Daily Cardiology Research Analysis
Three studies stand out today in cardiology: a post hoc analysis of the PRECISION trial shows aprocitentan robustly lowers blood pressure and albuminuria in CKD patients with resistant hypertension; a multicenter CCTA study integrates plaque burden and ΔCT-FFR to simultaneously predict short- and longer-term ACS risk; and a network meta-analysis of 64 RCTs finds no improvement in hard outcomes from intracoronary adjuncts during primary PCI for STEMI despite surrogate benefits, highlighting impor
Summary
Three studies stand out today in cardiology: a post hoc analysis of the PRECISION trial shows aprocitentan robustly lowers blood pressure and albuminuria in CKD patients with resistant hypertension; a multicenter CCTA study integrates plaque burden and ΔCT-FFR to simultaneously predict short- and longer-term ACS risk; and a network meta-analysis of 64 RCTs finds no improvement in hard outcomes from intracoronary adjuncts during primary PCI for STEMI despite surrogate benefits, highlighting important safety trade-offs.
Research Themes
- Resistant hypertension and cardiorenal protection
- CT-FFR and plaque imaging for dual-timeframe ACS risk
- Adjunctive intracoronary therapies in STEMI: efficacy vs safety
Selected Articles
1. Aprocitentan in Patients With Chronic Kidney Disease and Resistant Hypertension.
In CKD patients at high to very high KDIGO risk with resistant hypertension, aprocitentan achieved substantial office and nocturnal BP reductions and large, sustained decreases in urine albumin-to-creatinine ratio through 36 weeks, with good tolerability aside from early peripheral edema. These results suggest dual cardiovascular and renal benefits in a hard-to-treat population.
Impact: Targets the endothelin pathway in a high-risk, undertreated CKD subgroup, demonstrating both BP and albuminuria benefits in a phase 3 program. Findings can accelerate adoption and inform guidelines for resistant hypertension in CKD.
Clinical Implications: Consider aprocitentan as an add-on for resistant hypertension in CKD, with monitoring for early peripheral edema. Benefits in nocturnal BP and albuminuria may translate to improved cardiorenal outcomes; careful follow-up is warranted.
Key Findings
- At week 4, office SBP decreased by −13.5 mmHg (12.5 mg) and −16.6 mmHg (25 mg) versus −4.4 mmHg with placebo; the −16.4 mmHg reduction was maintained to week 36 on 25 mg.
- Nighttime ambulatory SBP fell by −9.6 and −13.8 mmHg (12.5/25 mg) vs −2.5 mmHg with placebo at week 4.
- Urine albumin-to-creatinine ratio decreased by −47.1% and −59.6% at week 4 vs −2.4% with placebo, sustained to −61.6% at week 36 on 25 mg.
- Aprocitentan was generally well tolerated without potassium or eGFR changes; early peripheral edema was the most common adverse event.
Methodological Strengths
- Phase 3 randomized framework with double-blind and withdrawal phases
- Predefined standardized background antihypertensive therapy and objective ambulatory BP and UACR assessments
Limitations
- Post hoc subgroup analysis in CKD (not primary endpoint population)
- Single program dataset; long-term clinical outcome benefits not assessed
Future Directions: Prospective CKD-focused trials powered for cardiorenal outcomes and edema management strategies; mechanistic studies on endothelin blockade effects on albuminuria and nocturnal BP.
2. Coronary computed tomography angiography plaque and flow patterns in acute coronary syndrome lesions.
A dual-timeframe CCTA model integrating stenosis, low-density plaque burden, and ΔCT-FFR provided simultaneous prediction of short-term (≤7 days) and long-term (≥30 days) ACS risk. ΔCT-FFR uniquely captured short-term hazard, and combined models outperformed stenosis-based assessment across external cohorts.
Impact: Introduces a practical, single-scan strategy to inform both immediate and future ACS risk, potentially streamlining ED and outpatient decision-making by combining plaque biology and noninvasive hemodynamics.
Clinical Implications: Incorporating ΔCT-FFR and LDP% into CCTA interpretation may improve triage beyond stenosis severity alone, identifying patients at near-term risk for ACS while informing longer-term management.
Key Findings
- Stenosis severity and low-density plaque burden predicted ACS risk in both ≤7-day and ≥30-day windows.
- ΔCT-FFR (proximal minus distal CT-FFR) was specifically associated with short-term (≤7 days) ACS risk.
- Combined models (stenosis + LDP% + ΔCT-FFR + population data) outperformed stenosis alone and demonstrated greater net clinical benefit across multiple external cohorts.
Methodological Strengths
- Multicenter development with external validation across multiple cohorts
- Integration of quantitative plaque metrics with noninvasive hemodynamic ΔCT-FFR
Limitations
- Abstract does not report exact sample size and event counts
- ΔCT-FFR and LDP% require high-quality imaging and standardization; prospective impact studies needed
Future Directions: Prospective trials to test management strategies guided by ΔCT-FFR and LDP% and to quantify effects on near-term events and resource utilization.
3. Intracoronary adjunctive therapies for ST-elevation myocardial infarction: a network meta-analysis of trials.
Across 64 RCTs in STEMI, no intracoronary adjunct improved mortality, MI, or HF hospitalization versus conventional primary PCI over ~8 months. Some agents reduced microvascular obstruction surrogates but carried safety trade-offs, such as increased AV block (adenosine) and bleeding (tirofiban).
Impact: Provides a comprehensive, rigorous synthesis that challenges routine use of intracoronary adjuncts in STEMI for hard outcomes and clarifies safety signals, guiding practice and future trial design.
Clinical Implications: Routine intracoronary adjunct use to improve hard outcomes in STEMI is not supported; consider selective use targeting microvascular surrogates with careful attention to arrhythmic and bleeding risks.
Key Findings
- No intracoronary adjunct reduced all-cause mortality, non-fatal MI, or HF hospitalization versus conventional primary PCI (mean follow-up ~8 months).
- Post-PCI TIMI 0–2 flow was reduced by adenosine (OR 0.40), verapamil (OR 0.22), tirofiban (OR 0.43), manual thrombus aspiration (OR 0.61), fibrinolytic + manual TA (OR 0.24), and tirofiban + manual TA (OR 0.32).
- Safety trade-offs: intracoronary adenosine increased AV block (OR 2.80), tirofiban increased any bleeding (IRR 1.65), while nicorandil reduced peri-procedural VF/SVT (OR 0.31).
Methodological Strengths
- Large-scale network meta-analysis of 64 randomized trials (n=27,243)
- Comprehensive assessment of efficacy and safety, including surrogate and hard outcomes
Limitations
- Mean follow-up ~8 months may miss longer-term effects
- Heterogeneity in adjunct protocols and eras; potential publication bias
Future Directions: Pragmatic trials targeting patient subsets most likely to benefit, with standardized adjunct protocols and clinically meaningful endpoints; mechanistic studies to link surrogate improvements to outcomes.