1.
Calcium channel blockers for preventing cardiomyopathy due to iron overload in people with transfusion-dependent beta thalassaemia.
Sadaf, A, Hasan, B, Das, JK, Colan, S, Alvi, N
The Cochrane database of systematic reviews. 2018;(7):CD011626
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Abstract
BACKGROUND Beta thalassaemia is a common inherited blood disorder. The need for frequent blood transfusions in this condition poses a difficult problem to healthcare systems. The most common cause of morbidity and mortality is cardiac dysfunction from iron overload. The use of iron chelation therapy has reduced the severity of systemic iron overload but specific, non-toxic treatment is required for removal of iron from the myocardium. OBJECTIVES To assess the effects of calcium channel blockers combined with standard iron chelation therapy in people with transfusion-dependent beta thalassaemia on the amount of iron deposited in the myocardium, on parameters of heart function, and on the incidence of severe heart failure or arrhythmias and related morbidity and mortality. SEARCH METHODS We searched the Cochrane Haemoglobinopathies Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books. We also searched ongoing trials databases, and the reference lists of relevant articles and reviews.Date of last search: 24 February 2018. SELECTION CRITERIA We included randomised controlled trials of calcium channel blockers combined with standard chelation therapy compared with standard chelation therapy alone or combined with placebo in people with transfusion-dependent beta thalassaemia. DATA COLLECTION AND ANALYSIS Two authors independently applied the inclusion criteria for the selection of trials. Two authors assessed the risk of bias of trials and extracted data and a third author verified these assessments. The authors used the GRADE system to assess the quality of the evidence. MAIN RESULTS Two randomised controlled trials (n = 74) were included in the review; there were 35 participants in the amlodipine arms and 39 in the control arms. The mean age of participants was 24.4 years with a standard deviation of 8.5 years. There was comparable participation from both genders. Overall, the risk of bias in included trials was low. The quality of the evidence ranged across outcomes from low to high, but the evidence for most outcomes was judged to be low quality.Cardiac iron assessment, as measured by heart T2*, did not significantly improve in the amlodipine groups compared to the control groups at six or 12 months (low-quality evidence). However, myocardial iron concentration decreased significantly in the amlodipine groups compared to the control groups at both six months, mean difference -0.23 mg/g (95% confidence interval -0.07 to -0.39), and 12 months, mean difference -0.25 mg/g (95% confidence interval -0.44 to -0.05) (low-quality evidence). There were no significant differences between treatment and control groups in serum ferritin (low-quality evidence), liver T2* (low-quality evidence), liver iron content (low-quality evidence) and left ventricular ejection fraction (low-quality evidence). There were no serious adverse events reported in either trial; however, one trial (n = 59) reported mild adverse events, with no statistically significant difference between groups (low-quality evidence). AUTHORS' CONCLUSIONS The available evidence does not clearly suggest that the use of calcium channel blockers is associated with a reduction in myocardial iron in people with transfusion-dependent beta thalassaemia, although a potential for this was seen. There is a need for more long-term, multicentre trials to assess the efficacy and safety of calcium channel blockers for myocardial iron overload, especially in younger children. Future trials should be designed to compare commonly used iron chelation drugs with the addition of calcium channel blockers to investigate the potential interplay of these treatments. In addition, the role of baseline myocardial iron content in affecting the response to calcium channel blockers should be investigated. An analysis of the cost-effectiveness of the treatment is also required.
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[Lipertance® The ASCOT single-pill combination has finally arrived].
Radermecker, RP
Revue medicale de Liege. 2017;(9):416-422
Abstract
The fixed association of atorvastatin, perindopril and amlodipine was recently launched by the firm SERVIER under the name of Lipertance®. It is the first fixed association of a statin, an ACE inhibitor and a calcium blocker present on the Belgian market to handle the risk factors that are hypertension and dyslipidemia which can be used both in primary and secondary cardiovascular prevention. The interests of such a triple combined therapy are many in terms of morbimortality reduction, as observed in ASCOT trial. Besides these results, the association of these three agents gives probably a synergic effect, which would be more effective to protect both heart and vessels. Moreover, a fixed association will improve treatment compliance and adherence, which are generally quite poor in the management of cardiovascular risk factors. Lipertance® is available with three different doses : 20/5/5 mg, 20/10/5 mg and 40/10/10 mg, respectively for atorvastatin, perindopril and amlodipine. Contraindications and side effects are the same as each component of this association and are well known.
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[A first drug combination for the treatment of arterial hypertension with a calcium channel antagonist (amlodipine besylate) and an angiotensin receptor blocker (valsartan): Exforge].
Krzesinski, JM, Scheen, AJ
Revue medicale de Liege. 2007;(11):688-94
Abstract
Hypertension is a common treatable risk factor for cardiovascular disease. Even when identified and treated, most patients with hypertension do not get to blood pressure goal and they often need at least two antihypertensive agents to achieve blood pressure control. Although various combination therapies are currently available for the treatment of hypertension, development of more powerful therapies is necessary to help implement guideline recommendations that call for more aggressive treatment options and early blood pressure control. Amlodipine/valsartan (Exforge) is a new combination of antihypertensive agents that lower blood pressure via calcium channel blockade and angiotensin receptor antagonism. This potent dual mechanism of action is also likely to attenuate compound-specific adverse events, such as amlodipine-related peripheral oedema. Currently available data show that such a combination is a well-tolerated treatment that gets different kinds of patients with all grades of hypertension to their blood pressure goal.