Heart Failure Blood Pressure Management And Pharmacoeconomics Research

This review summarized the up-to-date evidence to guide the application of systolic blood pressure(SBP)in predicting adverse events as well as SBP management for heart failure(HF).Higher SBP at admission was associated with better in-hospital and post-discharge outcomes in HF.In contrast,a "reversed J-shaped" or "U-shaped" association between the discharge SBP and adverse events was observed.Based on the compelling indications for heart failure with reduced ejection fraction(HFrEF)patients,renin-angiotensin-aldosterone system inhibitors and beta blockers,also as the first-line antihypertensive choices,should be initiated and up-titrated to improve their prognosis.Yet for those with low baseline SBP,such life-saving agents should be initiated and up-titrated to attain similar or even larger absolute benefits.Current evidence about HF with recovered ejection fraction indicates that the management should follow that for HFrEF.Because there is no evidence of any agent to improve the survival of HF patients with mid-range or preserved ejection fraction,blood pressure management plays a very important role as a cardiovascular risk control.A definite SBP target<130 mmHg was recommended by the American and Chinese guidelines.Renin-angiotensin-aldosterone system inhibitors should be given priority to be used to treat uncontrolled hypertension because their safety was tested in previous randomized clinical studies,while beta blocker,because of its potential harm,should not be generally prescribed unless there is a certain compelling indication.Prospective study is needed to explore the relationship between SBP and long-term outcomes,effect of anti-hypertension treatments,and optimal target blood pressure in heart failure patients.Part 2:Different Prognostic Association of Systolic Blood Pressure at Different Time Points with Post-discharge Events in Patients Hospitalized for Decompensated Heart FailureObjective:The association of systolic blood pressure(SBP)with prognosis in heart failure(HF)patients is paradoxical,and the time points of baseline SBP are also different across prior studies.We hypothesized that the levels of SBP at admission and at discharge had different associations with post-discharge events.Methods:The study population included patients hospitalized for decompensated HF in the Heart Failure Care Unit of Fuwai Hospital from January 1,2009 to December 31,2014.Patients were categorized into four groups based on the quartile of the admission SBP(<105 mmHg,105-119 mmHg,120-134 mmHg,and?135 mmHg).The primary outcome was a composite of cardiovascular death and heart transplantation.Multivariate Cox proportional-hazards and restricted cubic spline analyses were used to assess the relationships between SBP at different time points and outcomes.Results:In total,2005 patients were included,the median age was 59 years,and 69.9%were male.During a median follow-up of 48.4 months,768 patients experienced a primary outcome.Multivariate Cox analyses showed that compared with SBP<105 mmHg,higher SBP at admission was associated with better long-term primary outcome(105-119 mmHg,HR=0.764,95%CI=0.634-0.921,p value=0.005;120-134 mmHg,HR=0.658,95%CI=0.532-0.813,p value<0.001;? 135 mmHg,HR=0.657,95%CI=0.515-0.837,p value=0.001).Patients whose discharge SBP was higher than 135 mmHg had a similar primary outcome as those with SBP<105 mmHg(HR=0.969,95%CI=0.667-1.407,p value=0.867),and the results remained unchanged even after adjusting for admission SBP(HR=1.235,95%CI=0.835-1.826,p value=0.291).The results of restricted cubic spline analysis indicated similar associations.Conclusions:Higher SBP at admission is associated with less cardiovascular deaths/heart transplantations(a reverse J-shaped curve).In contrast,there is a U-shaped association between discharge SBP and cardiovascular death/heart transplantation.Part 3.The effect of SBP at discharge on outcomes by SBP at admission in non-heart failure with reduced ejection fraction patientsObjective:We hypothesized that discharge systolic blood pressure(SBP)had different associations with outcomes in non-HFrEF(left ventricular ejection fraction?40%)patients with or without high blood pressure(HBP)at admission.Methods:Non-HFrEF patients hospitalized for decompensated heart failure were consecutively recruited and were categorized into HBP(admission SBP?130 mmHg)group and non-HBP group.The primary outcome was a composite of cardiovascular death and heart transplantation.Multivariate Cox and penalized spline analyses were used to assess the relationships between' discharge SBP and outcomes.Results:Nine hundred and sixty-four non-HFrEF patients were enrolled,the median age was 63,61.0%were male,and 365(37.9%)patients were in HBP group.During a median follow-up of 71.8 months,a total of 284 patients experienced a primary outcome.In multivariate Cox analyses,non-HBP patients with higher discharge SBP were associated with a better outcome(per 10 mmHg increased,hazard ratio=0.796,95%CI:0.687-0923,p value=0.002).However,an opposite relationship between discharge SBP and the primary outcome was observed in HBP group(per 10 mmHg increased,hazard ratio=1.283,95%CI:1.075-1.531,p value=0.006).Results of penalized spline regression models showed that there was a U-shaped association between discharge SBP and outcomes in the total cohort.Compared with SBP=120 mmHg at discharge,the risk of the primary outcome increased when discharge SBP was below 99 mmHg in non-HBP group;in HBP group,a worse outcome was observed when discharged SBP was above 145 mmHg.Conclusion:Higher discharge SBP correlated with an increased risk of adverse events in non-HFrEF patients with admission SBP? 130 mmHg,as opposed to patients with admission SBP<130 mmHg.Part 4.Cost-effectiveness of adding dapagliflozin to standard treatment for heart failure with reduced ejection fraction patients in ChinaObjectives:This study was to determine the cost-effectiveness of dapagliflozin in heart failure with reduced ejection fraction(HFrEF)patients in China from a perspective of health care payers.Methods:We built a Markov model to perform a cost-effectiveness analysis comparing standard treatment+dapagliflozin(10 mg,q.d.)with standard treatment for HFrEF.The base case in our simulation was a 65-year old HFrEF patient and was modelled over 15 years.Inputs of the model were derived from the Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure trial and other relevant data from China.Costs,quality-adjusted life year(QALY),and incremental cost-effectiveness ratio(ICER)were estimated for adding dapagliflozin relative to standard treatment.Costs and QALY were discounted at a 4.2%rate annually.All costs are presented in 2017 US dollars.Dapagliflozin would be considered very cost-effective if the ICER was lower than a willingness-to-pay(WTP)threshold of $8573.4.Uncertainty was assessed in our model using one-way,two-way,and probabilistic sensitivity analysis.Results:In our base case,compared with standard treatment,adding dapagliflozin was more expensive($5829.4 vs.$4377.1)but more effective(4.82 vs.4.44 QALYs).The respondent ICER was $3827.6 per QALY gained at 15-year follow-up.When the simulated horizon was longer than 3.5 years,the respondent ICER became lower than the WTP threshold.The inputs with the largest impact on ICER were the cost of dapagliflozin,the cardiovascular mortality in both groups,and the cost of hospitalization for heart failure.Most results of sensitivity analysis were robust.Probabilistic sensitivity analysis showed a similar result as the base case(ICER=$4412.5 per QALY gained),In Monte Carlo simulation,at a WTP threshold of $8573.4 per QALY,dapagliflozin was considered very cost effective in 53.10%of the simulations.Conclusions:Dapagliflozin was a very cost-effective treatment option for HFrEF patients in China according to the result of our model.Our findings will help doctors and health care payers to make decisions in clinical practice.Future real-world studies of cost-effectiveness of dapagliflozin based on Chinese population were also needed.