Valsartan (Sacubitril) is a prescription medication, often branded as Diovan, used to treat high blood pressure, heart failure, and improve survival after a heart attack. It acts as an angiotensin II receptor blocker (ARB), relaxing blood vessels to lower blood pressure. Common side effects include dizziness, low blood pressure, headache, and fatigue.
Plaque Reduction: The EFFERVESCENT trial found that patients taking valsartan experienced a significant decrease in carotid bulb vessel wall area and improved plaque stability.
Clinical trials have demonstrated the ability of several blood pressure lowering medications to reduce cardiovascular disease. This includes Angiotensin-Converting Enzyme (ACE) Inhibitors, Angiotensin II Receptor Blockers (ARBs), Calcium Channel Blockers, Beta-Blockers, and Thiazide diuretics. Interestingly, several trials have demonstrated improvements in cardiovascular disease independent of blood pressure reduction, highlighting the possibility that some of these medications may achieve plaque stabilization. While several medications have demonstrated the ability to achieve plaque stabilization, the ability to induce atherosclerotic plaque regression has been most clearly demonstrated in trials evaluating Angiotensin Receptor Blockers (ARBs).
In one trial involving 100 patients with high blood pressure (hypertension) and established cardiovascular disease, participants were randomized to receive Olmesartan or Valsartan in addition to other guideline directed treatment.15 At six months, intravascular ultrasound was used to assess coronary artery plaque volume, for which both blood pressure lowering agents demonstrated a 4.7% reduction in coronary atherosclerosis, with no statistically significant difference between the two groups. Potential mechanisms to explain the observed benefits of ARBs include their ability to reduce vascular inflammation and increase collagen content in atherosclerotic plaque, both of which likely contribute to plaque stabilization and potential regression.
Vericiguat (brand name Verquvo) is a daily oral soluble guanylate cyclase (sGC) stimulator used to reduce the risk of cardiovascular death and hospitalization in adults with symptomatic chronic heart failure (ejection fraction <45%) following a recent worsening event (e.g., hospitalization or outpatient IV diuretic use). Common side effects include symptomatic low blood pressure (hypotension) and anemia
DOES NOT SHOW REVERSAL IN ATHEROSCLEROSIS
Dapagliflozin (commonly known by the brand name Farxiga) is a prescription medication used to manage type 2 diabetes, reduce the risk of hospitalization for heart failure, and manage chronic kidney disease. It belongs to the SGLT2 inhibitor drug class, working by helping the kidneys remove glucose and sodium from the body through urine.
Dapagliflozin, a SGLT2 inhibitor, shows significant potential in reducing, stabilizing, and potentially reversing atherosclerosis in diabetic models by mitigating plaque instability, inhibiting inflammation, and reducing macrophage infiltration. Studies suggest it improves endothelial function and plaque stability, decreasing cardiovascular risks.Key Findings on Dapagliflozin and Atherosclerosis:Plaque Stability: Dapagliflozin stabilizes diabetes-induced atherosclerotic plaques, reducing macrophages and cholesterol crystal deposition.Reduced Plaque Size: Research indicates a reduction in the size and burden of atherosclerotic plaques in the aortic root of models.
While Sodium-Glucose Cotransporter-2 (SGLT2) Inhibitors were initially developed for the treatment of diabetes, there is emerging evidence to suggest that these medications may contribute to atherosclerotic plaque regression.16 Among patients with type 2 diabetes, a prospective cohort study of 236 patients evaluated longitudinal changes in coronary atherosclerosis using coronary computed tomography angiography (CCTA). After a median duration of 14.6 months, it was demonstrated that SGLT2 inhibitor therapy was associated with significant reductions in overall plaque volume.16 While these findings persisted after the adjustment of cardiovascular risk factors and other medications, it is necessary to acknowledge that this trial was a prospective cohort study, rather than a randomized clinical trial, highlighting the need for further scientific evaluation.
While we await additional trials regarding SGLT2 Inhibitor therapy and atherosclerotic plaque regression, there is existing evidence demonstrating the ability of SGLT2 Inhibitor therapy to improve plaque stabilization through its ability to reduce peri-atherosclerotic inflammation, increase fibrous cap thickness, and reduced lipoprotein accumulation.17,18
Vutrisiran (marketed as Amvuttra) is an FDA-approved, subcutaneous RNAi therapeutic used to treat polyneuropathy of hereditary transthyretin-mediated amyloidosis (hATTR-PN) and cardiomyopathy (ATTR-CM) in adults. It works by silencing the TTR gene to reduce toxic protein buildup. Key side effects include low vitamin A levels, pain in limbs/joints, and breathing issues
Vutrisiran (marketed as Amvuttra) has not been proven to reverse traditional atherosclerosis (fatty plaque buildup in arteries).
Alirocumab (Praluent) and evolocumab (Repatha) are highly effective, generally safe PCSK9 inhibitor medications used to lower LDL-C (“bad” cholesterol) by ~60% in high-risk patients. Both are subcutaneous injections that, while reducing cardiovascular events, show similar efficacy, though some studies suggest evolocumab may offer slightly stronger LDL-C reduction (up to 9% more) and alirocumab might better reduce mortality in certain high-risk groups.
both alirocumab and evolocumab (PCSK9 inhibitors) have demonstrated the ability to reverse atherosclerosis by reducing coronary plaque volume and stabilizing existing plaques when added to high-intensity statin therapy. Imaging studies (IVUS/OCT) show these agents cause “plaque regression” (shrinking) and “delipidification” (removing fat) from artery walls, particularly when LDL-C levels drop below 50 mg/dL
Mavacamten (brand name Camzyos) is a first-in-class cardiac myosin inhibitor approved to treat adults with symptomatic NYHA Class II-III obstructive hypertrophic cardiomyopathy (oHCM). It reduces myocardial hypercontractility, improving functional capacity and symptoms. It is available only through a restricted REMS program due to risks of heart failure.
Camzyos does not reverse arterial plaque (atherosclerosis). Instead, it targets the underlying pathophysiology of HCM—the hypercontractility of the heart muscle
Sotatercept (brand name Winrevair) is a first-in-class, FDA-approved, subcutaneous injection for adults with pulmonary arterial hypertension (PAH, WHO Group 1) to improve exercise capacity and reduce the risk of clinical worsening. It works by restoring balance between pro- and anti-proliferative signaling pathways (inhibiting TGF-(\beta ) superfamily signaling). It is administered every 3 weeks at a dose of 0.3-0.7 mg/kg
Vascular Remodeling: Sotatercept works by balancing bone morphogenetic protein (BMP) signaling, which inhibits excessive cell proliferation in the pulmonary artery walls.Reverse Remodeling: Studies demonstrate that it can reduce the thickening (remodeling) of pulmonary vessels and reduce right ventricle size, improving its function and contraction.
MAYBE???
Empagliflozin (commonly brand-named Jardiance) is a prescription medication used to manage type 2 diabetes, reduce cardiovascular death in adults with heart disease/failure, and slow the progression of chronic kidney disease. It works by inhibiting the SGLT2 protein in the kidneys, allowing excess glucose to be excreted through urine. Common side effects include urinary tract infections (UTIs), genital yeast infections, increased urination, and hypotension (low blood pressure).
Empagliflozin (Jardiance) reduces, stabilizes, and potentially reverses arterial plaque progression by decreasing inflammation, vascular calcification, and oxidative stress. Studies show it reduces atherosclerotic lesion areas and improves endothelial function
Plaque Reduction & Stabilization: Preclinical studies found that empagliflozin reduces plaque size, increases collagen content, and lowers macrophage infiltration, which helps stabilize plaques and prevents rupture.
Selatogrel (ACT-246475) is an investigational, potent, selective, and reversible subcutaneous (P2Y_{12}) receptor antagonist designed for self-administration during suspected acute myocardial infarction (AMI). It provides rapid platelet inhibition within 15 minutes to prevent thrombosis, potentially reducing total ischemic time before hospital care.
it does not directly “reverse” or shrink existing fatty atherosclerotic plaques, studies suggest it can reduce preformed thrombus (blood clot) on top of a ruptured plaque.