Daily Cardiology Research Analysis
Analyzed 169 papers and selected 3 impactful papers.
Summary
Three randomized clinical trials stand out today: a phase III, double-blind program shows an ultra–low-dose triple fixed-dose combination achieves at least comparable (and in one trial superior) blood pressure reduction versus standard monotherapy; a large head-to-head antiplatelet RCT in diabetic multivessel PCI finds ticagrelor is not noninferior to prasugrel; and a multicenter RCT demonstrates CT-guided ventricular tachycardia ablation reduces procedure time with maintained efficacy and safety.
Research Themes
- Fixed-dose combination therapy optimization for hypertension
- Head-to-head antiplatelet strategies in high-risk PCI populations
- Imaging-guided electrophysiology to improve procedural efficiency
Selected Articles
1. Single-Pill Low-Dose Triple Combination Therapy vs Standard-Dose Monotherapy in Patients With Mild-to-Moderate Hypertension.
Two multicenter, double-blind phase III trials showed an ultra–low-dose triple fixed-dose combination matched amlodipine and was superior to losartan for 8-week SBP reduction, with similar tolerability and low discontinuation. These findings support single-pill, low-dose combination therapy as an effective initial option for mild-to-moderate hypertension.
Impact: Addresses a ubiquitous condition with scalable therapy; high-quality RCTs demonstrate efficacy and tolerability of a pragmatic fixed-dose triple regimen that may improve BP control rates.
Clinical Implications: Supports considering a low-dose triple fixed-dose combination as an initial therapy, particularly when aiming for faster BP control, while monitoring long-term outcomes beyond 8 weeks.
Key Findings
- LDC-ALC was noninferior to amlodipine for 8-week SBP reduction (LS mean −19.1 vs −19.9 mm Hg; noninferiority margin <3 mm Hg).
- LDC-ALC was noninferior and superior to losartan for SBP reduction (−19.9 vs −16.4 mm Hg; P = 0.037) with greater DBP reduction and higher control rates.
- Adverse events were similar across arms, ≤1% withdrawals, and no serious drug-related events.
Methodological Strengths
- Multicenter, randomized, double-blind, active-controlled phase III design with prespecified noninferiority and superiority testing
- Consistent findings across two independent trials with standardized endpoints
Limitations
- Short 8-week treatment period limits assessment of durability and long-term safety
- Conducted in a single country; generalizability to diverse populations and comorbidity profiles remains to be established
Future Directions: Evaluate long-term cardiovascular outcomes, adherence, and cost-effectiveness of low-dose triple combinations across diverse populations, including older adults and those with CKD or diabetes.
BACKGROUND: Single-pill low-dose combination (LDC) antihypertensive therapy is an emerging strategy for improving blood pressure (BP) control. Although previous phase II and pragmatic studies suggested promise, these are the first phase III, double-blind, active-controlled trials comparing a single-pill ultra-low-dose triple combination with standard-dose monotherapy. OBJECTIVES: In these studies, we sought to compare a single-pill combination of 1.67 mg amlodipine, 16.67 mg losartan potassium, and 4.17 mg chlorthalidone (LDC-ALC) with standard-dose monotherapy-5 mg amlodipine or 50 mg losartan potassium-in patients with mild-to-moderate hypertension. METHODS: HM-APOLLO-301 (Study 301, May 2022-June 2023) and HM-APOLLO-302 (Study 302, March-December 2024) were multicenter, randomized, double-blind, active-controlled, phase III studies in South Korea. Study 301 compared LDC-ALC and amlodipine; Study 302 compared LDC-ALC and losartan. Adults (≥19 years of age) with systolic blood pressure (SBP) 140 to <180 mm Hg and diastolic blood pressure (DBP) <110 mm Hg after 4-week placebo run-in were randomized to 8 weeks of treatment. The primary endpoint was SBP reduction at week 8, assessed first for noninferiority, then for superiority. RESULTS: In Study 301, LDC-ALC exhibited noninferiority to amlodipine in reducing SBP at week 8 (upper bound of 1-sided 97.5% CI: 2.8 mm Hg [<3 mm Hg noninferiority margin]), and similar efficacy (least-squares mean change: -19.1 vs -19.9 mm Hg; 95% CI: -1.5 to 3.1; P = 0.495), with similar DBP reduction and blood pressure control rate. In Study 302, LDC-ALC was both noninferior (upper bound of one-sided 97.5% CI: -0.6 mm Hg) and superior to losartan (least-squares mean change: -19.9 vs -16.4 mm Hg; 95% CI: -6.6 to -0.2; P = 0.037) in SBP reduction at week 8, with greater DBP reduction and a higher blood pressure control rate than losartan. Adverse events were similar between groups (LDC-ALC vs amlodipine: 11.7% vs 13.9%; LDC-ALC vs losartan: 6.4% vs 3.3%), with ≤1% treatment withdrawals and no serious drug-related events. CONCLUSIONS: Single-pill LDC-ALC achieved BP reductions similar to those with amlodipine and greater than those with losartan monotherapy over 8 weeks, with similar short-term tolerability. These findings support LDC-ALC as an effective and well tolerated alternative initial therapy for mild-to-moderate hypertension, expanding the set of validated strategies alongside established monotherapies. (A Study to Evaluate Efficacy and Safety of HCP1803 in Patients With Essential Hypertension [HM-APOLLO-301; NCT05362110]; A Study to Evaluate Efficacy and Safety of HCP1803 Compared to RLD2001-1 in Patients with Essential Hypertension [HM-APOLLO-302, NCT06438172]).
2. Computed tomography-guided vs conventional catheter ablation for ventricular tachycardia: the InEurHeart trial.
In a 14-center RCT of post-MI VT, CT-guided ablation significantly reduced procedure time (−19% ITT; −28% per-protocol) with similar safety and VT-free survival at 1 year compared with conventional ablation. VT burden decreased by 90% in the CT-guided group, indicating potential clinical efficiency gains.
Impact: Demonstrates a practical, imaging-integrated workflow that reduces procedure time without compromising outcomes, supporting adoption in electrophysiology labs and optimizing resource utilization.
Clinical Implications: CT integration may streamline VT ablation workflows, reduce anesthesia and lab time, and maintain safety, with consideration of imaging resources and training for broad implementation.
Key Findings
- CT-guided ablation reduced procedure duration by 19% (ITT) and 28% (per-protocol) versus conventional mapping.
- Major adverse events were low and comparable (1.8% CT-guided vs 3.5% conventional).
- VT-free survival at 1 year was similar (76.8% CT-guided vs 67.3% conventional; NS), while VT burden decreased by 90% in the CT-guided group.
Methodological Strengths
- Multicenter randomized design with clear, operational primary endpoint (procedure time)
- Assessment of both efficacy (VT incidence/burden) and safety with ITT and per-protocol analyses
Limitations
- Modest sample size limits power for clinical endpoints beyond procedure time
- Generalizability depends on access to high-quality CT imaging and integration workflows
Future Directions: Larger trials to test patient-centered outcomes (hospital stay, quality of life, recurrent VT requiring hospitalization) and cost-effectiveness across different EP settings.
BACKGROUND AND AIMS: Catheter ablation is performed in patients with recurrent ventricular tachycardia (VT) but remains complex and limited to experienced centres. Ventricular tachycardia ablation guided by pre-procedural imaging was shown promising in non-randomized trials. InEurHeart aims to evaluate computed tomography (CT)-guided VT ablation vs conventional ablation in a multicentre randomized controlled trial. METHODS: In 14 European centres, 113 patients with prior myocardial infarction and clinically significant VT were randomly assigned to CT-guided (n = 57) or conventional (n = 56) VT ablation. The primary objective was to demonstrate reduced procedural duration when using CT guidance. Secondary endpoints included efficacy (incidence and burden of ventricular arrhythmia), safety, as well as composite endpoints. RESULTS: The primary endpoint showed a significant decrease in procedure time favouring CT-guided ablation: 149 ± 51 to 120 ± 50 min, -19% [95% confidence interval (CI) -32; -7]; P = .0027 in intention to treat, and 149 ± 51 to 107 ± 38 min, -28% (95% CI -40; -16); P < .0001 per protocol. Major adverse events occurred in two (3.5%) in the conventional group vs one (1.8%) in the CT-guided group [-1.8% (95% CI -7.9; 4.3)]. Ventricular tachycardia-free survival at 1 year was achieved in 37 (67.3%) patients for conventional vs 43 (76.8%) for CT-guided VT ablation [9.5% (95% CI -10.4; 29.4), P = NS]. Ventricular tachycardia burden was decreased by 90% in the CT-guided group. CONCLUSIONS: In patients with ischaemic cardiomyopathy, CT-guided VT ablation reduces the procedure duration while maintaining a favourable efficacy and safety profile when compared with VT ablation without image integration.
3. Ticagrelor vs Prasugrel in Patients With Diabetes and Multivessel Coronary Artery Disease: The TUXEDO-2 Randomized Clinical Trial.
In 1800 diabetic patients with multivessel disease undergoing PCI, ticagrelor plus aspirin failed noninferiority to prasugrel plus aspirin for a 1-year composite of death, MI, stroke, or major bleeding. Numerically higher ischemic and bleeding events with ticagrelor were not statistically significant.
Impact: Provides direct comparative evidence to guide P2Y12 inhibitor selection in a high-risk, prevalent population; results may tilt practice toward prasugrel when not contraindicated.
Clinical Implications: For diabetic multivessel PCI patients without contraindications, prasugrel may be preferred over ticagrelor for DAPT. Individualize therapy considering bleeding risk, age, weight, and prior stroke/TIA.
Key Findings
- Primary composite at 1 year: 16.6% with ticagrelor vs 14.2% with prasugrel; ticagrelor did not meet noninferiority (risk difference 2.33%, 95% CI −2.07 to 6.74; NI P=0.84).
- Numerically higher ischemic composite (10.43% vs 8.63%) and major bleeding (8.41% vs 7.14%) with ticagrelor, not statistically significant.
- Large multicenter RCT focused on diabetic multivessel PCI population (85% triple-vessel disease).
Methodological Strengths
- Large, multicenter randomized design with prespecified noninferiority framework
- High-risk, clinically relevant population (diabetes with multivessel CAD)
Limitations
- Open-label design may introduce performance or ascertainment bias
- Conducted within one country; generalizability to other healthcare systems may vary
Future Directions: Subgroup analyses by insulin use, age, renal function, and ischemic/bleeding risk; pragmatic trials incorporating de-escalation or monotherapy strategies tailored to diabetic multivessel PCI.
IMPORTANCE: The optimal dual antiplatelet therapy after percutaneous coronary intervention (PCI) in patients with diabetes is not clearly defined. Although both ticagrelor and prasugrel are potent inhibitors of P2Y purinergic receptor 12 (P2Y12), evidence directly comparing their efficacy and safety in this high-risk group remains limited. OBJECTIVE: To compare the clinical outcomes of ticagrelor vs prasugrel, each in combination with aspirin, in patients with diabetes and multivessel coronary artery disease who underwent percutaneous coronary intervention. DESIGN, SETTING, AND PARTICIPANTS: The Ultrathin Strut vs Xience in a Diabetic Population With Multivessel Disease 2-India Study (TUXEDO-2) is an investigator-initiated, prospective, open-label, multicenter, 2 × 2 factorial design, 1:1 randomized clinical trial. Participants with diabetes and multivessel disease undergoing percutaneous coronary intervention were enrolled at 66 clinical sites from February 2020 to August 2024. INTERVENTIONS: Patients undergoing percutaneous coronary intervention were randomized to receive either ticagrelor or prasugrel, each in combination with low-dose aspirin. MAIN OUTCOMES AND MEASURES: The primary outcome was a composite of death, nonfatal myocardial infarction, stroke, or major bleeding as defined by the Bleeding Academic Research Consortium at 1 year. The trial was designed to test the noninferiority of ticagrelor compared with prasugrel with a noninferiority margin of 5%. RESULTS: Among the 1800 participants randomized, mean (SD) age was 60 (10) years with 1296 (72.0%) male participants, 436 (24.2%) receiving insulin therapy, and 1530 (85.0%) with triple-vessel disease. At 1 year, the primary end point occurred in 129 participants (16.6%) taking ticagrelor and 107 participants (14.2%) taking prasugrel (P = .12). The risk difference of 2.33 percentage points (95% CI, -2.07 to 6.74 percentage points) failed to meet the prespecified threshold for noninferiority (P = .84). There was numerically higher (but not statistically significant) composite of death, myocardial infarction, stroke (10.43% vs 8.63%; P = .30), and major bleeding (8.41% vs 7.14%; P = .19) with ticagrelor when compared with prasugrel. CONCLUSIONS AND RELEVANCE: In patients with diabetes and multivessel disease undergoing PCI, ticagrelor was not noninferior to prasugrel for the reduction of primary outcome at 1 year of follow-up. TRIAL REGISTRATION: CTRI/2019/11/022088.