By Jamie L.W. Kennedy, MD, FACC

Associate Professor, Division of Cardiology, Advanced Heart Failure & Transplant Cardiology, University of California, San Francisco

Dr. Kennedy reports no financial relationships relevant to this field of study.

SYNOPSIS: Systolic blood pressure less than 130 mmHg was associated with increased mortality in a Medicare population with systolic heart failure.

SOURCE: Arundel C, Lam PH, Gill GS, et al. Systolic blood pressure and outcomes in patients with heart failure with reduced ejection fraction. J Am Coll Cardiol 2019;73:3054-3063.

In patients with systolic heart failure, guidelines encourage tight blood pressure control, with target systolic blood pressure (SBP) less than 130 mmHg. This recommendation is based in part on the reduced incidence of systolic heart failure that occurred in the Systolic Blood Pressure Intervention Trial (SPRINT) with target SBP < 120 mmHg. Furthermore, numerous clinical trials have demonstrated the benefits of target doses of evidence-based heart failure medications. However, hypotension and resulting adverse events, from end organ dysfunction to falls and resulting injuries, are a significant concern. From the Organized Program to Initiate Lifesaving Treatment in Hospitalized Patients with Heart Failure (OPTIMIZE-HF) registry, a Medicare-linked data set of heart failure hospitalizations that occurred between March 1, 2003, and Dec. 31, 2004, Arundel et al selected 10,625 patients with ejection fractions ≤ 40% who were discharged alive. The authors excluded patients with labile blood pressure, defined as more than a 20 mmHg difference between admission and discharge, and nonphysiologic results (an SBP of > 300 mmHg or < 60 mmHg) for a sample of 5,615 patients. The authors used a propensity-matching algorithm to develop two cohorts with an SBP of less than 130 mmHg and ≥ 130 mmHg, each with 1,189 patients. The authors repeated the process to develop some additional cohorts with SBP readings of less than or equal to 110 mmHg, ≤ 129 mmHg, and > 130 mmHg. Outcomes included all-cause mortality, all-cause readmission, and heart failure readmission at 30-day, one-year, and six-year follow-up all the way up to Dec. 28, 2008 (median 2.3 years). The average age of the cohort was 76.5 years and 44.5% had diabetes, 34.55% had atrial fibrillation, and 25% had COPD. At discharge, 68.5% were treated with renin-angiotensin system inhibitors, 71% were treated with beta-blockers, 14.5% were treated with aldosterone antagonists, 83% were treated with diuretics, and 36% were treated with digoxin.

In the matched cohort, 30-day mortality occurred in 7% of patients with discharge SBP < 130 mmHg vs. 4% for patients with SBP ≥ 130 mmHg (hazard ratio [HR], 1.76; 95% confidence interval [CI], 1.24-2.48; P = 0.001). This association held over six years of follow-up, although at a smaller magnitude (HR, 1.15; 95% CI, 1.04-1.26; P = 0.005). There was no association between discharge SBP and 30-day readmissions. However, at one-year and long-term follow-up, lower SBP was associated with more readmissions (both heart failure and all-cause).

To further understand the relationship between SBP and mortality, the same analysis was repeated excluding patients with SBP < 110 mmHg. Similar to before, patients with SBP 110-129 mmHg died more often compared to those with SBP ≥ 130 mmHg at 30 days (6% vs. 4%; HR, 1.50; 95% CI, 1.03-2.19; P = 0.035) and one year (HR, 1.19; 95% CI, 1.02-1.39; P = 0.029), but not with longer-term mortality. There was no association with readmissions.

Clues to the outcome are found in the overall cohort prior to propensity matching. Patients in the group with SBP < 130 mmHg were more likely to have prior myocardial infarctions and arrhythmias, less likely to be treated with renin-angiotensin system inhibitors, more likely to be treated with diuretics and digoxin, and had a lower average ejection fraction — in sum, a patient population with a worse prognosis. Conversely, hypertension is associated with better outcomes in systolic heart failure and, as expected, was more common in the SBP ≥ 130 mmHg group. The propensity-matching algorithm attempted to balance these risk factors; however, there always is concern for unmeasured confounders. Thus, the authors concluded that randomized, controlled trials are needed to determine optimal SBP management for patients with heart failure with reduced ejection fraction.

COMMENTARY

This study targeted two questions in the management of patients with systolic heart failure. The first: “In patients with SBP ≥ 130 mmHg on target doses of evidence-based heart failure medications, is there benefit to further blood pressure lowering?” For patients like those in this study (the elderly hospitalized with heart failure), the answer is no. The applicability of these results to younger patients, and even elderly patients outside of a heart failure hospitalization, remains to be seen.

The more difficult dilemma is understanding the risk-benefit ratio of evidence-based heart failure therapies and blood pressure. Fortunately, there is some literature to provide guidance. The authors of the Carvedilol Prospective Randomized Cumulative Survival (COPERNICUS) trial studied the use of carvedilol in patients with New York Heart Association class III or IV heart failure despite treatment with renin-angiotensin system inhibitors and diuretics (minimum SBP for enrollment was 85 mmHg). Carvedilol was initiated at 3.125 mg twice a day and up-titrated every two weeks to a target dose of 25 mg twice a day as tolerated. Overall, carvedilol reduced all-cause mortality by 35% over a median follow-up of 10.4 months. The trial ended early because of significant improvement in survival with treatment.1

An analysis of the COPERNICUS data revealed that patients with the lowest SBP at enrollment certainly were at the highest risk of mortality, but the authors also realized the greatest benefit from treatment with carvedilol. Fortunately, worsening hypotension was uncommon, even with low baseline SBP. It is important to note that COPERNICUS and other pivotal trials of evidence-based heart failure therapies were conducted largely in the outpatient setting with gradual medication up-titration over weeks to months, primarily in younger patients with fewer comorbidities.

How will I practice going forward? It is hard to ignore the significant reduction in mortality seen with evidence-based heart failure medications. I will not be cutting back or discontinuing angiotensin-converting enzyme inhibitors for SBP of < 130 mmHg. Nevertheless, elderly patients certainly require more cautious medication titration: smaller steps over longer periods. I will pay more attention to assessing fall risk, as a hip fracture in an elderly patient with significant cardiac disease can be a terminal event. Perhaps most importantly, I will start discussing care goals earlier for patients with multiple high-risk features, recognizing that SBP < 130 mmHg at hospital discharge is one of those markers.

REFERENCE

  1. Packer M, Fowler MB, Roecker EB, et al. Effect of carvedilol on the morbidity of patients with severe chronic heart failure: Results of the Carvedilol Prospective Randomized Cumulative Survival (COPERNICUS) study. Circulation 2002;106:2194-2149.