Fall risk and cardiovascular outcomes of first-line antihypertensive medications in nursing home residents.

BACKGROUND: Little evidence exists about the comparative effects of first-line antihypertensive medications (i.e., renin-angiotensin-aldosterone converting enzyme inhibitors (RAASi), amlodipine, or thiazide diuretics) in older adults with limited life expectancy. We compared the rates of injurious falls and short-term cardiovascular events between different first-line antihypertensive medication classes in adults receiving care in nursing homes (NH). METHODS: This was a retrospective cohort of Medicare fee-for-service beneficiaries receiving care in NHs. Patients newly dispensed first-line antihypertensive medications were identified using Part D claims (2015-2018) and linked with clinical assessments (i.e., Minimum Data Set). Fall-related injuries (FRI), hip fractures, and major adverse cardiac events (MACE) outcomes were identified using hospitalization claims. Patients were followed from the date of antihypertensive dispensing until the occurrence of outcomes, death, disenrollment, or 6-month follow-up. Inverse-probability-of-treatment-weighted (IPTW) cause-specific hazards regression models were used to compare outcomes between patients who were new users of RAASi, amlodipine, or thiazides. RESULTS: Our cohort included 16,504 antihypertensive users (RAASi, n = 9574; amlodipine, n = 5049; thiazide, n = 1881). Mean age was 83.5 years (± 8.2), 70.6% were female, and 17.2% were non-white race. During a mean follow-up of 5.3 months, 326 patients (2.0%) experienced an injurious fall, 1590 (9.6%) experienced MACE, and 2123 patients (12.9%) died. The intention-to-treat IPTW hazard ratio (HR) for injurious falls for amlodipine (vs RAASi) use was 0.85 (95% confidence interval (CI) 0.66-1.08) and for thiazides (vs RAASi) was 1.22 (95% CI 0.88-1.66). The rates of MACE were similar between those taking anti-hypertensive medications. Thiazides were discontinued more often than other classes; however, inferences were largely unchanged in as-treated analyses. Subgroup analyses were generally consistent. CONCLUSIONS: Older adults with limited life expectancy experience similar rates of injurious falls and short-term cardiovascular events after initiating any of the first-line antihypertensive medications.

Chloride and Potassium Assessment Is a Helpful Tool for Differential Diagnosis of Thiazide-Associated Hyponatremia.

CONTEXT: Differential diagnosis of thiazide-associated hyponatremia (TAH) is challenging. Patients can either have volume depletion or a syndrome of inappropriate antidiuresis (SIAD)-like presentation. OBJECTIVE: To evaluate the impact of the simplified apparent strong ion difference in serum (aSID; sodium + potassium - chloride) as well as the urine chloride and potassium score (ChU; chloride - potassium in urine) in the differential diagnosis of TAH, in addition to assessment of fractional uric acid excretion (FUA). METHODS: Post hoc analysis of prospectively collected data from June 2011 to August 2013 from 98 hospitalized patients with TAH < 125 mmol/L enrolled at University Hospital Basel and University Medical Clinic Aarau, Switzerland. Patients were categorized according to treatment response in volume-depleted TAH requiring volume substitution or SIAD-like TAH requiring fluid restriction. We computed sensitivity analyses with ROC curves for positive predictive value (PPV) and negative predictive value (NPV) of aSID, ChU, and FUA in differential diagnosis of TAH. RESULTS: An aSID > 42 mmol/L had a PPV of 79.1% in identifying patients with volume-depleted TAH, whereas a value < 39 mmol/L excluded it with a NPV of 76.5%. In patients for whom aSID was inconclusive, a ChU < 15 mmol/L had a PPV of 100% and a NPV of 83.3%, whereas FUA < 12% had a PPV of 85.7% and a NPV of 64.3% in identifying patients with volume-depleted TAH. CONCLUSION: In patients with TAH, assessment of aSID, potassium, and chloride in urine can help identifying patients with volume-depleted TAH requiring fluid substitution vs patients with SIAD-like TAH requiring fluid restriction.

Empiric therapy for kidney stones.

Careful phenotyping of patients to classify those with kidney stones has a long and important history in revealing the chemical basis for stone formation. Advances in our genetic understanding of kidney stones will lead to incredible insights regarding the pathophysiology of this common disorder. At this time, both evaluation of urine chemistry and genotyping of patients are extremely useful in the setting of a university and research-based kidney stone clinic. For much of the world, in a more clinically focused setting, these techniques are neither available nor absolutely necessary. Careful implementation of an empiric prescription based on stone composition would have an important effect to reduce stone recurrence in the world's many stone formers. Increased fluid intake, generic dietary manipulations, and prescription of potassium citrate and thiazides are all appropriate empiric therapies for people with calcium and uric acid kidney stones.

Quality and cost considerations in hyponatraemic patients needing hospitalisation.

BACKGROUND: Hyponatraemia is the most common electrolyte disorder encountered in hospitalised patients and has an impact on outcome and survival. However, the risk factors are not yet sufficiently known. AIMS OF THE STUDY: This retrospective analysis was conducted with the primary objective to identify the incidence of hyponatraemia in patients, who need hospitalisation from any medical reason, focusing on the quality of treatment and the risk factors for recurrent or prolonged stay due to hyponatraemia. The secondary objectives were the calculation of costs of hyponatraemia caused by hospital stays in the canton of Basel-Landschaft and the additional extrapolation of these costs for the whole country of Switzerland. METHODS: 368 patients with a diagnosis of hyponatraemia admitted to three tertiary care centers in 2011 were included. We analysed the risk factors, causes and manifestations of hyponatraemia and their effects on length of stay and outcome. RESULTS: Female gender (62%), advanced age (average 75 ± 12 years) and the use of thiazides (r = 0.69, p = 0.03) represented the main risk factors with negative prognostic value concerning hyponatraemia. Hyponatraemia was never asymptomatic. Seventy-three patients (20%) were diagnosed with hyponatraemia due to SIADH (syndrome of inappropriate antidiuretic hormone secretion). The in-hospital mortality rate was 9%, irrespective of the severity of hyponatraemia, and every fifth patient had persistent neurological deficits on discharge from the hospital. Age (r = 0.65, p = 0.03), female sex (r = 0.49, p =0.12; in combination with age >75years r = 0.58, p = 0.049), resumption of risk medication (r = 0.563, p = 0.02) and persistent hyponatraemia on discharge (r = -0.51, p = 0.04) were associated with higher probability of relapse. Our data, extrapolated for Switzerland, yield uncovered annual costs of 93 million CHF, mostly due to in-hospital treatment longer than that reimbursed by SwissDRG (observed median of 9 days, cost coverage by SwissDRG 5 days for non-SIADH hyponatraemia and 6.5 days for SIADH). CONCLUSIONS: As even mild hyponatraemia is associated with an increased risk of morbidity and mortality, it is highly important to recognise it. Initial diagnostic evaluation, treatment based on volume status and thorough follow-up are crucial to avoid relapse. Hyponatraemia, based on the results of this retrospective study, constitutes a considerable medical and economic burden in Switzerland and has a serious impact on the hospital balance sheets.

Efficacy of Patient Activation Interventions With or Without Financial Incentives to Promote Prescribing of Thiazides and Hypertension Control: A Randomized Clinical Trial.

Importance: Evidence-based guidelines recommend thiazide diuretics as a first-line therapy for uncomplicated hypertension; however, thiazides are underused, and hypertension remains inadequately managed. Objective: To test the efficacy of a patient activation intervention with financial incentives to promote thiazide prescribing. Design, Setting, and Participants: The Veterans Affairs Project to Implement Diuretics, a randomized clinical trial, was conducted at 13 Veterans Affairs primary care clinics from August 1, 2006, to July 31, 2008, with 12 months of follow-up. A total of 61 019 patients were screened to identify 2853 eligible patients who were not taking a thiazide and not at their blood pressure (BP) goal; 598 consented to participate. Statistical analysis was conducted from December 1, 2017, to September 12, 2018. Interventions: Patients were randomized to a control group (n = 196) or 1 of 3 intervention groups designed to activate patients to talk with their primary care clinicians about thiazides and hypertension: group A (n = 143) received an activation letter, group B (n = 128) received a letter plus a financial incentive, and group C (n = 131) received a letter, financial incentive, and a telephone call encouraging patients to speak with their primary care clinicians. Main Outcomes and Measures: Primary outcomes were thiazide prescribing and BP control. A secondary process measure was discussion between patient and primary care clinician about thiazides. Results: Among 598 participants (588 men and 10 women), the mean (SD) age for the combined intervention groups (n = 402) was 62.9 (8.8) years, and the mean baseline BP was 148.1/83.8 mm Hg; the mean (SD) age for the control group (n = 196) was 64.1 (9.2) years, and the mean baseline BP was 151.0/83.4 mm Hg. At index visits, the unadjusted rate of thiazide prescribing was 9.7% for the control group (19 of 196) and 24.5% (35 of 143) for group A, 25.8% (33 of 128) for group B, and 32.8% (43 of 131) for group C (P < .001). Adjusted analyses demonstrated an intervention effect on thiazide prescribing at the index visit and 6-month visit, which diminished at the 12-month visit. For BP control, there was a significant intervention effect at the 12-month follow-up for group C (adjusted odds ratio, 1.73; 95% CI, 1.06-2.83; P = .04). Intervention groups exhibited improved thiazide discussion rates in a dose-response fashion: group A, 44.1% (63 of 143); group B, 56.3% (72 of 128); and group C, 68.7% (90 of 131) (P = .004). Conclusions and Relevance: This patient activation intervention about thiazides for hypertension resulted in two-thirds of patients having discussions and nearly one-third initiating a prescription of thiazide. Adding a financial incentive and telephone call to the letter resulted in incremental improvements in both outcomes. By 12 months, improved BP control was also evident. This low-cost, low-intensity intervention resulted in high rates of discussions between patients and clinicians and subsequent thiazide treatment and may be used to promote evidence-based guidelines and overcome clinical inertia. Trial Registration: ClinicalTrials.gov Identifier: NCT00265538.

Methodology to Estimate the Longitudinal Average Attributable Fraction of Guideline-recommended Medications for Death in Older Adults With Multiple Chronic Conditions.

BACKGROUND: Persons with multiple chronic conditions receive multiple guideline-recommended medications to improve outcomes such as mortality. Our objective was to estimate the longitudinal average attributable fraction for 3-year survival of medications for cardiovascular conditions in persons with multiple chronic conditions and to determine whether heterogeneity occurred by age. METHODS: Medicare Current Beneficiary Survey participants (N = 8,578) with two or more chronic conditions, enrolled from 2005 to 2009 with follow-up through 2011, were analyzed. We calculated the longitudinal extension of the average attributable fraction for oral medications (beta blockers, renin-angiotensin system blockers, and thiazide diuretics) indicated for cardiovascular conditions (atrial fibrillation, coronary artery disease, heart failure, and hypertension), on survival adjusted for 18 participant characteristics. Models stratified by age (≤80 and >80 years) were analyzed to determine heterogeneity of both cardiovascular conditions and medications. RESULTS: Heart failure had the greatest average attributable fraction (39%) for mortality. The fractional contributions of beta blockers, renin-angiotensin system blockers, and thiazides to improve survival were 10.4%, 9.3%, and 7.2% respectively. In age-stratified models, of these medications thiazides had a significant contribution to survival only for those aged 80 years or younger. The effects of the remaining medications were similar in both age strata. CONCLUSIONS: Most cardiovascular medications were attributed independently to survival. The two cardiovascular conditions contributing independently to death were heart failure and atrial fibrillation. The medication effects were similar by age except for thiazides that had a significant contribution to survival in persons younger than 80 years.

[Thiazides--a first choice against high blood pressure]. / Tiazider--et førstevalg mot høyt blodtrykk.

Thiazide therapy of hypertension has increased substantially in Norway during the last decade. This is caused partly by changed dosage recommendations - which has led to fewer side effects - and an increased awareness of the cost associated with hypertension therapy. Thiazide therapy is among one of the most cost-effective drug therapies within preventive cardiology. Prevention of primary endpoints such as cerebrovascular disease, cardiovascular mortality and congestive heart failure is well documented.

Hypertension treatment in a medicare population: adherence and systolic blood pressure control.

BACKGROUND: Despite substantial trial evidence that demonstrates the effectiveness of pharmacologic treatment for reducing blood pressure (BP) and cardiovascular events, many patients are nonadherent to their hypertension treatment. OBJECTIVES: The purpose of this study was to examine patient adherence to hypertension medications using pharmacy data (ie, outpatient, inpatient, and mail-order prescriptions) and the association between adherence measures and systolic BP (SBP) control. METHODS: The study included Medicare + Choice beneficiaries (aged > or = 65 years) who were continuously enrolled in an integrated delivery system in 2003, and who had documented hypertension and received > or = 1 hypertension drug in 2002. This analysis used automated clinical data and the 2000 US Census. We estimated 2 measures of hypertension treatment adherence in 2003 using the supply of dispensed drugs in days (proportion of days covered > or = 80%): (1) adherence to > or = 1 hypertension drug; and (2) adherence to the full hypertension treatment regimen. We defined the regimen by the number of hypertension drugs used concurrently in 2002. We assessed adherence annually and during the 30, 60, and 90 days before an SBP measurement. Logistic regression was used to examine the association between adherence and the number of drugs in the hypertension regimen, as well as the association between adherence and elevated SBP ( > or = 140 mm Hg). We adjusted for patient sociodemographic and clinical characteristics. RESULTS: The majority (52.8%) of patients had multidrug hypertension regimens. In 2003, 87.3% of subjects were adherent to > or = 1 hypertension drug; 72.1% were adherent to their full regimen. After adjustment, we found that subjects with multidrug regimens were significantly more likely to be adherent to > or = 1 drug and significantly less likely to be adherent to their full regimen, compared with patients on a 1-drug regimen. Over one-third of subjects had elevated SBP in 2003. Both adherence measures were associated with lower odds of having elevated SBP (eg, odds ratio = 0.87 [95% CI, 0.84-0.89] for adherence to the full regimen). For subjects with multidrug regimens, partial adherence and nonadherence to the regimen were associated with higher odds of having elevated SBP. CONCLUSIONS: Adherence measures using automated pharmacy data can identify patients who are nonadherent to their drug treatment regimen and who are more likely to have inadequately controlled BP. Adherence measures that account for the number of drugs in a patients' drug regimen might help identify additional patients at risk for poor BP outcomes due to partial treatment adherence.

The effects of mandatory prescribing of thiazides for newly treated, uncomplicated hypertension: interrupted time-series analysis.

BACKGROUND: The purpose of our study was to evaluate the effects of a new reimbursement rule for antihypertensive medication that made thiazides mandatory first-line drugs for newly treated, uncomplicated hypertension. The objective of the new regulation was to reduce drug expenditures. METHODS AND FINDINGS: We conducted an interrupted time-series analysis on prescribing data before and after the new reimbursement rule for antihypertensive medication was put into effect. All patients started on antihypertensive medication in 61 general practices in Norway were included in the analysis. The new rule was put forward by the Ministry of Health and was approved by parliament. Adherence to the rule was monitored only minimally, and there were no penalties for non-adherence. Our primary outcome was the proportion of thiazide prescriptions among all prescriptions made for persons started on antihypertensive medication. Secondary outcomes included the proportion of patients who, within 4 mo, reached recommended blood-pressure goals and the proportion of patients who, within 4 mo, were not started on a second antihypertensive drug. We also compared drug costs before and after the intervention. During the baseline period, 10% of patients started on antihypertensive medication were given a thiazide prescription. This proportion rose steadily during the transition period, after which it remained stable at 25%. For other outcomes, no statistically significant differences were demonstrated. Achievement of treatment goals was slightly higher (56.6% versus 58.4%) after the new rule was introduced, and the prescribing of a second drug was slightly lower (24.0% versus 21.8%). Drug costs were reduced by an estimated Norwegian kroner 4.8 million (0.58 million Euros, US$0.72 million) in the first year, which is equivalent to Norwegian kroner 1.06 per inhabitant (0.13 Euros, US$0.16). CONCLUSIONS: Prescribing of thiazides in Norway for uncomplicated hypertension more than doubled after a reimbursement rule requiring the use of thiazides as the first-choice therapy was put into effect. However, the resulting savings on drug expenditures were modest. There were no significant changes in the achievement of treatment goals or in the prescribing of a second antihypertensive drug.