Economic evaluation of ASCOT-BPLA: Antihypertensive treatment with an amlodipine-based regimen is cost-effective compared to an atenolol-based regimen

Copyright © 2010 BMJ Publishing Group Ltd & British Cardiovascular Society. Internal or personal use of this material is permitted. However, permission to reprint/republish this material must be obtained from the Publisher.Objective: To compare the cost effectiveness of an amlodipine-based strategy and an atenolol-based strategy in the treatment of hypertension in the UK and Sweden. Design: A prospective, randomised trial complemented with a Markov model to assess long-term costs and health effects. Setting: Primary care. Patients: Patients with moderate hypertension and three or more additional risk factors. Interventions: Amlodipine 5–10 mg with perindopril 4–8 mg added as needed or atenolol 50–100 mg with bendroflumethiazide 1.25–2.5 mg and potassium added as needed Main outcome measures: Cost per cardiovascular event and procedure avoided, and cost per quality-adjusted life-year gained. Results: In the UK, the cost to avoid one cardiovascular event or procedure would be €18 965, and the cost to gain one quality-adjusted life-year would be €21 875. The corresponding figures for Sweden were €13 210 and €16 856. Conclusions: Compared with the thresholds applied by NICE and in the Swedish National Board of Health and Welfare’s Guidelines for Cardiac Care, an amlodipine-based regimen is cost effective for the treatment of hypertension compared with an atenolol-based regimen in the population studied.The study was supported by the principal funding source, Pfizer, New York, USA

Heart rate variability and target organ damage in hypertensive patients

Background: We evaluated the association between linear standard Heart Rate Variability (HRV) measures and vascular, renal and cardiac target organ damage (TOD). Methods: A retrospective analysis was performed including 200 patients registered in the Regione Campania network (aged 62.4 ± 12, male 64%). HRV analysis was performed by 24-h holter ECG. Renal damage was assessed by estimated glomerular filtration rate (eGFR), vascular damage by carotid intima-media thickness (IMT), and cardiac damage by left ventricular mass index. Results: Significantly lower values of the ratio of low to high frequency power (LF/HF) were found in the patients with moderate or severe eGFR (p-value < 0.001). Similarly, depressed values of indexes of the overall autonomic modulation on heart were found in patients with plaque compared to those with a normal IMT (p-value <0.05). These associations remained significant after adjustment for other factors known to contribute to the development of target organ damage, such as age. Moreover, depressed LF/HF was found also in patients with left ventricular hypertrophy but this association was not significant after adjustment for other factors. Conclusions: Depressed HRV appeared to be associated with vascular and renal TOD, suggesting the involvement of autonomic imbalance in the TOD. However, as the mechanisms by which abnormal autonomic balance may lead to TOD, and, particularly, to renal organ damage are not clearly known, further prospective studies with longitudinal design are needed to determine the association between HRV and the development of TOD

Evaluation of C-reactive protein prior to and on-treatment as a predictor of benefit from atorvastatin: observations from the Anglo-Scandinavian Cardiac Outcomes Trial

&lt;p&gt;&lt;b&gt;Aims:&lt;/b&gt; We tested whether on-statin C-reactive protein is associated with cardiovascular (CV) outcome in the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT).&lt;/p&gt; &lt;p&gt;&lt;b&gt;Methods and results:&lt;/b&gt; ASCOT randomized a subset of 4853 patients with total cholesterol ≤6.5 mmol/L (250 mg/dL) to atorvastatin or placebo. In a case–control study during 5.5-year follow-up, 485 CV cases were age- and sex-matched with 1367 controls. Baseline LDL-cholesterol (LDL-c) and log-transformed C-reactive protein predicted CV events [odds ratio (OR) per 1 standard deviation (SD) 1.31 (95% confidence interval {CI}: 1.10, 1.56), P = 0.002 and OR 1.19 (1.05, 1.34), P = 0.006, respectively]. Including baseline C-reactive protein into a Framingham risk model very modestly improved risk prediction. Baseline C-reactive protein did not indicate the magnitude of the atorvastatin effect on CV outcome (P = 0.54). At 6 months, atorvastatin reduced median LDL-c by 40.3% and median C-reactive protein by 27.4%. In those randomized to atorvastatin, lower on-treatment LDL-c at 6 months was associated with a significant reduction in subsequent CV events [OR 0.41 (0.22, 0.75), P = 0.004] comparing those above and below the median (2.1 mmol/L). In contrast, C-reactive protein below the median (1.83 mg/L) compared with C-reactive protein above the median was not associated with a significant reduction in CV events [OR 0.86 (0.49, 1.51), P = 0.60]. Consequently, addition of on-treatment C-reactive protein to LDL-c did not improve prediction of statin efficacy.&lt;/p&gt; &lt;p&gt;&lt;b&gt;Conclusion:&lt;/b&gt; Among these hypertensive patients selected on the basis of traditional CV risk factors, C-reactive protein did not usefully improve the prediction of CV events and, critically, reduction in C-reactive protein associated with statin therapy was not a predictor of CV outcome alone or in combination with LDL-c.&lt;/p&gt

Acute treatment of migraine. Breaking the paradigm of monotherapy

BACKGROUND: Migraine is a highly prevalent disorder. The disability provoked by its attacks results in suffering as well as considerable economic and social losses. The objective of migraine acute treatment is to restore the patient to normal function as quickly and consistently as possible. There are numerous drugs available for this purpose and despite recent advances in the understanding of the mechanisms and different biological systems involved in migraine attacks, with the development of specific 5-HT agonists known as triptans, current options for acute migraine still stand below the ideal. DISCUSSION: Monotherapeutic approaches are the rule but up to one third of all patients discontinue their medications due to lack of efficacy, headache recurrence, cost and/or side effects. In addition, a rationale has been suggested for the development of polytherapeutic approaches, simultaneously aiming at some of the biological systems involved. This paper reviews the fundamentals for this changing approach as well as the evidence of its better efficacy. CONCLUSION: As a conclusion, most of the patients with a past history of not responding (no pain-free at 2 hours and/or no sustained pain-free at 24 hours) in at least 5 previous attacks should undergo a combination therapy suiting to their individual profile, which must include analgesics or non-steroidal anti-inflammatory agents plus a triptan or a gastro kinetic drug. The three-drug regimen may also be considered. In addition, changing the right moment to take it and the choice for formulations other than oral has also to be determined individually and clearly posted to the patient

Adverse events associated with unblinded, but not with blinded, statin therapy in the Anglo-Scandinavian Cardiac Outcomes Trial—Lipid-Lowering Arm (ASCOT-LLA): a randomised double-blind placebo-controlled trial and its non-randomised non-blind extension phase

BACKGROUND: In blinded randomised controlled trials, statin therapy has been associated with few adverse events (AEs). By contrast, in observational studies, larger increases in many different AEs have been reported than in blinded trials. METHODS: In the Lipid-Lowering Arm of the Anglo-Scandinavian Cardiac Outcomes Trial, patients aged 40-79 years with hypertension, at least three other cardiovascular risk factors, and fasting total cholesterol concentrations of 6·5 mmol/L or lower, and who were not taking a statin or fibrate, had no history of myocardial infarction, and were not being treated for angina were randomly assigned to atorvastatin 10 mg daily or matching placebo in a randomised double-blind placebo-controlled phase. In a subsequent non-randomised non-blind extension phase (initiated because of early termination of the trial because efficacy of atorvastatin was shown), all patients were offered atorvastatin 10 mg daily open label. We classified AEs using the Medical Dictionary for Regulatory Activities. We blindly adjudicated all reports of four prespecified AEs of interest-muscle-related, erectile dysfunction, sleep disturbance, and cognitive impairment-and analysed all remaining AEs grouped by system organ class. Rates of AEs are given as percentages per annum. RESULTS: The blinded randomised phase was done between February, 1998, and December, 2002; we included 101 80 patients in this analysis (5101 [50%] in the atorvastatin group and 5079 [50%] in the placebo group), with a median follow-up of 3·3 years (IQR 2·7-3·7). The non-blinded non-randomised phase was done between December, 2002, and June, 2005; we included 9899 patients in this analysis (6409 [65%] atorvastatin users and 3490 [35%] non-users), with a median follow-up of 2·3 years (2·2-2·4). During the blinded phase, muscle-related AEs (298 [2·03% per annum] vs 283 [2·00% per annum]; hazard ratio 1·03 [95% CI 0·88-1·21]; p=0·72) and erectile dysfunction (272 [1·86% per annum] vs 302 [2·14% per annum]; 0·88 [0·75-1·04]; p=0·13) were reported at a similar rate by participants randomly assigned to atorvastatin or placebo. The rate of reports of sleep disturbance was significantly lower among participants assigned atorvastatin than assigned placebo (149 [1·00% per annum] vs 210 [1·46% per annum]; 0·69 [0·56-0·85]; p=0·0005). Too few cases of cognitive impairment were reported for a statistically reliable analysis (31 [0·20% per annum] vs 32 [0·22% per annum]; 0·94 [0·57-1·54]; p=0·81). We observed no significant differences in the rates of all other reported AEs, with the exception of an excess of renal and urinary AEs among patients assigned atorvastatin (481 [1·87%] per annum vs 392 [1·51%] per annum; 1·23 [1·08-1·41]; p=0·002). By contrast, during the non-blinded non-randomised phase, muscle-related AEs were reported at a significantly higher rate by participants taking statins than by those who were not (161 [1·26% per annum] vs 124 [1·00% per annum]; 1·41 [1·10-1·79]; p=0·006). We noted no significant differences between statin users and non-users in the rates of other AEs, with the exception of musculoskeletal and connective tissue disorders (992 [8·69% per annum] vs 831 [7·45% per annum]; 1·17 [1·06-1·29]; p=0·001) and blood and lymphatic system disorders (114 [0·88% per annum] vs 80 [0·64% per annum]; 1·40 [1·04-1·88]; p=0·03), which were reported more commonly by statin users than by non-users. INTERPRETATION: These analyses illustrate the so-called nocebo effect, with an excess rate of muscle-related AE reports only when patients and their doctors were aware that statin therapy was being used and not when its use was blinded. These results will help assure both physicians and patients that most AEs associated with statins are not causally related to use of the drug and should help counter the adverse effect on public health of exaggerated claims about statin-related side-effects. FUNDING: Pfizer, Servier Research Group, and Leo Laboratories

Health-care costs of losartan and candesartan in the primary treatment of hypertension

A recent study of two widely used angiotensin receptor blockers reported a reduced risk of cardiovascular events (−14.4%) when using candesartan compared with losartan in the primary treatment of hypertension. In addition to clinical benefits, costs associated with treatment strategies must be considered when allocating scarce health-care resources. The aim of this study was to assess resource use and costs of losartan and candesartan in hypertensive patients. Resource use (drugs, outpatient contacts, hospitalizations and laboratory tests) associated with losartan and candesartan treatment was estimated in 14 100 patients in a real-life clinical setting. We electronically extracted patient data from primary care records and mandatory Swedish national registers for death and hospitalization. Patients treated with losartan had more outpatient contacts (+15.6%), laboratory tests (+13.8%) and hospitalizations (+13.8%) compared with the candesartan group. During a maximum observation time of 9 years, the mean total costs per patient were 10 369 Swedish kronor (95% confidence interval: 3109–17 629) higher in the losartan group. In conclusion, prescribing candesartan for the primary treatment of hypertension results in lower long-term health-care costs compared with losartan

Lack of effect of lowering LDL cholesterol on cancer: meta-analysis of individual data from 175,000 people in 27 randomised trials of statin therapy

&lt;p&gt;Background: Statin therapy reduces the risk of occlusive vascular events, but uncertainty remains about potential effects on cancer. We sought to provide a detailed assessment of any effects on cancer of lowering LDL cholesterol (LDL-C) with a statin using individual patient records from 175,000 patients in 27 large-scale statin trials.&lt;/p&gt; &lt;p&gt;Methods and Findings: Individual records of 134,537 participants in 22 randomised trials of statin versus control (median duration 4.8 years) and 39,612 participants in 5 trials of more intensive versus less intensive statin therapy (median duration 5.1 years) were obtained. Reducing LDL-C with a statin for about 5 years had no effect on newly diagnosed cancer or on death from such cancers in either the trials of statin versus control (cancer incidence: 3755 [1.4% per year [py]] versus 3738 [1.4% py], RR 1.00 [95% CI 0.96-1.05]; cancer mortality: 1365 [0.5% py] versus 1358 [0.5% py], RR 1.00 [95% CI 0.93–1.08]) or in the trials of more versus less statin (cancer incidence: 1466 [1.6% py] vs 1472 [1.6% py], RR 1.00 [95% CI 0.93–1.07]; cancer mortality: 447 [0.5% py] versus 481 [0.5% py], RR 0.93 [95% CI 0.82–1.06]). Moreover, there was no evidence of any effect of reducing LDL-C with statin therapy on cancer incidence or mortality at any of 23 individual categories of sites, with increasing years of treatment, for any individual statin, or in any given subgroup. In particular, among individuals with low baseline LDL-C (&#60;2 mmol/L), there was no evidence that further LDL-C reduction (from about 1.7 to 1.3 mmol/L) increased cancer risk (381 [1.6% py] versus 408 [1.7% py]; RR 0.92 [99% CI 0.76–1.10]).&lt;/p&gt; &lt;p&gt;Conclusions: In 27 randomised trials, a median of five years of statin therapy had no effect on the incidence of, or mortality from, any type of cancer (or the aggregate of all cancer).&lt;/p&gt

Flow propagation velocity is not a simple index of diastolic function in early filling. A comparative study of early diastolic strain rate and strain rate propagation, flow and flow propagation in normal and reduced diastolic function

BACKGROUND: Strain Rate Imaging shows the filling phases of the left ventricle to consist of a wave of myocardial stretching, propagating from base to apex. The propagation velocity of the strain rate wave is reduced in delayed relaxation. This study examined the relation between the propagation velocity of strain rate in the myocardium and the propagation velocity of flow during early filling. METHODS: 12 normal subjects and 13 patients with treated hypertension and normal systolic function were studied. Patients and controls differed significantly in diastolic early mitral flow measurements, peak early diastolic tissue velocity and peak early diastolic strain rate, showing delayed relaxation in the patient group. There were no significant differences in EF or diastolic diameter. RESULTS: Strain rate propagation velocity was reduced in the patient group while flow propagation velocity was increased. There was a negative correlation (R = -0.57) between strain rate propagation and deceleration time of the mitral flow E-wave (R = -0.51) and between strain rate propagation and flow propagation velocity and there was a positive correlation (R = 0.67) between the ratio between peak mitral flow velocity / strain rate propagation velocity and flow propagation velocity. CONCLUSION: The present study shows strain rate propagation to be a measure of filling time, but flow propagation to be a function of both flow velocity and strain rate propagation. Thus flow propagation is not a simple index of diastolic function in delayed relaxation