Forums » Open clinical » Cardiology » What is the action of carvedilol in heart faliure?
|
Re: What is the action of carvedilol in heart faliure?
posted at 6/7/2011 2:50 AM BST
on bmj.com
|
Posts: 627
First: 13/4/2011 Last: 18/6/2013 |
In Response to Re: What is the action of carvedilol in heart faliure?: Hi Joey, I think that mixed treatment comparisons address the issue of bias and heterogeneity better than earlier methods. However, if direct comparisons are available then obviously it takes precedence. Posted by Deb_D Dear Deb_D: My biostat brain is not exactly naive, but I am not following your thoughts right now. Any way I agree with you, sadian, and ranasaleem. Let´s try to see if we can organize a bit more the things between us and do this analytical work. All best, Joey |
|
|
Re: What is the action of carvedilol in heart faliure?
posted at 6/7/2011 6:07 PM BST
on bmj.com
|
Posts: 499
First: 12/7/2010 Last: 11/6/2013 |
Hi sadian, Regarding types of meta-analysis, there is the conventional meta-analysis that can be used to determine the effectiveness of a treatment taking the data from multiple trails overcoming the problems associated with low powered studies Meta regression analysis can be undertaken when there is heterogeneity among the reported trials. Meta analysis can also be undertaken to compare to treatments indirectly. One technique is adjusted indirect comparison by Bucher’s method, comparing the pooled effects of two trials. Network meta-analysis and multiple treatment comparisons are more advanced and complicated methods of comparing treatments that take into account both direct and indirect trials. Hi Joey, By older methods I mean Bucher’s method which can’t incorporate the direct comparison between two drugs. Also say an RCT shows one drug is effective than another while an indirect comparison says otherwise. Obviously we should be inclined to accept the RCT. But this raises another problem, what if the RCT is of poor quality? Should be take a poor quality RCT over a well conducted indirect comparison.
|
|
|
Re: What is the action of carvedilol in heart faliure?
posted at 7/7/2011 8:51 PM BST
on bmj.com
|
|
Posts: 627
First: 13/4/2011 Last: 18/6/2013 |
In Response to Re: What is the action of carvedilol in heart faliure?: Hi sadian, Regarding types of meta-analysis, there is the conventional meta-analysis that can be used to determine the effectiveness of a treatment taking the data from multiple trails overcoming the problems associated with low powered studies Meta regression analysis can be undertaken when there is heterogeneity among the reported trials. Meta analysis can also be undertaken to compare to treatments indirectly. One technique is adjusted indirect comparison by Bucher’s method, comparing the pooled effects of two trials. Network meta-analysis and multiple treatment comparisons are more advanced and complicated methods of comparing treatments that take into account both direct and indirect trials. Hi Joey, By older methods I mean Bucher’s method which can’t incorporate the direct comparison between two drugs. Also say an RCT shows one drug is effective than another while an indirect comparison says otherwise. Obviously we should be inclined to accept the RCT. But this raises another problem, what if the RCT is of poor quality? Should be take a poor quality RCT over a well conducted indirect comparison. Posted by Deb_D Hello Fellows: One issue that I find especially important when using beta-blockers in my heart failure patients is to always ask myself this single question: Is this patient left ventricle´s Frank-Starling Law optimised? Frank Starling Law: "The more the heart is stretched - until a certain point - the stronger the heart will contract" And perhaphs one unique pharmacological aspect of Carvedilol, but not of the others here mentioned beta blockers, is related to its enhanced vasodilation action via Alpha -1-adrenergic blockade with consequent lowering of the afterload, so increasing the stroke volume. Because: Stroke Volume (SV) = End Diastolic Volume (EDV) minus End Systolic Volume. or just: SV = EDV (dependent of preload) - ESV (dependent of afterload). All best, Joey |
|
|
Re: What is the action of carvedilol in heart faliure?
posted at 8/7/2011 8:34 AM BST
on bmj.com
|
Posts: 897
First: 17/6/2011 Last: 17/6/2013 |
Hi Joey, You raise an interesting point about why carvedilol might be better - in addition to this we might consider also overall effect on heart rate- we know that the lower the heart rate the longer you will live (OK a slight oversimplification but the general idea hold true particularly in those patients with IHD) and secondly how strongly these beta blockers inhibit the renin-angiotensin axis. Anyone have any date on this? BW, Sadian |
|
|
Re: What is the action of carvedilol in heart faliure?
posted at 8/7/2011 4:17 PM BST
on bmj.com
|
|
Posts: 627
First: 13/4/2011 Last: 18/6/2013 |
In Response to Re: What is the action of carvedilol in heart faliure?: Hi Joey, You raise an interesting point about why carvedilol might be better - in addition to this we might consider also overall effect on heart rate- we know that the lower the heart rate the longer you will live (OK a slight oversimplification but the general idea hold true particularly in those patients with IHD) and secondly how strongly these beta blockers inhibit the renin-angiotensin axis. Anyone have any date on this? BW, Sadian Posted by sadian Also, so-called Ancillary (sort of auxiliary, or secondary) effects unique to Carvedilol would be Anti-oxidant, inhibition of endothelin, and anti-apoptotic actions. These ancillary beta-blockers effects in heart failure would only be shared between Carvedilol and Nevibolol, but the latter would do it through a different mechanisms: increased nitric oxide production. Well, I always try to look at the clinical counterpart of the pharmacological studies, but in the case of Carvedilol, the clinical studies kind of give support to them. All best, Joey
|
|
|
Re: What is the action of carvedilol in heart faliure?
posted at 19/1/2013 4:57 PM GMT
on bmj.com
|
|
Posts: 897
First: 17/6/2011 Last: 17/6/2013 |
Well guys - we were too slow with our analysis! http://www.bmj.com/content/346/bmj.f55 but the conclusion was no different - in number terms carvedilol seems best but the overall effect appears to be a class effect. sadian |
|
|
Re: What is the action of carvedilol in heart faliure?
posted at 19/1/2013 6:05 PM GMT
on bmj.com
|
Posts: 3059
First: 27/3/2012 Last: 13/6/2013 |
There has already been a quality discussion on this topic. Compared to other cardioselective beta blockers, Carvedilol is considered superior in patients with CHF and concomitant comorbidities. Carvedilol is a beta-adrenergic antagonist with vasodilatory properties (alpha1-antagonism), which has been extensively evaluated in the treatment of patients with heart failure. In patients with chronic heart failure, carvedilol 1) Improves left-ventricular (LV) ejection fraction over 6 to 12 months of treatment, and 2. Attenuates LV remodelling. Carvedilol improves survival and reduces hospitalizations. Comparative studies with metoprolol in patients with heart failure have suggested that carvedilol is associated with greater survival benefit although differences in the preparation of metoprolol have left uncertainty in this area. Carvedilol has a high safety profile and the clinical benefits appear maintained across a wide range of patients with comorbidities such as diabetes and renal failure. Carvedilol has also been shown to attenuate LV remodeling and improve clinical outcomes in patients with LV dysfunction and/or heart failure following acute myocardial infarction. As a result of these data, carvedilol is recommended for treatment of patients with heart failure in heart-failure guidelines. 3) Effective beta-1 inhibition by carvedilol with as high a dose as possible is clearly important for the treatment of CHF. Patients with CHF and COPD tolerate carvedilol well with no significant reversible airflow limitation, but patients with CHF and asthma tolerate carvedilol poorly. Asthma remains a contraindication to beta-blockade. |
|
|
Re: What is the action of carvedilol in heart faliure?
posted at 29/1/2013 6:34 PM GMT
on bmj.com
|
|
Posts: 6
First: 29/1/2013 Last: 28/2/2013 |
Hi all, I found this discussion very interesting... I found on Pubmed this abstract http://www.ncbi.nlm.nih.gov/pubmed/14583895 (I couldn't get the full text), it seems to compare similar population, it is a post hoc analysis so maybe it hasn't the same statistical value of the original trials. Bye Massi |
Forums » Open clinical » Cardiology » What is the action of carvedilol in heart faliure?
