Sustained SBP control and long-term nursing home admission among Medicare beneficiaries.

OBJECTIVES: Sustaining SBP control reduces the risk for cardiovascular events that impair function but its association with nursing home admission has not been well studied. METHODS: We conducted an analysis of sustained SBP control and long-term nursing home admissions using data from the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) linked to Medicare claims restricted to participants with fee-for-service coverage, at least eight study visits with SBP measurements, who were not living in a nursing home during a 48-month baseline BP assessment period (n = 6557). Sustained SBP control was defined as less than 140 mmHg at less than 50%, 50% to less than 75%, 75% to less than 100%, and 100% of visits. Nursing home admissions were identified using the Medicare Long Term Care Minimum Data Set. RESULTS: The mean age of participants was 73.8 years and 44.3% were men. Over a median follow-up of 9.2 years, 844 participants (12.8%) had a nursing home admission. Rates of nursing home admission per 100 person-years were 16.3 for participants with SBP control at less than 50%, 14.1 at 50% to less than 75%, 7.8 at 75% to less than 100%, and 5.3 at 100% of visits. Compared with those with sustained SBP control at less than 50% of visits, hazard ratios (95% confidence intervals) for nursing home admission were 0.79 (0.66-0.93), 0.70 (0.58-0.84), and 0.57 (0.44-0.74) among participants with SBP control at 50% to less than 75%, 75% to less than 100%, and 100% of visits, respectively. CONCLUSION: Among Medicare beneficiaries in ALLHAT, sustained SBP control was associated with a lower risk of long-term nursing home admission.

Association of Sustained Blood Pressure Control with Lower Risk for High-Cost Multimorbidities Among Medicare Beneficiaries in ALLHAT.

BACKGROUND: Clustering of chronic conditions is associated with high healthcare costs. Sustaining blood pressure (BP) control could be a strategy to prevent high-cost multimorbidity clusters. OBJECTIVE: To determine the association between sustained systolic BP (SBP) control and incident multimorbidity cluster dyads and triads. DESIGN: Cohort study of Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) linked to Medicare claims. PARTICIPANTS: ALLHAT included adults with hypertension and ≥1 coronary heart disease risk factor. This analysis was restricted to 5234 participants with ≥ 8 SBP measurements during a 48-month BP assessment period. MAIN MEASURES: SBP control was defined as <140 mm Hg at <50%, 50 to <75%, 75 to <100%, and 100% of study visits during the BP assessment period. High-cost multimorbidity clusters included dyads (stroke/chronic kidney disease [CKD], stroke/chronic obstructive pulmonary disease [COPD], stroke/heart failure [HF], stroke/asthma, COPD/CKD) and triads (stroke/CKD/asthma, stroke/CKD/COPD, stroke/CKD/depression, stroke/CKD/HF, stroke/HF/asthma) identified during follow-up. KEY RESULTS: Incident dyads occurred in 1334 (26%) participants and triads occurred in 481 (9%) participants over a median follow-up of 9.2 years. Among participants with SBP control at <50%, 50 to <75%, 75 to <100%, and 100% of visits, 32%, 23%, 23%, and 19% of participants developed high-cost dyads, respectively, and 13%, 9%, 8%, and 5% of participants developed high-cost triads, respectively. Compared to those with sustained BP control at <50% of visits, adjusted HRs (95% CI) for incident dyads were 0.66 (0.57, 0.75), 0.67 (0.59, 0.77), and 0.51 (0.42, 0.62) for SBP control at 50 to <75%, 75 to <100%, and 100% of visits, respectively. The corresponding HRs (95% CI) for incident triads were 0.69 (0.55, 0.85), 0.56 (0.44, 0.71), and 0.32 (0.22, 0.47). CONCLUSIONS: Among Medicare beneficiaries in ALLHAT, sustained SBP was associated with a lower risk of developing high-cost multimorbidity dyads and triads.

Association of Sustained Blood Pressure Control with Multimorbidity Progression Among Older Adults.

BACKGROUND/OBJECTIVES: Due to the high costs and excess mortality associated with multimorbidity, there is a need to develop approaches for delaying its progression. High blood pressure (BP) is a common chronic condition and a risk factor for many additional chronic conditions, making it an ideal target for intervention. The purpose of this analysis was to determine the association between the level of sustained BP control and the progression of multimorbidity. DESIGN: Retrospective cohort study. SETTING: Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) linked to Medicare claims. PARTICIPANTS: A total of 6,591 ALLHAT participants with Medicare who had systolic BP (SBP) measurements at eight or more study visits. MEASUREMENTS: SBP control was categorized as lower than 140 mm Hg at less than 50%, 50% to less than 75%, 75% to less than 100%, and 100% of visits. Multimorbidity progression was defined by the number of incident chronic conditions, including arthritis, asthma, atrial fibrillation, cancer, chronic kidney disease, chronic obstructive pulmonary disease, coronary heart disease, dementia, depression, diabetes mellitus, heart failure, hyperlipidemia, osteoporosis, and stroke. Recurrent event survival analysis was used to calculate rate ratios (RRs) for the association of sustained SBP control with progression of multimorbidity. RESULTS: Rates of incident conditions per 10 person-years (95% CIs) were 5.2 (5.1-5.4), 4.7 (4.5-4.8), 4.4 (4.2-4.5), and 4.0 (3.8-4.2) for participants with SBP control at less than 50%, 50% to less than 75%, 75% to less than 100%, and 100% of visits, respectively, over a median follow-up of 9.0 years. Compared with participants with SBP control at less than 50% of visits, adjusted RRs (95% CIs) for multimorbidity progression were 0.90 (0.86-0.95), 0.85 (0.81-0.89), and 0.77 (0.72-0.82) for those with SBP control at 50% to less than 75%, 75% to less than 100%, and 100% of visits, respectively. CONCLUSIONS: Sustaining BP control may be an effective approach to slow multimorbidity progression and may reduce the population burden of multimorbidity.

Effects of Antihypertensive Class on Falls, Syncope, and Orthostatic Hypotension in Older Adults: The ALLHAT Trial.

Hypertension treatment has been implicated in falls, syncope, and orthostatic hypotension (OH), common events among older adults. Whether the choice of antihypertensive agent influences the risk of falls, syncope, and OH in older adults is unknown. ALLHAT (Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial) was a randomized clinical trial that compared the effects of hypertension first-step therapy on fatal coronary heart disease or nonfatal myocardial infarction (1994-2002). In a subpopulation of ALLHAT participants, age 65 years and older, we determined the relative risk of falls, syncope, OH, or a composite based on Centers for Medicare and Medicaid Services and Veterans Affairs claims, using Cox regression. We also determined the adjusted association of self-reported atenolol use (ascertained at the 1-month visit for indications other than hypertension) on outcomes in Cox models adjusted for age, sex, and race. Among 23 964 participants (mean age 69.8±6.8 years, 45% women, 31% non-Hispanic black) followed for a mean of 4.9 years, we identified 267 falls, 755 syncopes, 249 OH, and 1157 composite claims. There were no significant differences in the cumulative incidences of events across randomized drug assignments. However, amlodipine increased risk of falls during the first year of follow-up compared with chlorthalidone (hazard ratio [95% CI]: 2.24 [1.06-4.74]; P=0.03) or lisinopril (hazard ratio [95% CI]: 2.61 [1.03-6.72]; P=0.04). Atenolol use (N=928) was not associated with any of the 3 individual or composite claims. In older adults, the choice of antihypertensive agent had no effect on risk of fall, syncope, or OH long-term. However, amlodipine increased risk of falls within 1 year of initiation. These short-term findings require confirmation. Clinical Trial Registration- URL: http://www.clinicaltrials.gov. Unique identifier: NCT00000542.

Disparities in Socioeconomic Context and Association With Blood Pressure Control and Cardiovascular Outcomes in ALLHAT.

Background Observational studies demonstrate that communities of low socioeconomic status have higher blood pressure and worse cardiovascular outcomes. Yet, whether the clinical outcomes resulting from antihypertensive therapy vary by socioeconomic context in a randomized clinical trial, in which participants are treated under a standard protocol, is unknown. Methods and Results We used data from ALLHAT (Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial) to study the effect of socioeconomic context, defined as the county-level median household income, of study sites. We stratified sites into income quintiles and compared characteristics, blood pressure control, and cardiovascular outcomes among ALLHAT participants in the lowest- and highest-income quintiles. Among 27 862 qualifying participants, 2169 (7.8%) received care in the lowest-income sites (quintile 1) and 10 458 (37.6%) received care in the highest-income sites (quintile 5). Participants in quintile 1 were more likely to be women, to be black, to be Hispanic, to have fewer years of education, to live in the South, and to have fewer cardiovascular risk factors. After adjusting for baseline demographic and clinical characteristics, quintile 1 participants were less likely to achieve blood pressure control (<140/90 mm Hg) (odds ratio, 0.48; 95% CI, 0.37-0.63) and had greater all-cause mortality (hazard ratio [HR], 1.25; 95% CI, 1.10-1.41), heart failure hospitalizations/mortality (HR, 1.26; 95% CI, 1.03-1.55), and end-stage renal disease (HR, 1.86; 95% CI, 1.26-2.73), but lower angina hospitalizations (HR, 0.70; 95% CI, 0.59-0.83) and coronary revascularizations (HR, 0.71; 95% CI, 0.57-0.89). Conclusions Despite standardized treatment protocols, ALLHAT participants in the lowest-income sites experienced poorer blood pressure control and worse outcomes for some adverse cardiovascular events, emphasizing the importance of measuring and addressing socioeconomic context. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT00000542.

Effect of Statin Treatment vs Usual Care on Primary Cardiovascular Prevention Among Older Adults: The ALLHAT-LLT Randomized Clinical Trial.

Importance: While statin therapy for primary cardiovascular prevention has been associated with reductions in cardiovascular morbidity, the effect on all-cause mortality has been variable. There is little evidence to guide the use of statins for primary prevention in adults 75 years and older. Objectives: To examine statin treatment among adults aged 65 to 74 years and 75 years and older when used for primary prevention in the Lipid-Lowering Trial (LLT) component of the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT-LLT). Design, Setting, and Participants: Post hoc secondary data analyses were conducted of participants 65 years and older without evidence of atherosclerotic cardiovascular disease; 2867 ambulatory adults with hypertension and without baseline atherosclerotic cardiovascular disease were included. The ALLHAT-LLT was conducted from February 1994 to March 2002 at 513 clinical sites. Interventions: Pravastatin sodium (40 mg/d) vs usual care (UC). Main Outcomes and Measures: The primary outcome in the ALLHAT-LLT was all-cause mortality. Secondary outcomes included cause-specific mortality and nonfatal myocardial infarction or fatal coronary heart disease combined (coronary heart disease events). Results: There were 1467 participants (mean [SD] age, 71.3 [5.2] years) in the pravastatin group (48.0% [n = 704] female) and 1400 participants (mean [SD] age, 71.2 [5.2] years) in the UC group (50.8% [n = 711] female). The baseline mean (SD) low-density lipoprotein cholesterol levels were 147.7 (19.8) mg/dL in the pravastatin group and 147.6 (19.4) mg/dL in the UC group; by year 6, the mean (SD) low-density lipoprotein cholesterol levels were 109.1 (35.4) mg/dL in the pravastatin group and 128.8 (27.5) mg/dL in the UC group. At year 6, of the participants assigned to pravastatin, 42 of 253 (16.6%) were not taking any statin; 71.0% in the UC group were not taking any statin. The hazard ratios for all-cause mortality in the pravastatin group vs the UC group were 1.18 (95% CI, 0.97-1.42; P = .09) for all adults 65 years and older, 1.08 (95% CI, 0.85-1.37; P = .55) for adults aged 65 to 74 years, and 1.34 (95% CI, 0.98-1.84; P = .07) for adults 75 years and older. Coronary heart disease event rates were not significantly different among the groups. In multivariable regression, the results remained nonsignificant, and there was no significant interaction between treatment group and age. Conclusions and Relevance: No benefit was found when pravastatin was given for primary prevention to older adults with moderate hyperlipidemia and hypertension, and a nonsignificant direction toward increased all-cause mortality with pravastatin was observed among adults 75 years and older. Trial Registration: clinicaltrials.gov Identifier: NCT00000542.

Bayesian analysis of multi-type recurrent events and dependent termination with nonparametric covariate functions.

Multi-type recurrent event data occur frequently in longitudinal studies. Dependent termination may occur when the terminal time is correlated to recurrent event times. In this article, we simultaneously model the multi-type recurrent events and a dependent terminal event, both with nonparametric covariate functions modeled by B-splines. We develop a Bayesian multivariate frailty model to account for the correlation among the dependent termination and various types of recurrent events. Extensive simulation results suggest that misspecifying nonparametric covariate functions may introduce bias in parameter estimation. This method development has been motivated by and applied to the lipid-lowering trial component of the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial.

Cardiovascular risk assessment: addition of CKD and race to the Framingham equation.

BACKGROUND/AIMS: The value of the Framingham equation in predicting cardiovascular risk in African Americans and patients with chronic kidney disease (CKD) is unclear. The purpose of the study was to evaluate whether the addition of CKD and race to the Framingham equation improves risk stratification in hypertensive patients. METHODS: Participants in the ALLHAT were studied. Those randomized to doxazosin, older than 74 years, and those with a history of coronary heart disease were excluded. Two risk stratification models were developed using Cox proportional hazards models in a two-thirds developmental sample. The first model included the traditional Framingham risk factors. The second model included the traditional risk factors plus CKD, defined by estimated glomerular filtration rate categories, and stratification by race (black vs non-black). The primary outcome was a composite of fatal coronary heart disease, nonfatal myocardial infarction, coronary revascularization, and hospitalized angina. RESULTS: There were a total of 19,811 eligible subjects. In the validation cohort, there was no difference in C-statistics between the Framingham equation and the ALLHAT model including CKD and race. This was consistent across subgroups by race and sex and among those with CKD. One exception was among Non-Black women where the C-statistic was higher for the Framingham equation (0.68 vs 0.65, P = .02). In addition, net reclassification improvement was not significant for any subgroup based on race and sex, ranging from -5.5% to 4.4%. CONCLUSION: The addition of CKD status and stratification by race does not improve risk prediction in high-risk hypertensive patients.

Mortality and morbidity during and after the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial.

A randomized, double-blind, active-controlled, multicenter trial assigned 32,804 participants aged 55 years and older with hypertension and ≥ 1 other coronary heart disease risk factors to receive chlorthalidone (n=15,002), amlodipine (n=8898), or lisinopril (n=8904) for 4 to 8 years, when double-blinded therapy was discontinued. Passive surveillance continued for a total follow-up of 8 to 13 years using national administrative databases to ascertain deaths and hospitalizations. During the post-trial period, fatal outcomes and nonfatal outcomes were available for 98% and 65% of participants, respectively, due to lack of access to administrative databases for the remainder. This paper assesses whether mortality and morbidity differences persisted or new differences developed during the extended follow-up. Primary outcome was cardiovascular mortality and secondary outcomes were mortality, stroke, coronary heart disease, heart failure, cardiovascular disease, and end-stage renal disease. For the post-trial period, data are not available on medications or blood pressure levels. No significant differences (P<.05) appeared in cardiovascular mortality for amlodipine (hazard ratio [HR], 1.00; 95% confidence interval [CI], 0.93-1.06) or lisinopril (HR, 0.97; CI, 0.90-1.03), each compared with chlorthalidone. The only significant differences in secondary outcomes were for heart failure, which was higher with amlodipine (HR, 1.12; CI, 1.02-1.22), and stroke mortality, which was higher with lisinopril (HR, 1.20; CI, 1.01-1.41), each compared with chlorthalidone. Similar to the previously reported in-trial result, there was a significant treatment-by-race interaction for cardiovascular disease for lisinopril vs chlorthalidone. Black participants had higher risk than non-black participants taking lisinopril compared with chlorthalidone. After accounting for multiple comparisons, none of these results were significant. These findings suggest that neither calcium channel blockers nor angiotensin-converting enzyme inhibitors are superior to diuretics for the long-term prevention of major cardiovascular complications of hypertension.

Cost-effectiveness of chlorthalidone, amlodipine, and lisinopril as first-step treatment for patients with hypertension: an analysis of the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT).

OBJECTIVE: To evaluate the cost-effectiveness of first-line treatments for hypertension. BACKGROUND: The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) found that first-line treatment with lisinopril or amlodipine was not significantly superior to chlorthalidone in terms of the primary endpoint, so differences in costs may be critical for optimizing decision-making. METHODS: Cost-effectiveness analysis was performed using bootstrap resampling to evaluate uncertainty. RESULTS: Over a patient's lifetime, chlorthalidone was always least expensive (mean $4,802 less than amlodipine, $3,700 less than lisinopril). Amlodipine provided more life-years (LYs) than chlorthalidone in 84% of bootstrap samples (mean 37 days) at an incremental cost-effectiveness ratio of $48,400 per LY gained. Lisinopril provided fewer LYs than chlorthalidone in 55% of bootstrap samples (mean 7-day loss) despite a higher cost. At a threshold of $50,000 per LY gained, amlodipine was preferred in 50%, chlorthalidone in 40%, and lisinopril in 10% of bootstrap samples, but these findings were highly sensitive to the cost of amlodipine and the cost-effectiveness threshold chosen. Incorporating quality of life did not appreciably alter the results. Overall, no reasonable combination of assumptions led to 1 treatment being preferred in over 90% of bootstrap samples. CONCLUSIONS: Initial treatment with chlorthalidone is less expensive than lisinopril or amlodipine, but amlodipine provided a nonsignificantly greater survival benefit and may be a cost-effective alternative. A randomized trial with power to exclude "clinically important" differences in survival will often have inadequate power to determine the most cost-effective treatment.