Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Randomized Controlled Trial
. 2022 Oct;15(10):e008995.
doi: 10.1161/CIRCOUTCOMES.122.008995. Epub 2022 Oct 4.

Guideline-Directed Medical Therapy Attainment and Outcomes in Dialysis-Requiring Versus Nondialysis Chronic Kidney Disease in the ISCHEMIA-CKD Trial

Roy O Mathew  1   2 , David J Maron  3 , Rebecca Anthopolos  4 , Jerome L Fleg  5 , Sean M O'Brien  6   7 , Frank W Rockhold  6   7 , Carlo Briguori  8 , Marek F Roik  9 , Tomasz Mazurek  10 , Marcin Demkow  11 , Robert Malecki  12 , Zhiming Ye  13 , Upendra Kaul  14 , Marius Miglinas  15 , Gregg W Stone  16 , Ron Wald  17 , David M Charytan  4 , Mandeep S Sidhu  18 , Judith S Hochman  4 , Sripal Bangalore  4
Affiliations
Randomized Controlled Trial

Guideline-Directed Medical Therapy Attainment and Outcomes in Dialysis-Requiring Versus Nondialysis Chronic Kidney Disease in the ISCHEMIA-CKD Trial

Roy O Mathew et al. Circ Cardiovasc Qual Outcomes. 2022 Oct.

Abstract

Background: Patients with chronic kidney disease (CKD) on dialysis (CKD G5D) have worse cardiovascular outcomes than patients with advanced nondialysis CKD (CKD G4-5: estimated glomerular filtration rate <30 mL/[min·1.73m2]). Our objective was to evaluate the relationship between achievement of cardiovascular guideline-directed medical therapy (GDMT) goals and clinical outcomes for CKD G5D versus CKD G4-5.

Methods: This was a subgroup analysis of ISCHEMIA-CKD (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches-Chronic Kidney Disease) participants with CKD G4-5 or CKD G5D and moderate-to-severe myocardial ischemia on stress testing. Exposures included dialysis requirement at randomization and GDMT goal achievement during follow-up. The composite outcome was all-cause mortality or nonfatal myocardial infarction. Individual GDMT goal (smoking cessation, systolic blood pressure <140 mm Hg, low-density lipoprotein cholesterol <70 mg/dL, statin use, aspirin use) trajectory was modeled. Percentage point difference was estimated for each GDMT goal at 24 months between CKD G5D and CKD G4-5, and for association with key predictors. Probability of survival free from all-cause mortality or nonfatal myocardial infarction by GDMT goal achieved was assessed for CKD G5D versus CKD G4-5.

Results: A total of 415 CKD G5D and 362 CKD G4-5 participants were randomized. Participants with CKD G5D were less likely to receive statin (-6.9% [95% CI, -10.3% to -3.7%]) and aspirin therapy (-3.0% [95% CI, -5.6% to -0.6%]), with no difference in other GDMT goal attainment. Cumulative exposure to GDMT achieved during follow-up was associated with reduction in all-cause mortality or nonfatal myocardial infarction (hazard ratio, 0.88 [95% CI, 0.87-0.90]; per each GDMT goal attained over 60 days), irrespective of dialysis status.

Conclusions: CKD G5D participants received statin or aspirin therapy less often. Cumulative exposure to GDMT goals achieved was associated with lower incidence of all-cause mortality or nonfatal myocardial infarction in participants with advanced CKD and chronic coronary disease, regardless of dialysis status.

Registration: URL: https://www.

Clinicaltrials: gov; Unique identifier: NCT01985360.

Keywords: cardiovascular diseases; clinical trial; kidney; lipoproteins; secondary prevention.

PubMed Disclaimer

Figures

Figure 1.
Figure 1.
Percent of participants who attained a given number of guideline-directed medical therapy (GDMT) goals over follow-up, by chronic kidney disease (CKD) group. The count of non-missing values at each follow-up visit is appended below the visit month. The 5 GDMT goals include: No smoking; aspirin use; Low Density Lipoprotein-Cholesterol < 70 mg/dl; Systolic Blood Pressure < 140 mmHg; and being on a statin.
Figure 2.
Figure 2.
Predicted Probability of higher guideline-directed medical therapy (GDMT) goal attainment by chronic kidney disease (CKD) group. The panels represent the trajectories of attaining the represented total number of GDMT goals at target (>2, > 3, or >4) over study follow-up. The purple lines represent patients with CKD G5D, and the orange represent those with CKD G4–5. The 5 GDMT goals include: No smoking; aspirin use; Low Density Lipoprotein-Cholesterol < 70 mg/dl; Systolic Blood Pressure < 140 mmHg; and being on a statin
Figure 3:
Figure 3:. Differences in individual goal attainment between chronic kidney disease groups.
Figure 3a. Differences in probability of guideline-directed medical therapy (GDMT) goal attainment and 95% credible intervals at 24m for chronic kidney disease (CKD) G5D versus CKD G4–5. Estimates are displayed under two separate assumptions for missing values: missing at random (MAR) and missing not at random according to a pattern mixture model (PMM) approach. For example, compared to CKD G4–5, CKD G5D were approximately 7 percentage points less likely to receive statin therapy by 24 months. 95% CrI: 95% credible interval; LDL: low density lipoprotein; SBP: systolic blood pressure.
Figure 3b.
Figure 3b.
Predicted probability of individual guideline-directed medical therapy (GDMT) goal attainment over follow up by chronic kidney disease (CKD) group. The purple lines represent patients with CKD G5D, and the orange represent those with CKD G4–5. LDL: low density lipoprotein; SBP: systolic blood pressure.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

References

    1. Baigent C, Landray MJ, Reith C, Emberson J, Wheeler DC, Tomson C, Wanner C, Krane V, Cass A, Craig J, et al. The effects of lowering LDL cholesterol with simvastatin plus ezetimibe in patients with chronic kidney disease (Study of Heart and Renal Protection): a randomised placebo-controlled trial. Lancet. 2011;377:2181–2192. - PMC - PubMed
    1. Herrington WG, Emberson J, Mihaylova B, Blackwell L, Reith C, Solbu MD, Mark PB, Fellström B, Jardine AG, Wanner C, et al. Impact of renal function on the effects of LDL cholesterol lowering with statin-based regimens: a meta-analysis of individual participant data from 28 randomised trials. Lancet Diabetes Endocrinol. 2016;4:829–839. - PubMed
    1. Wright JT, Williamson JD, Whelton PK, Snyder JK, Sink KM, Rocco MV., Reboussin DM, Rahman M, Oparil S, Lewis CE, et al. A randomized trial of intensive versus standard blood-pressure control. New England Journal of Medicine. 2015; 373: 2103–16. - PMC - PubMed
    1. Malhotra R, Nguyen HA, Benavente O, Mete M, Howard BV., Mant J, Odden MC, Peralta CA, Cheung AK, Nadkarni GN, et al. Association between more intensive vs less intensive blood pressure lowering and risk of mortality in chronic kidney disease stages 3 to 5: A systematic review and meta-analysis. JAMA Internal Medicine. 2017;177:1498–1505. - PMC - PubMed
    1. Der Mesropian PJ, Shaikh G, Cordero Torres E, Bilal A, Mathew RO. Antihypertensive therapy in nondiabetic chronic kidney disease: a review and update. Journal of the American Society of Hypertension. 2018;12:154–181. - PubMed

Publication types

MeSH terms

Substances

Associated data