinically noted HDDs). How well the pharmacy HDDs correlated with clinically noted HDDs was calculated (using C statistics). To facilitate interpretation, HDDs were described in association with the number of medications. Results: A total of 316 patients (99.1%) were male; the mean (SD) age was 75.6 (7.2) years. Pharmacy HDDs were highly correlated (r = 0.92) with clinically noted HDDs, with a mean (SD) of 2.7 (1.8) for pharmacy HDDs and 2.8 (1.8) for clinically noted HDDs. Pharmacy HDDs correlated with high-intensity, clinically noted HDDs ranging from a C statistic of 92.8% (95% CI, 92.0%-93.7%) for 2 or more clinically noted HDDs to 88.1% (95% CI, 85.5%-90.6%) for 6 or more clinically noted HDDs. Conclusions and Relevance: This study suggests that health system pharmacy data may be used to accurately quantify hypertension regimen dose intensity. Together with clinic-measured BP, this tool can be used in future health system-based research or quality improvement efforts to fine-tune, manage, and optimize hypertension treatment in older adults.

Validation of a Health System Measure to Capture Intensive Medication Treatment of Hypertension in the Veterans Health Administration.

Importance: Blood pressure (BP) targets are the main measure of high-quality hypertension care in health systems. However, BP alone does not reflect intensity of pharmacological treatment, which should be carefully managed in older patients. Objectives: To develop and validate an electronic health record (EHR) data-only algorithm using pharmacy and BP data to capture intensive hypertension care (IHC), defined as 3 or more BP medications and BP less than 120 mm Hg, and to identify conditions associated with greater IHC, either through greater algorithm false-positive IHC, or by contributing clinically to delivering more IHC. Design, Setting, and Participants: This cross-sectional study was conducted among 319 randomly selected patients aged 65 years or older receiving IHC from the Veterans Health Administration (VHA) from July 1, 2011, to June 30, 2013. Data were collected from a total of 3625 primary care visits. Data were analyzed from January 2017 to March 2020. Exposures: Calibration and measurement of the algorithm for IHC (algorithm IHC). Main Outcomes and Measures: For each primary care visit, the reference standard, clinical IHC, was determined by detailed review of free-text clinical notes. The correlation in BP medication count between the EHR-only algorithm vs the reference standard and the sensitivity and specificity of the algorithm IHC were calculated. In addition, presence vs absence of contributing conditions acting in combination with hypertension management were measured to examine incidence of IHC associated with contributing conditions, including an acute condition that lowered BP (eg, dehydration), another condition requiring a BP target lower than the standard 140 mm Hg (eg, diabetes), or the patient needing a BP-lowering medication for a nonhypertension condition (eg, ß-blocker for atrial fibrillation) resulting in low BP. Results: Among 319 patients with 3625 visits (mean [SD] age, 75.6 [7.2] years; 3592 [99.1%] men), 911 visits (25.1%) had clinical IHC by the reference standard. The algorithm for determining medication count was highly correlated with the reference standard (r = 0.84). Sensitivity of detecting clinical IHC was 92.2% (95% CI, 89.3%-95.1%), and specificity was 97.2% (95% CI, 96.1%-98.3%), suggesting that clinical IHC can be identified from routinely collected data. Only 75 visits (2.1%) were algorithm IHC false positives, 55 visits (1.5%) involved IHC with contributing conditions, and 125 visits (3.5%) involved either false-positive or IHC with contributing conditions. Among select contributing conditions, congestive heart failure (37 patients [5.2%]) was most associated with a prespecified combined false-positive or IHC with contributing conditions rate higher than 5%. Conclusions and Relevance: These findings suggest that health system data can be used reliably to estimate IHC.

A simple clinical risk nomogram to predict mortality-associated geriatric complications in severely injured geriatric patients.

BACKGROUND: This study aimed to (1) identify inpatient complications associated with the greatest differential mortality risk between young and old patients with traumatic injury and (2) identify older patients at elevated risk for mortality-associated complications. METHODS: Secondary analysis of more than 280,000 patients hospitalized for traumatic injury in 2001 to 2005 collected by the National Trauma Data Bank was performed. Predictor variables include 21 hospital complications. We used each complication to predict odds of hospital mortality, stratified by old (65+ years) versus young (18-64 years) age, controlling for age, sex, and preexisting condition count. We defined mortality-associated geriatric complications (MGCs) as complications associated with more than two times risk of mortality in older patients compared with younger patients. We then used age, comorbidity, and sex to predict development of MGCs or death. RESULTS: We defined seven infectious and six noninfectious complications as MGCs (adjusted relative risk reduction for death associated with old age [aRRR] with 95% confidence interval [CI]): abscess (aRRR, 4.1; 95% CI, 3.6-4.5), wound infection (aRRR, 3.5; 95% CI, 3.2-3.9), empyema (aRRR, 3.4; 95% CI, 3.1, 3.8), urinary tract infection (aRRR, 3.3; 95% 3.0-3.6), pneumonia (aRRR, 3.1; 95% CI, 2.8-3.5), bacteremia (aRRR, 2.8; 95% CI, 2.6-3.0), aspiration pneumonia (aRRR, 2.6; 95% CI, 2.2-3.0), reduction/fixation failure (aRRR, 3.6; 95% CI, 3.3-3.9), pressure ulcer (aRRR, 3.3; 95% CI, 3.1-3.6), deep venous thrombosis (aRRR, 3.2; 95% CI, 2.9-3.6), pneumothorax (aRRR, 3.1; 95% CI, 2.5-3.7), and compartment syndrome (aRRR, 2.2; 95% CI, 1.5-2.9). We developed a graphical nomogram based on sex, age, and number of preexisting conditions to predict risk of MGCs (c statistic, 0.74). CONCLUSION: Older patients at risk for MGC development should be considered for targeted interventions to improve quality of care. LEVEL OF EVIDENCE: Prognostic/epidemiologic study, level III.