Cost-Effectiveness of Intensive versus Standard Blood-Pressure Control

BACKGROUND

In the Systolic Blood Pressure Intervention Trial (SPRINT), adults at high risk for cardiovascular disease who received intensive systolic blood-pressure control (target, <120 mm Hg) had significantly lower rates of death and cardiovascular disease events than did those who received standard control (target, <140 mm Hg). On the basis of these data, we wanted to determine the lifetime health benefits and health care costs associated with intensive control versus standard control.

METHODS

We used a microsimulation model to apply SPRINT treatment effects and health care costs from national sources to a hypothetical cohort of SPRINT-eligible adults. The model projected lifetime costs of treatment and monitoring in patients with hypertension, cardiovascular disease events and subsequent treatment costs, treatment-related risks of serious adverse events and subsequent costs, and quality-adjusted life-years (QALYs) for intensive control versus standard control of systolic blood pressure.

RESULTS

We determined that the mean number of QALYs would be 0.27 higher among patients who received intensive control than among those who received standard control and would cost approximately $47,000 more per QALY gained if there were a reduction in adherence and treatment effects after 5 years; the cost would be approximately $28,000 more per QALY gained if the treatment effects persisted for the remaining lifetime of the patient. Most simulation results indicated that intensive treatment would be cost-effective (51 to 79% below the willingness-to-pay threshold of $50,000 per QALY and 76 to 93% below the threshold of $100,000 per QALY), regardless of whether treatment effects were reduced after 5 years or persisted for the remaining lifetime.

CONCLUSIONS

In this simulation study, intensive systolic blood-pressure control prevented cardiovascular disease events and prolonged life and did so at levels below common willingness-to-pay thresholds per QALY, regardless of whether benefits were reduced after 5 years or persisted for the patient’s remaining lifetime. (Funded by the National Heart, Lung, and Blood Institute and others; SPRINT ClinicalTrials.gov number, NCT01206062.)

Reference: N Engl J Med 2017; 377:745-755 August 24, 2017

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Cardiovascular event rates and mortality according to achieved systolic and diastolic blood pressure in patients with stable coronary artery disease: an international cohort study

Background

The optimum blood pressure target in hypertension remains debated, especially in coronary artery disease, given concerns for reduced myocardial perfusion if diastolic blood pressure is too low. We aimed to study the association between achieved blood pressure and cardiovascular outcomes in patients with coronary artery disease and hypertension.

Methods

We analysed data from 22 672 patients with stable coronary artery disease enrolled (from Nov 26, 2009, to June 30, 2010) in the CLARIFY registry (including patients from 45 countries) and treated for hypertension. Systolic and diastolic blood pressures before each event were averaged and categorised into 10 mm Hg increments. The primary outcome was the composite of cardiovascular death, myocardial infarction, or stroke. Hazard ratios (HRs) were estimated with multivariable adjusted Cox proportional hazards models, using the 120–129 mm Hg systolic blood pressure and 70–79 mm Hg diastolic blood pressure subgroups as reference.

Findings

After a median follow-up of 5·0 years, increased systolic blood pressure of 140 mm Hg or more and diastolic blood pressure of 80 mm Hg or more were each associated with increased risk of cardiovascular events. Systolic blood pressure of less than 120 mm Hg was also associated with increased risk for the primary outcome (adjusted HR 1·56, 95% CI 1·36–1·81). Likewise, diastolic blood pressure of less than 70 mm Hg was associated with an increase in the primary outcome (adjusted HR 1·41 [1·24–1·61] for diastolic blood pressure of 60–69 mm Hg and 2·01 [1·50–2·70] for diastolic blood pressure of less than 60 mm Hg).

Interpretation

In patients with hypertension and coronary artery disease from routine clinical practice, systolic blood pressure of less than 120 mm Hg and diastolic blood pressure of less than 70 mm Hg were each associated with adverse cardiovascular outcomes, including mortality, supporting the existence of a J-curve phenomenon. This finding suggests that caution should be taken in the use of blood pressure-lowering treatment in patients with coronary artery disease.

Funding

Servier.

Reference: The Lancet, Volume 388, No. 10056, p2142–2152, 29 October 2016

Blood-Pressure and Cholesterol Lowering in Persons without Cardiovascular Disease

BACKGROUND

Elevated blood pressure and elevated low-density lipoprotein (LDL) cholesterol increase the risk of cardiovascular disease. Lowering both should reduce the risk of cardiovascular events substantially.

METHODS

In a trial with 2-by-2 factorial design, we randomly assigned 12,705 participants at intermediate risk who did not have cardiovascular disease to rosuvastatin (10 mg per day) or placebo and to candesartan (16 mg per day) plus hydrochlorothiazide (12.5 mg per day) or placebo. In the analyses reported here, we compared the 3180 participants assigned to combined therapy (with rosuvastatin and the two antihypertensive agents) with the 3168 participants assigned to dual placebo. The first coprimary outcome was the composite of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke, and the second coprimary outcome additionally included heart failure, cardiac arrest, or revascularization. The median follow-up was 5.6 years.

RESULTS

The decrease in the LDL cholesterol level was 33.7 mg per deciliter (0.87 mmol per liter) greater in the combined-therapy group than in the dual-placebo group, and the decrease in systolic blood pressure was 6.2 mm Hg greater with combined therapy than with dual placebo. The first coprimary outcome occurred in 113 participants (3.6%) in the combined-therapy group and in 157 (5.0%) in the dual-placebo group (hazard ratio, 0.71; 95% confidence interval [CI], 0.56 to 0.90; P=0.005). The second coprimary outcome occurred in 136 participants (4.3%) and 187 participants (5.9%), respectively (hazard ratio, 0.72; 95% CI, 0.57 to 0.89; P=0.003). Muscle weakness and dizziness were more common in the combined-therapy group than in the dual-placebo group, but the overall rate of discontinuation of the trial regimen was similar in the two groups.

CONCLUSIONS

The combination of rosuvastatin (10 mg per day), candesartan (16 mg per day), and hydrochlorothiazide (12.5 mg per day) was associated with a significantly lower rate of cardiovascular events than dual placebo among persons at intermediate risk who did not have cardiovascular disease. (Funded by the Canadian Institutes of Health Research and AstraZeneca; ClinicalTrials.gov number,NCT00468923.)

Blood-Pressure Lowering in Intermediate-Risk Persons without Cardiovascular Disease

BACKGROUND

Antihypertensive therapy reduces the risk of cardiovascular events among high-risk persons and among those with a systolic blood pressure of 160 mm Hg or higher, but its role in persons at intermediate risk and with lower blood pressure is unclear.

METHODS

In one comparison from a 2-by-2 factorial trial, we randomly assigned 12,705 participants at intermediate risk who did not have cardiovascular disease to receive either candesartan at a dose of 16 mg per day plus hydrochlorothiazide at a dose of 12.5 mg per day or placebo. The first coprimary outcome was the composite of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke; the second coprimary outcome additionally included resuscitated cardiac arrest, heart failure, and revascularization. The median follow-up was 5.6 years.

RESULTS

The mean blood pressure of the participants at baseline was 138.1/81.9 mm Hg; the decrease in blood pressure was 6.0/3.0 mm Hg greater in the active-treatment group than in the placebo group. The first coprimary outcome occurred in 260 participants (4.1%) in the active-treatment group and in 279 (4.4%) in the placebo group (hazard ratio, 0.93; 95% confidence interval [CI], 0.79 to 1.10; P=0.40); the second coprimary outcome occurred in 312 participants (4.9%) and 328 participants (5.2%), respectively (hazard ratio, 0.95; 95% CI, 0.81 to 1.11; P=0.51). In one of the three prespecified hypothesis-based subgroups, participants in the subgroup for the upper third of systolic blood pressure (>143.5 mm Hg) who were in the active-treatment group had significantly lower rates of the first and second coprimary outcomes than those in the placebo group; effects were neutral in the middle and lower thirds (P=0.02 and P=0.009, respectively, for trend in the two outcomes).

CONCLUSIONS

Therapy with candesartan at a dose of 16 mg per day plus hydrochlorothiazide at a dose of 12.5 mg per day was not associated with a lower rate of major cardiovascular events than placebo among persons at intermediate risk who did not have cardiovascular disease. (Funded by the Canadian Institutes of Health Research and AstraZeneca; ClinicalTrials.gov number, NCT00468923.)

Blood pressure lowering for prevention of cardiovascular disease and death: a systematic review and meta-analysis

Background

The benefits of blood pressure lowering treatment for prevention of cardiovascular disease are well established. However, the extent to which these effects differ by baseline blood pressure, presence of comorbidities, or drug class is less clear. We therefore performed a systematic review and meta-analysis to clarify these differences.

Method

For this systematic review and meta-analysis, we searched MEDLINE for large-scale blood pressure lowering trials, published between Jan 1, 1966, and July 7, 2015, and we searched the medical literature to identify trials up to Nov 9, 2015. All randomised controlled trials of blood pressure lowering treatment were eligible for inclusion if they included a minimum of 1000 patient-years of follow-up in each study arm. No trials were excluded because of presence of baseline comorbidities, and trials of antihypertensive drugs for indications other than hypertension were eligible. We extracted summary-level data about study characteristics and the outcomes of major cardiovascular disease events, coronary heart disease, stroke, heart failure, renal failure, and all-cause mortality. We used inverse variance weighted fixed-effects meta-analyses to pool the estimates.

Results

We identified 123 studies with 613 815 participants for the tabular meta-analysis. Meta-regression analyses showed relative risk reductions proportional to the magnitude of the blood pressure reductions achieved. Every 10 mm Hg reduction in systolic blood pressure significantly reduced the risk of major cardiovascular disease events (relative risk [RR] 0·80, 95% CI 0·77–0·83), coronary heart disease (0·83, 0·78–0·88), stroke (0·73, 0·68–0·77), and heart failure (0·72, 0·67–0·78), which, in the populations studied, led to a significant 13% reduction in all-cause mortality (0·87, 0·84–0·91). However, the effect on renal failure was not significant (0·95, 0·84–1·07). Similar proportional risk reductions (per 10 mm Hg lower systolic blood pressure) were noted in trials with higher mean baseline systolic blood pressure and trials with lower mean baseline systolic blood pressure (all ptrend>0·05). There was no clear evidence that proportional risk reductions in major cardiovascular disease differed by baseline disease history, except for diabetes and chronic kidney disease, for which smaller, but significant, risk reductions were detected. β blockers were inferior to other drugs for the prevention of major cardiovascular disease events, stroke, and renal failure. Calcium channel blockers were superior to other drugs for the prevention of stroke. For the prevention of heart failure, calcium channel blockers were inferior and diuretics were superior to other drug classes. Risk of bias was judged to be low for 113 trials and unclear for 10 trials. Heterogeneity for outcomes was low to moderate; the I2 statistic for heterogeneity for major cardiovascular disease events was 41%, for coronary heart disease 25%, for stroke 26%, for heart failure 37%, for renal failure 28%, and for all-cause mortality 35%.

Interpretation

Blood pressure lowering significantly reduces vascular risk across various baseline blood pressure levels and comorbidities. Our results provide strong support for lowering blood pressure to systolic blood pressures less than 130 mm Hg and providing blood pressure lowering treatment to individuals with a history of cardiovascular disease, coronary heart disease, stroke, diabetes, heart failure, and chronic kidney disease.

Funding

National Institute for Health Research and Oxford Martin School.

Different systolic blood pressure targets for people with history of stroke or transient ischaemic attack: PAST-BP (Prevention After Stroke—Blood Pressure) randomised controlled trial

Objective To assess whether using intensive blood pressure targets leads to lower blood pressure in a community population of people with prevalent cerebrovascular disease.

Design Open label randomised controlled trial.

Setting 99 general practices in England, with participants recruited in 2009-11.

Participants People with a history of stroke or transient ischaemic attack whose systolic blood pressure was 125 mm Hg or above.

Interventions Intensive systolic blood pressure target (<130 mm Hg or 10 mm Hg reduction from baseline if this was <140 mm Hg) or standard target (<140 mm Hg). Apart from the different target, patients in both arms were actively managed in the same way with regular reviews by the primary care team.

Main outcome measure Change in systolic blood pressure between baseline and 12 months.

Results 529 patients (mean age 72) were enrolled, 266 to the intensive target arm and 263 to the standard target arm, of whom 379 were included in the primary analysis (182 (68%) intensive arm; 197 (75%) standard arm). 84 patients withdrew from the study during the follow-up period (52 intensive arm; 32 standard arm). Mean systolic blood pressure dropped by 16.1 mm Hg to 127.4 mm Hg in the intensive target arm and by 12.8 mm Hg to 129.4 mm Hg in the standard arm (difference between groups 2.9 (95% confidence interval 0.2 to 5.7) mm Hg; P=0.03).

Conclusions Aiming for target below 130 mm Hg rather than 140 mm Hg for systolic blood pressure in people with cerebrovascular disease in primary care led to a small additional reduction in blood pressure. Active management of systolic blood pressure in this population using a <140 mm Hg target led to a clinically important reduction in blood pressure.

By Jonathan Mant et al, BMJ 2016;352:i708

Antenatal blood pressure for prediction of pre-eclampsia, preterm birth, and small for gestational age babies: development and validation in two general population cohorts

Study question Can routine antenatal blood pressure measurements between 20 and 36 weeks’ gestation contribute to the prediction of pre-eclampsia and its associated adverse outcomes?

Methods This study used repeated antenatal measurements of blood pressure from 12 996 women in the Avon Longitudinal Study of Parents and Children (ALSPAC) to develop prediction models and validated these in 3005 women from the Southampton Women’s Survey (SWS). A model based on maternal early pregnancy characteristics only (BMI, height, age, parity, smoking, existing and previous gestational hypertension and diabetes, and ethnicity) plus initial mean arterial pressure was compared with a model additionally including current mean arterial pressure, a model including the deviation of current mean arterial pressure from a stratified normogram, and a model including both at different gestational ages from 20-36 weeks.

Study answer and limitations The addition of blood pressure measurements from 28 weeks onwards improved prediction models compared with use of early pregnancy risk factors alone, but they contributed little to the prediction of preterm birth or small for gestational age. Though multiple imputation of missing data was used to increase the sample size and minimise selection bias, the validation sample might have been slightly underpowered as the number of cases of pre-eclampsia was just below the recommended 100. Several risk factors were self reported, potentially introducing measurement error, but this reflects how information would be obtained in clinical practice.

What this study adds The addition of routinely collected blood pressure measurements from 28 weeks onwards improves predictive models for pre-eclampsia based on blood pressure in early pregnancy and other characteristics, facilitating a reduction in scheduled antenatal care.

Funding, competing interests, data sharing UK Wellcome Trust, US National Institutes of Health, and UK Medical Research Council. Other funding sources for authors are detailed in the full online paper. With the exceptions of CM-W, HMI, and KMG there were no competing interests.

Corrie Macdonald-Wallis et al, BMJ 2015;351:h5948