Amlodipine-based Regimen Research Articles

Relationship Between Visit-to-Visit Blood Pressure Variability (BPV) and Kidney Function in Patients with Hypertension

Background/Aims: To investigate the impact of kidney function (using estimated glomerular filtration rate, [eGFR]) on blood pressure variability (BPV) via a retrospective post hoc analysis of patients with hypertension enrolled in two large clinical trials. Methods: Subject-level data were extracted from ASCOT (N=18,852) and ALLHAT (N=26,441) databases; both were randomized, active controlled studies, with treatment duration for hypertension ≥4 years. Visit-to-visit BPV was assessed using the square root of the coefficient of variation of systolic blood pressure (SBP) across visits from 12 weeks onwards. Baseline GFR, estimated by the simplified Modification of Diet in Renal Disease equation, was stratified into ≤60, 61-90, and >90 mL/min/1.73 m². The relationship between baseline eGFR and systolic BPV was analyzed using an analysis of covariance, with baseline factors considered as covariates. Studies were pooled and analyzed individually. Results: Patient characteristics were largely consistent between studies. In the pooled population (n=38,133) there were 19.1%, 62.9%, and 18.0% patients, with eGFR ≤60, 61-90, and > 90 mL/min/1.73 m², respectively. Patients with lower baseline eGFR had higher systolic BPV, in the pooled population and the individual analyses. Other baseline predictors of high systolic BPV included high SBP and age, being male, and a smoker. An amlodipine-based regimen was a negative predictor of high systolic BPV, vs. other antihypertensives, regardless of eGFR. Conclusions: Patients with declining renal function tended to have higher systolic BPV vs. those without, even after adjusting for risk factors. Amlodipine-based therapy reduced BPV more than other antihypertensive agents, regardless of level of eGFR.

Amlodipine and cardiovascular outcomes in hypertensive patients: meta-analysis comparing amlodipine-based versus other antihypertensive therapy

Background/AimsThis meta-analysis compared the effects of amlodipine besylate, a charged dihydropyridine-type calcium channel blocker (CCB), with other non-CCB antihypertensive therapies regarding the cardiovascular outcome.MethodsData from seven long-term outcome trials comparing the cardiovascular outcomes of an amlodipine-based regimen with other active regimens were pooled and analyzed.ResultsThe risk of myocardial infarction was significantly decreased with an amlodipine-based regimen compared with a non-CCB-based regimen (odds ratio [OR], 0.91; 95% confidence interval [CI], 0.84 to 0.99; p = 0.03). The risk of stroke was also significantly decreased (OR, 0.84; 95% CI, 0.79 to 0.90; p < 0.00001). The risk of heart failure increased slightly with marginal significance for an amlodipine-based regimen compared with a non-CCB-based regimen (OR, 1.14; 95% CI, 0.98 to 1.31; p = 0.08). However, when compared overall with β-blockers and diuretics, amlodipine showed a comparable risk. Amlodipine-based regimens demonstrated a 10% risk reduction in overall cardiovascular events (OR, 0.90; 95% CI, 0.82 to 0.99; p = 0.02) and total mortality (OR, 0.95; 95% CI, 0.91 to 0.99; p = 0.01).ConclusionsAmlodipine reduced the risk of total cardiovascular events as well as all-cause mortality compared with non-CCB-based regimens, indicating its benefit for high-risk cardiac patients.

Is amlodipine more cardioprotective than other antihypertensive drug classes?

Is amlodipine more cardioprotective than other antihypertensive drug classes?

Abstract 16804: Long-Term Differential Effects of Amlodipine and Atenolol based Antihypertensive Therapy on Left Ventricular Structure and Function: An ASCOT Sub-Study

Background: Both left ventricular hypertrophy (LVH) and impairment of LV diastolic function have been shown to be important predictors of morbidity and mortality in hypertension. Anti-hypertensive treatment can cause regression of LVH and improve LV diastolic function. However little is known about whether these changes are sustained with long term treatment. Methods: Six-hundred and sixty-nine patients (mean age 62 years, 78.9% male) in the ASCOT study who were randomised to either an amlodipine-based regimen (Amlod), or an atenolol-based antihypertensive regimen (Aten) had LV structure and diastolic function assessed by tissue Doppler echocardiography. Measurements were made a median time of 1.48 (Phase 1) and 3.49 (Phase 2) years after randomisation. Results: Blood pressure was lower in Amlod both at phase 1 (141/80 vs 146/83) and phase 2 (138/79 vs 143/82).Left ventricular mass index had significantly improved between Phase 1 and Phase 2 assessment in both treatment groups (Amlod: 119.6 to 116.6 g/m 2 , p=0.007, Aten: 121.8 to 117.2 g/m 2 , p&lt;0.001).At the initial Phase 1 assessment LV diastolic function was better in Amlod compared with Aten (e' 8.5cm/s versus 7.7cm/s, p&gt;0.001; E/e' 7.6 versus 8.1, p=0.008). With a further 2 years of antihypertensive therapy with good BP control there was a small, significant drop in e' but no change in E:e'with Amlod (e' Phase 2 8.1cm/s, versus phase 1 p&lt;0.001; E/e' Phase 2 7.8, versus phase 1 p=0.29); in contrast in Aten there was no change in e' but a small, significant rise in E:e' (e' Phase 2 7.7cm/s, versus phase 1 p=0.59; E/e' Phase 2 8.4, versus phase 1 p=0.02).By the end of the phase 2, after correction for age, gender and systolic blood pressure, e' in Amlod remained significantly higher than aten (p&lt;0.01). Conclusions: Patients with hypertension and good BP control had further regression of LV mass between 1.5 and 3.5 years of antihypertensive therapy with both Amlod and Aten. Those receiving Amlod had better echocardiographic indices of diastolic function at both time points when compared with Aten. Appropriate antihypertensive therapy may lead to early improvement of diastolic function and allow maintenance of a more normal pattern at longer follow-up with improvement in left ventricular mass. Character Count: 1926

Impact of amlodipine-based therapy among older and younger patients in the Anglo-Scandinavian Cardiac Outcomes Trial−Blood Pressure Lowering Arm (ASCOT-BPLA)

Older patients experience higher rates of cardiovascular disease than younger patients, but studies have suggested that relative risk reductions due to antihypertensive therapy are lower in older than younger patients. The Anglo-Scandinavian Cardiac Outcomes Trial-Blood Pressure Lowering Arm (ASCOT-BPLA) allowed an evaluation of the efficacy and safety of an amlodipine versus an atenolol-based antihypertensive regimen among older (≥ 65 years) and younger (<65 years) patients. In ASCOT-BPLA 19 257 patients (8137 aged ≥ 65 years and 11 020 <65 years) were randomly assigned to receive amlodipine or atenolol-based antihypertensive therapy. The primary endpoint (nonfatal myocardial infarction and fatal coronary heart disease) and seven secondary endpoints were consistent with the original trial design. All cardiovascular endpoints evaluated favoured the amlodipine-based regimen, significantly so in seven of the 16 age-stratified endpoints. Compared with the atenolol-based regimen, the amlodipine-based regimen reduced the relative risk of cardiovascular events by 17% in older and 15% in younger patients (P < 0.01). Overall, older patients experienced more cardiovascular events [n = 1625 (20%)] than younger patients [n = 1339 (12%)]. Discontinuations due to serious adverse events were low in both age groups and less frequent in the amlodipine-based versus atenolol-based regimen: 0.6 versus 1.1% among older patients and 0.4 versus 0.8% among younger patients. The amlodipine-based regimen reduced the relative risk of cardiovascular events more effectively than the atenolol-based regimen in both older and younger patients. However, because event rates were higher among older patients, the absolute benefits were greater for older compared with younger patients.

Natriuretic peptides and collagen biomarkers in patients with medical treatment for hypertension

Objective The Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT-BPLA) showed that an amlodipine-based regimen prevented more cardiovascular events than an atenolol-based regimen in patients at high risk of hypertension. The basis of this diff erence is partly unknown and may be due to their divergent eff ects on the remodelling process of hypertensive heart disease.Methods and results We measured plasma levels of aminoterminal propeptide of atrial natriuretic peptide (NT-proANP) and aminoter minal propeptide of B-type natriuretic peptide and serum levels of the aminoterminal propeptide of type I procollagen (PINP), aminoterminal propeptide of type III procollagen and type I collagen telopeptide in 93 patients randomized in the ASCOT study at baseline and after two and four years and compared them with echocardiographic parameters and blood pressure. NT-proANP decreased at two years by 22 (-484 - 153) pmol/l in the amlodipine-based regimen and increased by 109 (-297 - 1545) pmol/l in the atenolol-based regimen (P < 0.001), whereas no signifi cant diff erence in NT-proBNP between the arms was found. PINP levels increased by 1.8 (-29 - 31) μ g/l in the amlodipine-based regimen and decreased by 4.7 (-27 - 31) μ g/l in the atenolol-based regimen, whereas no diff erences were found in other collagen markers between the arms. Major echocardiographic changes were not found.Conclusions Our results show that the two treatment regimens of ASCOT-BPLA had diff erent eff ects on plasma natriuretic peptides and serological markers of collagen turnover, probably refl ecting divergent eff ects in cardiac remodelling.

The Effect of Losartan and Amlodipine on Left Ventricular Diastolic Function and Atherosclerosis in Japanese Patients with Mild-to-Moderate Hypertension (J-ELAN) study

This study was a prospective, randomized, open, blinded endpoint study to assess the effects of angiotensin II type 1 receptor blocker, losartan, compared with calcium channel blocker, amlodipine, on left ventricular (LV) diastolic function and atherosclerosis of the carotid artery in Japanese patients with mild-to-moderate hypertension, LV hypertrophy, diastolic dysfunction and preserved systolic function. Fifty-seven patients were randomly assigned to losartan- or amlodipine-based treatment groups and were followed up for 18 months. Blood pressure was similarly reduced by both regimens. Losartan shortened the transmitral E-wave deceleration time, and amlodipine reduced LV mass index; however, there was no significant difference in the percent changes of these indices between the two groups. Mean carotid intima-media thickness (mean IMT) as well as plaque score significantly increased in the amlodipine-based regimen (pre: 1.05±0.26 mm, follow-up: 1.23±0.33 mm, P=0.0015), but not in the losartan-based regimen (pre: 1.08±0.35 mm, follow-up: 1.16±0.52 mm, P=non-significant). The percent increase in mean IMT in the amlodipine-based regimen tended to be large compared with the losartan-based regimen (amlodipine: 19.8±23.7%, losartan: 6.9±23.3%, P=0.06). Under similar reduction of blood pressure, losartan is likely effective in protecting the progression of atherosclerosis of the carotid artery compared with amlodipine. Losartan may improve LV diastolic function, and amlodipine may attenuate LV hypertrophy; however, this study cannot make consecutive remarks about the superiority of either treatment regimen in the effects on cardiac function and geometry. This study has been registered at http://www.umin.ac.jp/ctr/listj/ (identifier C000000319).

Differential Effects of Antihypertensive Treatment on Left Ventricular Diastolic Function: An ASCOT (Anglo-Scandinavian Cardiac Outcomes Trial) Substudy

We hypothesized that an amlodipine-based regimen would have more favorable effects on left ventricular (LV) diastolic function. Different antihypertensive therapies may vary in their effect on LV diastolic function. The HACVD (Hypertension Associated Cardiovascular Disease) substudy of ASCOT (Anglo-Scandinavian Cardiac Outcomes Trial) collected detailed cardiovascular phenotypic data on a subset of 1,006 participants recruited from 2 centers (St. Mary's Hospital, London, and Beaumont Hospital, Dublin). Conventional and tissue Doppler echocardiography and measurement of plasma B-type natriuretic peptide (BNP) were performed approximately 1 year after randomization to atenolol-based or amlodipine-based antihypertensive treatment to assess LV diastolic function. On-treatment blood pressure (BP) (mean +/- SD) was similar in both groups: atenolol-based regimen, systolic BP of 137 +/- 17 mm Hg, diastolic BP of 82 +/- 9 mm Hg; amlodipine-based regimen, systolic BP of 136 +/- 15 mm Hg, diastolic BP of 80 +/- 9 mm Hg. Ejection fraction did not differ between groups, but early diastolic mitral annular velocity (E'), a measure of diastolic relaxation, was lower in patients on the atenolol-based regimen: atenolol-based regimen, 7.9 +/- 1.8; amlodipine-based regimen, 8.8 +/- 2.0. A measure of left ventricular filling pressure, E/E', and BNP were significantly higher in patients on the atenolol-based regimen. Differences in E', E/E', and BNP remained significant after adjustment for age and sex. Further adjustment for systolic BP, LV mass index, and heart rate had no impact on differences in mean E' or BNP. The difference in E/E' was attenuated. Patients receiving treatment with an amlodipine-based regimen had better diastolic function than patients treated with the atenolol-based regimen. Treatment-related differences in diastolic function were independent of BP reduction and other factors that are known to affect diastolic function.

Effects of β blockers and calcium-channel blockers on within-individual variability in blood pressure and risk of stroke

Analyses of some randomised trials show that calcium-channel blockers reduce the risk of stroke more than expected on the basis of mean blood pressure alone and that beta blockers are less effective than expected. We aimed to investigate whether the effects of these drugs on variability in blood pressure might explain these disparities in effect on stroke risk. The Anglo-Scandinavian Cardiac Outcomes Trial Blood Pressure Lowering Arm (ASCOT-BPLA) compared amlodipine-based regimens with atenolol-based regimens in 19 257 patients with hypertension and other vascular risk factors and the Medical Research Council (MRC) trial compared atenolol-based and diuretic-based regimens versus placebo in 4396 hypertensive patients aged 65-74 years. We expressed visit-to-visit variability of blood pressure during follow-up in the two trials as standard deviation (SD) and as transformations uncorrelated with mean blood pressure. For ASCOT-BPLA, we also studied within-visit variability and variability on 24 h ambulatory blood-pressure monitoring (ABPM). In ASCOT-BPLA, group systolic blood pressure (SBP) SD was lower in the amlodipine group than in the atenolol group at all follow-up visits (p<0.0001), mainly because of lower within-individual visit-to-visit variability. Within-visit and ABPM variability in SBP were also lower in the amlodipine group than in the atenolol group (all p<0.0001). Analysis of changes from baseline showed that variability decreased over time in the amlodipine group and increased in the atenolol group. The lower risk of stroke in the amlodipine group (hazard ratio 0.78, 95% CI 0.67-0.90) was partly attenuated by adjusting for mean SBP during follow-up (0.84, 0.72-0.98), but was abolished by also adjusting for within-individual SD of clinic SBP (0.99, 0.85-1.16). Findings were similar for coronary events. In the ABPM substudy, reduced variability in daytime SBP in the amlodipine group (p<0.0001) partly accounted for the reduced risk of vascular events, but reduced visit-to-visit variability in clinic SBP had a greater effect. In the MRC trial, group SD SBP and all measures of within-individual visit-to-visit variability in SBP were increased in the atenolol group compared with both the placebo group and the diuretic group during initial follow-up (all p<0.0001). Subsequent temporal trends in variability in blood pressure during follow-up in the atenolol group correlated with trends in stroke risk. The opposite effects of calcium-channel blockers and beta blockers on variability of blood pressure account for the disparity in observed effects on risk of stroke and expected effects based on mean blood pressure. To prevent stroke most effectively, blood-pressure-lowering drugs should reduce mean blood pressure without increasing variability; ideally they should reduce both.

Impact of choice of diastolic Korotkoff phase in childhood on the prediction to arterial compliance

primary endpoints are composite of non-fatal stroke/myocardial infarction and cardiovascular death. All patients will be followed-up for 4 years. Results: The characteristics of patients between the two groups were similar: mean age (61.5 ± 7.7) yrs with 19% history of cerebrovascular diseases, 12% coronary diseases, 18% diabetes, 42% dyslipidemia, and mean initial blood pressure of 157/93 mm Hg. After 8-week treatment, mean blood pressure in groups A and B was reduced to 133.0 ± 11.0/81.0 ± 7.6 and 132.9 ± 11.6/80.6 ± 7.9 mm Hg respectively. Blood pressure control rates reached 72.1% and 72.6% in groups A and T, respectively. Conclusion: Amlodipine-based antihypertensive combination regimens achieved satisfactory blood pressure control rate in patients with essential hypertension in this patient cohort.

Differences in the Magnitude of Wave Reflection Account for Differential Effects of Amlodipine- Versus Atenolol-Based Regimens on Central Blood Pressure

Antihypertensive agents may differ in their effects on central systolic blood pressure, and this may contribute to treatment-related differences in cardiovascular outcomes. In a substudy of the Anglo-Scandinavian Cardiac Outcome Trial, we investigated whether directly measured carotid systolic blood pressure differed between people randomized to amlodipine- and atenolol-based therapies and whether this is accounted for by differences in wave reflection patterns. Additional analysis was undertaken to establish whether differences in carotid systolic blood pressure predicted left ventricular mass, accounting for between-treatment differences in left ventricular mass index. Blood pressure and flow velocity were measured in the right carotid artery of 259 patients. Wave intensity analysis was used to separate and quantify forward and backward waves. Brachial blood pressure did not differ significantly between groups, but carotid systolic blood pressure (127 [12] versus 133 [15] mm Hg; P<0.001), the ratio of backward:forward pressure (0.48 [0.17] versus 0.53 [0.19]; P=0.01), and wave reflection index (19.8% [10.9%] versus 23.3% [13.3%]; P=0.02) were significantly lower in patients randomized to amlodipine-based therapy. Left ventricular mass index was also lower in this group, and adjustment for carotid blood pressure attenuated treatment differences to a greater extent than brachial blood pressure. Carotid systolic blood pressure was also a significant independent predictor of left ventricular mass index in a multivariate model. Carotid systolic blood pressure is lower in people randomized to amlodipine-based compared with atenolol-based treatment despite there being no significant difference in brachial blood pressure. This difference is attributable to a lesser magnitude of wave reflection in patients randomized to the amlodipine-based regimen.

Differential Effects of Antihypertensive Treatment on the Retinal Microcirculation

Changes in the retinal microcirculation are associated with hypertension and predict cardiovascular mortality. There are few data describing the impact of antihypertensive therapy on retinal vascular changes. This substudy of the Anglo-Scandinavian Cardiac Outcomes Trial compared the effects of an amlodipine-based regimen (373 patients) with an atenolol-based regimen (347 patients) on retinal microvascular measurements made from fundus photographs. The retinal photographs were taken at a stage in the trial when treatments were stable and blood pressure was well controlled. Amlodipine-based treatment was associated with a smaller arteriolar length:diameter ratio than atenolol-based treatment (13.32 [10.75 to 16.04] versus 14.12 [11.27 to 17.81], median [interquartile range]; P<0.01). The association remained significant after adjustment for age, sex, cholesterol, systolic and diastolic blood pressures, body mass index, smoking, and statin treatment. This effect appeared to be largely attributable to shorter retinal arteriolar segment lengths in the amlodipine-treated group and is best explained by the vasodilator effects of amlodipine causing the visible emergence of branching side vessels. Photographic assessment of the retinal vascular network may be a useful approach to evaluating microvascular structural responses in clinical trials of antihypertensive therapy.

Coronary heart disease benefits from blood pressure and lipid-lowering

Background We have reported the benefits of atorvastatin and of an amlodipine-based regimen on coronary heart disease (CHD) events in hypertensive patients in the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT). We report further analyses on the combined benefits of these interventions. Methods 19,342 hypertensive patients were randomised to either an amlodipine or an atenolol-based regimen in the ASCOT Blood Pressure-Lowering Arm (BPLA). 10,305 subjects with total cholesterol ≤ 6.5 mmol/L were further randomised to atorvastatin 10 mg or placebo in the Lipid-Lowering Arm (LLA). Estimates of CHD risk at baseline based on the Framingham algorithm were compared with observed and predicted event rates throughout ASCOT-LLA. Results Estimated baseline Framingham risk of CHD events was 22.8 per 1000 patient years. After 3.3 years, when the LLA was stopped, the actual CHD event rate had fallen to 4.8 per 1000 patient years—a reduction of 79% in those assigned amlodipine-based treatment and atorvastatin. Conclusions CHD benefits associated with BP and lipid lowering were larger than predicted by previous observational and trial data. We estimate that compared with pre-trial treatment, treating about 55 patients with the amlodipine-based regimen and atorvastatin would prevent one CHD event per year.

The Lifetime Cost Effectiveness of Amlodipine-Based Therapy Plus Atorvastatin Compared with Atenolol Plus Atorvastatin, Amlodipine-Based Therapy Alone and Atenolol-Based Therapy Alone

ASCOT (Anglo-Scandinavian Cardiac Outcomes Trial) showed in hypertensive patients that blood pressure-lowering treatment with an amlodipine-based regimen reduces events compared with an atenolol-based regimen and that atorvastatin was more effective than placebo. To assess the cost effectiveness of four alternative treatment strategies in patients with hypertension and three or more cardiovascular risk factors in the UK (from the UK NHS perspective) or Sweden (from the societal perspective): amlodipine-based plus atorvastatin, atenolol-based plus atorvastatin, amlodipine-based alone and atenolol-based alone. Based on the trial data, a Markov model was constructed where the risk of myocardial infarction, revascularization procedures and stroke and the long-term costs, quality of life and mortality associated with these events were estimated. Transition probabilities and costs (euro, 2007 values) were based on the patient-level trial data. Outcomes were reported as life-years gained and QALYs. In the latter case, utility reduction from events was based on a substudy in ASCOT patients. Treatment was applied for the duration of the lipid-lowering arm of the trial (3 years) and patients were then followed to the end of their life. Amlodipine-based therapy plus atorvastatin was the most expensive but also most effective treatment. Compared with amlodipine-based therapy alone, the cost to gain one QALY was euro 11,965 in the UK and euro 8,591 in Sweden. The incremental cost effectiveness of amlodipine-based therapy compared with atenolol-based therapy was euro 9,548 and euro 3,965 per QALY gained in the UK and Sweden, respectively. Atenolol-based therapy plus atorvastatin was eliminated through extended dominance. Applying the threshold values used by the National Institute for Health and Clinical Excellence (NICE) and the Swedish National Board of Health and Welfare, a combination of amlodipine-based therapy and atorvastatin appears to be cost effective in patients with hypertension and three or more additional risk factors.

All Thiazide‐Like Diuretics Are Not Chlorthalidone: Putting the ACCOMPLISH Study Into Perspective

All Thiazide‐Like Diuretics Are Not Chlorthalidone: Putting the ACCOMPLISH Study Into Perspective

The Anglo-Scandinavian Cardiac Outcomes Trial: blood pressure-lowering limb: effects in patients with type II diabetes

To compare the effects of two antihypertensive treatment strategies for the prevention of coronary heart disease and other cardiovascular events in the large subpopulation (n=5137) with diabetes mellitus in the blood pressure-lowering arm of the Anglo-Scandinavian Cardiac Outcomes Trial. Patients had either untreated hypertension or treated hypertension. For those with type II diabetes mellitus, inclusion criteria required at least two additional risk factors. Patients were randomized to amlodipine with addition of perindopril as required (amlodipine-based) or atenolol with addition of thiazide as required (atenolol-based). Therapy was titrated to achieve a target blood pressure of less than 130/80 mmHg. The trial was terminated early due to significant benefits on mortality and stroke associated with the amlodipine-based regimen. In patients with diabetes mellitus, the amlodipine-based treatment reduced the incidence of the composite endpoint--total cardiovascular events and procedures--compared with the atenolol-based regimen (hazard ratio 0.86, confidence interval 0.76-0.98, P=0.026). Fatal and nonfatal strokes were reduced by 25% (P=0.017), peripheral arterial disease by 48% (P=0.004) and noncoronary revascularization procedures by 57% (P<0.001). For the other endpoints included in the composite, the endpoint differences were less clear including coronary heart disease deaths and nonfatal myocardial infarctions (the primary endpoint), which were reduced nonsignificantly by 8% (hazard ratio 0.92, confidence interval 0.74-1.15). In the large diabetic subgroup in the blood pressure-lowering arm of the Anglo-Scandinavian Cardiac Outcomes Trial, the benefits of amlodipine-based treatment, compared with atenolol-based treatment, on the incidence of total cardiovascular events and procedures was significant (14% reduction) and similar to that observed in the total trial population (16% reduction).

ARB candesartan and CCB amlodipine in hypertensive patients: the CASE-J trial

The Candesartan Antihypertensive Survival Evaluation in Japan (CASE-J) trial was a comparative study of the angiotensin II receptor blocker (ARB), candesartan, and a calcium channel blocker (CCB), amlodipine, regarding the incidence of cardiovascular events in high-risk Japanese hypertensive patients. The study design was a prospective, multicenter, randomized, open-label, active-controlled, two-arm, parallel-group comparison study with a response-dependent dose titration and blinded assessment of the end point. The CASE-J trial enrolled 4728 patients, with a mean age of 63.8 years and a mean BMI of 24.6 kg/m2, who were randomly assigned to either candesartan- or amlodipine-based treatment regimens. Blood pressure was well controlled to the level of less than 140/80 mmHg in both of the treatment regimens. During 3.2 years of follow-up, primary cardiovascular events occurred in 134 patients in each of the two treatment-based regimens, resulting in no significant difference in the incidence of cardiovascular events between them (hazard ratio: 1.01; 95% confidence interval: 0.79–1.28; p = 0.969). In 404 patients with left ventricular hypertrophy, a significantly larger decrease in left ventricular mass index 3 years after enrollment was observed in candesartan-based (n = 205) than amlodipine-based (n = 199) regimens (-22.9 vs -13.4 g/m2, respectively; p = 0.023). Furthermore, new-onset diabetes occurred in fewer patients taking candesartan than in those taking amlodipine, resulting in a 36% relative risk reduction (p = 0.030). The CASE-J trial demonstrated that both an ARB, candesartan, and a CCB, amlodipine, equally suppressed the incidence of cardiovascular events. The ARB may confer more beneficial effects to hypertensive patients with left ventricular hypertrophy or for those at-risk of diabetes than CCB.

Long-term effects of candesartan and amlodipine on cardiovascular mortality and morbidity in Japanese high-risk hypertensive patients: Rationale, design, and characteristics of candesartan antihypertensive survival evaluation in Japan extension (CASE-J Ex)

Candesartan Antihypertensive Survival Evaluation in Japan (CASE-J) trial was conducted to compare the effects of the angiotensin II receptor blocker (ARB) candesartan and the calcium channel blocker (CCB) amlodipine on the incidence of cardiovascular (CV) events in Japanese high-risk hypertensive patients. After 3.2years follow-up, CV events rate was 17.6–17.7 per 1000 person-years in each group, which was much lower than we expected. Since it has not been known whether the same efficacy of two drugs is sustained beyond the current trial, a longer follow-up period will be needed. The Steering Committee of CASE-J trial decided to extend the trial for 3years as an observational study (CASE-J Ex). In CASE-J Ex, the primary end point is a composite of CV events and the secondary endpoints are all-cause death and new-onset diabetes. After Committee's decision, 245 doctors agreed to participate in CASE-J Ex and 2236 patients (1141 with candesartan-based regimens and 1095 with amlodipine-based regimens) were re-enrolled. The baseline characteristics of CASE-J Ex participants were similar to CASE-J participants and still balanced well between candesartan and amlodipine. Recently, the interest of antihypertensive treatment has focused to differentiation of the effects of antihypertensive agents on the incidence of CV events as well as blood pressure lowering effect. CASE-J Ex will clarify the long-term effects of ARB and CCB on CV mortality and morbidity. Additionally, because the number of diabetic patients is increased, the evidences from CASE-J Ex will be valuable.

Effects of Candesartan Compared With Amlodipine in Hypertensive Patients With High Cardiovascular Risks

The Candesartan Antihypertensive Survival Evaluation in Japan Trial was designed to compare the long-term effects of the angiotensin II receptor blocker candesartan and the calcium channel blocker amlodipine on the incidence of cardiovascular events, represented as a composite of sudden death and cerebrovascular, cardiac, renal, and vascular events in high-risk Japanese hypertensive patients. We conducted a prospective, randomized, open-label study with blinded assessment of the end point in 4728 Japanese hypertensive patients (mean age: 63.8 years; mean body mass index: 24.6 kg/m(2)). Patients were followed for an average of 3.2 years. Blood pressure was well controlled with both treatment-based regimens (systolic blood pressure/diastolic blood pressure: 136.1/77.3 mm Hg for candesartan-based regimens and 134.4/76.7 mm Hg for amlodipine-based regimens after 3 years). Primary cardiovascular events occurred in 134 patients with both the candesartan- and amlodipine-based regimens. The 2 treatment-based regimens produced no significant differences in cardiovascular morbidity or mortality in the high-risk Japanese hypertensive patients (hazard ratio: 1.01; 95% CI: 0.79 to 1.28; P=0.969). In each primary end point category, there was no significant difference between the 2 treatment-based regimens. New-onset diabetes occurred in fewer patients taking candesartan (8.7/1000 person-years) than in those taking amlodipine (13.6/1000 person-years), which resulted in a 36% relative risk reduction (hazard ratio: 0.64; 95% CI: 0.43 to 0.97; P=0.033). We disclosed that candesartan-based and amlodipine-based regimens produced no statistical differences in terms of the primary cardiovascular end point, whereas candesartan prevented new-onset diabetes more effectively than amlodipine.

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

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...