Pharmacological therapy
ILEANA PIÑA, SIDNEY GOLDSTEIN, MARK E DUNLAP in The Year in Heart Failure, 2005
Granger CB, McMurray JJ , Yusuf S, eta/. CHARM Investigators and Committees. Lancet 2003; 362: 772-6 BAcK oRo u ND. This study enrolled 2028 patients with symptomatic heart failure and an LVEF of 40% or less who were not receiving ACE Inhibitors because of previous Intolerance. The determination of ACE Inhibitor intolerance was made on clinical grounds prior to study enrolment, with ACE inhibitor cough (72%) being the most common reason for intolerance, followed by symptomatic hypotension (13%) and renal dysfunction (12%). Patients were randomly assigned candesartan (target dose 32 mg once dally) or matching placebo. The primary outcome of the study was the composite of cardiovascular death or hospital admission for heart failure. During a median follow-up of 33.7 months, 334 (33%) of 1013 patients in the candesartan group and 406 (40%) of 1015 In the placebo group had cardiovascular death or hospital admission for chronic heart failure (unadjusted HR 0.77; 95% Cl 0.67-0.89; P = 0.0004). Interestingly, despite a history of ACE inhibitor intolerance, rates of discontinuation of the study drug were similar in the candesartan (30%) and placebo (29%) groups. INTERPRETATIoN. This arm ofthe CHARM trial provides convincing evidence of ARB benefit in patients intole rant to ACE inhibitor by clinical criteria. Candesartan was generally well tole rated in this patie nt population and reduced cardiovascular mortality and morbidity in patients with symptomatic chronic heart failure and intolerance to ACE inhibitors.
Blood Pressure Management in Acute Stroke
Giuseppe Mancia, Guido Grassi, Konstantinos P. Tsioufis, Anna F. Dominiczak, Enrico Agabiti Rosei in Manual of Hypertension of the European Society of Hypertension, 2019
In the ACCESS study (Acute Candesartan Cilexetil Therapy in Stroke Survivors), 339 patients with acute IS and BP values greater than 180/105 mmHg were randomized to oral candesartan or placebo within 36 hours after admission and maintained on study drug for 7 days after randomization (8). The two groups did not differ regarding functional outcome and risk of stroke recurrence at 3 and 12 months, respectively. However, candesartan significantly reduced mortality and vascular events during the 12-month follow-up. The superiority of candesartan versus placebo over the secondary endpoint of the study triggered the design of a larger study. In the SCAST study (Scandinavian Candesartan Acute Stroke Trial), a phase III RCT, 2029 patients with acute IS (85%) or ICH (15%) and SBP (>140 mmHg) were randomized to oral candesartan or placebo using a design similar to ACCESS (9). The composite endpoint of major cardiovascular events did not differ between the two groups at 6 months. However, patients treated with candesartan had a worse functional outcome compared to those receiving placebo. In addition, a SCAST substudy showed that in patients with moderate to severe carotid artery disease treated with candesartan, progressive stroke occurred more frequently than in the placebo group (10).
Principles of Heart Failure Pharmacotherapy
Andreas P. Kalogeropoulos, Hal A. Skopicki, Javed Butler in Heart Failure, 2023
Candesartan is a prodrug that is primarily eliminated renally.13 Losartan undergoes hepatic metabolism and has an active metabolite, E3174, that is more potent and has a longer half-life than losartan.13 Valsartan is cleared predominantly in the feces as unchanged drug.13 Candesartan and losartan are dosed once daily, whereas valsartan is dosed twice daily when used for the treatment of HF.
Design and optimization of candesartan loaded self-nanoemulsifying drug delivery system for improving its dissolution rate and pharmacodynamic potential
Published in Drug Delivery, 2020
Ravinder Verma, Deepak Kaushik
Candesartan (kan” de sar’ tan) is a BCS II class drug that is widely used alone or in combination with other agents for therapy of hypertension and heart failure. It inhibits the renin-angiotensin system by blocking the angiotensin II type 1 receptor, which prevents the vasoconstriction and volume expansion induced by circulating angiotensin II, resulting in its antihypertensive potential. It is commercially available in 4, 8, 16 and 32 mg tablets generically (Candesar/Candosa/blopress/Camperten), under the trade name Atacand. It may be brought into play to treat hypertension, isolated systolic hypertension, left ventricular hypertrophy and diabetic nephropathy. It may also be used as a second-line drug for the treatment of heart failure, systolic dysfunction, myocardial infarction and coronary artery disease. Its typical dose is 16–32 mg “quaque die” in adults which is used for the long term (Zhao & Wang, 2018).
A Meta-analysis of antihypertensive effect of telmisartan versus candesartan in patients with essential hypertension
Published in Clinical and Experimental Hypertension, 2019
Di Zhao, Hui Liu, Pingshuan Dong
Although there is a general consensus that a continuous receptor blockade over a 24-hour period is desirable, the clinical relevance of other pharmacological differences between individual ARBs remains to be assessed (28). Telmisartan was reported to have the strongest PPAR γ affinity among ARBs and candesartan was reported to show the lowest affinity (29). Telmisartan may have beneficial effects in type 2 diabetes and the metabolic syndrome beyond its antihypertensive effect (17). Candesartan might alleviate arterial stiffness. Powerful and long-lasting AT1R blockade is needed for an ARB to exert effects in alleviating arterial stiffness and, of the various ARBs, candesartan because of its pronounced potency might be best suited to alleviating arterial stiffness (16). In addition, we couldn’t compare the effects of telmisartan and candesartan on blood glucose and lipids, since the majority of original articles didn’t include enough data.
Treatment of hypertension in the elderly in 2017/2018 - what’s new?
Published in Expert Opinion on Pharmacotherapy, 2019
The second study that contributed to influence the recent recommendations is the Heart Outcomes Prevention Evaluation (HOPE)–3 trial [32]. The goal of this trial was to assess whether antihypertensive therapy reduces the risk of cardiovascular events in persons at intermediate cardiovascular risk and with a lower BP (mean 138/81 mmHg at baseline). The 12,705 participants at intermediate risk who did not have cardiovascular disease were randomized to receive either candesartan at a dose of 16 mg per day plus hydrochlorothiazide at a dose of 12.5 mg per day or placebo. The trial included men 55 years of age or older and women 65 years of age or older. Mean age was actually 65.8 years. Therapy with candesartan/hydrochlorothiazide was not associated with a lower rate of major cardiovascular events than placebo in the overall group of patients. Yet, patients in the upper third of systolic BP (>143.5 mm Hg) had significantly lower rates of the primary endpoint (death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke) than those in the placebo group. These data suggest that drug therapy reduces the risk of cardiovascular events in patients with uncomplicated mild hypertension only if their systolic BP is above 140 mmHg.
Related Knowledge Centers
- Angiotensin II Receptor Type 1
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- Prodrug
- Heart Failure
- Angiotensin II Receptor Blocker
- Maintenance Dose
- Bioavailability
- Angiotensin II Receptor Type 1