Persistence with nebivolol in the treatment of hypertension: a retrospective claims analysis.

OBJECTIVE: Examine drug persistence by evaluating the hazard of discontinuation and of switching to different antihypertensive drugs in patients initiating treatment with a recently approved ß-blocker, nebivolol, versus other ß-blockers. METHODS: This retrospective analysis included all patients diagnosed with hypertension in the MarketScan Database (January 2007 - December 2008) with at least two medical claims and no prior ß-blocker prescriptions within 6 months of the initial prescription date. Multivariate Cox proportional hazard models (adjusted for baseline differences in demographics, previous use of other antihypertensive medications, initial doses and supply of medication, and number of distinct prescriptions at baseline) were used to assess the hazard of discontinuation, defined as the first prescription gap of ≥30 days, and to assess the hazard of switching to another antihypertensive drug, defined as a prescription fill for another antihypertensive drug within 15 days before and 30 days after discontinuation of the initial ß-blocker. RESULTS: Of the 173,200 patients included in the study population, the adjusted hazard of discontinuation for nebivolol-initiated patients was 8-20% lower than that of patients who initiated treatment with atenolol (hazard ratio [HR] 0.82, p < 0.001), metoprolol (HR 0.91, p < 0.001), carvedilol (HR 0.92, p < 0.001), or other ß-blockers (HR 0.80, p < 0.001). The adjusted hazard of nebivolol-treated patients switching to a different antihypertensive medication was 12-22% lower than that of the other four ß-blocker cohorts (atenolol: HR 0.80, p < 0.001; metoprolol: HR 0.86, p < 0.001; carvedilol: HR 0.88, p < 0.001; other ß-blockers: HR 0.78, p < 0.001). Sensitivity analyses defined discontinuation as prescription gaps of ≥45 days and ≥60 days and showed a lower hazard of discontinuation among patients initiating nebivolol than among patients initiating all other drug cohorts (p < 0.001). LIMITATIONS: Comparisons of non-randomized treatment groups may be confounded by unobserved differences in patients' baseline characteristics. CONCLUSIONS: Initiation with nebivolol was associated with greater persistence than initiation with atenolol, carvedilol, metoprolol, or other ß-blockers.

An economic evaluation of antihypertensive therapies based on clinical trials.

OBJECTIVE: Hypertension is a major issue in public health, and the financial costs associated with hypertension continue to increase. Cost-effectiveness studies focusing on antihypertensive drug combinations, however, have been scarce. The cost-effectiveness ratios of the traditional treatment (hydrochlorothiazide and atenolol) and the current treatment (losartan and amlodipine) were evaluated in patients with grade 1 or 2 hypertension (HT1-2). For patients with grade 3 hypertension (HT3), a third drug was added to the treatment combinations: enalapril was added to the traditional treatment, and hydrochlorothiazide was added to the current treatment. METHODS: Hypertension treatment costs were estimated on the basis of the purchase prices of the antihypertensive medications, and effectiveness was measured as the reduction in systolic blood pressure and diastolic blood pressure (in mm Hg) at the end of a 12-month study period. RESULTS: When the purchase price of the brand-name medication was used to calculate the cost, the traditional treatment presented a lower cost-effectiveness ratio [US$/mm Hg] than the current treatment in the HT1-2 group. In the HT3 group, however, there was no difference in cost-effectiveness ratio between the traditional treatment and the current treatment. The cost-effectiveness ratio differences between the treatment regimens maintained the same pattern when the purchase price of the lower-cost medication was used. CONCLUSIONS: We conclude that the traditional treatment is more cost-effective (US$/mm Hg) than the current treatment in the HT1-2 group. There was no difference in cost-effectiveness between the traditional treatment and the current treatment for the HT3 group.

Identifying iatrogenic depression using confirmatory factor analysis of the Center for Epidemiologic Studies Depression Scale in patients prescribed a verapamil-sustained-release-led or atenolol-led hypertension treatment strategy.

BACKGROUND: ß-blockers and calcium channel blockers are highly effective medications indicated for treatment and prevention of hypertension. However, the literature regarding the potential depressive effects of ß-blockers and calcium channel blockers is equivocal regarding whether one or both are associated with depression. OBJECTIVES: To determine whether self-reported depressive symptoms of older persons with hypertension and coronary artery disease and who were randomly assigned to a verapamil-sustained-release-led (Ve-led) or atenolol-led (At-led) hypertension treatment strategy were similar using confirmatory factor analytical models of the Center for Epidemiologic Studies Depression Scale (CES-D). METHODS: This study used a mail survey of patients enrolled in a substudy of an international randomized controlled clinical trial. Complete data on the CES-D after 1 year of treatment were obtained from 1019 study subjects. Multiple group confirmatory factor analysis (CFA) procedures were used to test for differences in the fit of the data to the initial 4-factor CES-D model among patients assigned to the 2 treatment groups after 12 months of therapy. A test of configural invariance was conducted by sequentially constraining various matrices to be equal across groups. The convergent validity of the model was tested by examining the standard errors of the lambda-X parameter estimates of the configural model. The factor loadings for like items were investigated across the 2 groups using a test of strong factorial invariance. Finally, the 2 treatment groups were compared on the 4 factors to detect differences in the model's parameters. RESULTS: Overall, the data fit the CFA models across the 2 treatment groups based on the 4-factor model. However, 3 items differed slightly, including appetite, depressed, and crying. The data suggested significant differences across groups on the positive affect, interpersonal relations, and somatic and retarded activity latent variables. CONCLUSIONS: The domains indicating less happiness and more depressive symptoms were most likely to be unfavorably impacted by the At-led treatment strategy. Given a choice between these equally effective high blood pressure treatment strategies, it may be prudent to use the Ve-led strategy. This is especially true if the risk of the occurrence of a mood-related side effect of the ß-blocker outweighs its other benefits in comparison.

An economic evaluation of antihypertensive therapies based on clinical trials

OBJECTIVE: Hypertension is a major issue in public health, and the financial costs associated with hypertension continue to increase. Cost-effectiveness studies focusing on antihypertensive drug combinations, however, have been scarce. The cost-effectiveness ratios of the traditional treatment (hydrochlorothiazide and atenolol) and the current treatment (losartan and amlodipine) were evaluated in patients with grade 1 or 2 hypertension (HT1-2). For patients with grade 3 hypertension (HT3), a third drug was added to the treatment combinations: enalapril was added to the traditional treatment, and hydrochlorothiazide was added to the current treatment. METHODS: Hypertension treatment costs were estimated on the basis of the purchase prices of the antihypertensive medications, and effectiveness was measured as the reduction in systolic blood pressure and diastolic blood pressure (in mm Hg) at the end of a 12-month study period. RESULTS: When the purchase price of the brand-name medication was used to calculate the cost, the traditional treatment presented a lower cost-effectiveness ratio [US$/mm Hg] than the current treatment in the HT1-2 group. In the HT3 group, however, there was no difference in cost-effectiveness ratio between the traditional treatment and the current treatment. The cost-effectiveness ratio differences between the treatment regimens maintained the same pattern when the purchase price of the lower-cost medication was used. CONCLUSIONS: We conclude that the traditional treatment is more cost-effective (US$/mm Hg) than the current treatment in the HT1-2 group. There was no difference in cost-effectiveness between the traditional treatment and the current treatment for the HT3 group.

[Study of the efficacy and safety of losartan versus atenolol for aortic dilation in patients with Marfan syndrome]. / Valoración de la eficacia y la seguridad del losartán frente al atenolol en la prevención de la dilatación de la aorta en el síndrome de Marfan.

INTRODUCTION AND OBJECTIVES: Marfan syndrome is an inherited disease of the connective tissue. Recent trials have indicated the use of losartan (a transforming growth factor beta inhibitor) in these patients prevents aortic root enlargement. The aim of our clinical trial is to assess the efficacy and safety of losartan versus atenolol in the prevention of progressive dilation of the aorta in patients with Marfan syndrome. METHODS: This is a phase III clinical trial conducted in two institutions. A total of 150 subjects diagnosed with Marfan syndrome, aged between 5 and 60 years, of both sexes, and who meet the Ghent diagnostic criteria will be included in the study, with 75 patients per treatment group. It will be a randomized, double blind trial with parallel assignment to atenolol versus losartan (50 mg per day in patients below 50 kg and 100 mg per day in patients over 50 kg). Both growth and distensibility of the aorta will be assessed with echocardiography and magnetic resonance. Follow-up will be 3 years. CONCLUSIONS: Efficacy of losartan versus atenolol in the prevention of progressive dilation of the aorta, improved aortic distensibility, and prevention of adverse events (aortic dissection or rupture, cardiovascular surgery, or death) will be assessed in this study. It will also show the possible treatment benefits at different age ranges and with relation to the initial level of aortic root dilation.

[Clinical-pharmacoeconomical aspects of ß-adrenoblockers use in patients with ischemic heart disease undergoing coronary artery bypass grafting].

Aim of this study was to assess clinical and pharmacoeconomic effects of long term use of adrenoblockers in patients with ischemic heart disease (IHD) undergoing coronary artery bypass grafting. Patients with IHD (n=294) were included in open, prospective, randomized clinical trial. The follow up period was 3 years. It was noted that long term use of bisoprolol in comparison with atenolol and metoprolol was characterized by more pronounced increase of exercise tolerance, lower rate of angina recurrence and lower expenses for treatment of patients with IHD.

Ivabradine: new drug. Best avoided in stable angina.

(1) The first-line symptomatic treatment for stable angina is a betablocker such as atenolol. Some calcium channel blockers such as verapamil, and the potassium channel agonist amlodipine, are second-line alternatives. Long-acting nitrate derivatives have poorly documented efficacy but can be used as adjuvants or as third-line treatments. (2) Ivabradine is derived from verapamil but appears to have a different mechanism of action, mainly lowering the heart rate. It was approved for sale in Europe through the centralised procedure for second-line treatment of stable angina. (3) Clinical evaluation of ivabradine only includes randomised controlled trials versus two other anti-angina drugs: atenolol and amlodipine. Three double-blind randomised controlled trials lasting 3 to 4 months, based on surrogate exercise endpoints, failed to show that ivabradine was any more effective than atenolol or amlodipine, or even more effective than placebo in patients already treated with amlodipine. (4) In two one-year double-blind randomised controlled trials comparing ivabradine with atenolol or amlodipine in a total of 704 patients, ivabradine was no more effective than the comparators in preventing angina attacks. (5) In head-to-head comparisons, serious coronary events were significantly more frequent with ivabradine than with atenolol (3.8% versus 1.5%). Severe arrhythmias were also more frequent with ivabradine than with atenolol (1.3% versus 0.7%) or amlodipine (0.6% versus 0.2%). (6) Ivabradine provokes phosphenes (flashing lights, etc.) in about 17% of patients in the short term. Information is inadequate to assess possible risks of retinal toxicity in the long term. (7) Ivabradine is metabolised by cytochrome P450 isoenzyme CYP 3A4; there is therefore a potentially high risk of pharmacokinetic interactions. (8) In practice, for long-term preventive treatment of angina it is better to avoid ivabradine and to use better-documented treatments: preferably a betablocker, or, if a betablocker cannot be used, verapamil or amlodipine.

[Medicamentous kidney protection in type 2 diabetic patients--is cheaper also more economical? A model calculation for Swiss health care]. / Medikamentöse Nephroprotektion bei Typ 2-Diabetikern--ist billiger auch ökonomischer? Eine Modellrechnung für Schweizer Verhältnisse.

Impaired renal function occurs in about 50% of patients suffering from type 2 diabetes, and diabetic nephropathy has become the leading cause of endstage renal disease. Reduction of blood pressure to levels around 120/80 mmHg is one of the most effective way to slow progression of diabetic nephropathy. Recent meta-analyses, however, have emphasized on the fact that ACE inhibitors (ACEI) and non-dihydropyridine calcium channel blockers (NDHP-CCB) exert nephro-protective effects which go beyond the effect of blood pressure reduction. This has lately been confirmed by a prospective trial in comparison to the betablocker atenolol. Based on these data, demographics of the Swiss population, literature data on mortality rates of type 2 diabetics with impaired renal function and studies on true costs of antihypertensives, we calculated the costs of a longterm intervention (20 years) with antihypertensives in 3536 middle-aged Swiss patients with type 2 diabetes and macro-albuminuria whose antihypertensive regimen was based either on the ACEI lisinopril, or the ND-HP-CCB verapamil, or the betablocker atenolol. Under atenolol, acquisition costs were lowest, whereas faster loss of renal function over time increased mortality rate and thus reduced the number of patients to be treated. Nevertheless, due to the fact that patients reached uremia and had to be dialyzed, 20 years of atenolol-based regimen with costs of 316 millions of Swiss francs turned out to be much more expensive than the lisinopril- or the verapamil-based regimen with 121 and 38 millions of Swiss francs, respectively. Thus, low acquisition cost is not necessarily the only important determinant of overall costs of drug therapy.

Assessment of quality of life by patient and spouse during antihypertensive therapy with atenolol and nifedipine gastrointestinal therapeutic system.

To evaluate differences in efficacy, safety, and quality of life, 394 male patients with mild-to-moderate hypertension were randomized to receive 20 weeks of either atenolol or nifedipine gastrointestinal therapeutic system (GITS) in a multicenter double-blind trial. A four-week placebo washout was followed by 8 weeks of titration and 12 weeks of maintenance therapy. Quality-of-life evaluation included clinical assessments by the patient and parallel take-home assessments by patient and spouse. Blood pressure was controlled equally in both groups. The total incidence of adverse reactions was similar in both groups, but a greater percentage of nifedipine GITS patients withdrew due to peripheral edema. Patients completing 20 weeks of therapy demonstrated a more favorable quality-of-life profile (P less than .05) for nifedipine GITS over atenolol in psychosocial (P less than .01), well-being (P less than .05), general affect (P less than .05), emotional ties (P less than .01), emotional control (P less than .05), vitality (P less than .05), and leisure (P less than .05) scores. Treatment differences were particularly pronounced for patients over 50 years of age and were not fully detectable until after 14 weeks of therapy. Deterioration in quality of life was associated with withdrawal. Spouses of younger patients receiving atenolol reported deterioration in sexual satisfaction as compared to spouses of patients taking nifedipine GITS (P less than .02). Thus age, length of trial, and third-party observation are important factors in quality-of-life assessment. Comparison of adverse reactions provides an incomplete measure of how well a drug is tolerated. In contrast, findings indicate that even subtle CNS-mediated effects on mood and well-being can be detected by quality-of-life evaluation.

Multicentre general practitioner assessment of 'Tenormin' and methyldopa.

A large scale study in general practice was set up to investigate the effects of transferring hypertensive patients from treatment with usually less than 1 g daily of methyldopa to atenolol ('Tenormin') 100 mg daily. The results demonstrate an improvement in blood pressure control with atenolol treatment and a reduction in the incidence of side-effects. The simple dosage regime, combined with proven effectiveness and a relative lack of side-effects makes atenolol a useful treatment for the hypertensive patient.