Effectiveness and tolerability of a trandolapril-based antihypertensive treatment regimen over 12 months in actual clinical care across Canada.

BACKGROUND AND OBJECTIVES: There is little information on the effects of trandolapril on renal function when used in Canadian general practice. We evaluated the use and blood pressure (BP) lowering effectiveness of trandolapril-based therapies in Canadian conditions of actual care and attempted to capture assessments of urinary albumin concentration (UAC) and estimated glomerular filtration rate (eGFR) in clinical practice. METHODS: This was a prospective, non-interventional, observational study in adults with uncontrolled hypertension, with or without co-morbidities, either treatment-naïve or uncontrolled on existing antihypertensive medications. Hypertension was not defined per protocol. Trandolapril doses (0.5, 1, 2, 4 mg) and subjects' continued medical care were all at the discretion of the treating physician. Data were gathered after 3, 6 and 12 months. RESULTS: 7,993 patients entered the study and 4,983 patients attended the Month 12 visit. Most patients (91.7 %) received trandolapril as a new prescription. At 12 months, 72.9 % of patients without diabetes and 34.4 % with diabetes were controlled (targets <140/90 and 130/80 mmHg, respectively) and 79.2 % of patients with diabetes had BP below 140/90 mmHg. Evaluable eGFR data were available for 25.1, 21.2 and 21.7 % of patients at Months 3, 6 and 12, respectively, and UAC data for 9.6, 8.2 and 9.0 % of patients at the same time points. Treatment was well tolerated. Dropout rates were 37.7 % after 12 months. CONCLUSION: Effective, sustained and well-tolerated double-digit BP reduction is achievable with a trandolapril-based treatment regimen for all patient groups. It appears that for diabetic patients blood pressure control as per Canadian Hypertension Education Program recommendations is yet challenging. The results also illuminate the persistent gap between treatment guidelines and actual care.

Blood pressure control rates with an antihypertensive regimen including trandolapril in a Canadian usual-care setting.

INTRODUCTION: The aim of the study was to assess the effects on blood pressure (BP) levels and control rates in hypertensive subjects receiving trandolapril as monotherapy or as part of an antihypertensive regimen in everyday Canadian clinical practice. METHODS: The MAVIKtory study was a multicenter, single-arm observational study in 601 primary-care centers in Canada. Diabetic and nondiabetic subjects were included, who were treated with trandolapril for hypertension in accordance with usual practices and national guidelines. Subjects received trandolapril as a new prescription, alone, or in combination with prior therapy. Treatment regimens were at the discretions of the treating physicians. Subjects were followed for 6 months. The primary outcomes measures were the percentage of subjects reaching BP targets set by their physicians after 6 months of therapy, and the percentage of subjects reaching the guidelines targets (systolic blood pressure [SBP]/diastolic blood pressure [DBP] < 140/90 mm Hg) after 6 months as assessed by their physicians. Other outcomes were the percentage of diabetic subjects reaching BP targets, and tolerability. RESULTS: A total of 8787 subjects were enrolled and included in the intention-to-treat population. Starting doses of trandolapril were 1 or 2 mg in the majority of subjects and remained unchanged in 51.9% of the population at 6 months. The target of < 140/90 (< 130/80) mm Hg was reached by 67.3% of the population. The lower mean physician-set target of 133.4/83.3 mm Hg for nondiabetic subjects and 128.6/79.3 mm Hg for diabetic subjects was reached by 52.2%. Mean reductions from baseline to month 6 were 19.4 mm Hg (95% CI: [-19.9 to -19.0]) in SBP, and 10.1 mm Hg (95% CI: [-10.4 to -9.8]) in DBP. Cough was the most commonly reported adverse event, reported in 4.2% of all subjects. CONCLUSION: Trandolapril demonstrated a favorable safety and effectiveness profile. SBP reductions of approximately 20 mm Hg and control rates > 65% could be achieved over 6 months.

Effectiveness of a trandolapril-based treatment regimen in subjects with isolated systolic hypertension in Canada.

OBJECTIVE: This report evaluates the effectiveness of a titration-based, escalating dose regimen based on trandolapril in subjects with isolated systolic hypertension (ISH) treated in Canadian clinical practice. METHODS: Substudy of the TRAIL (Trandolapril Regimen Applied In real Life) study; a prospective, open-label, single cohort, multicentre study in 192 Canadian primary care practices. Subjects with ISH received trandolapril therapy, initiated at 1 mg/day (0.5 mg/day in subjects on diuretics) and increased to 2 or 4 mg at 4 and 9 weeks, respectively, in those not achieving blood-pressure (BP) targets, subject to tolerability. If BP was not controlled after 14 weeks of treatment subjects could be put on trandolapril 4 mg/verapamil 240 mg while continuing the diuretic, or verapamil could be added to the existing regimen. The observation period was 26 weeks. The primary outcome measure was the achievement of target BP levels after 14 weeks. RESULTS: Systolic BP (SBP) was significantly (p < 0.01) reduced from 167.3 +/- 8.7 mmHg at baseline to 136.8 +/- 14.0 mmHg (means +/- SD) at Week 14. The reductions were maintained at Week 26: mean SBP at this time point was 137.4 +/- 12.5 mmHg. The target BP levels of < or =140/90 mmHg at Week 14 was reached by 67% of subjects with ISH. Among study limitations were the observational design; the lack of randomisation and control group, and the fact that subjects with ISH represented a comparatively small number of subjects. CONCLUSIONS: A titration-based, escalating-dose regimen based on trandolapril is effective in subjects with ISH under treatment conditions seen in general clinical practice in Canada.

A 26-week, prospective, open-label, uncontrolled, multicenter study to evaluate the effect of an escalating-dose regimen of trandolapril on change in blood pressure in treatment-naive and concurrently treated adult hypertensive subjects (TRAIL).

OBJECTIVE: This study evaluated the effectiveness of an escalating-dose regimen of trandolapril in subjects with stage 1 or stage 2 hypertension. METHODS: This was a 26-week, prospective, open-label,multicenter study in Canadian primary care centers. Subjects with hypertension who were treatment naive or whose disease was uncontrolled on current first-line antihypertensive monotherapy were treated with trandolapril for 26 weeks alone or in addition to their current treatment. Uncontrolled hypertension was defined as systolic/diastolic blood pressure (SBP/DBP) >or=140/90 mm Hg in subjects with no other risk factors or >or=130/80 mm Hg in subjects with diabetes or kidney disease. Trandolapril therapy was initiated at 1 mg/d and was titrated as required to 2 or 4 mg at 4 and 9 weeks after initiation of treatment, respectively, in those not achieving BP targets. At 14 weeks after treatment initiation, subjects not achieving BP targets could receive a combination of trandolapril 4 mg plus a calcium channel blocker (verapamil 240 mg) with or without a diuretic. Primary outcome was the percentage of patients reaching target BP after 14 weeks. RESULTS: A total of 1683 subjects from 192 general practice clinics across Canada completed the 14-week trandolapril dose-optimization phase, and 1650 completed the full 26-week follow-up. Mean (SD) age was 56.6 (12.6) years, and 49.2% of the subjects were men. At baseline, 82.4% (1359/1650) of subjects were antihypertensive-treatment naive. At the trial end, 73.4% (95% CI, 70.9-75.9) of subjects achieved a target level of SBP/DBP <140/90 mm Hg. The mean (SD) reductions in SBP and DBP were -21.5 (14.0) and -11.9 (9.1) mm Hg, respectively (P < 0.001), and -22.4 (14.0) and -12.7 (9.0) mm Hg, respectively (P < 0.001), at 26 weeks. A total of 343 predominantly mild, nonserious adverse events were attributed to the study drugs, reported by 252 (15.3%) of the 1650 subjects. The most frequently reported nonserious adverse events were cough (6.3%); gastrointestinal disorders (2.3%), predominantly nausea; and headache (2.1%). No serious adverse events were attributed to the study treatment. Trandolapril was generally well tolerated. CONCLUSIONS: A titration-based, escalating-dose regimen of trandolapril was effective and well tolerated in the management of these subjects who were antihypertensive-treatment naive or whose disease was uncontrolled on a diuretic or a calcium channel blocker in this open-label, uncontrolled, multicenter study. Overall, 73.4% of subjects achieved their target blood pressure goal (<140/90 mm Hg).

Empirical validation of guidelines for the management of pharyngitis in children and adults.

CONTEXT: Recent guidelines for management of pharyngitis vary in their recommendations concerning empirical antibiotic treatment and the need for laboratory confirmation of group A streptococcus (GAS). OBJECTIVE: To assess the impact of guideline recommendations and alternative approaches on identification and treatment of GAS pharyngitis in children and adults. DESIGN, SETTING, AND PARTICIPANTS: Throat cultures and rapid antigen tests were performed on 787 children and adults aged 3 to 69 years with acute sore throat attending a family medicine clinic in Calgary, Alberta, from September 1999 to August 2002. Recommendations from 2 guidelines (those of the Infectious Diseases Society of America and of the American College of Physicians-American Society of Internal Medicine/American Academy of Family Physicians/US Centers for Disease Control and Prevention) were compared with rapid testing alone, a clinical prediction rule (ie, the modified Centor score), and a criterion standard of treatment for positive throat culture results only. MAIN OUTCOME MEASURES: Sensitivity and specificity of each strategy for identifying GAS pharyngitis, total antibiotics recommended, and unnecessary antibiotic prescriptions. RESULTS: In children, sensitivity for streptococcal infection ranged from 85.8% (133/155; 95% confidence interval [CI], 79.3%-90.0%) for rapid testing to 100% for culturing all. In adults, sensitivity ranged from 76.7% (56/73; 95% CI, 65.4%-85.8%) for rapid testing without culture confirmation of negative results to 100% for culturing all. In children, specificity ranged from 90.3% (270/299; 95% CI, 86.4%-93.4%) for use of modified Centor score and throat culture to 100% for culturing all. In adults, specificity ranged from 43.8% (114/260; 95% CI, 37.7%-50.1%) for empirical treatment based on a modified Centor score of 3 or 4 to 100% for culturing all. Total antibiotic prescriptions were lowest with rapid testing (24.7% [194/787]; 95% CI, 21.7%-27.8%) and highest with empirical treatment of high-risk adults (45.7% [360/787]; 95% CI, 42.2%-49.3%), due to a high rate of unnecessary prescriptions in adults (43.8% [146/333]; 95% CI, 38.4%-49.4%). CONCLUSIONS: Guideline recommendations for the selective use of throat cultures but antibiotic treatment based only on positive rapid test or throat culture results can reduce unnecessary use of antibiotics for treatment of pharyngitis. However, empirical treatment of adults having a Centor score of 3 or 4 is associated with a high rate of unnecessary antibiotic use. In children, strategies incorporating throat culture or throat culture confirmation of negative rapid antigen test results are highly sensitive and specific. Throat culture of all adults or those selected on the basis of a clinical prediction rule had the highest sensitivity and specificity.

Absence of symptomatic benefit of lansoprazole, clarithromycin, and amoxicillin triple therapy in eradication of Helicobacter pylori positive, functional (nonulcer) dyspepsia.

OBJECTIVES: The aim of this study was to compare the effect of a combination of lansoprazole, clarithromycin, and amoxicillin (LCA) versus placebo on the severity of symptoms in functional dyspepsia patients who were positive for Helicobacter pylori (H. pylori). METHODS: This was a double-blind, randomized, controlled clinical trial in adult patients with functional dyspepsia who were H. pylori positive. Patients were randomized to 7-day treatment with LCA or identical looking placebo. H. pylori status was confirmed by the urea breath test performed at baseline, at 6 wk, and at 6 and 12 months. The severity of eight upper GI symptoms was measured on a five-point Likert scale. The main outcomes were the change in average severity of the dyspepsia summary score of the eight symptoms and the proportion of patients who improved >/=4 points on the dyspepsia summary score. RESULTS: A total of 157 patients were included in the intention-to-treat analysis. LCA achieved cure of H. pylori infection in 82% of patients compared to 6% in the placebo group. The severity of dyspepsia symptoms improved over the 12-month study period, but for none of the outcome measures was there a significant difference between LCA and placebo. CONCLUSIONS: There was no difference in sustained improvement of dyspepsia symptoms when LCA was compared with placebo. An 82% cure rate of H. pylori infection was observed with LAC.

An open-label, randomized, multicenter, comparative study of the efficacy and safety of 7 days of treatment with clarithromycin extended-release tablets versus clarithromycin immediate-release tablets for the treatment of patients with acute bacterial exacerbation of chronic bronchitis.

OBJECTIVE: The aim of this study was to compare the efficacy and safety of clarithromycin extended-release (ER) tablets and immediate-release (IR) tablets. METHODS: This was a Phase III, open-label, randomized, multicenter, comparative study in ambulatory patients with a diagnosis of acute exacerbation of chronic bronchitis (AECB). Eligible patients were randomized 1:1 to receive either 1 clarithromycin ER 500-mg tablet QD for 7 days or 1 clarithromycin IR 250-mg tablet BID for 7 days. Clinical and bacteriologic responses were assessed within 48 hours after the last dose of study drug and at a test-of-cure visit 21 +/- 2 days posttreatment. RESULTS: Of 233 patients randomized, 162 (86/117 [73.5%] in the ER group and 76/115 [66.1%] in the IR group) completed the study protocol. Compliance did not differ significantly between the treatment groups; however, significantly fewer patients in the ER group reported missing doses of study medication than in the IR group (7/118 [5.9%] vs 16/115 [13.9%]; P = 0.04). The clinical cure rates for the clarithromycin ER and IR groups were 81.0% (68/84) and 82.1% (64/78) and the clinical success (clinical cure plus clinical improvement) rates were 94.0% [79/84] and 89.7% [70/78], respectively. There were insufficient data for analysis of bacteriologic efficacy. However, bacteria were eradicated or presumed eradicated in 71.4% (10/14) and 79.2% (19/24) of patients in the ER and IR groups, respectively. The number of adverse events (AEs) considered to be possibly or probably related to study drug (23.4% [52/222] of patients receiving clarithromycin ER and 24.4% [43/176] of patients receiving clarithromycin IR) was similar between groups, as was the severity of these events (94.2% [49/52] in the ER group classified as mild or moderate vs 93.0% [40/43] in the IR group). Overall, the most commonly reported AEs were diarrhea, nausea, abdominal pain, headache, and taste disturbance. CONCLUSION: Clarithromycin ER 500-mg tablets QD for 7 days were as effective and well tolerated as clarithromycin IR 250-mg tablets BID for 7 days in treating adults with AECB.