Blood pressure control and stroke or bleeding risk in anticoagulated patients with atrial fibrillation: Results from the ROCKET AF Trial

doi:10.1016/j.ahj.2016.05.001

American Heart Journal

Volume 178, August 2016, Pages 74-84

https://doi.org/10.1016/j.ahj.2016.05.001 Get rights and content

Background

We conducted a retrospective analysis examining the association between systolic blood pressure (SBP) or hypertension bracket and stroke risk in patients with atrial fibrillation (AF).

Methods

The study included 14,256 anticoagulated patients in the ROCKET AF trial. Cox proportional hazards models were used to compare the risk of adverse outcomes by European Society of Cardiology hypertension bracket and screening SBP.

Results

In total, 90.5% of patients had hypertension (55.8% controlled, 34.6% uncontrolled). The adjusted risk of stroke or systemic embolism (SE) increased significantly for every 10–mm Hg increase in screening SBP (hazard ratio [HR] 1.07, 95% CI 1.02-1.13). There was a trend toward an increased adjusted risk of stroke or SE in patients with controlled (HR 1.22, 95% CI 0.89-1.66) and uncontrolled hypertension (HR 1.42, 95% CI 1.03-1.95) (P = .06). In contrast, the adjusted risk of major bleeding was similar between hypertensive brackets and did not vary significantly by screening SBP. The benefit of rivaroxaban versus warfarin in preventing stroke or SE was consistent among patients regardless of SBP (P interaction = .69).

Conclusions

In a trial of anticoagulated patients with AF, increasing screening SBP was independently associated with stroke and SE, and one-third of patients had uncontrolled hypertension. The relative effectiveness and safety of rivaroxaban versus warfarin were consistent across all levels of screening SBP. A single SBP may be an important factor in reducing the overall risk of stroke and SE in anticoagulated patients with AF.

Section snippets

Methods

The methods used in the ROCKET AF trial have been previously reported.¹⁸ Briefly, ROCKET AF was a prospective, multicenter, international, double-blind, randomized controlled trial in patients with nonvalvular AF and moderate to high risk of stroke based on a CHADS₂ (Congestive heart failure, Hypertension, Age >/= 75 years, Diabetes mellitus, Prior Stroke or TIA or Thromboembolism₂) score of at least 2. Patients were randomly assigned to 20 mg once daily of rivaroxaban (15 mg once daily in

Study patients

A total of 14,264 patients with AF from 1,178 centers in 45 countries were randomly assigned to treatment in ROCKET AF between December 18, 2006, and June 17, 2009. From the total trial, 14,256 patients had known baseline hypertension status and screening SBP. As shown in Table I, 90.5% of patients in ROCKET AF had hypertension: 55.8% were controlled at screening, and 34.6% were uncontrolled at screening. Among patients with uncontrolled hypertension at screening, 3,958 patients (80.1%) were

Discussion

In this analysis of >12,000 patients with hypertension in the ROCKET AF trial, there are 4 major findings. First, one-third of patients in this contemporary clinical trial of AF had uncontrolled screening SBP. Second, screening SBP was associated with a higher risk of stroke or systemic embolism, stroke, and ischemic stroke but not bleeding risk. Third, there was a trend toward higher risk of stroke or systemic embolism with uncontrolled screening SBP. Finally, there was no evidence of

Limitations

There are multiple limitations to a subgroup analysis of a large, randomized controlled trial. First, as a post hoc analysis, the findings must be considered hypothesis generating. Second, our use of a single screening SBP to classify patients is subject to error and does not take into account accumulated cardiovascular risk that is a function of the magnitude of blood pressure derangement and the length of time that derangement exists. Although we have attempted to address this deficiency by

Conclusions

In this large, randomized controlled trial, a single SBP was significantly linearly related to the risk of stroke, and stroke or systemic embolism, in anticoagulated patients with AF and high stroke risk. Furthermore, the relationship between screening SBP and outcomes was independent of treatment anticoagulant. Up to one-third of trial participants had uncontrolled blood pressure at screening.

Funding sources

This work and the ROCKET AF trial were supported by Janssen Research & Development and Bayer HealthCare. The Duke Clinical Research Institute coordinated the trial, managed the database, and undertook the primary analysis independent of the sponsors. The authors had complete access to the data and were responsible for writing and submitting the manuscript for publication.

Disclosures

S. Vemulapalli: research grant; Boston Scientific. Honoraria; Medtronic.

A. S. Hellkamp: none.

W. S. Jones: none.

J. P. Piccini: research grant; ARCA Biopharma, GE Healthcare, Johnson & Johnson, ResMed. Consultant/Advisory Board; Johnson & Johnson, Forest Laboratories, Spectranetics, Medtronic.

K. W. Mahaffey: Consultant/Advisory Board; AstraZeneca, Bayer, Bristol-Myers Squibb, Forest, Johnson & Johnson, WebMD.

R. C. Becker: Consultant/Advisory Board; Bayer, Janssen, Daiichi Sankyo, Portola, Regado

Acknowledgments

The authors would like to thank Morgan deBlecourt and Elizabeth Cook for editorial assistance.

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Modern anticoagulation therapy has dramatically reduced the risk of stroke and systemic thromboembolism in people with atrial fibrillation (AF). However, AF still impairs quality of life, increases the risk of stroke and heart failure, and is linked to cognitive impairment. There is also a recognition of the residual risk of thromboembolic complications despite anticoagulation. Hence, AF management is evolving towards a more comprehensive understanding of risk factors predisposing to the development of this arrhythmia, its’ complications and interventions to mitigate the risk. This review summarises the recent advances in understanding of risk factors for incident AF and managing these risk factors. It includes a discussion of lifestyle, somatic, psychological, and socioeconomic risk factors. The available data call for a practice shift towards a more individualised approach considering an increasingly broader range of health and patient factors contributing to AF-related health burden. The review highlights the needs of people living with co-morbidities (especially with multimorbidity), polypharmacy and the role of the changing population demographics affecting the European region and globally.
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Citation Excerpt :
In the Outcomes Registry for the Better Treatment of AF (ORBIT AF), each 5 mm Hg increase in systolic blood pressure over follow-up was associated with a 5% increase in stroke or transient ischemic attack (hazard ratio [HR], 1.05; 95% confidence interval [CI], 1.01–1.08; P = .01), a 5% increase in the risk of myocardial infarction (HR, 1.05; 95% CI, 1.00–1.11; P = .04) and a 3% increase in major bleeding events (HR, 1.03; 95% CI, 1.00–1.06; P = .04).17 In the Rivaroxaban versus Warfarin for non-valvular Atrial Fibrillation (ROCKET-AF) study, a similar increase in risk was observed with each 10 mm Hg increase in baseline blood pressure associated with an increased risk of stroke or systemic embolism (HR, 1.07; 95% CI, 1.02–1.13).18 Growing trends in overweight and obesity have reached pandemic proportions.
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Clinical InvestigationBlood pressure control and stroke or bleeding risk in anticoagulated patients with atrial fibrillation: Results from the ROCKET AF Trial

Background

Methods

Results

Conclusions

Section snippets

Methods

Study patients

Discussion

Limitations

Conclusions

Funding sources

Disclosures

Acknowledgments

Lancet

J Am Coll Cardiol

J Thromb Haemost

Am J Cardiol

J Am Coll Cardiol

J Thromb Haemost

Lancet

Increasing trends in hospitalization for atrial fibrillation in the United States, 1985 through 1999: implications for primary prevention

Circulation

A risk score for predicting stroke or death in individuals with new-onset atrial fibrillation in the community: the Framingham Heart Study

JAMA

Vital signs: prevalence, treatment, and control of hypertension—United States, 1999-2002 and 2005-2008

MMWR

The seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: the JNC 7 report

JAMA

2013 ESH/ESC guidelines for the management of arterial hypertension: the Task Force for the Management of Arterial Hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC)

Eur Heart J

Clinical Investigation
Blood pressure control and stroke or bleeding risk in anticoagulated patients with atrial fibrillation: Results from the ROCKET AF Trial