Daily Cardiology Research Analysis
Analyzed 172 papers and selected 3 impactful papers.
Summary
Implementation gaps in cardiology remain prominent: two large real‑world studies show that quadruple guideline‑directed therapy for HFrEF is underused, delayed, and discontinuation-prone, yet adherence/persistence correlate with better outcomes. A multinational JACC study demonstrates that adding urine albumin/creatinine ratio (UACR) to eGFR nearly doubles CKD detection in coronary disease and identifies higher near‑term risk, revealing underuse of cardio‑renal protective therapy.
Research Themes
- Implementation of guideline-directed medical therapy in heart failure
- Cardio-renal risk assessment and screening
- Health equity and system barriers influencing therapy uptake
Selected Articles
1. Chronic Kidney Disease Screening in Patients With Coronary Heart Disease: The Multinational INTERASPIRE Study.
In a 14-country cohort of CAD patients, CKD was present in 32% by KDIGO criteria; without UACR testing, 51.3% of CKD cases would have been missed. Higher KDIGO risk categories predicted early composite CV events independent of other risk factors, yet cardio‑renal protective therapies were underused.
Impact: Demonstrates that adding UACR to eGFR substantially improves CKD detection and short‑term risk stratification in CAD across diverse regions, directly informing screening policy.
Clinical Implications: Implement routine UACR plus eGFR screening in all CAD patients and close treatment gaps by initiating SGLT2 inhibitors, RASi/ARNi, and other cardio‑renal protective strategies per KDIGO/ACC guidance.
Key Findings
- CKD prevalence was 32% among CAD patients using KDIGO risk stratification.
- Without UACR testing, 51.3% of CKD cases would have remained undetected.
- High KDIGO risk groups had the highest 1‑year incidence of composite CV events, independent of other risk factors.
- Use of cardio‑renal protective therapies was low across KDIGO risk strata.
Methodological Strengths
- Multinational cohort spanning all WHO regions with standardized kidney assessments (eGFR and UACR).
- Risk classification by KDIGO and adjusted analyses linking risk to near‑term outcomes.
Limitations
- Observational design with potential residual confounding.
- Incomplete kidney data for a subset and median follow‑up limited to ~1 year.
Future Directions: Test implementation strategies to scale UACR screening, evaluate cost‑effectiveness and health outcomes of closing treatment gaps, and assess longitudinal impact across diverse health systems.
BACKGROUND: Chronic kidney disease (CKD) is an important risk factor for the progression of coronary artery disease (CAD). OBJECTIVES: The purposes of this study were to quantify the prevalence of CKD in CAD patients from 14 countries from all World Health Organization regions and to evaluate the prognostic value of estimated glomerular filtration rate (eGFR) and urinary albumin/creatinine ratio (UACR). METHODS: A total of 4,548 patients with CAD were included (79.6% were males; age range: 18-80 years). They were assessed for eGFR and UACR 6 to 24 months after the CAD diagnosis. Complete information on kidney function and cardio-renal protective therapy was available for 3,865 patients and follow-up data after a median of 1 year were available for 3,577 (92.5%). RESULTS: CKD according to the Kidney Disease Improving Global Outcomes classification was present in 32% of whom 19.7% were classified as low-moderate, 6.9% as high, and 5.6% as very high risk. Without UACR, 51.3% of them would have been undetected. The primary event, first of cardiovascular death, myocardial infarction, stroke, and hospitalization for heart failure, was observed in 7.9%, with the highest incidence in the Kidney Disease Improving Global Outcomes high-risk group (men: 13.0%; women: 11.8%). This relationship was independent of other risk factors and evident soon after the index examination. Only a minority of the patients received adequate cardio-renal protective therapy. CONCLUSIONS: Early screening for CKD in patients with CAD is important and should preferably include both eGFR and UACR to provide a complete diagnosis. Without UACR, half of those with CKD would remain undetected. Treatment with cardio-renal protective therapy was low, providing great potential for improvement.
2. Time to Quadruple Therapy After Initial Diagnosis of Heart Failure With Reduced Ejection Fraction.
In 52,850 Veterans with incident HFrEF, only 21.2% achieved concurrent β‑blocker, RASi/ARNi, MRA, and SGLT2i, with a median TTQ of 197 days. Copays reduced the likelihood of achieving quadruple therapy, while race/ethnicity and outpatient diagnosis were associated with faster attainment.
Impact: Quantifies system‑level timeliness and equity gaps in HFrEF GDMT, identifies modifiable barrier (copays), and provides a pragmatic metric (TTQ) for quality improvement.
Clinical Implications: Adopt protocols to initiate all 4 foundational therapies within weeks of diagnosis, remove or reduce copays, and track TTQ as a performance metric to close mortality‑relevant treatment gaps.
Key Findings
- Only 21.2% achieved quadruple therapy over a median 2.9 years; median TTQ was 197 days.
- Prescription copays were associated with an 8% lower rate of achieving quadruple therapy.
- Black and Hispanic veterans achieved quadruple therapy faster than White veterans after adjustment.
- Outpatient diagnosis and comorbid diabetes were associated with higher achievement; CKD with lower achievement.
Methodological Strengths
- Very large nationwide cohort with pharmacy fill–based overlap to define concurrent therapy.
- Adjusted time‑to‑event modeling with granular demographics and clinical covariates.
Limitations
- Observational design in a predominantly male Veteran population limits generalizability.
- Pharmacy fills proxy exposure and do not capture dose optimization or true ingestion.
Future Directions: Prospective implementation trials to shorten TTQ, evaluate copay elimination, and link TTQ improvements to morbidity/mortality benefits and healthcare equity.
IMPORTANCE: Timely prescription of quadruple guideline-directed medical therapies (GDMTs) for patients with heart failure with reduced ejection fraction (HFrEF) is associated with improved morbidity and mortality, yet contemporary estimates of time to quadruple therapy (TTQ) and the factors associated with its achievement remain unknown. OBJECTIVE: To characterize TTQ and factors associated with TTQ in HFrEF. DESIGN, SETTING, AND PARTICIPANTS: This was a retrospective cohort study including patients with incident HFrEF from the Veterans Health Administration database during the January 1, 2020, to December 31, 2023, period. Study data were analyzed from November 2024 to December 2025. EXPOSURES: Primary factors included race and ethnicity, sex, and copay status (priority group). Secondary factors included clinical characteristics. MAIN OUTCOMES AND MEASURES: The main outcome included quadruple therapy according to pharmacy fill data-concurrent use of evidence-based β-blockers, renin-angiotensin system inhibitors, mineralocorticoid receptor antagonists, and sodium-glucose cotransporter-2 inhibitors. TTQ was defined as the first date that all 4 medication classes overlapped, based on dispense date and days' supply. RESULTS: Among 52 850 patients with incident HFrEF (median [SD] age, 71.8 [11] years; 51 473 male [97%]; 10 791 Black [20%]; 2528 Hispanic [5%]; 35 867 White [68%]; 3664 other [7%]), 11 217 (21.2%) achieved quadruple therapy over a median (IQR) follow-up of 2.9 (1.9-3.9) years. The median (IQR) TTQ was 197 (49-528) days. After adjustment, Black patients (hazard ratio [HR], 1.22; 95% CI, 1.15-1.30), Hispanic patients (HR, 1.21; 95% CI, 1.09-1.33), and those from other racial or ethnic groups (HR, 1.11; 95% CI, 1.02-1.20) had higher rates of quadruple therapy than White patients. There was no difference in TTQ in females vs males (HR, 0.97; 95% CI, 0.86-1.09). Prescription copays (priority groups 2-8) were associated with an 8% lower rate of achieving quadruple therapy (HR, 0.92; 95% CI, 0.87-0.96) than no prescription copay (priority group 1). Rates of quadruple therapy were higher among veterans with an outpatient HFrEF diagnosis vs inpatient (22.2% vs 14.2%), with diabetes vs without diabetes (23.6% vs 19.3%), and without chronic kidney disease vs with chronic kidney disease (22.5% vs 18.1%). CONCLUSION AND RELEVANCE: Results of this cohort study suggest that opportunities exist to improve both the rate and timeliness of quadruple therapy as only 21.2% of patients with HFrEF achieved it, with a median follow-up of 2.9 years and TTQ of 6 months. Medication copays represent a modifiable barrier, providing a potential target for interventions to enhance TTQ.
3. Heart failure with reduced ejection fraction in Sweden: patient adherence and persistence to quadruple pharmacotherapy prescription.
In 35,215 Swedish HFrEF patients, quadruple therapy increased to ~60% by 2023; MRA adoption lagged (~73%). Adherence and 12‑month persistence were high overall and independently associated with lower HF hospitalization/CV death, supporting achievable real‑world implementation gains.
Impact: Provides contemporary nationwide benchmarks for uptake, adherence, and persistence of quadruple HFrEF therapy and links medication implementation to outcomes.
Clinical Implications: Prioritize initiation and retention of all 4 foundational agents, with targeted efforts to improve MRA adoption and minimize discontinuations; monitor persistence and dose optimization.
Key Findings
- By 2023, quadruple therapy use reached ~60%; MRA adoption remained the main limiter (~73%).
- Adherence (PDC ≥80%) was high: BB 95%, RASi/ARNi 95%, MRA 90%, SGLT2i 94%; quadruple 85%.
- 12‑month persistence was 67% for quadruple therapy; better adherence/persistence linked to lower HF hospitalization/CV death.
Methodological Strengths
- Large nationwide registry spanning the SGLT2i era with linkage to pharmacy refill data.
- Adjusted associations between adherence/persistence metrics and clinical outcomes.
Limitations
- Observational design with potential residual confounding and selection bias.
- Dose optimization and reasons for discontinuation not fully captured by refill metrics.
Future Directions: Evaluate interventions to increase MRA adoption, address discontinuation drivers, and test whether persistence/dose‑optimization programs improve survival and QoL.
BACKGROUND AND AIMS: Real-world uptake of heart failure with reduced ejection fraction (HFrEF) treatments relies on physician prescriptions but also on patient adherence. This study assessed implementation of, patient adherence and persistence with quadruple HFrEF therapy in the contemporary setting, and associations with morbidity/mortality. METHODS: Patients with HFrEF enrolled in the Swedish Heart Failure Registry between January 2016 and December 2023 were included. Using pharmacy refills, patients with ≥80% proportion of days covered were categorized as adherent and with dispensations at 12 ± 2 months post-index as persistent. RESULTS: In 35 215 patients with HFrEF [median age 74 (interquartile range 64-80) years; 28% female], use of all four HFrEF foundational therapies increased between 2016 and 2023: in 2023, 93% used beta-blockers (BB), 95% renin-angiotensin-system inhibitors (RASi)/angiotensin receptor-neprilysin inhibitors (ARNi), 73% mineralocorticoid receptor antagonists (MRA), 83% sodium-glucose co-transporter 2 inhibitors (SGLT2i), and 60% quadruple therapy. The proportion of patients who were adherent and persistent, respectively, to BB was 95% and 90%, RASi/ARNi 95% and 89%, MRA 90% and 77%, SGLT2i 94% and 86%, and quadruple therapy 85% and 67%. Good adherence and persistence for BB, RASi/ARNi, and MRA and good adherence for SGLT2i were independently associated with lower heart failure hospitalization/cardiovascular death. CONCLUSIONS: By 2023, use of quadruple therapy reached ∼60%, being mostly limited by lower adoption of MRA (∼73%). Patient adherence to foundational therapies was high and appeared associated with better prognosis. These data suggest that improvements in the uptake of and adherence to quadruple HFrEF pharmacotherapy are achievable in real-word heart failure care, although suboptimal dosing and frequent discontinuations remain important areas of further implementation.