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Integrated analysis of valsartan has demonstrated clear dose-dependent efficacy and ability to achieve BP goals at doses of – mg ; however, there is a notable absence of head-to-head trials comparing valsartan dose mg with other creditcardonline.pwon: Rockville Pike, Bethesda, MD. · Experts share four things patients should know about the recent recall by the FDA and 22 countries of several blood pressure and heart drugs containing valsartan, including alternatives and a.
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For other ARBs at comparable doses, valsartan achieves comparable antihypertensive efficacy. Valsartan has a strong dose—response relationship when increasing from 80 mg to mg or mg. Hypertension currently affects approximately one billion adults globally. It is a major risk factor for cardiovascular diseases CV and stroke and is associated with metabolic syndromes including insulin resistance and lipid abnormalities. The risk of hypertension increases with age and is associated with gender and ethnicity.
The morbidity and mortality associated with uncontrolled hypertension result in a substantial economic burden as a result of drug costs, hospitalisations, surgery and other healthcare resources.
This cost is compounded by the humanistic burden and effect on quality of life associated with lifestyle modifying adverse events. The global proliferation of cost effective, tolerable long-term therapy is paramount for reducing this growing catastrophe. The renin-angiotensin-aldosterone-system RAAS plays an integral role in the pathophysiology of hypertension, functioning as a primary regulator in the control of fluid volume, electrolyte balance and blood volume.
In conjunction, angiotensin II causes potent vasoconstriction, aldosterone secretion and sympathetic activation, all of which contribute to the development of hypertension. Angiotensin II receptor blockers ARBs modulate the RAAS system by blocking the activation of angiotensin II AT 1 receptors resulting in, among other effects, vasodilatation, reduced secretion of vasopressin and reduced production and secretion of aldosterone.
There are currently six ARBs used as first line treatment in hypertension: As the first ARBs were introduced in the mids, numerous clinical trials have been conducted to evaluate their efficacy and tolerability.
Valsartan is a non-peptide, orally active and specific angiotensin II antagonist, which demonstrates high affinity to the AT1 receptor subtype. Although widely used in the control of hypertension, its use at higher dose is less widespread.
In , valsartan was approved at starting doses of mg and since then, there has been continuing evidence supporting its efficacy in reducing blood pressure BP and protecting against clinical events. Studies demonstrate that the placebo-like tolerability and once daily dosing schedule of valsartan result in improved patient compliance and treatment persistence, resulting in increased drug efficacy 7 , 8.
Furthermore, this tolerability has been found to be stable over a wide dosing range 9. These advantages, in addition to the comparative cost-effectiveness of valsartan, mean that it remains a favourable option for long-term control of adult hypertension Integrated analysis of valsartan has demonstrated clear dose-dependent efficacy and ability to achieve BP goals at doses of — mg 11 ; however, there is a notable absence of head-to-head trials comparing valsartan dose mg with other ARBs.
The only study to date is a recent publication by Giles et al. Results of this study demonstrate a dose effect throughout: These results confirm that use of valsartan at and mg improve BP control. Results encourage further comparisons at doses of mg. Lack of other head-to-head trials motivates the need for indirect comparison. In the absence of said trials, meta-analysis is useful for comparing ARBs at a range of dosing options. No meta-analysis to date has compared high-dose mg valsartan with other ARBs.
Hence, the purpose of this meta-analysis is to compare high-dose valsartan with other ARBs in short-term, monotherapy trials with none or forced titration. A computerised systematic literature search was conducted using the following databases: Both English and German randomised control trials were searched for, which were published between October and May The following inclusion criteria were applied: The following exclusion criteria were applied: Studies with unacceptable methods of randomised allocation, double blinding and reporting of withdrawals were excluded.
Table 1 shows drugs and dosages considered, and which doses are considered comparable between drugs. Doses are categorised as low, medium or high and are compared with one another within doses. ARB, angiotensin II receptor blocker.
Two independent reviewers completed all phases of literature selection, review and data abstraction. Discrepancies were resolved by third party consensus.
Selected studies were quality assessed using a quality assessment tool in accordance with Cochrane Specifications 13 see Appendix S1. Data were abstracted to a customised data extraction sheet which was performed by two reviewers and cross-checked for consistency. For inclusion in the meta-analysis, follow-up must be between 6 and 12 weeks. Where more than one result is available in this period, from interim analysis, the latest result has been used.
The analysis is performed by dose. In the case of forced titration studies, the dose is taken as the maximum dose the patient was titrated to, rather than the starting dose. A random-effect meta-regression model was used to estimate the overall mean change in SBP and DBP from baseline to follow-up.
This model adjusts the estimate of the overall mean change in BP for the baseline BP. Figure 1 illustrates the relationship between baseline BP and change in BP, clearly showing that the reduction in BP is higher in trials with patients with higher BP at baseline.
The model estimates the treatment effect by drug and dose. Full details of these models are given in the Appendix. The linear regression weighted by the inverse of the variance of the change in SBP is also shown.
The area of each circle is inversely proportional to this variance. Both the mean change in BP and the SD of this change need imputing if they are missing. Baseline BP data are complete as this is a requirement for study selection. Missing mean change in BP was imputed as the difference between mean follow-up and mean baseline BP. When reported, the change from baseline BP is commonly the complete case outcome. When missing, outcomes on all randomised patients were reported at baseline and the complete cases reported at follow-up, so imputing missing values in this way is assuming non-informative drop out.
Missing SD of the change from baseline outcome was imputed from the reported SEM or the confidence intervals. If these were not given, then it was imputed using an imputation model, which uses the mathematical relationship between the SD at baseline, the SD at follow-up and the SD of the change in BP.
Data from all the trial arms were used for imputing the missing SD, even if they contained treatments other than ARBs, doses not included in the analysis or elective titration arms. Details of this imputation are given in the Appendix. Figure 2 shows the trial flow of selection stages for studies considered for inclusion in the meta-analysis.
From a total of RCT titles for the publication period, abstracts were reviewed, of which were excluded. The most commonly excluded studies failed to meet the patient population inclusion criteria and hypertension thresholds.
Summary information from the treatment arms of the RCTs abstracted is given in Table 2. Study characteristics and summary data extracted from the studies included in the analysis.
The results show a dose—response relationship for all ARBs. In particular, a large change in response is noted for valsartan when increasing from 80 to mg and above. Greater mean reduction in BP with valsartan and mg was statistically significant compared with losartan mg. Indirect comparison demonstrates greater mean change in SBP and DBP from baseline in favour of valsartan mg over losartan mg: No significant difference in BP reduction is seen for valsartan 80 mg compared with losartan 50 mg: Similarly, candesartan 16 mg is less effective in reducing DBP than valsartan mg, with a difference in mean change in DBP of 1.
All other ARBs demonstrate comparable efficacy across dosing ranges. Positive numbers indicate that valsartan is superior to the comparator, negative numbers that valsartan is inferior. This is interpreted as an average increase of 1 mmHg in the study mean baseline BP leads to an increase of 0. Previous similar meta-analyses have failed to compare the antihypertensive efficacy of valsartan mg with other ARBs.
In , Conlin et al. Main inclusion criteria were prospective; double-blind RCTs with placebo run in of 4—5 weeks; patient population with mild-to-moderate hypertension DBP:
If you're current or former military, you'd better read this. In conjunction, angiotensin II causes potent vasoconstriction, aldosterone secretion and sympathetic activation, all of which contribute to the development of hypertension.
This model adjusts the estimate of the overall mean change in BP for the baseline BP.