Effective dose response and tolerability of candesartan cilexetil in isolated systolic hypertension: a clinical experience trial

Neutel, Joel M.; Moser, M.; Mr, Weir; Edwards, David A.; Harris, S.D.; Michelson, Eric L.; Wang, R.

doi:10.1016/s0895-7061(00)00582-3

Cited by 4 publications

(3 citation statements)

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“…Its effects in ISH have not been extensively studied. In an open label, community‐based trial, another AIIA was usually given in combination with hydrochlorothiazide (HCTZ) and was shown to reduce SBP in patients with ISH 23 . This paper reports the results of a multicenter, randomized, double‐blind, placebo‐controlled trial conducted to assess the efficacy and tolerability of a losartan‐based regimen in the treatment of ISH.…”

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confidence: 99%

The Effect of a Losartan‐Based Treatment Regimen on Isolated Systolic Hypertension

Cushman

Brady

Gazdick

et al. 2002

J of Clinical Hypertension

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This study was conducted to compare the antihypertensive efficacy and tolerability, over 12 weeks, of a losartan-based treatment regimen and placebo in patients with isolated systolic hypertension. Three hundred eight patients > or =35 years of age with isolated systolic hypertension, defined as trough sitting blood pressure between 140 and 200 mm Hg systolic and between 70 and 89 mm Hg diastolic, were randomized to losartan 50 mg (n=157) or placebo (n=151) once daily, with titration as necessary to achieve a goal trough sitting systolic blood pressure (SBP) <140 mm Hg. At baseline, mean trough sitting SBP was 140-159 mm Hg in 20.5% of patients, 160-179 mm Hg in 62.7%, and 180-200 mm Hg in 16.9%, and was similar in the two groups (losartan, 165.3 mm Hg; placebo, 166.1 mm Hg). At 12 weeks, mean trough sitting SBP decreased significantly (p<0.001) in both the losartan-based treatment group (by 19.2 mm Hg) and in the placebo group (by 7.6 mm Hg). The reduction in sitting SBP was significantly greater for losartan than placebo (-11.6 mm Hg; 95% confidence interval, -14.8 to -8.4). In patients with isolated systolic hypertension, a once-daily losartan-based treatment regimen significantly lowered SBP. The losartan-based regimen exhibited antihypertensive efficacy that was superior to that of placebo, with a similar tolerability profile.

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mentioning

confidence: 99%

The Effect of a Losartan‐Based Treatment Regimen on Isolated Systolic Hypertension

Cushman

Brady

Gazdick

et al. 2002

J of Clinical Hypertension

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“…Candesartan cilexetil, 16-32 mg once-daily, either alone or as an add-on therapy, reduced SBP/DBP from 158/81 mmHg to 142/76 mmHg, a mean reduction of -16.5/-4.5 mmHg. 8 When used as monotherapy, candesartan cilexetil reduced Figure 6, the BP-lowering effects of candesartan cilexetil were noticeable in all demographic groups, though perhaps a little less so in African Americans. Titration of candesartan cilexetil from 16-32 mg daily, either alone or as an add-on therapy, facilitated further BP reduction as shown in Figure 7, and resulted in an overall control rate (SBP <130 mmHg) of 49%.…”

Section: Antihypertensive Effects Of Candesartan Cilexetil Either Alomentioning

confidence: 93%

Use of angiotensin II receptor blockers alone and in combination with other drugs: a large clinical experience trial

Weir

Wang

2001

J Renin Angiotensin Aldosterone Syst

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Angiotensin II (Ang II) receptor blockers are the newest class of antihypertensive drugs to be developed. No large-scale clinical trials have been performed to evaluate their efficacy alone, or in combination with other drugs. A large-scale, eight week, open-label, non-placebo-controlled, single-arm trial evaluated the efficacy, tolerability and dose-response of candesartan cilexetil, 16-32 mg once-daily, either as monotherapy or as part of combination therapy, in a diverse hypertensive population in actual practice settings. 6465 patients with high blood pressure, of whom 52% were female and 16% African American, with a mean age of 58 years, were included. 5446 patients had essential hypertension and 1014 patients had isolated systolic hypertension. In order to be included in this study, patients had either untreated or uncontrolled hypertension (systolic blood pressure (SBP) 140-179 mmHg and/or diastolic blood pressure (DBP) 90-109 mmHg inclusive at baseline), despite a variety of other antihypertensive drugs. Of the 5156 patients with essential hypertension and at least one post baseline efficacy measurement, the mean pretreatment blood pressure (BP) was 156/97 mmHg. Candesartan cilexetil monotherapy reduced mean SBP/DBP by 18.0/12.2 mmHg. Similarly, in the 964 patients with isolated systolic hypertension and at least one post baseline efficacy measurement, candesartan cilexetil monotherapy reduced SBP/DBP from 158/81 by 16.5/4.5 mmHg. Candesartan cilexetil was similarly effective when employed as add-on therapy. When added to baseline antihypertensive medication in 51% of the patients with essential hypertension not achieving BP control, additional reduction in BP was achieved regardless of the background therapy, including diuretics (17.8/11.7 mmHg) calcium antagonists (16.6/11.2 mmHg), beta-blockers (16.5/10.4 mmHg), angiotensin-converting enzyme inhibitors (ACE-I) (15.3/10.0 mmHg), and alpha blockers (16.4/10.4 mmHg). Likewise, when candesartan cilexetil was used as add-on therapy in patients with isolated systolic hypertension, there was a consistent further reduction of mean SBP/DBP, regardless of the background therapy. Moreover, these monotherapeutic or add-on efficacy benefits were seen regardless of age (<65 or >65 years), gender, or race. Despite the open-label design of the study which enhances efficacy owing to the placebo effect, the Ang II receptor blocker, candesartan cilexetil either alone, or as an add-on therapy, is highly effective for assisting in the control of systolic and diastolic hypertension.

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“…1,3 Several trials in elderly patients with isolated systolic hypertension showed that ARBs effectively reduce systolic BP with a lesser decrease in diastolic BP, resulting thereby in substantial reduction of pulse pressure. [87][88][89][90] It is important to note that these beneficial effects are achieved with a placebo-like tolerability. [88][89][90] A substudy of the Losartan Intervention for End point Reduction trial (LIFE) in 1326 subjects with isolated systolic hypertension and left ventricular hypertrophy showed that, for the same BP reduction, the ARB losartan was better tolerated and more effective than the beta-blocker atenolol in regressing left ventricular hypertrophy and in 92,93 and irbesartan has been shown to be more effective than the calcium antagonist amlodipine.…”

Section: Effects Of Antihypertensive Drugs On Arterial Stiffnessmentioning

confidence: 99%

Angiotensin receptor blockade in the challenging era of systolic hypertension

Stergiou

2004

J Hum Hypertens

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Systolic blood pressure is a major cardiovascular risk factor which is often associated with arterial stiffness. Markers of arterial stiffness, such as pulse pressure and carotid-femoral pulse wave velocity, have been proved independent predictors of cardiovascular risk. Recent evidence suggests that the renin-angiotensin system is involved in the pathogenesis of systolic hypertension and arterial stiffness. Outcome trials have shown impressive cardiovascular protection by reducing systolic blood pressure (BP) with drug treatment. However, in clinical practice systolic hypertension remains largely uncontrolled, first, because systolic BP goal is more difficult to be reached than diastolic and, second, because physicians are often reluctant to intensify treatment in patients with systolic BP close to 150 mmHg. Recent trials have focused on the effects of antihypertensive drugs not only on blood pressure, but also on pulse pressure and pulse-wave velocity. Blockade of the renin-angiotensin-aldosterone system, using angiotensin-converting enzyme inhibitors and more recently angiotensin receptor blockers, has been shown to provide beneficial effects on arterial stiffness that appear to be independent of their antihypertensive effects. Recent outcome trials have shown significant cardiovascular protection with angiotensin receptor blockers. These drugs have an excellent placebolike profile of adverse effects which is maintained when these drugs are combined with low-dose diuretics. Therefore, an angiotensin receptor blocker-based treatment strategy appears to be an attractive and evidencebased approach for the management of systolic hypertension, the reduction of arterial stiffness and the prevention of cardiovascular disease.

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Effective dose response and tolerability of candesartan cilexetil in isolated systolic hypertension: a clinical experience trial

Cited by 4 publications

References 0 publications

The Effect of a Losartan‐Based Treatment Regimen on Isolated Systolic Hypertension

The Effect of a Losartan‐Based Treatment Regimen on Isolated Systolic Hypertension

Use of angiotensin II receptor blockers alone and in combination with other drugs: a large clinical experience trial

Angiotensin receptor blockade in the challenging era of systolic hypertension

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