Comparing the Effects of a Stroke Medicine in Older Adults with and without Chronic Kidney Disease

This project has results

Abstracts

Public Abstract

Download this abstract: English (pdf)

What was the research about?

Current medical guidelines recommend a type of medicine called ACE/ARBs to help patients live longer and protect their kidneys after a stroke. But studies show that rates of kidney disease have gone up at the same time that more people have been using this medicine. Additional research may help show if some patients shouldn’t take ACE/ARBs after a stroke.

In this study, the research team wanted to learn about the effects of taking ACE/ARBs for patients over age 65 who’ve had a stroke. The team reviewed Medicare claims for stroke survivors with and without chronic kidney disease, or CKD. CKD is a health problem in which the kidneys don’t remove waste from the blood well. The team compared patients in areas of the country with different rates of ACE/ARB use. The team looked at how many patients lived and how many had kidney problems over two years.

What were the results?

The study found that taking an ACE/ARB had different effects on survival for patients with and without CKD. Among patients without CKD, in areas where more patients took ACE/ARBs, more were alive after two years. Among patients with CKD in these areas, fewer were alive after two years. However, the study may not have had enough patients with CKD to say for sure what effect ACE/ARBs had on patient survival.

The amount of kidney problems over two years was similar for patients with or without CKD, regardless of how many people took ACE/ARBs in their area.

What did the research team do?

The research team looked at Medicare claims for 35,679 patients who had a stroke in 2010. All patients were over age 65, and 25 percent of these patients had CKD. Among patients with CKD, 60 percent were women, 79 percent were white, 14 percent were black, and 7 percent were other races. Among patients without CKD, 66 percent were women, 85 percent were white, 9 percent were black, and 6 percent were other races.

The research team compared the effects of taking an ACE/ARB on patients with and without CKD.

What were the limits of the study?

The study used the rates of ACE/ARB use from Medicare claims in 2010 in its analysis. Results may have been different if the study used rates from other years.

Future research could continue to explore whether ACE/ARB use should differ for patients with and without CKD. Future research could also focus on finding new methods that can detect the effect of ACE/ARB use in small groups of patients.

How can people use the results?

Researchers could look at this study when planning future research to examine the effects of ACE/ARB use among patients with and without CKD.

Professional Abstract

Objective

To estimate the beneficial and detrimental effects of using angiotensin system antagonists (ACE/ARBs) for secondary stroke prevention among patients over age 65, with and without chronic kidney disease (CKD), who had a stroke and had Medicare

Study Design

Design Elements Description
Design Empirical study
Data Sources and Data Sets Medical claims data for 35,679 patients who were over 65 who had an incident ischemic stroke in 2010
Analytic Approach Linear probability and instrumental variable models
Outcomes 2-year survival, 2-year renal events

In this empirical study, the research team applied linear probability and instrumental variable models to a clinical scenario in which the treatment has different beneficial and detrimental effects for different patients, but it is unclear which patient subgroups would benefit from the treatment. An instrumental variable is one that has a strong relationship with treatment choice but does not appear related to study outcomes. Because of geographic variation in practice, this study used local ACE/ARB treatment rates as the instrumental variable.

The research team analyzed the Medicare claims data for 35,679 patients who had a stroke in 2010. Of these, 25% had CKD. Among patients with CKD, 60% were female, 79% were white, 14% were black, and 7% were other races. Among patients without CKD, 66% were female, 85% were white, 9% were black, and 6% were other races.

Using standard regression and instrumental variable methods, the research team examined the effect of receiving ACE/ARBs after hospitalization for a stroke on patient survival and renal events, such as acute kidney failure or end-stage renal disease. In addition to the total population analysis, the team stratified the study population into patients with and without CKD to explore the differences in ACE/ARB treatment effects.

Results

The instrumental variable-based analysis of the total study population suggested that as local ACE/ARB treatment rates increased, two-year renal event risk decreased. The research team did not observe any significant improvement in two-year survival rates.

The instrumental variable estimates for two-year survival among patients with CKD was different from the estimate for patients without CKD (p<0.05). Among patients without CKD, two-year survival rates increased as local ACE/ARB treatment rates increased (p<0.05). Among patients with CKD, two-year survival rates decreased as local ACE/ARB treatment rates increased. This estimate appeared clinically significant, but because of the relatively small sample size of patients with CKD, it was not statistically significant. The research team did not find differences in two-year renal event risk between patients with and without CKD.

Limitations

Results may differ in studies using an instrumental variable other than the local ACE/ARB treatment rates in 2010.

Conclusions and Relevance

Current medical guidelines suggest that ACE/ARBs extend life and protect kidney function for all patients who have had strokes. In this study, ACE/ARB treatment effects among patients who had strokes varied by CKD status, suggesting that the outcome expectations associated with ACE/ARBs may differ for patients with and without CKD.

Future Research Needs

Future research could continue to explore whether ACE/ARB use should differ for patients with and without CKD. Future research could also examine alternative methods to detect treatment effects within relatively small patient subpopulations.

This project's final research report is expected to be available by November 2019.

Peer Review Summary

Peer review of PCORI-funded research helps make sure the report presents complete, balanced, and useful information about the research. It also assesses how the project addressed PCORI’s Methodology Standards. During peer review, experts read a draft report of the research and provide comments about the report. These experts may include a scientist focused on the research topic, a specialist in research methods, a patient or caregiver, and a healthcare professional. These reviewers cannot have conflicts of interest with the study.

The peer reviewers point out where the draft report may need revision. For example, they may suggest ways to improve descriptions of the conduct of the study or to clarify the connection between results and conclusions. Sometimes, awardees revise their draft reports twice or more to address all of the reviewers’ comments. 

Peer reviewers commented, and the researchers made changes or provided responses. The comments and responses included the following:

  • Reviewers said the report is well written but difficult to read given the complex statistical terminology. In response, the researchers wrote the introduction to be more direct and contain less jargon.
  • Reviewers wondered how the study results can be used given that baseline characteristics of the patient population led to heterogeneous effects on multiple outcomes. The researchers agreed that their results cannot be easily generalized to other populations. The researchers emphasized that the goal of this methods study was to help show that investigators should not be looking for the effective treatment for a given population but the most effective mix of treatments for that population, such that a specific patient could not do better switching to a different treatment.

Conflict of Interest Disclosures

View the COI disclosure form.

Journal Articles

Results of This Project

Journal of the American Heart Association

Use of Angiotensin-Converting Enzyme Inhibitors and Angiotensin Receptor Blockers for Geriatric Ischemic Stroke Patients: Are the Rates Right?

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Project Details

Principal Investigator
John Brooks, PhD
Project Status
Completed; PCORI Public and Professional Abstracts Posted
Project Title
Understanding Treatment Effect Estimates When Treatment Effects Are Heterogeneous for More Than One Outcome
Board Approval Date
September 2013
Project End Date
February 2019
Organization
University of South Carolina^
Year Awarded
2013
State
South Carolina
Year Completed
2018
Project Type
Research Project
Health Conditions 
Kidney Diseases
Renal Failure
Chronic Kidney Disease
Cardiovascular Diseases
Congestive Heart Failure
Stroke
Funding Announcement
Improving Methods for Conducting Patient-Centered Outcomes Research
Project Budget
$1,003,163
Study Registration Information
HSRP20143590

^John Brooks, PhD was affiliated with the University of Iowa when this project was funded.

Page Last Updated: 
May 29, 2019