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  • Srikanth Bathini, MD

Cardioprotective drug use in patients with AKI - Analysis of deficits and opportunities to treat

Illustrations by: Corina Teodosiu,MD


AcademicCME (www.academiccme.com) is accrediting this educational activity for CE and CME for clinician learners. Please go to https://academiccme.com/kicr_blogposts/ to claim credit for participation.


Patients with acute kidney injury (AKI) post myocardial infarction (MI) have a higher all-cause mortality. Patients experiencing AKI alone have an associated 2-fold increased mortality risk compared to patients diagnosed with MI alone. Patients with AKI may have associated chronic kidney disease (CKD), cardiovascular disease and other underlying risk factors may contribute to this higher mortality risk. In fact, patients diagnosed with AKI have an associated 86% increased risk of CV mortality and a 38% rise in CV events . Additionally, the risk of CV events rises significantly in patients requiring dialysis following a diagnosis of AKI. Finally, the duration of AKI is a strong predictor of long term mortality. Renal recovery is associated with a lower mortality rate.


Brar et al retrospectively studied patients who developed CKD after AKI noting patients prescribed statins post-AKI had lower risk of hospitalizations and mortality after a 2-year follow up period. Despite this, the use of statins is not fully implemented following acute MI due to an apprehension of drug induced complications.


The use of renin angiotensin aldosterone system (RAAS) inhibition following an AKI episode is uncommon due to the assumption that AKI recovery may be delayed with premature initiation. Furthermore, the discontinuation of RAASi in the setting of AKI is widely practiced to avoid hyperkalemia. Chou et al evaluated the effect of RAAS inhibitor initiation after kidney recovery in patients with cardiac surgery associated with AKI. They were able to demonstrate a lower risk of CKD development. In a retrospective cohort study looking at patients prescribed angiotensin converting enzyme inhibitors (ACEi) or angiotensin receptor blockers (ARB) within 6 months of hospitalization, a lower mortality risk was identified. Interestingly, an increased risk of repeat hospitalization from renal causes was also observed. The latter finding has not been reproduced in recent studies. The timing of initiation or resumption of RAASi following kidney injury remains controversial.


RAAS inhibitors, β-blockers and statins are considered standard of care and reduce long term mortality following acute MI. Kidney injury often results in delay or disruption in the receipt of goal directed therapy. Leung et al demonstrated that patients with stage 2 and 3 AKI post-coronary angiography experienced a reduction in ACEi/ARB, β-blocker and statin prescription by 120 days of hospital discharge (64%, 73% and 65%, respectively) compared to 83% in patients without AKI. Delay in initiation or resumption of goal directed therapy in our vulnerable and high risk CV populations contributes to CV and mortality risk, which is no doubt confounded by the additive risk of AKI.


The patterns of cardioprotective drug use in patients with AKI presents an opportunity to improve current practices. Munoz et al sought to quantify and compare the differences in time with dispensing ACE/ARB, β-blockers and statins in patients with a history of MI with and without AKI.


Visual abstract by @Brian_rifkin


Methods:

This was a propensity-score matched, population-based study with a cohort of patients aged 66 years and above, who survived an MI and hospitalization between January 1, 2008, and March 31, 2017. The patients with more than one eligible admission were considered only for the first hospitalization.

Exclusion Factors:

  • Patients with history of maintenance hemodialysis

  • History of kidney transplantation

  • Admissions during which serum creatinine was not estimated.

The drugs evaluated are included below. Each subgroup was further analyzed according to KDIGO stages of AKI.


1. Warfarin

2. Direct Oral Anticoagulant

3. P2Y12 inhibitors

4. Loop Diuretics

5. Thiazide Diuretics

6. Mineralocorticoid receptor antagonist

7. DHP calcium channel blocker

8. Biguanide

9. NSAIDs

Analysis:

The research team used a multivariate logistic regression model to estimate propensity scores for the risk of developing AKI during the index hospitalization. They included age, sex, place of residence, mean income, drug utilization, healthcare utilization, baseline kidney function (serum creatinine and proteinuria) details of the hospitalization including interventions. They aimed to propensity match each patient with AKI to a patient without AKI 1:1.


Results:

The final analysis comprised two large matched groups: 21,452 patients with AKI 1:1 to similar patients without AKI. In the AKI group, 17,834 (83%), 2391 (11%), and 1227 (6%) patients experienced KDIGO stages 1, 2, and 3 AKI, respectively, and 256 (1%) received dialysis. The mean discharge serum creatinine was 128 (75) mmol/l (1.4 [0.8] mg/dl), and 7244 patients (34%) had a discharge serum creatinine that exceeded 25% of their prehospital baseline value. The mean follow-up time was 297.3 (122.9) days in the AKI group and 307.9 (114.1) days in the control group. The total person-years of follow-up were 17,642 and 18,083 years in the AKI and control groups, respectively.


The patients with AKI had a lower baseline eGFR, a greater likelihood of proteinuria, and a greater likelihood of being on an ACEi/ARB and statin at baseline. Overall, those with AKI had longer length of hospital stay, greater frequency of sepsis and fewer percutaneous coronary interventions.


AKI was associated with less frequent prescription of cardio-protective drugs including ACEi/ARB, β-blockers, and statins within one year of discharge from the hospital (Table 1). The prescription of these drugs was inversely proportional to the stage of AKI (figure 1).


Table 1. Prescription frequency of drugs post hospitalization with AKI. Adapted from Munoz et al


Figure 1. Association of different severities of AKI with the primary outcome and dispensing of ACEi/ARB, β-blocker, and statin.

The association of ACEi/ARB, β-blocker, and statin dispensing after AKI did not differ based on diabetes mellitus, pre-existing heart failure, or the occurrence of MI during the index hospitalization (figure2).


Figure 2. Association of AKI with dispensing of an ACEi/ARB, β-blocker, and statin (all 3 drugs) within 1 year of hospital discharge, stratified by prespecified subgroups.

Strengths of the study:

The current study had more than 42,000 matched patients with a previous history of MI, including more than 3500 patients with KDIGO stage 2 to 3 AKI. The investigators could retrieve accurate information with respect to treatment prescriptions and had details of complete follow-up.


Limitations of the study:

This is a single center study, with an elderly population (age> 66 years). Specific indications that warranted use/ stop of the drugs in question were not assessed by the team. The propensity score matching model used by the authors might have reduced confounding, but it cannot eliminate it completely.


Conclusion:

AKI after MI is associated with hesitancy to prescribe certain cardio-protective drugs. The use of RAAS inhibitors is presumably hindered by the assumption that they cause persistent AKI or may delay renal recovery. Statins and beta-blockers too were less likely to be prescribed in stage 2 and stage 3 AKI. This marks the influence of a kidney event on the prescription patterns of physicians.


The current practices depicted in this study represent a large unmet need for effective CV risk reduction. Recent studies have demonstrated that RAAS inhibition was not associated with an increased risk of recurrent AKI. However, the timing of initiation or resumption of RAASi following kidney injury remains controversial. There is a need for nephrology associations to provide education, assistance, and guidance to primary care physicians during follow-up of AKI, especially in the setting of MI. The inertia surrounding the under-utilization of cardioprotective drugs such as RAAS inhibitors needs a collective and coordinated effort of physicians and nurses. Overall, this new found deficiency highlights a great opportunity to reduce morbidity and mortality in AKI survivors.


The improved outcomes afforded by more liberal usage of cardioprotective agents after MI is something that we all should bear in mind while treating patients with coexisting AKI.


AcademicCME (www.academiccme.com) is accrediting this educational activity for CE and CME for clinician learners. Please go to https://academiccme.com/kicr_blogposts/ to claim credit for participation.



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