[Prescription of renin-angiotensin-aldosterone system blockers in patients with stage 3 chronic kidney disease]. / Prescripción de fármacos bloqueadores del sistema renina angiotensina en pacientes con enfermedad renal crónica etapa 3 en atención primaria de salud.

BACKGROUND: To reduce the progression of chronic kidney disease (CKD) and cardiovascular risk, the guidelines recommend the blockade of the renin-angiotensin-aldosterone system (RAAS) in patients with proteinuria. AIM: To assess the frequency of enalapril or losartan use in diabetics or hypertensive patients with stage 3 CKD. MATERIAL AND METHODS: Review of clinical records of patients with CKD in an urban primary care clinic. RESULTS: We identified 408 subjects aged 40 to 98 years (66% women) with stage 3 CKD. Sixty six percent had only hypertension and 34% were diabetic with or without hypertension. Seventy four percent received RAAS blockers (52% used enalapril, 45% losartan and 2% both medications). RAAS blockers were used in 70% of hypertensive and 78% of diabetic patients. The prescription in hypertensive diabetics with microalbuminuria was lower than in those without microalbuminuria (72% vs 87%, p < 0.05), but the opposite occurred in pure hypertensive patients with and without microalbuminuria (88% vs 69%, p < 0.05). There were no significant differences in blood pressure levels, microalbuminuria or serum potassium levels between RAAS blocker users and non-users. No differences were observed either between enalapril and losartan users. CONCLUSIONS: The adherence to clinical guidelines is insufficient and users of the recommended drugs did not achieve the expected goals.

Renoprotective Effect of Angiotensin-Converting Enzyme Inhibitors and Angiotensin II Receptor Blockers in Diabetic Patients with Proteinuria.

BACKGROUND/AIMS: Limited evidence exists on the choice of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) in diabetic patients with nephropathy. We aim to assess the renal effectiveness and safety of these drugs among diabetic nephropathy patients. METHODS: This retrospective cohort study was conducted with diabetic nephropathy patients who initiated ACEI or ARB monotherapy. The primary outcome was a composite of end stage of renal disease and renal transplantation, and the secondary outcome was all-cause mortality. The safety endpoint was hyperkalemia. RESULTS: Three thousand seven hundred and thirty-nine ACEI users and 3,316 ARB users were identified. ARBs seemed to be inferior to ACEIs given their poorer renal outcome (HR 1.31; 95% CI, 1.15-1.50) and higher risk of hyperkalemia (HR 1.17; 95% CI, 1.04-1.32). Among the four ACEIs compared, captopril was an inferior treatment choice given its poorer renal outcomes (HR 1.42; 95% CI, 1.05-1.93) and higher mortality rate (HR 1.25; 95% CI, 1.01-1.55). Irbesartan appeared to be a poorer treatment choice among the three ARBs compared, given its inferior renal protective effect (HR 1.35; 95% CI, 1.03-1.78). CONCLUSIONS: Our findings suggest ACEIs as a relatively more renoprotective and safer treatment as compared to ARBs. Captopril and irbesartan may be inferior to the other ACEIs and ARBs respectively.

Analysis of purity profiles of generic lisinopril tablets marketed in Croatia.

In view of an increasing number of generic drugs emerging, a comparative study was performed including the approved lisinopril preparations in the form of tablets marketed in Croatia, to compare purity profiles of generic drugs versus the original medicinal product. Several batches of each individual medicinal product at different stages of their shelf life were analyzed. Impurities were determined by means of high performance liquid chromatography (HPLC). Impurity profiles were demonstrated to be specific for each individual drug. Original drug, as compared to its generic copies, had the lowest values and also the lowest variability of all the tested parameters--type, total number and content of impurities--suggesting that its manufacturing process is to certain degree better controlled compared to other manufacturers. A characteristic impurity C appearing in all the assessed preparations has the lowest levels in the original drug, whereas the amount of the highest unknown impurity does not exceed 0.10% in any of the analyzed preparations. Although the original drug stands out from all the generic preparations with its purity, it can be generally concluded that, as regarding impurities levels, all the analyzed medicinal products are within the ranges of specification limits; accordingly, it is therefore not expected that, in case of lisinopril tablets, administration of the original drug as compared to any of its generic drugs, will be safer for the patient.

Effects of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers on all-cause mortality, cardiovascular death, and cardiovascular events among peritoneal dialysis patients: A protocol for systematic review.

BACKGROUND: Based on the International Society for peritoneal dialysis (PD) recommendations, blockade of renin-angiotensin systems with an angiotensin-converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARB) improves residual kidney function in PD patients. However, the long-term effectiveness of ACEI/ARB use in PD patients has not been fully elucidated. We, therefore, intend to perform a systematic review and meta-analysis to summarize the effects of ACEI/ARB use on long-term mortality, cardiovascular outcomes, and adverse events among PD patients. METHODS: This systematic review will include both randomized controlled trials and non-randomized studies in adult PD patients. We also plan to incorporate data from our cohort study in Thai PD population into this review. We will search PubMed, Medline, EMBASE, Cochrane Library, Web of Science, Scopus, CINAHL, and grey literature from inception to February 29, 2019, with no language restrictions. The process of study screening, selection, data extraction, risk of bias assessment, and grading the strength of evidence will be performed independently by a pair of reviewers. Any discrepancy will be resolved through a team discussion and/or consultation with the third reviewer. The pooled effects estimate and 95% confidence intervals will be estimated using DerSimonian-Laird random-effects models. Heterogeneity will be assessed by the Cochran Q test, I index and tau-squared statistics. The funnel plots along with the Begg and Egger test and trim and fill method will be performed to investigate any evidence of publication bias. Preplanned subgroup analyses and random-effects univariate meta-regressions will be performed to quantify the potential sources of heterogeneity based on studies- and patient-characteristics. RESULTS: This will be the first systematic review and meta-analysis to summarize the long-term effectiveness of renin-angiotensin system inhibitors in PD populations. CONCLUSION: In summary, this systematic review and meta-analysis will summarize the effectiveness of ACEI/ARB on long-term mortality, cardiovascular outcomes, and adverse events among adult PD patients by integrated all available evidences. ETHICS AND DISSEMINATION: Based on the existing published data, an ethical approval is not required. The findings will be disseminated through scientific meetings and publications in peer-reviewed journals.PROSPERO registration number: CRD42019129492.

Joint Commission still sees room for improvement.

Discharge instructions for heart failure patients, pneumococcal screening, ACE inhibitor at discharge still areas of concern. Requiring a standard process for continual quality measurement, reporting, and improvement has contributed to improvement. Processes are not yet 'ingrained in facilities and systems and process redesign'; the right things don't happen in 'all encounters' all the time.

Validity of Performance and Outcome Measures for Heart Failure.

Background Numerous quality metrics for heart failure (HF) care now exist based on process and outcome. What remains unclear, however, is if the correct quality metrics are being emphasized. To determine the validity of certain measures, we compared correlations between measures and reliability over time. Measures assessed include guideline-recommended ß-blocker (BB), any BB, angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker, mineralocorticoid receptor antagonist, and hydralazine/isosorbide dinitrate (in blacks) use among candidates, 30-day mortality, 1-year mortality, and 30-day readmission. Methods and Results This was an observational cohort analysis using chart review and electronic resources for 55 735 patients from 102 Veterans Affairs medical centers hospitalized with HF from 2008 to 2013. Assessments of convergent validity and reliability were performed. Significant correlations were found between in-hospital rates of ACE inhibitor use and the following measures: BB use, 30-day mortality, and 1-year mortality. Guideline-recommended BB use was also significantly correlated with mineralocorticoid receptor antagonists, 30-day mortality, and 1-year mortality. There was no correlation between 30-day readmission rates and any therapy or mortality. Measure reliability over time was seen for guideline-recommended BBs ( r=0.57), mineralocorticoid receptor antagonists ( r=0.50), 30-day mortality ( r=0.29), and 1-year mortality ( r=0.31). ACE inhibitor and readmission rates were not reliable measures over time. Conclusions BB use, ACE inhibitor use, mortality, and mineralocorticoid receptor antagonist use are valid measures of HF quality. Thirty-day readmission rate did not seem to be a valid measure of HF quality of care. If the goal is to identify high-quality HF care, the emphasis on decreasing readmission rates might be better directed towards improving usage of the recommended therapies.

Effect of dual compared to no or single renin-angiotensin system blockade on risk of renal replacement therapy or death in predialysis patients: PREPARE-2 study.

Current guidelines on hypertension treatment in chronic kidney disease (CKD) patients discourage combined angiotensin-converting enzyme inhibitor (ACEi) and angiotensin II receptor blocker (ARB) use due to the risk of an increased kidney function decline. However, dual compared to single renin-angiotensin system (RAS) blockade may have more efficacy with regard to hypertension and proteinuria. Among incident predialysis patients (CKD 4-5), we compared dual with no or single RAS blockade regarding kidney function decline and risk of renal replacement therapy (RRT) or death. In a multicenter cohort study, 495 incident predialysis patients (>18 years) were included between 2004 and 2011 and followed until RRT, death, or October 2016. At baseline, patients were divided into four categories: nonuser, single or dual user of ACEi and/or ARB. Cox models were used to estimate the hazard ratio for the combined end point RRT or death. Differences in decline of kidney function among the four drug groups were compared with a linear mixed model. A total of 119 patients were nonusers, 164 ACEi users, 133 ARB users, and 79 dual RAS users. Compared to nonusers, the multivariable adjusted hazard ratio (95% confidence interval) for the combined end point was 0.75 (0.65 to 0.86) for ACEi users, 0.87 (0.76 to 1.00) for ARB users, and 0.79 (0.67 to 0.94) for dual RAS users. The average annual decline in kidney function did not differ among the four groups. We observed in predialysis patients that compared to no RAS blockade, both dual RAS blockade and single ACEi use were associated with about 20%-25% lower risk of RRT or death, without difference in kidney function decline.

Gender disparities in the diagnosis and treatment of non-ST-segment elevation acute coronary syndromes: large-scale observations from the CRUSADE (Can Rapid Risk Stratification of Unstable Angina Patients Suppress Adverse Outcomes With Early Implementation of the American College of Cardiology/American Heart Association Guidelines) National Quality Improvement Initiative.

OBJECTIVES: We hypothesized that significant disparities in gender exist in the management of patients with non-ST-segment elevation (NSTE) acute coronary syndromes (ACS). BACKGROUND: Gender-related differences in the diagnosis and treatment of ACS have important healthcare implications. No large-scale examination of these disparities has been completed since the publication of the revised American College of Cardiology/American Heart Association guidelines for management of patients with NSTE ACS. METHODS: Using data from the CRUSADE (Can Rapid Risk Stratification of Unstable Angina Patients Suppress Adverse Outcomes with Early Implementation of the American College of Cardiology/American Heart Association Guidelines) National Quality Improvement Initiative, we examined differences of gender in treatment and outcomes among patients with NSTE ACS. RESULTS: Women (41% of 35,875 patients) were older (median age 73 vs. 65 years) and more often had diabetes and hypertension. Women were less likely to receive acute heparin, angiotensin-converting enzyme inhibitors, and glycoprotein IIb/IIIa inhibitors and less commonly received aspirin, angiotensin-converting enzyme inhibitors, and statins at discharge. The use of cardiac catheterization and revascularization was higher in men, but among patients with significant coronary disease, percutaneous revascularization was performed in a similar proportion of women and men. Women were at higher risk for unadjusted in-hospital death (5.6% vs. 4.3%), reinfarction (4.0% vs. 3.5%), heart failure (12.1% vs. 8.8%), stroke (1.1% vs. 0.8%), and red blood cell transfusion (17.2% vs. 13.2%), but after adjustment, only transfusion was higher in women. CONCLUSIONS: Despite presenting with higher risk characteristics and having higher in-hospital risk, women with NSTE ACS are treated less aggressively than men.

Reporting on the Strategies Needed to Implement Proven Interventions: An Example From a "Real-World" Cross-Setting Implementation Study.

UNLABELLED: The objective of this study was to empirically demonstrate the use of a new framework for describing the strategies used to implement quality improvement interventions and provide an example that others may follow. Implementation strategies are the specific approaches, methods, structures, and resources used to introduce and encourage uptake of a given intervention's components. Such strategies have not been regularly reported in descriptions of interventions' effectiveness, or in assessments of how proven interventions are implemented in new settings. This lack of reporting may hinder efforts to successfully translate effective interventions into "real-world" practice. A recently published framework was designed to standardize reporting on implementation strategies in the implementation science literature. We applied this framework to describe the strategies used to implement a single intervention in its original commercial care setting, and when implemented in community health centers from September 2010 through May 2015. Per this framework, the target (clinic staff) and outcome (prescribing rates) remained the same across settings; the actor, action, temporality, and dose were adapted to fit local context. The framework proved helpful in articulating which of the implementation strategies were kept constant and which were tailored to fit diverse settings, and simplified our reporting of their effects. Researchers should consider consistently reporting this information, which could be crucial to the success or failure of implementing proven interventions effectively across diverse care settings. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT02299791.

A hard look at angiotensin receptor blockers in heart failure.

Multiple trials over the past several years have examined indications for angiotensin receptor blockers (ARBs) in the treatment of left ventricular dysfunction, both acutely after myocardial infarction and in chronic heart failure. Yet despite these data, there is still confusion regarding the efficacy of ARBs as monotherapy in these patient populations, as well as the specific indications for combination ARB/angiotensin-converting enzyme (ACE) inhibitor therapy. We examine the key differences among the trials-including the ACE inhibitor dose, the ARB and its dose, blood pressure reduction, and patient populations-to present our perspective on ARB use, alone or in combination with ACE inhibitors, in patients with chronic heart failure and post-myocardial infarction left ventricular dysfunction. We conclude that ACE inhibitors remain the first-line therapy for left ventricular dysfunction. Angiotensin receptor blockers should be reserved for monotherapy in ACE intolerant patients and for combination therapy in symptomatic class II/III patients with chronic heart failure.

A conversation with Drs. Kaplan and Moser about conflicting data, confusing results, and some recent treatment recommendations for the management of hypertension.

Following a hypertension symposium in Baltimore, MD, on June 1, 2005, Dr. Wendy Post from the Johns Hopkins University School of Medicine, Baltimore, MD, had the opportunity to interview two of the outstanding hypertension experts in the United States on several controversial issues in hypertension management. Dr. Norman Kaplan is Clinical Professor of Medicine at the Southwestern Health Science Center in Dallas, TX, and Dr. Marvin Moser is Clinical Professor of Medicine at the Yale University School of Medicine, New Haven, CT. Both have been leaders in the field of hypertension treatment and education for more than 40 years. Dr. Kaplan's book Clinical Hypertension has been a standard textbook since 1973 and is now in its ninth edition. Dr. Marvin Moser was the Senior Medical Consultant to the National High Blood Pressure Education Program from 1974 to 2002 and was Chairman of the first Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure and a member of the six subsequent committees. His book Clinical Management of Hypertension is in its seventh edition. Drs. Moser and Kaplan were corecipients of the 2004 International Society of Hypertension Award for Outstanding Contributions to Hypertension Treatment and Education and have lectured extensively throughout the United States and overseas.

Importance of in-hospital initiation of evidence-based medical therapies for heart failure-a review.

Patients who have had heart failure (HF) face very high risks of hospitalization and mortality. Despite the compelling scientific evidence that angiotensin-converting enzyme inhibitors, aldosterone antagonists, and beta blockers decrease rates of hospitalization and mortality in patients who have had HF, these life-prolonging therapies continue to be underused. Many studies in a variety of clinical settings have documented that important numbers of patients who have had HF are not receiving treatment with these evidence-based therapies, which are recommended by national guidelines, when guided by conventional care. This HF treatment gap results from a variety of complex issues, including lack of systems and disease management programs. This gap in beta-blocker therapy may be due in part to persisting perceptions, despite recent evidence to the contrary, that it should be delayed until patients who developed HF have been stable for 2 to 4 weeks after hospital discharge and that its initiation results in a substantial risk of worsening HF. Conversely, recent clinical trial evidence has substantiated that beta blockers can be safely initiated for patients with HF in the hospital and that there are early benefits, including decreased risks of mortality and hospitalization for worsening HF. It has become increasingly evident that in-hospital initiation of evidence-based cardiovascular therapies and patient education have a positive effect on long-term patient compliance and clinical outcomes. Adopting in-hospital initiation of these therapies as the standard of care (in the absence of contraindications or intolerance) in patients who have HF and stabilized systolic dysfunction could substantially improve treatment rates, decrease the risk of future hospitalizations, and prolong life in the large number of patients who are hospitalized each year for HF.

Comparison of treatment initiation with bisoprolol vs. enalapril in chronic heart failure patients: rationale and design of CIBIS-III.

BACKGROUND: Angiotensin-converting-enzyme (ACE) inhibitors and beta-blockers are standard therapy for chronic heart failure (CHF). beta-blockers are recommended to be initiated after ACE-inhibitors, but this order is not evidence based. The initiation order may be important since many, especially elderly CHF patients cannot tolerate target doses of both. Data suggest that beta-blockers may be more important to CHF patients than ACE-inhibitors, especially in early stages of CHF. AIMS: To compare the effect on combined death or hospitalisation of initial monotherapy with either bisoprolol or enalapril, followed by combination therapy. METHODS: One-thousand CHF patients without ACE-inhibitor, beta-blocker or angiotensin-receptor-blocker therapy will be randomised 1:1 to monotherapy with either enalapril or bisoprolol for 6 months, followed by combined therapy for 6-18 months. The primary objective is to show non-inferiority for bisoprolol-first vs. enalapril-first regarding combined death or hospitalisation. If that is shown, superiority for bisoprolol-first will be tested. CONCLUSIONS: If the trial shows non-inferiority for bisoprolol-first vs. enalapril-first, the first CHF therapy may be chosen based on individual judgement in each patient. If bisoprolol-first is superior to enalapril-first, a beta-blocker should be given prior to an ACE-inhibitor in CHF, and the paradigm of testing CHF compounds against a background of ACE-inhibitor therapy will be challenged.

Comparative effects of 2.5 and 5 mg cilazapril versus placebo on daily blood pressure load.

The antihypertensive efficacy of 2.5 and 5 mg cilazapril and placebo in lowering 24-h ambulatory blood pressure (ABP) and BP load were compared in 42 patients with mild to moderate hypertension. After a 2-week placebo run-in period, patients were randomized double-blind to receive either 2.5 mg cilazapril (n = 14), 5 mg cilazapril (n = 14), or placebo (n = 14) for 4 weeks. There were no significant differences in 24-h and awake ABP or in office BP between 2.5 and 5 mg cilazapril. Moreover, the percentage of patients that had BP control (mean daytime ABP less than 90 mm Hg) was 14% in the placebo group, 64% and 71% with 2.5 and 5 mg cilazapril, respectively. Furthermore, the percentage of BP load was similar with both regimens (29 v 36%). These observations indicate that 2.5 and 5 mg cilazapril have equipotent antihypertensive efficacy.

Safety and tolerability of fluvastatin with concomitant use of antihypertensive agents. An analysis of a clinical trial database.

The coexistence of hypercholesterolemia and hypertension often requires concomitant drug treatments. Thus, it is interesting to evaluate the efficacy, safety, and tolerability of the new lipid-lowering agent fluvastatin, a 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA)-reductase inhibitor, in patients receiving concomitant antihypertensive/cardiovascular drug treatments. A retrospective analysis was based on data from controlled clinical trials in which 1815 patients were treated with fluvastatin and 783 patients received placebo. The daily dose of fluvastatin was > or = 20 mg. At least one of the following drug treatments was taken by 445 of the fluvastatin-treated patients (24.5%) and 181 of those receiving placebo (23.1%): beta-adrenergic-receptor blockers (fluvastatin: n = 182; placebo: n = 84); diuretics (fluvastatin: n = 168; placebo: n = 72); calcium antagonists (fluvastatin: n = 161; placebo: n = 69); and angiotensin-converting enzyme (ACE) inhibitors (fluvastatin: n = 101; placebo: n = 30). The majority of patients received monotherapy with one of the above-mentioned antihypertensive agents (fluvastatin: 69%; placebo: 65%). The efficacy of fluvastatin in modifying low-density lipoprotein (LDL)- and high-density lipoprotein (HDL)-cholesterol and triglyceride levels was not consistently different in patients taking a given antihypertensive compared with the overall group and the patients not taking the antihypertensive agent. In patients taking fluvastatin and antihypertensives, confirmed (measured at two consecutive occasions) increases more than three times the upper limit of normal in aspartate aminotransferase (ASAT) and alanine aminotransferase (ALAT) occurred in only two patients. One case involved the concomitant use of a beta-blocker (ASAT and ALAT) and the other a diuretic (ALAT).(ABSTRACT TRUNCATED AT 250 WORDS)

Inhibition of angiotensin-converting enzyme--a new concept of medical treatment of male infertility?

OBJECTIVES: To evaluate the effectiveness of systemic captopril therapy. DESIGN: Randomized double-blind study. SETTING: Andrology Unit at the Department of Dermatology, University of Munich, Munich, Germany. PATIENTS: Infertile men suffering from oligozoospermia (5-20 x 10(6) spermatozoa/mL) and/or asthenozoospermia. INTERVENTIONS: Captopril was given orally; samples of seminal plasma were collected twice before treatment and 4 and 12 weeks after captopril administration. MAIN OUTCOME MEASURE: Semen parameters, pregnancy rate, ACE activity, and kinin levels. RESULTS: After 4 weeks of therapy, significant differences between verum group and placebo group were found concerning ACE activity and kinin levels. Sperm density improved significantly after 12 weeks of captopril therapy. All other semen parameters remained unchanged. The pregnancy rate was not improved. CONCLUSIONS: The suitability of captopril in the therapy of oligozoospermia and/or asthenozoospermia for improvement of male infertility seems to be limited.

What is the optimal blood pressure in patients with diabetes mellitus?

Cardiovascular disease is the number one cause of death in patients with type 2 diabetes mellitus. This condition leads to an increased risk of premature mortality in patients with ischemic heart disease and stroke. Many risk factors besides hyperglycemia in itself contribute to this increased risk, acting in a synergistic fashion. One of the most important risk factors is hypertension. Several recent clinical trials have shown the benefits of reducing high blood pressure in patients with diabetes mellitus to lower levels than have previously been recommended in clinical guidelines. In both the United Kingdom Prospective Diabetes Study (UKPDS) and the Hypertension Optimal Treatment (HOT) study a significant trend for increased benefits associated with lower diastolic blood pressure levels was shown. Therefore, clinicians should be encouraged to do more to treat hypertension in patients with type 2 diabetes mellitus and increase the proportion of patients in whom acceptable blood pressure control is achieved. For example, in Sweden, acceptable blood pressure control is currently only achieved in about 20 to 25% of patients with type 2 diabetes mellitus. Recent evidence also points to the primary importance of a tight blood pressure control. This implies drug combination treatment for the majority of patients. Therefore, the clinician must be able to use a broad variety of antihypertensive drugs, and from these drugs choose alternative combinations with pharmacological synergism.

Future challenges in quality improvement in heart failure.

This is the final installment in a series reporting on the Centers for Medicare & Medicaid Services (CMS) initiatives to improve care for Medicare beneficiaries with heart failure through its Quality Improvement Organization (QIO) contractors during the 1999-2002 contract cycle. Previous columns have reported on a nation-wide hospital-based effort, the National Heart Failure project, and a more limited outpatient-based effort, the Heart Failure Practice Improvement Effort. After 3 years of experience with the National Heart Failure project, it is appropriate to highlight the issues pertinent to future quality improvement initiatives in heart failure care.

Analysis of ACE-inhibitors by CE using alkylsulfonic additives.

Capillary electrophoresis (CE) was applied to the determination of angiotensin-converting enzyme (ACE) inhibitors in pharmaceuticals (tablets). Since a free solution CE system failed to reach a complete separation of closely related compounds (lisinopril, ramipril, benazepril, quinapril), alkylsulfonic additives (sodium heptansulfonate and (+)-10-camphorsulphonic acid) were added to the running buffer: improved separations were obtained suggesting a favourable effect of ion-pairing interactions between analytes and additives. The separations were carried out in acidic medium and a systematic investigation of electrophoretic parameters was made to evaluate the performance of the selected additives. Under the optimized conditions, ramipril and benazepril in their commercial dosage forms were determined confirming the applicability of the developed CE approach to the analysis of pharmaceutical samples; the results were also compared with those obtained applying a previously described and validated HPLC method.

Use of ambulatory blood pressure monitoring to evaluate the selective angiotensin II receptor antagonist, telmisartan, and other antihypertensive drugs.

Telmisartan (Micardis (R)) is a new, orally active, long-acting angio-tensin (Ang) II receptor antagonist that is effective in the treatment of hypertension. Ambulatory blood pressure monitoring (ABPM) has emerged as an important method for evaluating the consistency of the antihypertensive effects of a drug throughout the dosing interval. ABPM was used to evaluate the antihypertensive efficacy of telmisartan in several placebo-controlled, double-blind, multicenter studies. Patients with mild-to-moderate hypertension were allocated randomly to groups to receive telmisartan 40 or 80 mg, losartan 50 mg, or placebo, once daily in a 6-week, fixed-dose study, or telmisartan 40-120 mg, amlodipine 5-10 mg, or placebo, once daily in a 12-week, dose-titration study. Patients treated with telmisartan 40 and 80 mg or placebo in a separate 4-week, fixed-dose study were included in an additional analysis. Telmisartan 40 and 80 mg significantly decreased mean ambulatory systolic blood pressure (SBP) and diastolic blood pressure (DBP) relative to placebo for the entire 24 h period and in the following intervals: day (6 a.m. to 10 p.m.), morning (6 a.m. to noon), night (10 p.m. to 6 a.m), and the last 4 h of the dosing interval (P<0.01). Notably, telmisartan 40 or 80 mg was more effective than losartan, especially during the last 4-6 h of the dosing interval (P<0.05). Telmisartan 40- 120 mg tended to be more effective than amlodipine 5-10 mg in reducing SBP and DBP in each time interval, with significant differences between treatments noted for DBP in the last 4 h of the dosing interval and in the morning (P < 0.05). ABPM also revealed that the magnitude of the blood pressure decreasing effect with telmisartan was consistent throughout the dosing interval. These results demonstrate that telmisartan maintains a normal circadian blood pressure pattern and provides full 24 h blood pressure control with once-daily dosing.