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.
BACKGROUND: Hypertension is a cause and consequence of chronic kidney disease (CKD). Resistant hypertension is common and often difficult to control in patients with CKD. This post hoc analysis evaluated the efficacy and safety of aprocitentan (with standardized background antihypertensive therapy) in patients with CKD and resistant hypertension, a group with high morbidity and mortality risk and limited treatment options. METHODS: The PRECISION study (Parallel-Group, Phase 3 Study With Aprocitentan in Subjects With Resistant Hypertension) consisted of part 1: 4-week, double-blind (aprocitentan 12.5 and 25 mg versus placebo); part 2: 32-week, single-blind (aprocitentan 25 mg); and part 3: 12-week, double-blind withdrawal (aprocitentan 25 mg versus placebo). In participants with CKD, aprocitentan's effect on blood pressure (BP), urine albumin-to-creatinine ratio, and safety was evaluated. RESULTS: Of 730 participants in PRECISION, 147 had CKD categorized as KDIGO high risk or very high risk. At week 4, aprocitentan 12.5 mg, aprocitentan 25 mg, and placebo reduced office systolic BP by -13.5, -16.6, and -4.4 mm Hg, respectively; this was maintained with aprocitentan 25 mg to week 36 (-16.4 mm Hg). At week 4, reductions in nighttime ambulatory systolic BP were -9.6, -13.8, and -2.5 mm Hg, respectively. Changes in urine albumin-to-creatinine ratio were -47.1%, -59.6%, and -2.4%, respectively, maintained with aprocitentan 25 mg to week 36 (-61.6%). Aprocitentan was generally well tolerated (no change in potassium or estimated glomerular filtration rate); early peripheral edema was the most common adverse event. CONCLUSIONS: Aprocitentan was well tolerated; efficiently lowered BP, particularly nighttime ambulatory BP; and markedly reduced urine albumin-to-creatinine ratio in participants with CKD and resistant hypertension. Aprocitentan may confer considerable cardiovascular and kidney-protective benefits in these difficult-to-treat patients. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03541174.
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.
Acute coronary syndrome (ACS) risk stratification requires assessment across different time frames. This multicenter study investigated whether a single coronary computed tomography angiography (CCTA) scan could provide integrated short-term (≤7 days) and long-term (≥30 days) risk assessment. The study developed and validated dual-timeframe models combining population health data, stenosis severity, quantitative low-density plaque burden (LDP%), and the hemodynamic parameter ΔCT-FFR (CT-derived fractional flow reserve [CT-FFR] proximal to the lesion minus CT-FFR distal to the lesion). Key findings indicate that while stenosis and LDP% predicted ACS risk in both time frames, ΔCT-FFR was specifically associated with short-term risk. The combined models demonstrated superior performance and greater net clinical benefit compared to using stenosis severity alone, as confirmed in multiple external cohorts. These results establish that a single CCTA examination can simultaneously assess immediate and future ACS risk.
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.
AIMS: This network meta-analysis of randomized controlled trials (RCTs) evaluates the comparative safety and efficacy of intra-coronary (IC) pharmacological and procedural treatments - on top of balloon angioplasty and stent placement - on clinical outcomes and surrogate endpoints of coronary microvascular obstruction (CMVO) in patients with ST-elevation myocardial infarction (STEMI). METHODS AND RESULTS: Two electronic databases were searched for eligible studies. Primary efficacy endpoints included all-cause mortality, non-fatal myocardial infarction (MI), and heart failure (HF) hospitalization. Primary safety endpoints included peri-procedural arrhythmias including atrioventricular blocks (AVBs) and ventricular fibrillation/sustained ventricular tachycardia (VF/SVT), any bleeding, and stroke. Secondary efficacy endpoints included the occurrence of post-procedural thrombolysis in myocardial infarction (TIMI) flow grade 0-2 and ST-segment resolution.A total of 64 RCTs involving 27,243 patients were included. In mixed comparisons, no treatment significantly reduced the incidence of primary efficacy endpoints compared to conventional primary PCI during a mean follow-up of 8 months. Several treatments significantly reduced the occurrence of post-PCI TIMI 0-2 flow grade [adenosine: 0.40 (odds ratio), (95% Confidence Interval 0.24-0.68); verapamil: 0.22 (0.07-0.69); tirofiban:0.43 (0.27-0.71); manual thrombus aspiration (TA): 0.61 (0.45-0.82); fibrinolytic + manual TA: 0.24 (0.12-0.48); tirofiban + manual TA: 0.32 (0.14-0.75)], compared to conventional primary PCI. IC administration of tirofiban increased the risk of any bleeding [incidence rate ratio: 1.65 (1.11-2.45)], while IC adenosine increased the risk of peri-procedural AVBs [OR: 2.80 (1.14-6.84)].Nicorandil reduced the incidence of peri-procedural VF/SVT [OR: 0.31 (0.12-0.81)]. CONCLUSIONS: Adjunctive IC treatments during primary PCI do not influence hard clinical outcomes compared to conventional therapy within a mean 8-month follow-up, although several of them lead to an improvement in surrogate endpoints of CMVO.