Cost-Effectiveness Analysis of Evolocumab Therapy in Patients at High Risk of Cardiovascular Events in the Context of the Brazilian Unified Health System. / Análise de Custo-Efetividade da Terapia com Evolocumabe em Pacientes com Alto Risco de Eventos Cardiovasculares no Contexto do SUS ­ Brasil.

BACKGROUND: Hypertrophic cardiomyopathy (HCM) and left ventricular hypertrophy (LVH) secondary to systemic hypertension (HTN) may be associated with left atrial (LA) functional abnormalities. OBJECTIVES: We aimed to characterize LA mechanics in HCM and HTN and determine any correlation with the extent of left ventricular (LV) fibrosis measured by cardiac magnetic resonance (CMR) in HCM patients. METHODS: Two-dimensional speckle tracking-derived longitudinal LA function was acquired from apical views in 60 HCM patients, 60 HTN patients, and 34 age-matched controls. HCM patients also underwent CMR, with measurement of late gadolinium enhancement (LGE) extension. Association with LA strain parameters was analyzed. Statistical significance was set at p<0.05. RESULTS: Mean LV ejection fraction was not different between the groups. The E/e' ratio was impaired in the HCM group and preserved in the control group. LA mechanics was significantly reduced in HCM, compared to the HTN group. LA strain rate in reservoir (LASRr) and in contractile (LASRct) phases were the best discriminators of HCM, with an area under the curve (AUC) of 0.8, followed by LA strain in reservoir phase (LASr) (AUC 0.76). LASRr and LASR-ct had high specificity (89% and 91%, respectively) and LASr had sensitivity of 80%. A decrease in 2.79% of LA strain rate in conduit phase (LASRcd) predicted an increase of 1cm in LGE extension (r2=0.42, ß 2.79, p=0.027). CONCLUSIONS: LASRr and LASRct were the best discriminators for LVH secondary to HCM. LASRcd predicted the degree of LV fibrosis assessed by CMR. These findings suggest that LA mechanics is a potential predictor of disease severity in HCM.

FUNDAMENTO: Em associação às estatinas, os inibidores da pró-proteína convertase subtilisina/kexina tipo 9 (PCSK9) demonstraram ser eficazes na redução de eventos cardiovasculares em pacientes de alto risco. OBJETIVO: Analisar a custo-efetividade da implementação de evolocumabe para pacientes com alto risco de eventos cardiovasculares no contexto do Sistema Único de Saúde (SUS) no Brasil. MÉTODOS: Um modelo de Markov foi utilizado, baseando-se em uma amostra ambulatorial de pacientes com doença arterial coronariana. Os desfechos primários analisados foram infarto agudo do miocárdio, acidente vascular cerebral isquêmico (AVCi), revascularização do miocárdio e morte cardiovascular. O resultado foi expresso por meio da razão de custo-efetividade incremental (RCEI), considerando-se uma taxa de desconto de 5% ao ano, e uma análise de sensibilidade foi realizada, tendo em vista a imprecisão de valores. RESULTADOS: Selecionaram-se 61 pacientes com risco cardiovascular estimado em 35% em 10 anos, se em uso de atorvastatina 80mg/dia, e em 22,75%, se adicionado o evolocumabe. O custo global por paciente no período de 10 anos foi de R$ 46.522,44 no grupo em monoterapia com atorvastatina versus R$ 236.141,85 na terapia combinada, com uma efetividade global de 0,54 e 0,73, respectivamente. Isso resultou em uma RCEI R$ 1.011.188,07 (R$ 864.498,95 a R$ 1.296.748,43) por desfecho cardiovascular evitado. CONCLUSÕES: Apesar de não existirem padrões nacionais para custo-efetividade, os dados encontrados sugerem que a estratégia de associação do evolocumabe à terapia com estatina não é, no momento, custo-efetiva.

Análise de Custo-Efetividade da Terapia com Evolocumabe em Pacientes com Alto Risco de Eventos Cardiovasculares no Contexto do SUS - Brasil / Cost-Effectiveness Analysis of Evolocumab Therapy in Patients at High Risk of Cardiovascular Events in the Context of the Brazilian Unified Health System

Resumo Fundamento: Em associação às estatinas, os inibidores da pró-proteína convertase subtilisina/kexina tipo 9 (PCSK9) demonstraram ser eficazes na redução de eventos cardiovasculares em pacientes de alto risco. Objetivo: Analisar a custo-efetividade da implementação de evolocumabe para pacientes com alto risco de eventos cardiovasculares no contexto do Sistema Único de Saúde (SUS) no Brasil. Métodos: Um modelo de Markov foi utilizado, baseando-se em uma amostra ambulatorial de pacientes com doença arterial coronariana. Os desfechos primários analisados foram infarto agudo do miocárdio, acidente vascular cerebral isquêmico (AVCi), revascularização do miocárdio e morte cardiovascular. O resultado foi expresso por meio da razão de custo-efetividade incremental (RCEI), considerando-se uma taxa de desconto de 5% ao ano, e uma análise de sensibilidade foi realizada, tendo em vista a imprecisão de valores. Resultados: Selecionaram-se 61 pacientes com risco cardiovascular estimado em 35% em 10 anos, se em uso de atorvastatina 80mg/dia, e em 22,75%, se adicionado o evolocumabe. O custo global por paciente no período de 10 anos foi de R$ 46.522,44 no grupo em monoterapia com atorvastatina versus R$ 236.141,85 na terapia combinada, com uma efetividade global de 0,54 e 0,73, respectivamente. Isso resultou em uma RCEI R$ 1.011.188,07 (R$ 864.498,95 a R$ 1.296.748,43) por desfecho cardiovascular evitado. Conclusões: Apesar de não existirem padrões nacionais para custo-efetividade, os dados encontrados sugerem que a estratégia de associação do evolocumabe à terapia com estatina não é, no momento, custo-efetiva.

Abstract Background: Hypertrophic cardiomyopathy (HCM) and left ventricular hypertrophy (LVH) secondary to systemic hypertension (HTN) may be associated with left atrial (LA) functional abnormalities. Objectives: We aimed to characterize LA mechanics in HCM and HTN and determine any correlation with the extent of left ventricular (LV) fibrosis measured by cardiac magnetic resonance (CMR) in HCM patients. Methods: Two-dimensional speckle tracking-derived longitudinal LA function was acquired from apical views in 60 HCM patients, 60 HTN patients, and 34 age-matched controls. HCM patients also underwent CMR, with measurement of late gadolinium enhancement (LGE) extension. Association with LA strain parameters was analyzed. Statistical significance was set at p<0.05. Results: Mean LV ejection fraction was not different between the groups. The E/e' ratio was impaired in the HCM group and preserved in the control group. LA mechanics was significantly reduced in HCM, compared to the HTN group. LA strain rate in reservoir (LASRr) and in contractile (LASRct) phases were the best discriminators of HCM, with an area under the curve (AUC) of 0.8, followed by LA strain in reservoir phase (LASr) (AUC 0.76). LASRr and LASR-ct had high specificity (89% and 91%, respectively) and LASr had sensitivity of 80%. A decrease in 2.79% of LA strain rate in conduit phase (LASRcd) predicted an increase of 1cm in LGE extension (r2=0.42, β 2.79, p=0.027). Conclusions: LASRr and LASRct were the best discriminators for LVH secondary to HCM. LASRcd predicted the degree of LV fibrosis assessed by CMR. These findings suggest that LA mechanics is a potential predictor of disease severity in HCM.

Assessment of Carotid Intima Media Thickness and Left Ventricular Mass Index in Children with Idiopathic Nephrotic Syndrome.

BACKGROUND: Children with nephrotic syndrome (NS) are at a greater risk of atherosclerosis due to recurrent exposures to hyperlipidemia, hypertension, and immunosuppressive medications. CIMT (carotid intima media thickness) is a reliable marker for assessment of atherosclerosis of large and medium-sized blood vessels; endothelial dysfunction and increased CIMT usually precede the development of cardiovascular diseases. Some manifestations of NS, like proteinuria and hyperlipidemia, are associated with an increased risk of cardiac morbidity and mortality. The aim of the current study was to evaluate the carotid intima media thickness and LVM (left ventricular mass) thickness in children with nephrotic syndrome. SUBJECTS AND METHODS: Eighty-one children with nephrotic syndrome and 100 healthy children as controls were enrolled in the study. The inclusion criteria were: disease duration of minimum of 12 months, glomerular filtration rate >60mL/min/1.73m 2 and children aged two years or more at the time of study. CIMT and left ventricular mass index, lipid profile, protein/creatinine ratio in urine and kidney function tests were done for cases and controls after approval of internal ethical committee. RESULTS: The mean CIMT (mm) was significantly higher in NS (0.51± 0.12) compared to controls (0.42± 0.09) (P <0.001). LVM and LVM Index were significantly higher in NS than controls (p< 0.001, for both). Subsequently, CIMT was significantly correlated to duration of the disease (p< 0.001), LVM index was significantly correlated with duration of the disease, body mass index (BMI), blood pressures and triglycerides level (p< 0.05). CONCLUSION: Children with NS are at increasing risk to develop atherosclerosis as measured by CIMT. LVM was significantly higher in NS and positively correlated to BP, disease duration, triglyceride levels and BMI.

Association between long-term prescription of febuxostat and the progression of heart failure with preserved ejection fraction in patients with hypertension and asymptomatic hyperuricemia.

Both hypertension and hyperuricemia are closely associated with the morbidity and mortality of heart failure. This study was designed to evaluate the influences of long-term xanthine oxidase inhibitor (febuxostat) prescription on left ventricular hypertrophy (LVH), left ventricular (LV) diastolic function, and new-onset heart failure with preserved ejection fraction (HFpEF) in these patients. Using a propensity score matching of 1:2 ratio, this retrospective claims database study compared febuxosatat prescription (n = 96) and non-urate-lowering therapy (n = 192) in patients with hypertensive left ventricular hypertrophy (LVH) and asymptomatic hyperuricemia. With a follow-up of 36 months, febuxostat significantly decreased the level of serum uric acid as well as generated more prominent improvement in LVH and LV diastolic function. Besides, the new-onset symptomatic HFpEF occurred in 2 of 96 patients in febuxostat group and 13 of 192 patients in non-urate-lowering group (P = 0.091). No increased risk for major adverse cardiovascular events in patients prescribed with febuxostat was noted. In conclusion, long-term febuxostat exposure was associated with protective effects in terms of LVH or LV diastolic dysfunction in patients with hypertensive LVH and asymptomatic hyperuricemia. Febuxostat also displayed a trend for reduced risk of new-onset HFpEF in this population.

Nocturnal systolic hypertension is a risk factor for cardiac damage in the untreated masked hypertensive patients.

The nocturnal blood pressure (BP) has been identified as a prognostic factor for cardiovascular events. This study aimed to investigate the association between different patterns of nocturnal masked hypertension (MH) and the echocardiographic parameters in the untreated nocturnal MH patients. A total of 721 untreated MH patients (309 females and 412 males, mean age = 56.59 ± 15.20 years) from June 2006 and June 2016 were included and divided into nocturnal systolic MH (n = 77), nocturnal diastolic MH (n = 232), and nocturnal systolic/diastolic MH (n = 412) groups according to the ambulatory blood pressure monitoring. Baseline characteristics, office BP values, ambulatory BP monitoring parameters, and echocardiographic parameters were compared among the three groups. The independent factors associated with echocardiographic parameters were analyzed by multivariate linear regression. The nocturnal systolic group had the highest ratio of males, mean age, and office systolic BP (SBP), and the lowest office, 24-hour, daytime, nocturnal diastolic BP and heart rate among the three groups. The nocturnal diastolic group had the lowest interventricular septum (IVS) thickness, left atrium (LA) dimension, and left ventricular (LV) mass among the three groups. Multivariate linear regression analysis revealed that 24-hour, daytime, and nocturnal SBPs were all positively associated with LA dimension, IVS thickness, and LV mass (all B were positive and P < .050). Pearson's correlation analysis showed that nocturnal SBP was positively correlated with LA dimension, IVS thickness, and LV mass. These results suggested that different patterns of nocturnal MH had different echocardiographic outcomes. Nocturnal SBP was the independent factor associated with the echocardiographic parameters.

Assessment and management of fluid overload in children on dialysis.

Dysregulation of intravascular fluid leads to chronic volume overload in children with end-stage kidney disease (ESKD). Sequelae include left ventricular hypertrophy and remodeling and impaired cardiac function. As a result, cardiovascular complications are the commonest cause of mortality in the pediatric dialysis population. The clinical need to optimize intravascular volume in children with ESKD is clear; however, its assessment and management is the most challenging aspect of the pediatric dialysis prescription. Minimizing chronic fluid overload is a key priority; however, excessive ultrafiltration is toxic to the myocardium and can precipitate intradialytic symptoms. This review outlines emerging objective techniques to enhance the assessment of fluid overload in children on dialysis and outlines evidence for current management strategies to address this clinical problem.

Cardiovascular Health Status and Incidence of Heart Failure in the Framingham Offspring Study.

BACKGROUND: The American Heart Association Cardiovascular Health (CVH) score is inversely associated with cardiovascular disease, but its relations to cardiac remodeling traits and heart failure (HF) incidence have not been examined. METHODS AND RESULTS: A 14-point score was constructed for each participant based on the presence of poor, intermediate, or ideal status on each of the 7 CVH metrics (ideal score=14). We related the CVH score to echocardiographic traits cross-sectionally and to HF incidence prospectively in the Framingham Offspring Study. In age- and sex-adjusted models, a higher CVH score was associated with lower left ventricular (LV) mass, LV wall thickness, LV diastolic dimension, and left atrial dimension (P<0.01 for all; n=2392; mean age, 58 years; 56% women), and with a 12% to 15% lower odds of prevalent LV concentric remodeling and concentric hypertrophy, respectively (P<0.0001 for both). On follow-up (mean, 12.3 years), 188 incident HF events were observed in 3201 participants (mean age, 59 years; 53% women). In age- and sex-adjusted Cox proportional hazard models, the CVH score was inversely associated with HF incidence (hazard ratio per 1-point higher CVH score, 0.77; 95% confidence interval, 0.72-0.83). This association was partially attenuated upon adjustment for LV mass and interim myocardial infarction (hazard ratio, 0.84; 95% confidence interval, 0.76-0.93), and it was consistent for HF with preserved and reduced ejection fractions. CONCLUSIONS: In our community-based sample, comprised predominantly of middle-aged white individuals of European descent, better CVH was associated with lower HF incidence, in part due to a lower prevalence of adverse cardiac remodeling.

Telmisartan: just an antihypertensive agent? A literature review.

INTRODUCTION: The modulation of the renin angiotensin aldosterone system (RAAS) is an important pathway in managing high blood pressure, and its overexpression plays a key role in target end-organ damage. Telmisartan is an angiotensin II receptor blocker (ARB) with unique pharmacologic properties, including the longest half-life among all ARBs; this leads to a significant and 24-h sustained reduction of blood pressure. Telmisartan has well-known antihypertensive properties, but there is also strong clinical evidence that it reduces left ventricular hypertrophy, arterial stiffness and the recurrence of atrial fibrillation, and confers renoprotection. AREAS COVERED: This paper reviews telmisartan's pharmacological properties in terms of efficacy for hypertension control and, importantly, focuses on its new therapeutic indications and their clinical implications. EXPERT OPINION: ONTARGET (ongoing telmisartan alone and in combination with ramipril global endpoint trial) demonstrated, that telmisartan confers cardiovascular protective effects similar to those of ramipril, but with a better tolerability. Moreover, recent investigations focused on the capability of telmisartan to modulate the peroxisome proliferator-activated receptor-gamma (PPAR-γ), an established target in the treatment of insulin resistance, diabetes and metabolic syndrome, whose activation is also correlated to anti-inflammatory and, finally, anti-atherosclerotic properties. Telmisartan shows peculiar features that go beyond blood pressure control. It presents promising and unique protective properties against target end-organ damage, potentially able to open a scenario of new therapeutic approaches to cardiovascular disease.

Valsartan plus hydrochlorothiazide: a review of its use since its introduction.

INTRODUCTION: This review focuses on the role of the fixed-dose combination (FDC) drug valsartan/hydrochlorothiazide (HCTZ) in the treatment of hypertension. Effective blood pressure control often is not achieved with monotherapy and, instead, requires combinations of drugs with different mechanisms of action to produce additive or synergistic effects. AREAS COVERED: FDC valsartan/HCTZ enhances not only efficacy for blood pressure control but also provides beneficial effects on target organs beyond that expected from arterial pressure reduction alone. Data describe key clinical trial experiences with the FDC, with particular attention to efficacy and tolerability. Literature searches of these various topics were conducted in January 2011. There is evidence of potential benefits with this combination associated with left ventricular hypertrophy, left ventricular dysfunction and renal disease. The FDC is an effective treatment for patients with hypertension and is superior to monotherapy than either drug alone. EXPERT OPINION: In addition to the benefits of each drug, valsartan/HCTZ's metabolic interactions reduce some of the negative effects of both compounds. With its increased simplicity, minimal side-effect profile and efficacy without a significant cost penalty, valsartan/HCTZ represents an excellent choice for antihypertensive therapy.

Frequent Hemodialysis Network (FHN) randomized trials: study design.

Observational studies suggest improvements with frequent hemodialysis (HD), but its true efficacy and safety remain uncertain. The Frequent Hemodialysis Network Trials Group is conducting two multicenter randomized trials of 250 subjects each, comparing conventional three times weekly HD with (1) in-center daily HD and (2) home nocturnal HD. Daily HD will be delivered for 1.5-2.75 h, 6 days/week, with target eK(t)/V(n) > or = 0.9/session, whereas nocturnal HD will be delivered for > or = 6 h, 6 nights/week, with target stdK(t)/V of > or = 4.0/week. Subjects will be followed for 1 year. The composite of mortality with the 12-month change in (i) left ventricular mass index (LVMI) by magnetic resonance imaging, and (ii) SF-36 RAND Physical Health Composite (PHC) are specified as co-primary outcomes. The seven main secondary outcomes are between group comparisons of: change in LVMI, change in PHC, change in Beck Depression Inventory score, change in Trail Making Test B score, change in pre-HD serum albumin, change in pre-HD serum phosphorus, and rates of non-access hospitalization or death. Changes in blood pressure and erythropoiesis will also be assessed. Safety outcomes will focus on vascular access complications and burden of treatment. Data will be obtained on the cost of delivering frequent HD compared to conventional HD. Efforts will be made to reduce bias, including blinding assessment of subjective outcomes. Because no large-scale randomized trials of frequent HD have been previously conducted, the first year has been designated a Vanguard Phase, during which feasibility of randomization, ability to deliver the interventions, and adherence will be evaluated.

Non-invasive magnetic resonance imaging assessment of myocardial changes and the effects of angiotensin-converting enzyme inhibition in diabetic rats.

A non-invasive cine magnetic resonance imaging (MRI) technique was developed to allow, for the first time, detection and characterization of chronic changes in myocardial tissue volume and the effects upon these of treatment by the angiotensin-converting enzyme (ACE) inhibitor captopril in streptozotocin (STZ)-diabetic male Wistar rats. Animals that had been made diabetic at the ages of 7, 10 and 13 weeks and a captopril-treated group of animals made diabetic at the age of 7 weeks were scanned. The findings were compared with the results from age-matched controls. All animal groups (n = 4 animals in each) were consistently scanned at 16 weeks. Left and right ventricular myocardial volumes were reconstructed from complete data sets of left and right ventricular transverse sections which covered systole and most of diastole using twelve equally incremented time points through the cardiac cycle. The calculated volumes remained consistent through all twelve time points of the cardiac cycle in all five experimental groups and agreed with the corresponding post-mortem determinations. These gave consistent myocardial densities whose values could additionally be corroborated by previous reports, confirming the validity of the quantitative MRI results and analysis. The myocardial volumes were conserved in animals whose diabetes was induced at 13 weeks but were significantly increased relative to body weight in animals made diabetic at 7 and 10 weeks. Captopril treatment, which was started immediately after induction of diabetes, prevented the development of this relative hypertrophy in both the left and right ventricles. We have thus introduced and validated quantitative MRI methods in a demonstration, for the first time, of chronic myocardial changes in both the right and left ventricles of STZ-diabetic rats and their prevention by the ACE inhibitor captopril.

Antihypertensive therapy: how to evaluate the benefits.

For more than 30 years, the benefits of antihypertensive therapy have been assessed in randomized trials that monitor cardiovascular events. Even greater benefits can result if prevention of (1) congestive heart failure, (2) left ventricular hypertrophy, and (3) progression to more severe hypertension is taken into consideration. However, quantifying the benefits in order to calculate the cost-effectiveness of treatment is not easy. Taking absolute risk and benefit as the only guide to treatment decisions may result in limiting therapy only to elderly hypertensive patients and hypertensive patients with complications. Furthermore, randomized trials, of which the duration is necessarily short, are likely to underestimate treatment benefits. An alternative to such an approach is the actuarial approach: treatment benefits are calculated from the actuarial data showing the reduction in life expectancy associated with any given blood pressure increase. The cost of antihypertensive therapy per year of life gained calculated in this way is much lower than the cost calculated from randomized trials. In an uncertain area such as that of cost-effectiveness evaluation, it is important that both approaches are taken into consideration by physicians, patients, politicians, and officers of national health systems.

[Therapy of arterial hypertension: benefits, costs, challenges]. / La terapia dell'ipertensione arteriosa: benefici, costi, sfide.

For more than 30 years the benefits of antihypertensive therapy have been assessed by randomized trials measuring cardiovascular events. Even greater benefits are found if prevention of congestive heart failure, left ventricular hypertrophy, and progression to more severe hypertension are considered. Quantifying the benefits in order to calculate cost-effectiveness of treatment is not easy, however. Taking absolute risk and absolute benefit as a guide to treatment decision, though an important approach, may result in limiting therapy to elderly and complicated hypertensives only. Furthermore randomized trials, whose duration is necessarily short, are likely to underestimate treatment benefits. An alternative is the actuarial approach, by which treatment benefits are calculated from the actuarial data showing the reduction in life expectancy associated with any given blood pressure increase. The cost of antihypertensive therapy per year of life gained, as calculated by the actuarial approach, is much lower than the cost calculated on the basis of the outcomes of randomized trials. In an uncertain area such as that of cost-effectiveness evaluation, it is important that both approaches be brought to the consideration of physicians, patients, politicians, and officers of national health systems.

Acute and long-term effects of thrombolysis after anterior wall acute myocardial infarction with serial assessment of infarct expansion and late ventricular remodeling.

This study investigates the impact of thrombolysis on infarct expansion and subsequent left ventricular (LV) remodeling in patients with anterior wall acute myocardial infarction (AMI). We evaluated 51 consecutive patients (24 treated with thrombolysis) with anterior wall AMI by 2-dimensional echocardiography in the following sequence: days 1, 2, 3, and 7, after 3 and 6 weeks, and after 3, 6, and 12 months. LV end-diastolic and end-systolic volume indexes were determined from apical 2- and 4-chamber views using Simpson's biplane formula. Infarct and total LV perimeters were determined in the same views and their ratio expressed as infarct percentage. Infarct expansion was defined as: (1) an increase in infarct percentage and total perimeter >5% on days 2 to 3 in either of the views, or (2) initial infarct percentage >50% with an increase in total perimeter >5% on days 2 to 3. Coronary angiography was performed in 43 patients before discharge, and patency of the infarct-related artery was assessed using Thrombolysis in Myocardial Infarction trial criteria. Infarct expansion was detected in 23 patients. Infarct perimeter steadily decreased in patients with versus without thrombolysis and in patients with patent versus occluded infarct-related arteries. Furthermore, by logistic regression, thrombolysis (p = 0.007) and potency of the infarct-related artery (p = 0.02) were strong negative predictors of expansion, whereas initial infarct perimeter (p = 0.009) was directly associated with subsequent expansion. End-systolic volume index was higher in patients with expansion from day 1 (p = 0.003) through the end of the study (p = 0.021), and end-diastolic volume index was higher in these patients from day 2 (p = 0.012) through 12 months (p = 0.015). Thus thrombolysis, initial infarct size, and infarct-related artery patency are major predictors of infarct expansion after anterior wall AMI.

Assessment of effects of two anti-hypertensive regimens on overall cardiovascular risk.

Anti-hypertensive drugs differ in their effects on other cardiovascular risk factors. To date there have been few attempts to quantitate the impact of such differences. Twenty five unmedicated patients with primary hypertension were randomised to initial therapy with either the calcium antagonist, felodipine, or a diuretic and doses titrated to achieve similar levels of blood pressure (BP). Second drugs were added if needed (metoprolol and prazosin, respectively). The aim was to determine over 1 year whether similar anti-hypertensive effects were associated with differences in a multivariate index of overall cardiovascular risk. The target supine diastolic blood pressure (DBP) (85 mm Hg) required the second agent in four of 13 evaluable patients in the felodipine group and six of 10 in the diuretic group. There was a significant rise in serum cholesterol and a fall in serum potassium in the diuretic group, but not in the felodipine group. Cardiovascular risk scores were ranked in percentiles in relation to the age-matched general population. This score fell to a greater degree in felodipine patients particularly over the first 6 months, but remaining lower at 12 months. Left ventricular hypertrophy assessed by echocardiography, another measure of cardiovascular risk, was generally unchanged by either regimen. At equivalent blood pressure levels, the calcium antagonist-based regimen had a greater benefit on cardiovascular risk, particularly in the first 6 months of therapy. This method may be widely applicable in the assessment of anti-hypertensive therapy.