Pharmacology  ·  Cardiovascular

SGLT2 Inhibitors and Additional Agents

The fourth survival pillar and three additional tools for selected patients

• SGLT2 inhibitors block glucose and sodium reabsorption in the proximal tubule, producing mild osmotic diuresis that reduces ventricular filling pressures — but their benefit in heart failure exceeds what this modest diuretic effect alone would predict, and the mechanism of the excess benefit remains under active investigation.
• SGLT2 inhibitors are the first drug class proven to improve outcomes across the full ejection fraction spectrum, including heart failure with preserved ejection fraction, which had resisted nearly every previous pharmacological treatment attempt; they are recommended regardless of whether the patient has diabetes.
• Vericiguat directly stimulates the enzyme that nitric oxide normally activates to produce vasodilation — because it bypasses the need for nitric oxide itself, it remains effective in advanced heart failure where nitric oxide availability is reduced, distinguishing it from nitrates which lose effectiveness in the same setting.
• Hydralazine and isosorbide dinitrate combine arterial vasodilation (hydralazine, reducing afterload) with venous vasodilation (isosorbide dinitrate, reducing preload), producing hemodynamic effects similar to RAAS blockade through a RAAS-independent pathway; guidelines specifically recommend adding this combination in self-identified Black patients with heart failure with reduced ejection fraction who remain symptomatic despite standard therapy.
• Ivabradine slows the sinoatrial node pacemaker without reducing contractility, allowing further heart rate reduction in patients already on maximally tolerated beta-blocker doses; it is contraindicated in atrial fibrillation and its most characteristic adverse effect is visual phosphenes.