Abstract
Given the concern that beta-blocker use may be associated with an increased risk for heart failure (HF) in populations with a normal left ventricular systolic function, we evaluated the association between beta-blocker use and incident HF events as well as loop diuretic initiation in the Systolic Blood Pressure Intervention Trial (SPRINT). SPRINT had demonstrated that a blood pressure (BP) target of <120mmHg reduced cardiovascular outcomes compared with <140mmHg in adults with at least one cardiovascular risk factor and without HF. The lower rate of the composite primary outcome in the 120mmHg group was primarily driven by a reduction in HF events. Subjects on a beta-blocker for the entire trial duration were compared with subjects who never received a beta-blocker after 1:1 propensity score matching. A competing-risk survival analysis by beta-blocker status was performed to estimate the effect of the drug on incident HF and was then repeated for a secondary endpoint of CVD death. Among the 3,284 propensity score matched subjects beta-blocker exposure was associated with an increased HF risk (hazard ratio 5.86; 95% CI 2.73–13.04; p<0.001). A sensitivity analysis of propensity score matched cohorts with history of coronary artery disease or atrial fibrillation revealed the same association (hazard ratio 3.49; 95% CI 1.15–10.06; p=0.028). In conclusion, beta-blocker exposure in this secondary analysis was associated with increased incident HF in hypertensive subjects without HF at baseline.
Keywords: preserved ejection fraction, Hypertension, Heart Failure, Quality and Outcomes, Beta-blockers
INTRODUCTION
Hypertension is prevalent and a major driver of cardiovascular disease (CVD) morbidity and mortality 1, including heart failure (HF), stroke, and coronary artery disease (CAD) 2, 3. The Systolic Blood Pressure Intervention Trial (SPRINT) was designed to evaluate whether a systolic blood pressure (BP) target of <120mmHg in patients without HF and ≥1 CVD risk factor would reduce cardiovascular events 4. The trial was stopped early after interim analyses revealed that the primary composite outcome was reduced in the lower BP arm. 4 Although patients with symptomatic HF were generally excluded from enrollment, the main benefit of a lower BP was a marked reduction in incident HF (Figure 1) 4. The SPRINT protocol encouraged participating investigators to use antihypertensive medications supported by evidence from large, randomized trials as first-line agents. The use of beta-blockers was reserved for presence of a secondary indication. Nonetheless, at the conclusion of SPRINT more than a third of the participants were receiving beta-blockers 4. Several data from randomized trials and secondary analyses suggest an association between beta-blocker use and decompensated HF in patient populations with predominantly normal ejection fractions 6–8. The objective of our study was to investigate whether beta-blocker exposure was a risk factor for incident heart failure in a trial cohort with predominantly normal ejection fractions and cardiac risk factors.
Figure 1: Cumulative Incidence of Events Contributing to Primary Composite Outcome -.
Cumulative incidence of events contributing to the SPRINT primary composite outcome stratified by treatment group, higher BP target (<140mmHg) vs. lower BP target (<120mmHg). Percentages to the right of the lower BP target bars represent the relative difference between lower BP and higher BP targets. MI= myocardial infarction, ACS = acute coronary syndrome, HF = incident heart failure, CVD = cardiovascular disease.
METHODS
The SPRINT design and results have been described in detail 4. In brief, the trial was a multicenter, open-label, randomized trial enrolling 9,361 subjects in the United States and Puerto Rico with a systolic BP of ≥130 mmHg who had no history of diabetes or stroke but who had ≥1 CVD risk factor. Subjects were enrolled to either 1) intensive BP control with a target systolic BP of ≤120 mmHg (lower BP arm) or 2) standard BP control with target systolic BP of ≤140mmHg (higher BP arm). Included subjects were ≥50 years of age and met pre-specified BP criteria with accompanying requirements for number of antihypertensive medications.
CVD risk factors could include one or more of the following: 1) known presence of clinical or subclinical CVD (other than stroke); 2) stable chronic kidney disease (CKD) with an eGFR 20–59 mL/min/1.73 m2; 3) Framingham Risk Score for 10-year CVD risk ≥ 15%; and/or 4) age ≥ 75 years. Clinical CVD included prior MI or acute coronary syndrome (ACS), prior vascular intervention or surgery for obstructive arteriosclerosis, an established ≥50% arterial stenosis, or an abdominal aortic aneurysm (AAA) ≥5cm with or without repair. Subclinical CVD included individuals with a coronary artery calcium score ≥400 Agatston units within the previous two years, ankle brachial index < 0.90 within the previous two years or left ventricular hypertrophy (LVH) by ECG, echocardiogram report, or other cardiac imaging modality within the prior two years. Participants with symptomatic HF in the 6 months preceding enrollment or who were known to have EF < 35% were excluded 5.
A specific antihypertensive medication regimen was not prescribed. Instead, a treatment algorithm emphasizing initiation of a two or three drug regimen preferentially utilizing a combination of a thiazide-type diuretic and/or an ACE-I or ARB and/or CCB was recommended based on clinical trial data. The use of beta-blockers as part of the hypertension treatment regimen was only advised in specific clinical scenarios including the setting of underlying coronary artery disease, as a heart rate-controlling agent with atrial fibrillation, impaired renal function, or electrolyte abnormalities that would preclude ACE-I/ARB/thiazide diuretics. Hypertension remained the primary indication for the use of all medication classes, with further selection based off concomitant comorbidities. For study follow-up visits, titration of agents already in use or addition of preferred agents was recommended 5.
The baseline visit included lab testing, vital signs, anthropomorphic data, ECG, medical history, demographic characteristics, medication inventory, and quality of life surveys. For the next three months, participants returned for monthly follow-up visits, which included a comprehensive medical history, assessments of vital signs and medication inventories for the first 3 months. Thereafter, interval study visits occurred every 3 months for the remainder of the first year, and then annually. A medication inventory was included at each visit 5.
The de-identified SPRINT database was obtained from the National Heart, Lung, and Blood Institute Biologic Specimen and Data Repositories Information Coordinating Center (BioLINCC). The database included 9,361 randomized subjects. Of those, 17 subjects were excluded based on incomplete medication inventories. As it was our goal to examine incident HF, we also excluded the 332 subjects with a history of HF (enrolled in the trial based on a history of HF without symptoms in the preceding 6 months and with EF documented above 35%). The remaining analyzed population included 9,012 subjects as shown in Figure 2. Baseline and follow-up medication inventories were used in order to determine the use of beta-blockers and other major antihypertensive classes such as ACE-I/ARB, thiazides and CCBs.
Figure 2: Flow Diagram of Analyzed Population -.
Flow diagram of patient inclusions and exclusions leading to the analyzed population. SPRINT indicates Systolic Blood Pressure Intervention Trial
The primary endpoint of this secondary analysis was incident HF defined as hospitalization or emergency department visit for HF requiring intravenous loop diuretics 9. The secondary endpoint was death from CVD with causes including MI, stroke, or postmortem findings of an acute CVD event.
For the primary analysis, we compared subjects on a beta-blocker for the entire trial with subjects who never received a beta-blocker in order to assess the risk of incident HF and beta-blocker status. To correct for a maximal number of confounding variables, we created propensity score matched (PSM) cohorts. After estimation of the propensity score, subjects within the subgroups were matched in a 1:1 ratio to the controls accounting for 27 confounding variables: age, sex, race, prior MI, prior ACS, carotid artery disease, peripheral arterial disease (PAD), aortic stenosis, AAA ≥ 5cm, calcium score >400, low ankle brachial index (ABI), left ventricular hypertrophy (LVH) on ECG, study arm, Framingham risk, systolic BP, diastolic BP, number of antihypertensive agents at enrollment, smoking status, aspirin use, estimated glomerular filtration rate, high density lipoprotein (HDL), total cholesterol, body mass index (BMI), statin use, and anti-hypertensive class use. We used the ‘nearest neighbor’ matching algorithm with a caliper size of 1% of the SD of the estimated propensity score to construct a matched-paired sample10. This caliper size is more stringent than typically recommended for observational studies11 and allows for optimal matching of comorbidities, i.e. myocardial infarction (MI) and antihypertensive medication use. Following the PSM, we conducted a competing-risk survival analysis by beta-blocker status to estimate the effect of the drug on incident HF accounting for acute MI and all-cause death as competing risk. We repeated the analysis for the secondary endpoint of CVD death.
The PSM analysis was repeated for the subjects with a potential beta-blocker indication such as history of MI, ACS, coronary revascularization, and history of atrial fibrillation or atrial fibrillation on the baseline ECG. To compare the impact of the other major antihypertensive classes on HF, we repeated the PSM analyses for patients who did not change ACE-I/ARB, thiazide or CCB status during the trial. The impact of beta-blockers on objective variables, such as heart rate and systolic BP, was analyzed using linear mixed-effect models controlling for multiple comorbidities (fixed-effects). As multiple data points were available for each subject, a patient identifier was used as random effect.
RESULTS
This secondary analysis of SPRINT included 9,012 participants with a median age of 67 years (interquartile range [IQR] 61–75). Median follow-up was 3.3 years, with 8,736 (96.93%) subjects followed after one year, 8,736 subjects followed after two years, and 6,076 subjects followed after three years. Of these, 4,501 (50%) had been randomized to the lower BP arm, 3,218 (36%) were women, and 3,803 (42%) were non-white (Table 1). A history of acute MI was present in 576 (6%) subjects and 397 (4%) had a history of ACS. Most of the trial participants were using between 1 and 3 antihypertensive medications at baseline. Overall, 3,248 (36%) subjects were on a beta-blocker at the beginning of the trial and 2,813 (31%) received beta-blockers for the entire trial. 3,284 subjects were matched using a propensity score.
Table 1.
Baseline characteristics of subjects with hypertension and without heart failure in SPRINT
| Variable | Overall Cohort N (%) |
|---|---|
| (N=9,012) | |
| Age (median [IQR]) | 67.0 [61.0, 75.0] |
| Women | 3218 (36%) |
| Black | 2669 (30%) |
| Hispanic | 965 (11%) |
| Other | 169 (2%) |
| White | 5209 (58%) |
| Lower BP target arm | 4501 (50%) |
| 10y Framingham risk (median [IQR]) | 17.7 [12.0, 25.6] |
| Systolic BP (median [IQR]) (mm Hg) | 138.0 [130.0, 149.0] |
| DBP (median [IQR]) (mm Hg) | 78.0 [70.0, 86.0] |
| Number of antihypertensive agents | |
| 0 | 868 (10%) |
| 1 | 2700 (30%) |
| 2 | 3178 (35%) |
| 3 | 1795 (20%) |
| 4 | 455 (5%) |
| 5 | 15 (0%) |
| 6 | 1 (0%) |
| Current smoker | 1192 (13) |
| Aspirin | 4530 (50) |
| Statin | 3850 (43) |
| Cholesterol (median [IQR]) | 187.0 [162.0, 215.0] |
| BMI (median [IQR]) (kg/m2) | 29.0 [25.8, 32.9] |
| History of Acute Myocardial Infarction | 576 (6%) |
| History of Acute Coronary Syndrome | 397 (4%) |
| Coronary revascularization | 790 (9%) |
| Left ventricular hypertrophy on ECG | 396 (4%) |
| Beta-blocker | |
| At Baseline | 3248 (36%) |
| Sometimes | 4626 (51%) |
| Never | 4386 (49%) |
| Entire Trial Duration | 2813 (31%) |
| ACE-I/ARB | |
| At Baseline | 5853 (65%) |
| Sometimes | 7705 (85%) |
| Never | 1307 (15%) |
| Always | 5128 (57%) |
| CCB | |
| At Baseline | 3612 (40%) |
| Sometimes | 6184 (69%) |
| Never | 2828 (31%) |
| Always | 3152 (35%) |
| Thiazide | |
| At Baseline | 4516 (50%) |
| Sometimes | 6754 (75%) |
| Never | 2258 (25%) |
| Always | 3260 (36%) |
ACS = acute coronary syndrome, Acute MI = Acute myocardial infarction, BMI = Body Mass Index, DBP = Diastolic Blood Pressure, SBP = Systolic Blood Pressure, IQR = Interquartile Range, LVH = Left Ventricular Hypertrophy, ECG = Electrocardiogram.
An analysis of subjects who received beta-blockers for the entire trial compared with subjects who never received a beta-blocker was well balanced in terms of concomitant blood pressure medications (Table 2). The types of beta-blockers used and dosing was similar to the overall cohort (Supplement Tables 1 and 2). In the matched group that never received beta-blockers, there were 6 incident HF events and in the group that received beta-blockers for the entire trial there were 41 HF events. The cumulative incidence of HF and competing events are shown in figure 3. This analysis confirmed a positive association between beta-blocker use and incident HF (HR 5.86, CI 2.63–13.04; p<0.001).
Table 2.
Baseline characteristics and propensity score matched cohorts of subjects on beta-blocker (beta-blocker) for the entire trial versus those never on a beta-blocker for the duration of the trial (no beta-blocker)
| Before Propensity Score Matching | After Propensity Score Matching | |||||
|---|---|---|---|---|---|---|
| Variable | No Beta-blocker | Beta-blocker | p-value | No Beta-blocker | Beta-blocker | p-value |
| Number of patients | 6199 | 2813 | 1642 | 1642 | ||
| Age (median [IQR]) | 66.0 [60.0,75.0] | 68.0 [61.0,76.0] | <0.001 | 67.0 [61.0, 76.0] | 67.0 [61.0, 76.0] | 0.822 |
| Female | 2182 (35%) | 1036 (37%) | 0.141 | 600 (37%) | 599 (36%) | 1.000 |
| Race | <0.001 | 0.966 | ||||
| Black | 1920 (31%) | 749 (27%) | 453 (28%) | 453 (28%) | ||
| Hispanic | 698 (11%) | 267 (9%) | 184 (11%) | 175 (11%) | ||
| Other | 119 (2%) | 50 (2%) | 33 (2%) | 33 (2%) | ||
| White | 3462 (56%) | 1747 (62%) | 972 (59%) | 981 (60%) | ||
| Acute Myocardial Infarction | 205 (3%) | 371 (13%) | <0.001 | 78 (5%) | 81 (5%) | 0.871 |
| Acute Coronary Syndrome | 159 (3%) | 238 (8%) | <0.001 | 63 (4%) | 63 (4%) | 1.000 |
| Carotid Revascularization | 111 (2%) | 150 (5%) | <0.001 | 43 (3%) | 43 (3%) | 1.000 |
| Peripheral Arterial Disease | 60 (1%) | 61 (2%) | <0.001 | 25 (2%) | 20 (1%) | 0.548 |
| Stenosis >50% of | 108 (2%) | 154 (5%) | <0.001 | 43 (3%) | 41 (2%) | 0.912 |
| Ascending Aortic Aneurysm >= 5cm without repair 4 | 30 (0) | 25 (1%) | 0.032 | 14 (1%) | 9 (1%) | 0.403 |
| Calcium score>400 | 13 (0%) | 13 (0%) | 0.063 | 7 (0%) | 7 (0%) | 1.000 |
| Low ABI<=90 | 26 (0%) | 22 (1%) | 0.042 | 8 (0%) | 7 (0%) | 1.000 |
| Left Ventricular Hypertrophy on ECG | 233 (4%) | 163 (6%) | <0.001 | 73 (4%) | 76 (5%) | 0.867 |
| Lower BP target arm control arm | 2909 (47%) | 1592 (57%) | <0.001 | 885 (54%) | 881 (54%) | 0.916 |
| 10y Framingham Risk >15% | 3771 (61%) | 1778 (63%) | 0.042 | 1017 (62%) | 1032 (63%) | 0.614 |
| Systolic BP (median [IQR]) | 138.0 [129.0, | 139.0 [130.0, 151.0] | 0.001 | 139.0 [130.0, 149.0] | 139.0 [130.0, 150.0] | 0.688 |
| Diastolic BP (median [IQR]) | 79.0 [71.0, 86.0] | 77.0 [69.0, 85.0] | <0.001 | 78.0 [70.0, 85.0] | 78.0 [70.0, 86.8] | 0.849 |
| Number of antihypertensive agents | <0.001 | 0.577 | ||||
| 0 | 778 (13%) | 90 (3%) | 90 (5%) | 86 (5%) | ||
| 1 | 2194 (35%) | 506 (18%) | 431 (26%) | 432 (26%) | ||
| 2 | 2156 (35%) | 1022 (36%) | 676 (41%) | 716 (44%) | ||
| 3 | 886 (14%) | 909 (32%) | 386 (24%) | 352 (21%) | ||
| >3 | 185 (3%) | 286 (10%) | 59 (4%) | 56 (3%) | ||
| Smoking category | 0.001 | 0.552 | ||||
| Never | 2818 (46%) | 1180 (42%) | 723 (44%) | 704 (43%) | ||
| Former | 2545 (41%) | 1267 (45%) | 715 (44%) | 714 (43%) | ||
| Current | 830 (13%) | 362 (13%) | 204 (12%) | 224 (14%) | ||
| Aspirin | 2849 (46%) | 1681 (60%) | <0.001 | 889 (54%) | 874 (53%) | 0.624 |
| EGFR (median | 72.6 [60.2, | 68.8 [54.9, 82.3] | <0.001 | 71.3 [57.8, 83.9] | 71.6 [57.9, 84.4] | 0.778 |
| HDL (median | 51.0 [44.0, | 48.0 [41.0, 58.0] | <0.001 | 50.0 [43.0, 60.0] | 49.0 [42.0, 60.0] | 0.168 |
| Cholesterol | 190.0 [166.0, | 181.0 [154.0, | <0.001 | 187.0 [162.0, | 186.0 [159.0, 214.0] | 0.738 |
| Body Mass Index (median [IQR]) | 28.9 [25.8, 32.7] | 29.1 [25.9, 33.1] | 0.065 | 29.1 [26.1, 33.0] | 29.1 [25.7, 33.0] | 0.402 |
| Statin | 2335 (38%) | 1515 (54%) | <0.001 | 732 (45%) | 761 (46%) | 0.326 |
| ACE-I at baseline or initiated during the trial | 5362 (86%) | 2343 (83%) | <0.001 | 1396 (85%) | 1370 (83%) | 0.231 |
| CCB at baseline or initiated during the trial | 4289 (69%) | 1895 (67%) | 0.088 | 1113 (68%) | 1095 (67%) | 0.527 |
| Thiazide at baseline or initiated during the trial | 4708 (76%) | 2042 (73%) | 0.001 | 1252 (76%) | 1241 (76%) | 0.683 |
ACE-I=Angiotensin Converting Enzyme Inhibitor, ARB = Angiotensin Receptor Blocker, CCB = Calcium channel blocker, Acute MI = Acute myocardial infarction, ACS = Acute coronary Syndrome, IQR = Interquartile range, PAD = Peripheral Artery Disease, HDL = High-Density Lipoprotein, BMI = Body Mass Index, AAA = Abdominal Aortic Aneurysm, SBP = Systolic Blood Pressure, DBP = Diastolic Blood Pressure, ABI = Ankle Brachial Index, LVH = Left ventricular hypertrophy, EGFR = Estimated Glomerular Filtration Rate.
Figure 3: Events by Beta-blocker Use or Non-Use for the Entire Trial in the Propensity Score Matched Cohort -.
Cumulative incidence plot of acute heart failure exacerbation (in red) in the propensity score matched cohort of patients who stayed on a beta-blocker during the whole trial (full line) versus patient who were never on the drug (dotted line). The competing risk of all-cause death and acute MI for both groups is represented in black. In the matched group without beta-blockers, there were 6 events of incident heart failure decompensation and 72 competing events. In the matched group with beta-blockers, there were 41 incident heart failure events and 133 competing events.
The analysis of patients with a potential indication for beta-blocker use - i.e. history of MI, ACS, prior coronary revascularization or atrial fibrillation – demonstrated a positive association of beta-blocker use and incident HF in the propensity score matched analysis (Supplement. Table 3). In the propensity score matched cohort of subjects who remained on an antihypertensive drug class for the trial versus subjects that were never exposed, no significant association was seen between beta-blockers and risk of CVD death (Supplement. Table 4).
Beta-blocker use versus non-use was associated with a lower heart rate (−5.09 beats per minute, p<0.001; Supplement. Table 5). Systolic BP was not different between beta-blocker users and non-users.
DISCUSSION
In this secondary analysis of SPRINT of hypertensive subjects with at least one CVD risk factor but without HF, beta-blocker use was associated with a higher risk of incident HF including in those subjects for whom a traditional indication was identified.
The enrollment criteria ensured that most patients had a normal ejection fraction and would not receive concealed benefits from HF medications such as ACE-I/ARBs or beta-blockers. The SPRINT results suggest that the major benefit of a lower blood pressure is a reduction of HF (HR 0.62, CI 0.45–0.84, p=0.002). This result may not be surprising as hypertension and age are the most important risk factors for the development of HF 12, 13 and BP reduction has been consistently shown to have a protective effect 12. In contrast, beta-blocker use was consistently associated with a higher risk of HF including in the cohort with recommended beta-blocker use e.g. history of ACS, myocardial infarction and atrial fibrillation.
The prevalence of CAD in the SPRINT population was below 20% and the prevalence of AF was less than 10%; however, over 50% of subjects received beta-blockers at some point during the study. Alternative reasons for beta-blocker use e.g. renal disease limiting the use of first-line agents or resistant hypertension on >3 first-line agents were also not common in this population (Table 2) 9. In our analyses we attempted to correct for co-morbidities and clinical scenarios that could favor beta-blocker use. Nonetheless, beta-blockers were consistently associated with an increased risk for incident heart failure. Adverse or neutral effects of beta-blockers on HF and other cardiovascular outcomes in subjects with normal EFs have previously been documented in hypertension trials, prospective and observational CAD studies in the reperfusion era, and in HF with preserved ejection fraction (HFpEF) 15–17 18.
Randomized trials that directly compared beta-blockers to other antihypertensive medications have not yielded such clear results. Subjects in the LIFE hypertension trial randomized to atenolol had significantly more CVD events compared with losartan. Similarly, atenolol was less efficacious than amlodipine in preventing major CV events in the ASCOT trial, mostly driven by an excess in strokes. Nonetheless, incident HF was uncommon and statistically not different16 19. Whereas LIFE and ASCOT excluded patients older than 80 and 79 years of age, respectively, SPRINT did not have an upper age limit. The median age for HF events in SPRINT was 77 years and 25% were older than 81 years. SPRINT was also enriched with HF emergency room visits, raising statistical power 4, 16, 19. Prior analyses of patient cohorts with presumably normal EFs receiving beta-blockers similarly have shown inconsistent results with respect to the effect of beta-blockers on HF outcomes 20–22, probably influenced by factors such as baseline patient CVD risk, inclusion and exclusion criteria, sample size, and study duration.
Some of the adverse outcomes associated with beta-blockers may be explained by their heart rate lowering effects. Lower heart rates are known to increase central BP because of reflected systemic arterial pressure waves that coincide with the ongoing systolic ejection. In addition, lower heart rates prolong diastolic filling that can only be accomplished at higher filling pressures as LV compliance declines. These effects combine to increase ventricular wall stress, which explains why natriuretic peptide levels are higher with beta-blockers in historic hypertension studies and in HFpEF 8, 23, 24. Subjects with higher blood pressures have a higher HF risk and are therefore more susceptible to the adverse effect of beta-blockers as suggested in our individual analyses of the SPRINT treatment arms 12, 25, 26.
Prior studies of beta-blockers in populations with preserved ejection fractions have also varied considerably in their conclusions regarding their effects on CVD mortality 6, 18, 27–31. It may be possible that the anti-ischemic and anti-arrhythmic effects of beta-blockers convey some mortality benefits in specific subgroups of patients with normal ejection fractions. Mechanisms by which such subgroups may derive benefit from beta-blockade include attenuation of ischemia, modest suppression of ventricular arrhythmias, or by prevention of tachycardia-induced cardiomyopathy, though these hypotheses have not been formally evaluated.
Patients were randomized to a BP target and not a specific medication class, with the SPRINT protocol allowing for multiple antihypertensive agents to be prescribed at the discretion of the participating provider. As beta-blockers vary in selectivity and pharmacokinetics, a dose-effect analysis is not possible. While propensity score matching attempted to equalize baseline risks amongst subjects, it is not a substitute for prospective randomization. To mitigate the risk of including patients with reduced EFs, we excluded all patients with a remote history of HF. However, subjects with a reduced EF that may have been inadvertently enrolled or subjects that developed a reduced EF during the trial should have derived benefits from beta-blocker therapy.
In conclusion, our findings demonstrate a positive association between beta-blocker use and incident heart failure in a cohort of patients with baseline hypertension. Given the high prevalence of beta-blocker use in hypertensive patients and their association with heart failure, prospective clinical trials that examine both the safety and efficacy of beta-blockers in populations with normal ejections fractions are needed.
Supplementary Material
Table 3.
Hazard Ratios for HF in the Propensity Score Matched Cohorts of Subjects That Stayed on an Anti-Hypertensive Class for the Entire Trial versus Never on this Class During the Trial
| Anti-Hypertensive Class | HR | 2.5% CI | 97.5% CI | p-value |
|---|---|---|---|---|
| Beta-blocker | 5.86 | 2.63 | 13.04 | <0.001 |
| ACE-I/ARB | 1.71 | 0.86 | 3.38 | 0.12 |
| CCB | 1.68 | 0.87 | 3.24 | 0.12 |
| Thiazide | 0.71 | 0.4 | 1.24 | 0.23 |
Table 3 – Hazard ratios from the survival analysis modelling for incident heart failure decompensation accounting for the competing risk of cardiovascular death and Acute MI in propensity score matched cohorts of patients who did not change the antihypertensive class for the whole duration of the trial (always or never). Matched cohorts for each antihypertensive class were generated. ACE-I=Angiotensin Converting Enzyme Inhibitor, ARB = Angiotensin Receptor Blocker, CCB = Calcium Channel Blocker.
Funding/Support:
This work was supported by grant R01 HL-122744 from the National Institutes of Health (Dr Meyer) and grant K23 HL135273 from the National Institutes of Health (Dr Juraschek).
Footnotes
Conflict of Interest Disclosures:
D.N.S., J.D.L., T.B.P., P.G., M.I., S.P.J., G.B.D., P.W.C.: None
M.M.: Has licensed patents on the use of pacemakers to prevent and treat HFpEF. The relationship is modest.
Declaration of interests
The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:
Markus Meyer reports financial support was provided by National Institutes of Health. Stephen P. Juraschek reports financial support was provided by National Institutes of Health.
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