Dr Yevgeniy Khariton discusses CHAMP-HF, the association between sacubitril/valsartan initiation and health status outcomes in heart failure with reduced ejection fraction.
This observational analysis was that in a real world cohort tsukuba travel sartain was associated with very large substantial improvements in disease-specific quality of life and this was largely driven by a large number of patients in the tsukuba travel sartain cohort experiencing a health status improvement of at least greater than or equal to 20 points which
Was measured by the kcc q or the kansas city cardiomyopathy questionnaire so to really understand the context the reason for why this analysis was performed you really have to think about two things in relation to the preceding paradigm h-f trial now for those that aren’t too familiar with the trial it was a randomized control trial that sought to investigate the
Differences in terms of cardiovascular outcomes between patients that were prescribed chemical compound lcd six nine six what we now refer to as tsukuba trillville sartain versus those patients that were prescribed in a liberal and what the investigators found using a disease specific measures such as the kcc qed was that at eight months those patients in the
Tsukuba travel sartain arm had less deterioration in their quality of life compared to those that were prescribed in a liberal now this was an outcome that was measured again at eight months now the thing to really remember here is that one of the shortcomings of paradigm hf goes back to their pre randomization protocol and if you look closely all patients prior
To randomization had to undergo a mandatory intensification period when they were first treated with enalopril and then with higher doses of tsukuba travel sartain to confirm their tolerability prior to them having been randomized it was only after the randomization period that they were first assessed in terms of their health status now this poses a little bit of
A problem because if you’re trying to assess short-term health status benefits of this agent you really want to compare the outcome assessment to a true baseline and arguably the true baseline health status for these patients was way before the intensification period and so that was one major issue that we needed to address in order to truly identify short-term
Benefits of tsukuba trial valsartan in our cohort the second issue is that paradigm hf was a randomized control trial and with the limitations of a randomized control trial all patients were exposed to very stringent criteria and they were monitored under a closer supervision compare that to champ hf the centerpiece of our analysis where patients were monitored
In a real-world observational registry giving clinicians a clearer understanding of the benefits of an agent such as the ku patrol valsartan in a real-world cohort and those are kind of the two primary reasons as to why this analysis is substantial and very complimentary impactful to the medical community so to really understand the study design again you have to
Recall that champ hf is an observational registry and what that means is that unlike a randomized control trial where patients are randomized to receive one of two different treatments patients in an observational registry are being treated by different physicians under many different settings and they’re being prescribed medications at different periods of time
And so as you can imagine if we’re comparing two different kinds of patients to different treatment arms those treatment arms may be different in terms of their clinical characteristics and so to really level out those two treatment arms we have to propose what’s called a propensity analysis where we match patients based on certain characteristics and we assess
For a appropriate match after that afterwards using what we call standardized differences so this was a propensity matched analysis where we managed one patient that was prescribed to kabuto valsartan to two patients that were prescribed essentially no tsukuba travel started so they were in the know arnie cohort and we took all of those matched patients and then
Subjected them to a linear regression analysis where our outcome was changed in k ccq over time and that was the primary way by which we conducted this analysis notably patients in the champion chef registry were included across the entire us so very heterogeneous population minimal inclusion criteria which increases the generalizability of our findings due to the
More heterogeneous population that was included in the registry our findings after having conducted the analysis were number one when we look at change in kc’s the q score we really have to first understand how the kcc q this health status instrument is scored so plus 5 plus 10 and plus 20-point improvements of considered small moderate and large improvements in
Health status now what we first found after we performed our linear regression analysis we’re that those patients in the our new cohort experienced on average about 6 points of a health status improvement over the course of an average of 32 days compared to those in the know our new cohort those that were not prescribed tsukuba chil valsartan that experienced an
Average of about three and a half point improvement so here again you’re looking at the average benefit across both across each individual group over that period of time and this is a little different than what i just described for the small moderate and large point improvements for the kcc q so to that end what we next went to do is assess the different proportions
Of patients that experienced 5 10 and 20 point improvements and that’s where we saw the real compelling data where a very large a substantial number of patients in the arney cohorts those prescribes to cubicle valsartan experience greater than or equal to 20 points over those that were in the know our new cohort what that translates to is that for one patient to
Experience a least moderate health status improvement that greater than or equal to 10 points about 16 patients would have to be treated with this medication similarly for one patient to experience a large health status benefit of greater than or equal to 20 points as assessed by the kcc q approximately 11 patients would have to be treated so these are relatively
Small number needed to treat and what this really means is that we’ve taken a drug such as tsukuba travel sartain whose efficacy has been shown in a randomized control trial and we brought it closer to the clinical setting and applied it to an individual patient so if further contextualizes the meaning of the significance of this agent for an individual patient
That is receiving care within a clinic so moving forward you have to remember is that we have performed this observational analysis this registry within this observational data set and it complements what we have learned from the paradigm hf trial so moving forward when it comes to a guideline recommendations and implementation of the clinical practice we have to
Bear in mind that even though both paradigm hf and champ hf have their own limitations we have seen strong signals in terms of health status improvements from both and so what i would encourage providers to consider is that in those patients that are having heart failure symptoms aside from the cardiovascular mortality rehospitalization benefits of tsukuba trail
Valsartan it poses a very strong potential to improve patient’s health status their symptoms function and quality of life which is the second and equally as important goal of heart failure management to add on to the research that we are currently doing what we have to really understand is who are the patients that are benefitting tremendously as opposed to less so
From tsukuba chill valsartan in order to do that we need to perform a heterogeneity of treatment analysis where we further define patients based on their clinical associate demographic characteristics to really understand which patient is the one that is more ideal to prescribe tsukuba travel sarki alone just for the health status benefit so while we have already
Discussed it from a cardiovascular mortality and heart failure hospitalization standpoint all patients may have an improvement we want to be very selective at times about those patients that may may experience a ho status improvement as well and that’s why we want to further understand who are the patients that are experiencing these benefits so that we can bring
The research that we have seen from paradigm hf and from this analysis and to bring it closer into in patient care and outpatient care
Transcribed from video
HFA 2018: CHAMP-HF -Sacubitril/Valsartan Initiation In HF – Dr Yevgeniy Khariton By Radcliffe