Medication Adherence and Blood Pressure Control: A Scientific Statement From the American Heart Association.

The widespread treatment of hypertension and resultant improvement in blood pressure have been major contributors to the dramatic age-specific decline in heart disease and stroke. Despite this progress, a persistent gap remains between stated public health targets and achieved blood pressure control rates. Many factors may be important contributors to the gap between population hypertension control goals and currently observed control levels. Among them is the extent to which patients adhere to prescribed treatment. The goal of this scientific statement is to summarize the current state of knowledge of the contribution of medication nonadherence to the national prevalence of poor blood pressure control, methods for measuring medication adherence and their associated challenges, risk factors for antihypertensive medication nonadherence, and strategies for improving adherence to antihypertensive medications at both the individual and health system levels.

A Telehealth-supported, Integrated care with CHWs, and MEdication-access (TIME) Program for Diabetes Improves HbA1c: a Randomized Clinical Trial.

BACKGROUND: Many individuals with diabetes live in low- or middle-income settings. Glycemic control is challenging, particularly in resource-limited areas that face numerous healthcare barriers. OBJECTIVE: To compare HbA1c outcomes for individuals randomized to TIME, a Telehealth-supported, Integrated care with CHWs (Community Health Workers), and MEdication-access program (intervention) versus usual care (wait-list control). DESIGN: Randomized clinical trial. PARTICIPANTS: Low-income Latino(a) adults with type 2 diabetes. INTERVENTIONS: TIME consisted of (1) CHW-participant telehealth communication via mobile health (mHealth) for 12 months, (2) CHW-led monthly group visits for 6 months, and (3) weekly CHW-physician diabetes training and support via telehealth (video conferencing). MAIN MEASURES: Investigators compared TIME versus control participant baseline to month 6 changes of HbA1c (primary outcome), blood pressure, body mass index (BMI), weight, and adherence to seven American Diabetes Association (ADA) standards of care. CHW assistance in identifying barriers to healthcare in the intervention group were measured at the end of mHealth communication (12 months). KEY RESULTS: A total of 89 individuals participated. TIME individuals compared to control participants had significant HbA1c decreases (9.02 to 7.59% (- 1.43%) vs. 8.71 to 8.26% (- 0.45%), respectively, p = 0.002), blood pressure changes (systolic: - 6.89 mmHg vs. 0.03 mmHg, p = 0.023; diastolic: - 3.36 mmHg vs. 0.2 mmHg, respectively, p = 0.046), and ADA guideline adherence (p < 0.001) from baseline to month 6. At month 6, more TIME than control participants achieved > 0.50% HbA1c reductions (88.57% vs. 43.75%, p < 0.001). BMI and weight changes were not significant between groups. Many (54.6%) TIME participants experienced > 1 barrier to care, of whom 91.7% had medication issues. CHWs identified the majority (87.5%) of barriers. CONCLUSIONS: TIME participants resulted in improved outcomes including HbA1c. CHWs are uniquely positioned to identify barriers to care particularly related to medications that may have gone unrecognized otherwise. Larger trials are needed to determine the scalability and sustainability of the intervention. CLINICAL TRIAL: NCT03394456, accessed at https://clinicaltrials.gov/ct2/show/NCT03394456.

Reducing the Burden of Diabetes Treatment: A Review of Low-cost Oral Hypoglycemic Medications.

BACKGROUND: The vast majority of individuals diagnosed with diabetes are low/middle income and may have access to only three of the 11 oral hypoglycemic medications (OHMs) due to cost: metformin intermediate release (IR) or extended release (ER), sulfonylureas (glimepiride, glipizide, glyburide), and pioglitazone. Sulfonylureas and pioglitazone have had significant controversy related to potential adverse events, but it remains unclear whether these negative outcomes are class, drug, or dose-related. OBJECTIVE: We conducted a narrative review of low-cost OHMs. METHODS: We evaluated the maximum recommended (MAX) compared to the most effective (EFF) daily dose, time-to-peak change in HbA1c levels, and adverse events of low-cost oral hypoglycemic medications. RESULTS: We found that the MAX was often greater than the EFF: metformin IR/ER (MAX: 2,550/2,000 mg, EFF: 1,500-2,000/1,500-2,000 mg), glipizide IR/ER (MAX: 40/20 mg, EFF: 20/5 mg), glyburide (MAX: 20 mg, EFF: 2.5-5.0 mg), pioglitazone (MAX: 45 mg, EFF: 45 mg). Time-to-peak change in HbA1c levels occurred at weeks 12-20 (sulfonylureas), 25-39 (metformin), and 25 (pioglitazone). Glimepiride was not associated with weight gain, hypoglycemia, or negative cardiovascular events relative to other sulfonylureas. Cardiovascular event rates did not increase with lower glyburide doses (p<0.05). Glimepiride and pioglitazone have been successfully used in renal impairment. CONCLUSION: Metformin, glimepiride, and pioglitazone are safe and efficacious OHMs. Prescribing at the EFF rather than the MAX may avoid negative dose-related outcomes. OHMs should be evaluated as individual drugs, not generalized as a class, due to different dosing and adverse-event profiles; Glimepiride is the preferred sulfonylurea since it is not associated with the adverse events as others in its class.

Telemedicine Training and Support for Community Health Workers: Improving Knowledge of Diabetes.

Background: Community health workers (CHWs) are a well-established source to improve patient health care, yet their training and support remain suboptimal. This limits program expansion and potentially compromises patient safety. The objective of the study was to evaluate the feasibility and acceptability of weekly training and support by telemedicine (videoconferencing). Materials and Methods: CHWs (n = 6) who led diabetes group visits for low-income Latinos met weekly with a health care professional for training and support. Feasibility and acceptability outcome measures included telemedicine usability, knowledge of diabetes (baseline to 6 months), and program satisfaction. Results: Telemedicine training and support were found to be feasible and acceptable as measured by usability (Telehealth Usability Questionnaire: average 4.7/5.0, ±0.4), knowledge (Diabetes Knowledge Test: pretest 15.8 ± 1.3, posttest 21.8 ± 1.2, p < 0.001, respectively), and satisfaction (Texas Department of State Health Services survey: average 5.8/6.0, ±0.5). All CHWs preferred telemedicine to in-person training. Conclusions: Telemedicine is a feasible and acceptable modality to train and support CHWs.

A Narrative Review of Diabetes Group Visits in Low-Income and Underserved Settings.

BACKGROUND: Prior studies have supported the efficacy of diabetes group visits. However, the benefit of diabetes group visits for low-income and underserved individuals is not clear. The purpose of this study was to conduct a narrative review in order to clarify the efficacy of diabetes group visits in low-income and underserved settings. METHODS: The authors performed a narrative review, categorizing studies into nonrandomized and randomized. RESULTS: A total of 14 studies were identified. Hemoglobin A1c was the most commonly measured outcome, which improved for the majority of group visit participants. Preventive care showed consistent improvement for intervention arms. There were several other study outcomes including metabolic (i.e., blood pressure), behavioral (i.e., exercise), functional (i.e., quality of life), and system-based (i.e., cost). CONCLUSION: Diabetes group visits for low-income and underserved individuals resulted in superior preventive care but the impact on glycemic control remains unclear.

Dual Therapy Appears Superior to Monotherapy for Low-Income Individuals With Newly Diagnosed Type 2 Diabetes.

BACKGROUND: There are variable recommendations regarding initiating monotherapy or dual therapy in patients with newly diagnosed type 2 diabetes (T2D). Clear initial strategies are of particular importance in underserved settings where access to care and financial burdens are significant barriers. OBJECTIVES: To provide descriptive data of metabolic outcomes to therapy regimens for low-income individuals with newly diagnosed T2D placed on oral hypoglycemic agents (OAs). METHODS: We conducted a retrospective chart review of low-income individuals with newly diagnosed T2D initiated on OAs. We provided descriptive data and then evaluated the effects of OA regimens (ie, mono-, dual-, transition [from mono to dual or vice versa] therapy) on hemoglobin A1c (A1c) (baseline to 12 months). RESULTS: A total of 309 patients were included in the study. At 12 months, the mean decrease in A1c for the entire sample was -2.36% (9.37% to 7.01%). Patients prescribed dual therapy had a greater change of A1c compared to those taking monotherapy with metformin (-1.11%, P < .01). Patients who transitioned therapies did not differ in change of A1c compared to monotherapy. CONCLUSION: Initiation of dual therapy was superior to metformin monotherapy or transitioning therapies and may be preferred for low-income individuals with newly diagnosed T2D.

Designing and evaluating health systems level hypertension control interventions for African-Americans: lessons from a pooled analysis of three cluster randomized trials.

OBJECTIVES: African-Americans (AAs) have a high prevalence of hypertension and their blood pressure (BP) control on treatment still lags behind other groups. In 2004, NHLBI funded five projects that aimed to evaluate clinically feasible interventions to effect changes in medical care delivery leading to an increased proportion of AA patients with controlled BP. Three of the groups performed a pooled analysis of trial results to determine: 1) the magnitude of the combined intervention effect; and 2) how the pooled results could inform the methodology for future health-system level BP interventions. METHODS: Using a cluster randomized design, the trials enrolled AAs with uncontrolled hypertension to test interventions targeting a combination of patient and clinician behaviors. The 12-month Systolic BP (SBP) and Diastolic BP (DBP) effects of intervention or control cluster assignment were assessed using mixed effects longitudinal regression modeling. RESULTS: 2,015 patients representing 352 clusters participated across the three trials. Pooled BP slopes followed a quadratic pattern, with an initial decline, followed by a rise toward baseline, and did not differ significantly between intervention and control clusters: SBP linear coefficient = -2.60±0.21 mmHg per month, p<0.001; quadratic coefficient = 0.167± 0.02 mmHg/month, p<0.001; group by time interaction group by time group x linear time coefficient=0.145 ± 0.293, p=0.622; group x quadratic time coefficient= -0.017 ± 0.026, p=0.525). RESULTS were similar for DBP. The individual sites did not have significant intervention effects when analyzed separately. CONCLUSION: Investigators planning behavioral trials to improve BP control in health systems serving AAs should plan for small effect sizes and employ a "run-in" period in which BP can be expected to improve in both experimental and control clusters.

A technology-based quality innovation to identify undiagnosed hypertension among active primary care patients.

PURPOSE: The goal of this study was to develop a technology-based strategy to identify patients with undiagnosed hypertension in 23 primary care practices and integrate this innovation into a continuous quality improvement initiative in a large, integrated health system. METHODS: In phase 1, we reviewed electronic health records (EHRs) using algorithms designed to identify patients at risk for undiagnosed hypertension. We then invited each at-risk patient to complete an automated office blood pressure (AOBP) protocol. In phase 2, we instituted a quality improvement process that included regular physician feedback and office-based computer alerts to evaluate at-risk patients not screened in phase 1. Study patients were observed for 24 additional months to determine rates of diagnostic resolution. RESULTS: Of the 1,432 patients targeted for inclusion in the study, 475 completed the AOBP protocol during the 6 months of phase 1. Of the 1,033 at-risk patients who remained active during phase 2, 740 (72%) were classified by the end of the follow-up period: 361 had hypertension diagnosed, 290 had either white-coat hypertension, prehypertension, or elevated blood pressure diagnosed, and 89 had normal blood pressure. By the end of the follow-up period, 293 patients (28%) had not been classified and remained at risk for undiagnosed hypertension. CONCLUSIONS: Our technology-based innovation identified a large number of patients at risk for undiagnosed hypertension and successfully classified the majority, including many with hypertension. This innovation has been implemented as an ongoing quality improvement initiative in our medical group and continues to improve the accuracy of diagnosis of hypertension among primary care patients.

Characteristics, drug combinations and dosages of primary care patients with uncontrolled ambulatory blood pressure and high medication adherence.

Most studies on the prevalence and determinants of resistant hypertension (RH) do not account for white coat hypertension, medication non-adherence, or use of suboptimal treatment dosages. We studied the characteristics, drug combinations, and dosages of patients on at least three antihypertensives of different classes who had uncontrolled blood pressure on 24-hour ambulatory blood pressure monitoring and high medication adherence measured by electronic monitoring. The data were collected as part of the baseline measures of a hypertension control trial. Of 140 monitored primary care patients, all with uncontrolled office blood pressure, 69 (49%) were on at least three antihypertensives of different classes. Of these 69, 15 (22%) were controlled on ambulatory blood pressure monitoring, 20 (29%) were uncontrolled and non-adherent, leaving only 34 (49%) adherent to their medications and having uncontrolled ambulatory hypertension (uncontrolled RH). Thirty-one (91%) of the 34 uncontrolled RH patients were prescribed a diuretic, of which 24 were on hydrochlorothiazide 25 mg. Less than half of the patients on angiotensin-converting enzyme inhibitor, angiotensin receptor blocker, or calcium channel blocker were prescribed maximal doses of these agents. Half of the RH can be attributed to white coat effect and poor medication adherence, and all of the remaining patients were on apparently suboptimal drug combinations and/or dosages. Primary care physicians need to be educated regarding the optimal treatment of RH.

Patterns of nonadherence to antihypertensive therapy in primary care.

Nonadherence to medications is an important cause of poor blood pressure control. Long-acting antihypertensive agents could theoretically be beneficial in partially adherent patients, who are commonly seen in contemporary practice. Little has been reported about the duration of drug holidays (DHs) in treated hypertensives outside of generally compliant patients in phase 4 clinical trials. The authors described patterns of nonadherence to single and multiple antihypertensives in a random sample of 120 primary care patients with uncontrolled hypertension. Adherence to up to 3 antihypertensives was measured by electronic monitoring. Frequencies of single-day omissions and DHs of 2 consecutive days (DH2), 3 days (DH3), or ≥4 days (DH≥4) for each drug were calculated. Overall, 89 (74%) of patients had at least a 1-day omission. A single day omission was found in 61.4% of the patients taking 1 drug, followed by DH≥4 (28.1%), DH2 (26.3%), and DH3 (8.8%). In patients using multiple drugs, single-day omissions were also most common, followed by DH≥4, DH2, and DH3. Omissions of ≤3 days comprise on average 74% of all omissions. Although encouraging full adherence remains important, it may be prudent to prescribe long-acting antihypertensive agents, which can compensate for the majority of dose omissions.

Self-efficacy and barriers to multiple behavior change in low-income African Americans with hypertension.

Behavioral risk factors are among the preventable causes of health disparities, yet long-term change remains elusive. Many interventions are designed to increase self-efficacy, but little is known about the effect on long-term behavior change in older, low-income African Americans, especially when facing more problematic barriers. A cohort of 185 low-income African-Americans with hypertension reported barriers they encountered while undergoing a multiple behavior change trial from 2002 to 2006. The purpose of the present study was to explore the relationships between self-efficacy, barriers, and multiple behavior change over time. Higher self-efficacy seemed to be partially helpful for smoking reduction and increasing physical activity, but not for following a low-sodium diet. Addiction was indirectly associated with less reduction in smoking through lower self-efficacy. Otherwise, different barriers were associated with behavior change than were associated with self-efficacy: being "too busy" directly interfered with physical activity and "traditions" with low-sodium diet; however, they were neither the most frequently reported barriers, nor associated with lower self-efficacy. This suggests that an emphasis on self-efficacy alone may be insufficient for overcoming the most salient barriers encountered by older African Americans. Additionally, the most common perceived barriers may not necessarily be relevant to long-term behavioral outcomes.

Predictors of antihypertensive medication adherence in two urban health-care systems.

BACKGROUND: Most studies on patient-related predictors of adherence used self-reported measures or pharmacy databases to measure adherence. We identified predictors of antihypertensive medication adherence measured by Medication Event Monitoring System (MEMS), the gold standard for adherence assessment, in uncontrolled, predominantly African-American (AA) hypertensives from large urban public and private primary care clinics. METHODS: As part of the baseline data collection of a cluster-randomized trial for hypertension control, we measured adherence in a random sample of 124 participants using MEMS caps. We also included the data of 52 patients in intervention clinics who subsequently completed MEMS monitoring on referral from their provider. Participants were classified as adherent if they took ≥ 80% of all prescribed doses. Multivariate logistic regression was used to predict adherence. RESULTS: Of 176 patients monitored, 61 (34.6%) took <80% of prescribed doses. AA ethnicity (odds ratio (OR) AA vs. Hispanic = 0.36; 95% confidence interval (CI) 0.15-0.86), female sex (OR = 0.38; 95% CI 0.15-0.91), and public clinics as source of care (OR public clinics vs. private clinics = 0.45; 95% CI 0.20-0.97) were independently associated with lower adherence. Higher adherence was seen in patients monitored by clinician order in the intervention clinics (OR intervention sample vs. random baseline sample = 2.15; 95% CI 0.96-4.81) and diabetic patients (OR = 2.05; 95% CI 1.01-4.15). All analyses were adjusted for education, employment status, and other potentially confounding factors. CONCLUSIONS: AA ethnicity, female gender and attending a publicly funded primary care clinic were associated with lower adherence. Whether targeting these groups for special interventions would improve overall adherence needs further study.

Warfarin resistance associated with parenteral nutrition.

Warfarin is widely used as an oral anticoagulant for the prevention and long-term treatment of venous thromboembolism and for the prevention of thromboembolic complications associated with atrial fibrillation, heart valve replacement and myocardial infarction. Warfarin exerts its anticoagulation effect by inhibiting the enzymes responsible for the cyclic interconversion of vitamin K in the liver. Vitamin K serves as a cofactor required for the carboxylation of the vitamin K-dependent coagulation proteins. By inhibiting the supply of vitamin K in the production of these proteins, warfarin indirectly slows their rate of synthesis. The authors describe a 46-year-old patient readily anticoagulated for a deep venous thrombosis who then required large doses of warfarin after initiation of total parenteral nutrition, which included lipid preparation that contained vitamin K, in addition to vitamin K required for the daily parenteral nutrition. The effect of total parenteral nutrition with vitamin K on anticoagulation is discussed.

Effect of a physician uncertainty reduction intervention on blood pressure in uncontrolled hypertensives--a cluster randomized trial.

BACKGROUND: Clinical inertia, provider failure to appropriately intensify treatment, is a major contributor to uncontrolled blood pressure (BP). Some clinical inertia may result from physician uncertainty over the patient's usual BP, adherence, or value of continuing efforts to control BP through lifestyle changes. OBJECTIVE: To test the hypothesis that providing physicians with uncertainty reduction tools, including 24-h ambulatory BP monitoring, electronic bottle cap monitoring, and lifestyle assessment and counseling, will lead to improved BP control. DESIGN: Cluster randomized trial with five intervention clinics (IC) and five usual care clinics (UCC). SETTING: Six public and 4 private primary care clinics. PARTICIPANTS: A total of 665 patients (63 percent African American) with uncontrolled hypertension (BP ≥140 mmHg/90 mmHg or ≥130/80 mmHg if diabetic). INTERVENTIONS: An order form for uncertainty reduction tools was placed in the IC participants' charts before each visit and results fed back to the provider. OUTCOME MEASURES: Percent with controlled BP at last visit. Secondary outcome was BP changes from baseline. RESULTS: Median follow-up time was 24 months. IC physicians intensified treatment in 81% of IC patients compared to 67% in UCC (p < 0.001); 35.0% of IC patients and 31.9% of UCC patients achieved control at the last recorded visit (p > 0.05). Multi-level mixed effects longitudinal regression modeling of SBP and DBP indicated a significant, non-linear slope difference favoring IC (p (time × group interaction) = 0.048 for SBP and p = 0.001 for DBP). The model-predicted difference attributable to intervention was -2.8 mmHg for both SBP and DBP by month 24, and -6.5 mmHg for both SBP and DBP by month 36. CONCLUSIONS: The uncertainty reduction intervention did not achieve the pre-specified dichotomous outcome, but led to lower measured BP in IC patients.

Does reducing physician uncertainty improve hypertension control?: rationale and methods.

Hypertension affects nearly one third of the US population overall, and the prevalence rises sharply with age. In spite of public educational campaigns and professional education programs to encourage blood pressure measurement and control of both systolic and diastolic control to <140/90 mm Hg (or 130/80 mm Hg if diabetic), 43% of treated hypertensives do not achieve the recommended Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure target. Among blacks, 48% are uncontrolled on treatment. The majority of persons classified as poorly controlled hypertensives have mild systolic blood pressure elevation (in the range of 140 to 160 mm Hg). We hypothesized that physician uncertainty regarding the patient's usual blood pressure, as well as uncertainty regarding the extent of medication nonadherence, represent an important barrier to further reductions in the proportion of uncontrolled hypertensives in the United States. Using cluster randomization, 10 primary care clinics (6 from a public health care system and 4 from a private clinic system) were randomized to either the uncertainty reduction intervention condition or to usual care. An average of 68 patients per clinic were recruited to serve as units of observation. Physicians in the 5 intervention clinics were provided with a specially designed study form that included a graph of recent blood pressure measurements in their study patients, a check box to indicate their assessment of the adequacy of the patient's blood pressure control, and a menu of services they could order to aid in patient management. These menu options included 24-hour ambulatory blood pressure monitoring; electronic bottle cap assessment of medication adherence, followed by medication adherence counseling in patients found to be nonadherent; and lifestyle assessment and counseling followed by 24-hour ambulatory blood pressure monitoring. Physicians in the 5 usual practice clinics did not have access to these services but were informed of which patients had been enrolled in the study. Substudies carried out to further characterize the study population and interpret intervention results included ambulatory blood pressure monitoring and electronic bottle cap monitoring in a random subsample of patients at baseline, and audio recording of patient-physician encounters after intervention implementation. The primary study end point was defined as the proportion of patients with controlled blood pressure (<140/90 mm Hg or <130/80 mm Hg if diabetic). Secondary end points include actual measured clinic systolic and diastolic blood pressure, patient physician communication patterns, physician prescribing patient self-reported lifestyle and medication adherence, physician knowledge, attitude and beliefs regarding the utility of intervention tools to achieve blood pressure control, and the cost-effectiveness of the intervention. Six-hundred eighty patients have been randomized, and 675 remain in active follow-up after 1.5 years. Patient closeout will be complete in March 2009. Analyses of the baseline data are in progress. Office-based blood pressure measurement error and bias, as well as physician and patient beliefs about the need for treatment intensification, may be important factors that limit further progress in blood pressure control. This trial will provide data on the extent to which available technologies not widely used in primary care will change physician prescribing behavior and patient adherence to prescribed treatment.

Blood pressure control in the elderly: can you have too much of a good thing?

Hypertension (especially systolic hypertension) is very common in older persons. Systolic hypertension occurs because large conduit arteries become stiffer with age. Strong evidence from randomized trials suggests that treating systolic blood pressures initially higher than 160 mm Hg is extremely beneficial, and a recent trial extended this conclusion to healthy persons over 80 years of age. However, the only trial that has directly tested the use of more aggressive treatment goals (< 140 mm Hg) in the elderly did not show benefit in those older than 75. Risks of overtreating hypertension for the elderly include falls and orthostatic hypotension, and the most compromised older persons may be the most likely to experience adverse effects. Our current state of knowledge requires clinical judgment that balances the immediacy of adverse effects versus the potential but unproven benefits of treatment in deciding whether to treat the elderly more aggressively than the goals used in randomized trials.