MANAGEMENT OF RISKS OF ADVERSE DRUG REACTIONS ACCORDING TO ADR REPORT FORM DATA FROM LVIV REGION HEALTHCARE FACILITIES IN 2022.

The study aimed to analyse the adverse drug reactions report form data received by the State Expert Center of the Ministry of Health of Ukraine from healthcare professionals in the Lviv region in 2022. Regarding specific types of medicines, the ones with proven cause-and-effect relationships that caused the highest frequency of adverse drug reactions incidents were chemotherapeutic agents (35.5%), medicines affecting the cardiovascular system (20.3%), and non-steroidal anti-inflammatory drugs (8%). Within the penicillin class, amoxicillin potentiated by clavulanate (67%) and amoxicillin (29%) were the dominant drugs showing the highest incidence rate of adverse reactions. Among cephalosporins, ceftriaxone (46%) and cefixime (15%) were found to take the lead in terms of adverse reaction frequency. The highest proportion among all adverse drug reactions caused by penicillins and cephalosporins was attributed to allergic reactions. To confirm or rule out immediate or delayed type allergies in patients, as well as in patients with a history of immediate-type allergic reactions to ß-lactams and planned administration of another ß-lactam, it is necessary to conduct skin testing (skin prick test, or, in the case of parenteral administration, intradermal test) with the planned ß-lactam antibiotic. The second highest proportion of induced adverse drug reactions was attributed to drugs affecting the cardiovascular system (20.3%). The leading medications in the angiotensin-converting enzyme inhibitors category were enalapril (47%) and the combination of lisinopril with hydrochlorothiazide (24%). In the angiotensin II receptor blockers category of medications, valsartan (30%) and telmisartan-hydrochlorothiazide combination (20%) ranked highest. In the category of CCB drugs, amlodipine (66%) and nifedipine (20%) held the leading positions. among angiotensin-converting enzyme inhibitors, enalapril caused the most prevalent and predicted adverse reaction, that of cough, affecting 10.5% of patients, whereas, with the combination therapy of lisinopril and hydrochlorothiazide, the cough was observed in only 5.2% of patients. Angiotensin II receptor blockers have a better safety profile, particularly concerning cough. Analysis of adverse drug reactions reports for angiotensin II receptor blockers showed no cases of cough with valsartan and telmisartan-hydrochlorothiazide combination. Among calcium channel blocker medications, amlodipine emerged to rank highest, causing one of the predicted adverse drug reactions, that of lower extremity oedema in 64% of patients. The second position was taken by the combination of amlodipine with valsartan, which showed a statistically significant reduction of 14.3% (p≤0.05) in the incidence of oedema. Using amlodipine at a dose of 5 mg in combination with sartan medicines as angiotensin receptor blockers is an effective therapeutic alternative not only for enhancing blood pressure control in hypertensive patients but also for improving the safety profile of amlodipine. Among all the non-steroidal anti-inflammatory drugs prescribed to patients in the Lviv region in 2022, the highest number of adverse reactions was associated with the administration of diclofenac, ibuprofen, paracetamol, and nimesulide, causing adverse drug reactions in 22%, 19%, 17%, and 10% of cases, respectively. The most common systemic manifestations of adverse reactions with these non-steroidal anti-inflammatory drugs were allergic reactions (63.4%) and gastrointestinal disorders (26.8%). From an evidence-based medicine perspective, the most justified approach for primary and secondary prevention of gastrointestinal complications is the use of proton pump inhibitors.

Optical Metabolic Imaging for Assessment of Radiation-Induced Injury to Rat Kidney and Mitigation by Lisinopril.

The kidney is one of the most radiosensitive organs; it is the primary dose-limiting organ in radiotherapies for upper abdominal cancers. The role of mitochondrial redox state in the development and treatment of renal radiation injury, however, remains ill-defined. This study utilizes 3D optical cryo-imaging to quantify renal mitochondrial bioenergetics dysfunction after 13 Gy leg-out partial body irradiation (PBI). Furthermore, the mitigating effects of lisinopril (lisino), an anti-hypertensive angiotensin converting enzyme inhibitor, is assessed in renal radiation-induced injuries. Around day 150 post-irradiation, kidneys are harvested for cryo-imaging. The 3D images of the metabolic indices (NADH, nicotinamide adenine dinucleotide, and FAD, flavin adenine dinucleotide) are acquired, and the mitochondrial redox states of the irradiated and irradiated + lisino kidneys are quantified by calculating the volumetric mean redox ratio (NADH/FAD). PBI oxidized renal mitochondrial redox state by 78%. The kidneys from the irradiated + lisino rats showed mitigation of mitochondrial redox state by 93% compared to the PBI group. The study provides evidence for an altered bioenergetics and energy metabolism in the rat model of irradiation-induced kidney damage. In addition, the results suggest that lisinopril mitigates irradiation damage by attenuating the oxidation of mitochondria leading to increase redox ratio.

Cost-Effectiveness of Sacubitril-Valsartan in Patients With Heart Failure With Reduced Ejection Fraction.

BACKGROUND: Sacubitril-valsartan therapy reduces cardiovascular mortality compared with enalapril therapy in patients with heart failure with reduced ejection fraction. OBJECTIVE: To evaluate the cost-effectiveness of sacubitril-valsartan versus angiotensin-converting enzyme inhibitor therapy in patients with chronic heart failure. DESIGN: Markov decision model. DATA SOURCES: Clinical trials, observational analyses, reimbursement data from the Centers for Medicare & Medicaid Services, drug pricing databases, and Centers for Disease Control and Prevention life tables. TARGET POPULATION: Patients at an average age of 64 years, New York Heart Association (NYHA) class II to IV heart failure, and left ventricular ejection fraction of 0.40 or less. TIME HORIZON: Lifetime. PERSPECTIVE: Societal. INTERVENTION: Treatment with sacubitril-valsartan or lisinopril. OUTCOME MEASURES: Life-years, quality-adjusted life-years (QALYs), costs, heart failure hospitalizations, and incremental cost-effectiveness ratios. RESULTS OF BASE-CASE ANALYSIS: The sacubitril-valsartan group experienced 0.08 fewer heart failure hospitalization, 0.69 additional life-year, 0.62 additional QALY, and $29 203 in incremental costs, equating to a cost per QALY gained of $47 053. The cost per QALY gained was $44 531 in patients with NYHA class II heart failure and $58 194 in those with class III or IV heart failure. RESULTS OF SENSITIVITY ANALYSIS: Sacubitril-valsartan treatment was most sensitive to the duration of improved outcomes, with a cost per QALY gained of $120 623 if the duration was limited to the length of the trial (median, 27 months). No variations in other parameters caused the cost to exceed $100 000 per QALY gained. LIMITATION: The benefit of sacubitril-valsartan is based on a single clinical trial. CONCLUSION: Treatment with sacubitril-valsartan provides reasonable value in reducing cardiovascular mortality and morbidity in patients with NYHA class II to IV heart failure. PRIMARY FUNDING SOURCE: U.S. Department of Veterans Affairs and Institute for Clinical and Economic Review.

[Comparative Assessment of Effects of Free and Fixed Combinations of Hypotensive Drugs on Quality of Life of Patients With Arterial Hypertension of High and Very High Risk].

PURPOSE: comparative assessment of effects of free and fixed combinations of hypotensive drugs on quality of life (QL) of patients with arterial hypertension (AH) of high and very high risk of cardiovascular complications. MATERIAL: Study group comprised 120 patients (70% men, 30% women, age 45-65 years) with degree II (20.9%) and III (79.1%) A. Duration of AH was 10.6+/-2.89 years. Risk was high in 58 (48.3%), very high - in 62 (51.7%) patients. Patients were randomized into 3 groups with different second step therapy. Patients of group 1 received amlodipine + ramipril, group 2 - amlodipine + lisinopril, group 3 - fixed amlodipine/lisinopril combination. If necessary bisoprolol and indapamide were added at 3-rd and 4-th step, respectively. Assessment of QL was carried out prior to therapy and at the end of 14-th week of intervention by means of Short Form-36 (SF-36). RESULTS: Use of fixed amlodipine/lisinopril combination in patients with AH with high and very high risk of cardiovascular complications compared with free combinations of amlodipine and lisinopril or ramipril was associated with statistically significant improvement of a number of QL parameters as assessed by SF-36 questionnaire: physical functioning, bodily pain, general health, social functioning, and mental health.

Renoprevention: A new concept for reengineering nephrology care--an economic impact and patient outcome analysis of two hypothetical patient management paradigms in the CCU.

BACKGROUND: The impact of acute kidney injury (AKI) on chronic kidney disease (CKD) progression remains uncertain; the common belief is that AKI in CKD is short-lived with subsequent full recovery. However 25.2% of end-stage renal disease (ESRD) Medicare patients all experienced antecedent AKI. We recently described a new syndrome of ESRD following AKI, the syndrome of rapid-onset end-stage renal disease (SORO-ESRD). Renoprevention, which we described in 2009, is the application of preventative measures to reduce AKI incidence. METHODS: This is a descriptive study based on real clinical experience. Two hypothetical 69-year-old Caucasian male patients, A and B, with symptomatic coronary artery disease (CAD) presented for elective cardiac catheterization and subsequent coronary artery bypass graft procedures; renoprevention was applied in patient A but not in B. RESULTS: Aggressive fluid repletion, withholding Lisinopril 40 mg once daily (QD) 1 week before hospitalization (hydralazine substituted) in A-earlier discharge after 6 days, transient minimal change in serum creatinine. Patient B continued on Lisinopril 40 mg QD, experienced prolonged hypotension needing pressors-severe oliguric AKI, volume overload, daily RRT for 6 days, recovered kidney function, was discharged after 20 days. Hospital charges were $68,580 (A) versus $154,650 (B). If patient B had developed ESRD (SORO-ESRD), the savings would be humongous. CONCLUSION: A more forceful and pragmatic application of renoprevention strategies in the coronary care unit (CCU)-preemptive withholding of nephrotoxics including renin angiotensin aldosterone system (RAAS) blockers, aggressive prevention of perioperative hypotension, avoiding nephrotoxic exposure as contrast, and antibiotics-leads to less AKI, potentially less SORO-ESRD, better patient outcomes, and massive dollar savings. Such paradigm shifts would constitute major rethinking in current nephrology practice, a form of nephrology practice reengineering.

Does bargaining affect Medicare prescription drug plan reimbursements to independent pharmacies?

OBJECTIVE: To examine how pharmacy bargaining activities affect reimbursement rates in Medicare Part D prescription drug plan (PDP) contracts, controlling for pharmacy quality attributes, market structures, and area socioeconomic status. DESIGN: Cross-sectional study. SETTING: Six Medicare regions throughout the United States between October and December 2009. PARTICIPANTS: Random sample of 1,650 independent pharmacies; 321 returned surveys containing sufficient responses for analysis. INTERVENTION: Pharmacies were surveyed regarding PDP reimbursement rates, costs, and cash prices of two popular prescription drugs (atorvastatin calcium [Lipitor-Pfizer] and lisinopril, 1-month supply of a common strength), as well as pharmacy bargaining activities and quality attributes. Data also were used from the National Council for Prescription Drug Programs pharmacy database, the 2000 U. S. Census, and the 2006 Economic Census on local market structures and area socio-economic status. MAIN OUTCOME MEASURE: PDP reimbursement rates. RESULTS: For the brand-name drug atorvastatin calcium, the PDP reimbursement was positively related to a pharmacy's request for a contract change (ß = 0.887, P < 0.05), whereas other bargaining activities were not significantly related to PDP reimbursement. However, for the generic drug lisinopril, no bargaining activities were found to be significantly related to the PDP reimbursement. CONCLUSION: Pharmacy request for a contract change was associated with higher reimbursement rates for the brand-name drug atorvastatin calcium in PDP contracts, after controlling for pharmacy quality attributes, local market structures, and area socioeconomic status; this finding likely applies to other brand-name drugs because of the structure of the contracts. Our results suggest that independent pharmacies are more likely to acquire higher reimbursement rates by engaging in active bargaining with third-party payers.

Controlling hypertension and hypotension immediately post stroke (CHHIPS)--a randomised controlled trial.

OBJECTIVES: To assess the effects of acute pressor and depressor blood pressure (BP) manipulation on 2-week death and dependency following acute stroke and investigate the safety and efficacy of such treatments. DESIGN: A multicentre, prospective, randomised, double-blind, placebo-controlled titrated-dose trial. SETTING: Five hospitals in England. PARTICIPANTS: Patients over 18 years admitted to hospital with a clinical diagnosis of suspected stroke and either (1) symptom onset < 36 hours and hypertension, defined as systolic BP (SBP) < 160 mmHg (depressor arm), or (2) symptom onset < 12 hours and hypotension, defined as SBP < or = 140 mmHg (pressor arm). INTERVENTIONS: Patients were allocated to either the pressor or the depressor arm depending on blood pressure at randomisation. The ratio of allocation to active intervention versus matched placebo was 2:1 for the depressor arm and 1:1 for the pressor arm. MAIN OUTCOME MEASURES: The primary end point was death and dependency at 2 weeks, with dependency defined as a modified Rankin score < 3. Secondary end points were the safety of acute pressor (0-12 hours post stroke) and depressor (0-36 hours post stroke) BP manipulation in stroke patients; whether effects of BP reduction are influenced by stroke type (ischaemic versus haemorrhagic); whether alternative routes for administration of antihypertensive therapy (including sublingual and intravenous) are effective in dysphagic stroke patients; whether effects of BP manipulation are influenced by the time to treatment; and the short- and medium-term cost-effectiveness of such therapy in the acute post-stroke period on subsequent disability or death. RESULTS: 180 patients were recruited over the 36-month trial period, 179 in the depressor arm and one in the pressor arm (who received placebo). No significant difference was found in death or dependency at 2 weeks between those receiving active depressor treatment with lisinopril or labetalol and those receiving placebo, although numbers recruited to the trial were lower than projected. Active treatment was not associated with an increase in early neurological deterioration despite significantly greater reductions in BP at 24 hours and 2 weeks with active therapy compared with placebo. Active treatment was generally well tolerated and treatment discontinuation rates were similar in active and placebo groups. Survival analysis showed that the active treatment group had a lower mortality at 3 months than the placebo group (p = 0.05). The pressor arm was closed early because of problems with recruitment, so no conclusions can be drawn regarding this therapy. CONCLUSIONS: Oral and sublingual lisinopril and oral and intravenous labetalol are effective BP-lowering agents in acute cerebral infarction and haemorrhage and do not increase the likelihood of early neurological deterioration. The study was not sufficiently powered to detect a difference in disability or death at 2 weeks. However, the 3-month difference in mortality in favour of active treatment is of interest, although care must be taken in interpretation of the results. Further work is needed to confirm this and to assess whether there are differences in the effectiveness of labetalol compared with lisinopril in terms of reducing death or dependency after acute stroke, and whether the introduction of treatment post stroke earlier than was achieved here would be of greater benefit.

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.

Angiotensin-converting enzyme inhibitor therapy for coronary artery disease and diabetes mellitus.

OBJECTIVES: To use a population management strategy to increase the proportion of patients with coronary artery disease (CAD) and diabetes receiving target-dose angiotensin-converting enzyme (ACE) inhibitor therapy and to assess the safety and tolerability of this initiative. STUDY DESIGN: Prospective cohort. METHODS: Patients were eligible for enrollment if they were not receiving target-dose ACE inhibitor therapy. Clinical pharmacy specialists were responsible for initiation, titration, and appropriate follow-up of ACE inhibitor therapy. RESULTS: A total of 453 subjects were enrolled. Their mean age was 67.9 years and 77% were male. At baseline, 30.9% (n = 140) of eligible patients were on no ACE inhibitor therapy and no patients were at the target dose. The mean systolic blood pressure, serum creatinine, and serum potassium values were 128.0 mm Hg, 1.0 mg/dL, and 4.4 mEq/dL, respectively. At follow-up, 8.2% (n = 37; P < .001) were on no ACE inhibitor therapy and 68.7% (n = 311; P < .001) of patients had achieved the target dose. From baseline to follow-up, mean systolic blood pressure decreased 4.4 mm Hg (P < .001). Changes in serum potassium or creatinine were not clinically significant. Of the 142 subjects unable to achieve the target dose, 31 experienced hypotension, 29 did not have the dose increased because of the potential for hypotension, and 23 experienced cough. CONCLUSION: A population management approach to increasing the proportion of patients with CAD and diabetes who receive target-dose ACE inhibitor therapy was effective and safe.

Valsartan versus lisinopril or extended-release metoprolol in preventing cardiovascular and renal events in patients with hypertension.

PURPOSE: The objective of this study was to compare cardiovascular and renal events in patients with hypertension receiving the angiotensin II-receptor blocker valsartan versus those receiving the angiotensin-converting-enzyme lisinopril or the beta-blocker metoprolol succinate in an extended-release formulation. METHODS: A retrospective study was conducted using a health insurance claims database spanning the period from January 1997 through December 2003 and representing approximately 40 million members enrolled in over 70 health plans across the United States. Study subjects included all persons in the database with two or more outpatient prescriptions for valsartan, lisinopril, or extended-release metoprolol and two or more prior claims with a diagnosis of hypertension. Those with a history of major cardiovascular or renal events (diagnosis of myocardial infarction, stroke, heart failure, ventricular arrhythmias, or cardiac arrest; coronary revascularization procedure; diagnosis of renal failure; or dialysis or kidney transplantation) or using other antihypertensive medications except diuretics during the 12 months before treatment with valsartan, lisinopril, or extended-release metoprolol were excluded. Risks of major cardiovascular or renal event during follow-up were analyzed using Cox proportional hazards regression. RESULTS: A total of 29,357 antihypertensive patients were identified who initiated therapy with valsartan (n = 6,645), lisinopril (n = 17,320), or extended-release metoprolol (n = 5,392). In multivariate analyses, therapy with valsartan was associated with a significantly lower risk of a major cardiovascular or renal event versus extended-release metoprolol (heart rate [HR], 0.70; 95% confidence interval [CI], 0.56-0.87; p = 0.0015). Patients receiving valsartan had a nominally lower risk of a major cardiovascular or renal event than those receiving lisinopril, although this difference was not statistically significant (HR, 0.89; 95% CI, 0.74-1.07; p = 0.1987). CONCLUSION: Results of this observational study suggest that the use of valsartan may reduce the risk of major cardiovascular and renal events compared with extended-release metoprolol.

[Combined therapy with amlodipin and lisinopril in arterial hypertension: efficacy of a low-dose combination].

AIM: To assess antihypertensive efficacy of a low-dose combination of amlodipin with lisinopril in the treatment of patients with arterial hypertension (AH) of the second degree. MATERIAL AND METHODS: A total of 42 patients with the second degree of AH (16 males, 26 females, mean age 55-9 +/- 1.9 years) entered an open, comparative and controlled trial. They were divided into three groups by the treatment. Group 1 (n = 14) received amlodipin (normodipin, Gedeon Richter) monotherapy in a mean dose 8.9 +/- 0.6 mg/day, group 2 (n = 12) - lisinopril (diroton, Gedeon Richter) in a mean dose 17.5 +/- 1.4 mg/day, group 3 (n = 16) was given combined therapy with amlodipin+lisinopril in a dose 6.8 +/- 0.7 and 8.7 +/- 0.6 mg/day, respectively. The drugs were given for 12 weeks. The efficacy of the treatment was assessed by the results of 24-h monitoring of blood pressure, echocardiography, endothelium-related vasodilatation of the brachial artery (ERVD), dopplerographic investigation of circulation in the middle cerebral artery (MCA), heart rate and cost-effect estimation. RESULTS: Combined low-dose treatment with amlodipin and lisinopril for 12 weeks allowed achievement of target blood pressure in more patients and lower systolic and diastolic blood pressure than monotherapy with each of the drugs. There was also a positive effect on E/A index, ERVD, MCA circulation. CONCLUSION: Low-dose combined treatment with lisinopril and amlodipin is more effective and cost-efficient. Moreover, lisinopril addition to amlodipin corrects side effects of amlodipin on central nervous system.

Medication adherence before an increase in antihypertensive therapy: a cohort study using pharmacy claims data.

BACKGROUND: Less than one third of patients with hypertension achieve optimal blood pressure control. Poor medication adherence has been identified as one contributor to uncontrolled blood pressure. OBJECTIVE: This study was conducted to test the hypothesis that patients who require an increase in their antihypertensive regimen have poorer adherence with medication compared with patients who remain on a stable regimen. METHODS: Health plan enrollment and pharmacy claims data were used to perform a prospective cohort study and a nested case-control study in patients newly starting antihypertensive therapy. In the prospective cohort study, cumulative medication adherence (CMA, the percentage of days the patient had pills available, calculated as the total number of days of medication dispensed, excluding the final prescription, divided by the total number of days between the first and last antihypertensive prescriptions in the observation period) was compared between patients who required an increase in therapy and patients who remained on a stable antihypertensive regimen. In the nested case-control analysis, interval medication adherence (IMA, the ratio of the number of days of medication dispensed in a single prescription divided by the number of days until the next prescription is filled) during the prescription interval immediately before an increase in the antihypertensive regimen was compared with a similar interval in control patients without an increase matched by age, medication, number of days of medication dispensed, and months since initiation of therapy. RESULTS: The study included data from 5089 patients (mean [SD] age, 47.8 [13.0] years; 50.0% women). Over a median (interquartile range) of 23 (9-49) months of initial antihypertensive treatment, 935 patients (18.4%) had an increase in regimen. After adjusting for age, duration of treatment, number of prescribing physicians, and specific medication, patients with a regimen increase had a 12.0% higher CMA compared with patients remaining on a stable regimen (P < 0.001). IMA for the period immediately before the increase was not significantly different in patients with an increase compared with matched controls (98.3% vs 101.0%, respectively). CONCLUSIONS: Among these insured patients newly starting antihypertensive therapy, patients who required an increase in therapy had similar or slightly better medication adherence compared with patients remaining on a stable regimen. Poor adherence was not predictive of intensification of the antihypertensive regimen.

High prevalence of orthostatic hypotension and its correlation with potentially causative medications among elderly veterans.

BACKGROUND: Orthostatic hypotension (OH) is defined as a reduction of systolic blood pressure of at least 20 mmHg, or diastolic blood pressure of at least 10 mmHg from a sitting to a standing position. It is a common physical finding among older adults and associated with significant morbidity and mortality. Use of medications that have the potential to induce OH, particularly concomitant use of several of such medications, is a major factor for the development of OH. OBJECTIVES: To describe the prevalence of symptomatic and asymptomatic OH in veterans aged 75 years and older attending a geriatric clinic, and to assess the association between OH and the number of potentially causative medications used. METHODS: Charts of all patients who attended a VA geriatric clinic (Michael E. DeBakey VA Medical Center) during the period of 1 June 2002 to 1 June 2003 were reviewed retrospectively for (i) the use of potentially causative medications, i.e. medications that were reported to cause OH in at least 1% of the general population and that were available in the VA formulary, (ii) the presence or absence of OH, and (iii) the presence or absence of symptomatic OH. Patients with primary autonomic dysfunction, Parkinson's disease, and patients who were unable to stand, or who had no assessment for both sitting and standing blood pressure for other reasons were excluded. RESULTS: A total of 505 individual patients attended the clinic during the study period, and 342 patients fit the inclusion criteria. About 189 of these patients (55%) had OH. Among patients with OH, 61 patients (33%) were symptomatic, including 52 patients who had falls. The prevalence of OH in patients receiving zero, one, two, and three or more potentially causative medications was 35, 58, 60 and 65% respectively. Receiving hydrochlorothiazide was associated with the highest prevalence of OH (65%), followed by receiving lisinopril (60%), trazodone (58%), furosemide (56%) and terazosin (54%). CONCLUSION: The prevalence of OH is very high in older veterans and significantly related to the number of concurrent causative medications used. Providers should be educated to reduce the amount of potentially causative medications in the elderly and better assess patients in which use of such medications is necessary to avoid symptomatic OH.

Do evidence-based treatments provide incremental benefits to patients with congestive heart failure already receiving angiotensin-converting enzyme inhibitors? A secondary analysis of one-year outcomes from the Assessment of Treatment with Lisinopril and Survival (ATLAS) study.

BACKGROUND: In patients with congestive heart failure (CHF), use of submaximal doses of angiotensin-converting enzyme (ACE) inhibitors (ie, low-dose ACE inhibitors) represents usual care in routine clinical practice, whereas high-dose ACE inhibitors, beta-blockers, and digoxin have each been shown to improve outcomes. OBJECTIVE: We examined whether treatment with high dose-ACE inhibitors, beta-blockers, and digoxin would each provide incremental benefits over that achieved with usual care and whether concurrent use of high-dose ACE inhibitors, beta-blockers, and digoxin would provide maximal benefits. METHODS: We conducted a secondary analysis of a randomized, controlled, active-comparator trial. Specifically, we studied 1-year outcomes data from the Assessment of Treatment with Lisinopril and Survival trial (ATLAS), which assessed high-dose ACE inhibitors (mean dosage, 33.2 mg daily lisinopril) versus low-dose ACE inhibitors (mean dosage, 4.5 mg daily lisinopril) in patients of any age with advanced CHF in 287 centers in 19 countries in the 1990s. In our analysis, patients were classified by their use of low-dose or high-dose ACE inhibitors, beta-blockers, and/or digoxin at the time of randomization. The primary outcome of interest was the ATLAS composite end point of all-cause mortality or hospitalization for any reason at 1 year. Multiple logistic regression analyses were used to adjust for baseline differences in patient characteristics. RESULTS: The 3164 patients in the ATLAS study had a mean (SD) age of 64 (10) years; 2516 patients (80%) were men and 648 (20%) were women; mean (SD) left-ventricular ejection fraction was 23% (6%); and 2671 patients (84%) had New York Heart Association class III or IV symptoms. At 1 year, the mortality rate was 13% (408 patients); 43% (1369 patients) had > or =1 hospitalization; and the composite end point of mortality or hospitalization was 47% (1489 patients). Most patients (2873; 91%) remained on their initial treatment regimen. Compared with low-dose ACE inhibitors (n = 471), the composite end point decreased incrementally with the use of high-dose ACE inhibitors (n = 475) (adjusted odds ratio [aOR], 0.93; P = NS), high-dose ACE inhibitors plus beta-blockers (n = 72) (aOR, 0.89; P = NS), and high-dose ACE inhibitors plus beta-blockers plus digoxin (n = 77) (aOR, 0.47; P = 0.006). In absolute proportions, patients receiving high-dose ACE inhibitors plus beta-blockers plus digoxin for 1 year had 12% fewer deaths and hospitalizations than patients receiving low-dose ACE inhibitors alone. CONCLUSIONS: Compared with usual care for patients with CHF, in this analysis, an evidence-based strategy that incorporated high-dose ACE inhibitors plus beta-blockers plus digoxin was associated with incrementally greater reductions in morbidity and mortality. These findings support treatment guidelines that recommend the concurrent use of all available proven efficacious treatment in patients with advanced CHF.

High- versus low-dose angiotensin converting enzyme inhibitor therapy in the treatment of heart failure: an economic analysis of the Assessment of Treatment with Lisinopril and Survival (ATLAS) trial.

BACKGROUND: Angiotensin-converting enzyme (ACE) inhibitors reduce heart failure death and hospitalization. Prescribed doses often are lower than randomized clinical trial (RCT) targets and practice guideline recommendations. OBJECTIVE: To assess the cost-effectiveness of high- versus low-dose ACE inhibitor therapy in the ATLAS trial. STUDY DESIGN: A 19-nation RCT of high-dose (32.5-35.0 mg/day) versus low-dose (2.5-5.0 mg/day) lisinopril in 3164 patients with class II-IV heart failure and left ventricular ejection fraction < or = 30%. METHODS: Data on clinical outcomes and major cost events (hospitalizations and drug utilization) were collected prospectively. Hospital costs were estimated using Medicare and representative managed care diagnosis-related group reimbursement rates. ACE inhibitor drug costs were estimated using US average wholesale prices. Costs were discounted at 3% annually. RESULTS: Patients in the high-dose lisinopril group had fewer hospitalizations (1.98 vs 2.22, P = .014) and hospital days (18.28 vs 22.22, P = .002), especially heart failure hospitalizations (0.64 vs 0.80, P = .006) and heart failure hospital days (6.02 vs 7.45, P = .028) compared with the low-dose group. The high-dose lisinopril group also had lower heart failure hospital costs (dollars 5114 vs dollars 6361, P = .006) but higher ACE inhibitor drug costs (dollars 1368 vs dollars 855, P = .0001). Total hospital and drug costs were similar between high- and low-dose lisinopril groups (mean difference dollars -875, 95% CI dollars -2613 to dollars 884). Sensitivity analyses confirmed these findings. CONCLUSIONS: Cost savings from fewer heart failure hospitalizations offset higher ACE inhibitor costs in the high-dose group. The improved clinical outcomes were achieved without increased treatment costs.