Daily Cardiology Research Analysis
Three clinically impactful cardiology studies stood out today: (1) a multicenter randomized trial showed amiloride is noninferior to spironolactone for resistant hypertension with similar blood pressure reduction and favorable tolerability; (2) a subgroup analysis of the STOPDAPT-3 trial cautions against immediate aspirin-free prasugrel monotherapy in high-bleeding-risk acute coronary syndrome; and (3) diastolic perfusion pressure predicted limited response to vasoactive escalation and potential
Summary
Three clinically impactful cardiology studies stood out today: (1) a multicenter randomized trial showed amiloride is noninferior to spironolactone for resistant hypertension with similar blood pressure reduction and favorable tolerability; (2) a subgroup analysis of the STOPDAPT-3 trial cautions against immediate aspirin-free prasugrel monotherapy in high-bleeding-risk acute coronary syndrome; and (3) diastolic perfusion pressure predicted limited response to vasoactive escalation and potential benefit from early VA-ECMO in cardiogenic shock.
Research Themes
- Optimization of antihypertensive therapy in resistant hypertension
- Personalizing antiplatelet strategies after PCI in high bleeding risk
- Hemodynamic phenotyping to guide mechanical circulatory support in cardiogenic shock
Selected Articles
1. Spironolactone vs Amiloride for Resistant Hypertension: A Randomized Clinical Trial.
In a 14-center randomized trial (n=118), amiloride was noninferior to spironolactone for reducing home systolic blood pressure at 12 weeks in resistant hypertension, with similar rates of achieving SBP <130 mmHg. Safety was favorable with only one discontinuation for hyperkalemia in the amiloride arm and no gynecomastia in either group.
Impact: This head-to-head randomized trial offers practice-changing evidence that amiloride can substitute for spironolactone in resistant hypertension, potentially avoiding endocrine adverse effects while maintaining efficacy.
Clinical Implications: Amiloride can be considered a first-line add-on alternative to spironolactone in resistant hypertension, particularly for patients at risk for spironolactone-related adverse effects (e.g., gynecomastia) or hyperkalemia monitoring constraints.
Key Findings
- Amiloride achieved noninferiority to spironolactone for 12-week change in home systolic BP (difference −0.68 mmHg; 90% CI −3.50 to 2.14).
- Achievement of SBP <130 mmHg was similar between groups at home and in-office measurements.
- Safety profile was favorable: one hyperkalemia-related discontinuation in the amiloride arm and no gynecomastia in either group.
Methodological Strengths
- Randomized, multicenter trial with blinded endpoint assessment.
- Pre-registered noninferiority design with explicit margin and standardized run-in therapy.
Limitations
- Modest sample size (n=118) and 12-week follow-up limit long-term safety/effectiveness inferences.
- Open-label design may introduce performance bias despite blinded endpoint adjudication.
Future Directions: Longer-term, larger-scale RCTs comparing mineralocorticoid receptor antagonism vs epithelial sodium channel blockade on clinical outcomes (CV events, kidney function, adverse effects), and head-to-head comparisons across diverse populations.
IMPORTANCE: Amiloride has been proposed as an alternative to spironolactone for treating resistant hypertension. However, no randomized clinical trials have compared the efficacy of spironolactone and amiloride in patients with resistant hypertension. OBJECTIVE: To determine whether amiloride is noninferior to spironolactone in reducing home-measured systolic blood pressure (SBP) in patients with resistant hypertension. DESIGN, SETTING, AND PARTICIPANTS: Prospective, open-label, blinded end-point randomized clinical trial conducted at 14 sites in South Korea. From November 16, 2020, to February 29, 2024, 118 patients with home SBP of 130 mm Hg or greater after a 4-week run-in period with a fixed-dose triple medication combination (angiotensin receptor blocker, calcium channel blocker, and thiazide) were enrolled. INTERVENTION: Patients were randomized in a 1:1 ratio to receive 12.5 mg/d of spironolactone (n = 60) or 5 mg/d of amiloride (n = 58). If home SBP remained 130 mm Hg or greater and serum potassium was less than 5.0 mmol/L after 4 weeks, dosages were increased to 25 mg/d and 10 mg/d, respectively. MAIN OUTCOMES AND MEASURES: The primary end point was the between-group difference in home SBP change at week 12, with a noninferiority margin of -4.4 mm Hg for the lower bound of the confidence interval. Secondary end points included achievement rates of home- and office-measured SBP of less than 130 mm Hg. RESULTS: The median age of the study population was 55 years, with 70% male. There were no differences between groups in demographic characteristics other than use of α-blockers (8.6% in the amiloride group and 0% in the spironolactone group). The mean baseline home SBPs were 141.5 (SD, 7.9) mm Hg and 142.3 (SD, 8.5) mm Hg in the amiloride and spironolactone groups, respectively. At week 12, mean home SBP measurements were changed from baseline by -13.6 (SD, 8.6) mm Hg and -14.7 (SD, 11.0) mm Hg in the amiloride and spironolactone groups, respectively (between-group difference in change, -0.68 mm Hg; 90% CI, -3.50 to 2.14 mm Hg), with amiloride demonstrating noninferiority to spironolactone. Home-measured achievement rates of SBP less than 130 mm Hg in the amiloride and spironolactone groups were 66.1% and 55.2%, respectively, and office-measured achievement rates of SBP less than 130 mm Hg were 57.1% and 60.3%, respectively, with no difference between the 2 groups. One case of hyperkalemia-related discontinuation occurred in the amiloride group, with no cases of gynecomastia in either group. CONCLUSIONS AND RELEVANCE: Amiloride was noninferior to spironolactone in lowering home SBP, suggesting that it could be an effective alternative for treatment of resistant hypertension. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04331691.
2. Aspirin-Free Strategy for PCI in Patients With High Bleeding Risk With or Without Acute Coronary Syndrome: A Subgroup Analysis From the STOPDAPT-3 Trial.
In HBR patients undergoing PCI (n=3258), aspirin-free prasugrel monotherapy did not reduce major bleeding at 1 month regardless of ACS status. A signal of excess cardiovascular events, particularly myocardial infarction, was observed in ACS but not in non-ACS, suggesting aspirin-free strategies may be reasonable in non-ACS HBR but risky in ACS.
Impact: Provides timely randomized evidence to calibrate the rapidly adopted aspirin-free PCI strategies, highlighting differential risk by ACS status in HBR patients.
Clinical Implications: For HBR patients with ACS, avoid immediate aspirin-free prasugrel monotherapy given the signal for increased MI; DAPT remains favored. In non-ACS HBR, aspirin-free prasugrel monotherapy may be considered to balance bleeding and ischemic risk.
Key Findings
- Among 3,258 HBR patients (1,803 ACS; 1,455 non-ACS), aspirin-free prasugrel monotherapy did not reduce major bleeding at 1 month versus DAPT in either subgroup.
- A signal of excess cardiovascular events, especially myocardial infarction, was seen in ACS with aspirin-free strategy but not in non-ACS.
- Findings support selective use of aspirin-free strategies post-PCI in non-ACS HBR, but caution in ACS.
Methodological Strengths
- Randomized comparison within a large HBR cohort with ACS/non-ACS stratification.
- Clinically relevant hard endpoints (bleeding, MI) at early post-PCI time point.
Limitations
- Subgroup analysis; not powered primarily for ACS vs non-ACS interaction.
- Short-term (1-month) bleeding assessment; longer-term ischemic/bleeding tradeoffs need evaluation.
Future Directions: Prospective trials tailoring aspirin discontinuation timing by ACS status and bleeding/ischemic risk, including longer-term outcomes and other P2Y12 inhibitors.
BACKGROUND: The effects of the aspirin-free strategy on bleeding and cardiovascular events were unknown in patients with high bleeding risk (HBR), with or without acute coronary syndrome (ACS), undergoing percutaneous coronary intervention. METHODS: We conducted a subgroup analysis stratified by ACS among patients with HBR in the STOPDAPT-3 trial (Short and Optimal Duration of Dual Antiplatelet Therapy-3), which randomly compared no-aspirin (prasugrel monotherapy) with dual antiplatelet therapy (DAPT) in patients with ACS and HBR. RESULTS: There were 3258 patients with HBR, including 1803 ACS and 1455 non-ACS patients. The effects of no-aspirin compared with DAPT at 1 month after percutaneous coronary intervention were not significant for major bleeding regardless of ACS or non-ACS (7.3% versus 7.9%; hazard ratio [HR], 0.91 [95% CI, 0.65-1.28], and 3.1% versus 2.9%; HR, 1.06 [95% CI, 0.58-1.93]; CONCLUSIONS: The aspirin-free strategy compared with the DAPT strategy failed to reduce major bleeding in patients with HBR irrespective of ACS. There was a signal of the excess risk of the aspirin-free strategy relative to the DAPT strategy for cardiovascular events, myocardial infarction in particular, in patients with ACS, but not in patients with non-ACS. The aspirin-free strategy may be considered as a potential treatment option after percutaneous coronary intervention in patients with non-ACS. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04609111.
3. Diastolic Perfusion Pressure Predicts Response to Inotropes and Vasopressors and Benefit From Mechanical Circulatory Support in Cardiogenic Shock.
In a CS cohort (n=93), lower diastolic perfusion pressure predicted limited improvement in cardiac power output index despite escalation of inotropes/vasopressors. Post hoc ECMO-CS analyses suggested patients with lower DPP might derive greater survival benefit from early VA-ECMO, supporting DPP as a pragmatic bedside metric for triage.
Impact: Bridges a critical evidence gap by linking a simple pressure-derived index (DPP) to drug responsiveness and potential benefit from mechanical support, enabling physiology-based personalization in cardiogenic shock.
Clinical Implications: Use DPP (DBP − RAP) to identify CS patients unlikely to respond to escalating inotropes/vasopressors and prioritize early VA-ECMO consideration; integrate DPP into shock team pathways for rapid triage.
Key Findings
- Lower baseline DPP was associated with limited increase in cardiac power output index despite escalation of vasoactive inotropes/vasopressors.
- In post hoc analyses of ECMO-CS, patients with lower DPP appeared to derive greater survival benefit from early VA-ECMO.
- DPP offers a simple bedside hemodynamic metric to guide escalation to mechanical circulatory support.
Methodological Strengths
- Objective hemodynamic endpoint (cardiac power output index) linked to vasoactive escalation.
- Complementary evidence from a randomized trial dataset (ECMO-CS) via post hoc analysis.
Limitations
- Single-cohort observational component with modest sample size (n=93).
- Post hoc analysis in ECMO-CS; prospective validation of DPP-guided strategies is needed.
Future Directions: Prospective, randomized trials testing DPP-guided escalation (drug optimization vs early VA-ECMO) and validating DPP thresholds across etiologies of cardiogenic shock.
BACKGROUND: Hemodynamic response to escalation of vasoactive drugs has not been well-characterized in patients with cardiogenic shock (CS). We tested the hypothesis that lower diastolic perfusion pressure (DPP=diastolic blood pressure-right atrial pressure) was associated with more limited hemodynamic response to uptitration of vasoactive drugs and with possible benefit from early mechanical circulatory support in patients with CS. METHODS: This study consisted of 2 parts: (1) we evaluated the relationship between baseline DPP and changes in cardiac power output index (CPOI) in response to increase in vasoactive drugs in a cohort of patients with CS (n=93) and (2) we compared all-cause mortality based on baseline DPP in a post hoc analysis of the ECMO-CS trial (Extracorporeal Membrane Oxygenation in the Therapy of Cardiogenic Shock). CPOI responders were defined as postescalation CPOI ≥0.28 W/m RESULTS: Vasoactive inotrope score escalated from 11.2±3.9 to 24.5±4.7. Escalation of vasoactive drugs was associated with increases in CPOI to 0.23±0.06 W/m CONCLUSIONS: Lower DPP was associated with more limited hemodynamic response to escalation of vasoactive drugs and potentially greater benefit from early venoarterial extracorporeal membrane oxygenation in CS.