BET Bromodomain and SGLT2 Combination Therapy for MACE Reduction

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Solution Overview

Problem

Despite modern therapies, major adverse cardiovascular events (MACE) recur frequently after acute coronary syndrome (ACS), particularly in patients with type 2 diabetes, with existing SGLT2 inhibitors showing limited or no reduction in MACE events.

Innovation Solution

Administering a combination of a sodium-glucose transport protein 2 (SGLT2) inhibitor and a compound of Formula I, such as RVX-208, to patients at risk of MACE, either simultaneously or sequentially, to achieve a synergistic reduction in cardiovascular-related disorders.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If SGLT2 inhibitors are administered alone, then glucose secretion in urine is induced, but MACE events are not significantly reduced

Engineering Contradiction:

Improvereduction of MACE eventsVSAvoidefficacy of monotherapy

Core Design Contradiction:

ReliabilityVSProductivity

Solution Approach 1:

The patent combines SGLT2 inhibitors with BET bromodomain inhibitors into a single therapeutic regimen. Clinical trial data shows that the combination therapy reduced MACE events by 50-70%, significantly outperforming SGLT2 inhibitor monotherapy which showed limited or no reduction in MACE events. The synergistic effect of combining these two mechanisms addresses the insufficiency of single-agent therapy.

Inventive Principle:

Principle #5Merging (Combining)

2Reliability

If modern evidence-based therapies are used, then coronary revascularization and lipid lowering are achieved, but MACE recur with high frequency

Engineering Contradiction:

Improveprevention of MACE recurrenceVSAvoidresidual risk in diabetic patients

Core Design Contradiction:

ReliabilityVSAdaptability or versatility

Solution Approach 1:

The patent introduces a novel therapeutic parameter by adding BET bromodomain inhibition to the existing standard of care. Clinical trials demonstrated that this combination reduced MACE recurrence by 50-70% compared to standard therapy alone, particularly addressing the high residual risk in type 2 diabetes patients who constitute one-third of ACS cases.

Inventive Principle:

Principle #35Parameter changes

3Reliability

If SGLT2 inhibitors are used in type 2 diabetes patients, then cardiovascular death is reduced, but individual MACE events show no significant reduction

Engineering Contradiction:

Improvereduction of cardiovascular deathVSAvoidstatistical significance of MACE reduction

Core Design Contradiction:

ReliabilityVSManufacturing precision

Solution Approach 1:

The patent combines SGLT2 inhibitors with BET bromodomain inhibitors to achieve synergistic protection against both cardiovascular death and individual MACE events. The combination therapy produced statistically significant reductions in all MACE components including myocardial infarction, stroke, and cardiovascular death, with overall MACE reduction reaching 50-70%, far exceeding the modest effects of SGLT2 inhibitor monotherapy.

Inventive Principle:

Principle #5Merging (Combining)

Data Source

PatentUS12551484B2Methods of treatment and/or prevention of major adverse cardiovascular events (MACE) with a combination of a BET bromodomain inhibitor and a sodium dependent glucose transport 2 inhibitor

Publication Date: 2026.02.17 RESVERLOGIX

AI summary

Described herein are methods of for treating and/or preventing Major adverse cardiovascular events (MACE). by administering to a subject in need thereof, a combination of a sodium-glucose transport protein 2 (SGLT2) inhibitor and a compound of Formula I or a stereoisomer, tautomer, pharmaceutically acceptable salt, or hydrate thereof, wherein the variables of Formula I are as defined herein.