Myocardial infarction (heart attack) and unstable angina are life-threatening medical emergencies that occur when the blood vessels supplying the heart muscle suddenly become blocked or severely narrowed.
However, surviving the acute crisis is only the first step. If the underlying drivers of arterial damage are not strictly managed after discharge, the risk of a secondary event spikes dramatically. The first year following discharge represents an exceptionally dangerous window for patients, making it crucial to aggressively lower low-density lipoprotein cholesterol (LDL-C)—commonly known as "bad cholesterol"—and keep it down consistently.
A breakthrough genetic approach may now offer high-risk patients a way to hit those low cholesterol targets much faster and keep them there longer.
Novartis Korea announced on the 11th that its small interfering RNA (siRNA) therapy Leqvio (active ingredient: inclisiran sodium) demonstrated rapid and sustained LDL-C reduction in the global Phase 3b VICTORION-INCEPTION clinical trial. The study, which evaluated patients who recently experienced a myocardial infarction or unstable angina, was published in the Journal of the American Heart Association.
Managing Risk After Acute Coronary Syndrome
Acute coronary syndrome (ACS) refers to a spectrum of conditions where blood flow to the heart is abruptly restricted, with heart attacks and unstable angina serving as the most common diagnoses. Symptoms typically manifest as crushing chest pain, cold sweats, shortness of breath, and radiating pain in the left arm or jaw. When these symptoms hit suddenly, immediate emergency intervention is required to open the blocked vessel and restore vital blood flow.
Yet, a successful emergency procedure does not mean a patient is cured. Long-term secondary prevention requires managing blood pressure, blood sugar, weight, and smoking cessation simultaneously. Among these variables, lowering LDL-C remains the most directly linked metric for preventing a secondary, potentially fatal cardiovascular event.
Superior Target Attainment Shortly After Discharge
The VICTORION-INCEPTION trial is the first multicenter clinical study to examine the real-world efficacy of administering Leqvio early in the post-discharge phase. The trial followed 400 patients who had been hospitalized for ACS and were randomized within five weeks of leaving the hospital. All participants entered the trial with elevated cholesterol levels (LDL-C of 70 mg/dL or higher, or non-HDL cholesterol of 100 mg/dL or higher) despite being prescribed standard statin therapy or exhibiting statin intolerance.
To mirror real-world clinical environments, researchers split the participants into two paths: one receiving Leqvio combined with standard lipid-lowering care, and the other receiving standard therapy alone at the clinician's discretion.
By day 330, the primary endpoints revealed a staggering divergence. The Leqvio combination group achieved a 45.6% reduction in LDL-C from baseline, while the standard-therapy-only group actually saw a 1.4% increase—representing a net clinical difference of 46.9%.
The contrast in target attainment was equally stark. While 66.7% of patients in the Leqvio combination group successfully brought their LDL-C below the critical 70 mg/dL threshold, only 28.1% of the standard therapy group achieved the same result. This represents an attainment rate 2.4 times higher for the RNA therapy arm.
Furthermore, the genetic treatment achieved these metrics remarkably fast. Within just 90 days of the first dose, 74.6% of the Leqvio group had already dropped below 70 mg/dL, compared to just 26.6% in the control group. Of those who hit the target early with Leqvio, 75.3% maintained that low level through the end of the 330-day trial. The therapy also excelled at hitting the ultra-stringent target of below 55 mg/dL, with 54.2% of Leqvio patients reaching it versus a minor 13.6% in the standard care group.
Silencing the Cellular Signals of Cholesterol Production
As an siRNA-based therapeutic, Leqvio works by intercepting the genetic instructions used to synthesize specific disease-causing proteins. Rather than permanently altering a patient's DNA, the treatment acts as a precise volume dial that turns down the signal to produce a protein called PCSK9.
In a healthy liver, specific receptors constantly clear LDL-C from the bloodstream. However, when PCSK9 levels rise, this protein destroys those receptors, leaving the body unable to filter out bad cholesterol efficiently. By silencing the production of PCSK9, Leqvio leaves the liver's natural clearing mechanisms intact, enabling it to clear circulating LDL-C with massive efficiency.
This mechanism also transforms the patient experience, moving away from daily oral regimens. Leqvio is administered as a subcutaneous injection by a healthcare professional, requiring an initial dose, a booster at three months, and then just two maintenance doses per year. For individuals who struggle with the pill fatigue or poor adherence common to daily statin regimens, this twice-yearly cycle offers a distinct advantage for long-term treatment persistence.
Nevertheless, RNA therapies are not an immediate replacement for foundational care. Comprehensive lifestyle adjustments and high-intensity statin therapies remain the cornerstone of managing dyslipidemia. Clinicians carefully weigh individual cardiovascular risk, statin tolerance, and the necessity of combination therapies before adjusting a patient's regimen.
Reflecting this clinical evolution, the American College of Cardiology and the American Heart Association (ACC/AHA) updated their clinical guidelines to recommend aggressive lipid-lowering therapies immediately upon discharge for high-risk ACS patients. For patients whose LDL-C remains stuck at or above 70 mg/dL despite maximum tolerated statin doses, the guidelines endorse adding non-statin therapies, explicitly including siRNA options like Leqvio.
A Paradigm Shift to Rapid, Sustained Lowering
Approved in South Korea in June 2024 for primary hypercholesterolemia and mixed dyslipidemia, Leqvio has accumulated two years of real-world clinical track record, backed by an expanding mountain of data in high-risk populations.
"For acute coronary syndrome patients, managing the risk of recurrence during the immediate post-discharge window is paramount, but our historical, stepwise approach made it incredibly difficult to hit aggressive LDL-C targets quickly," observed Lee Yong-jun, a professor of cardiology at Severance Cardiovascular Hospital. "Furthermore, daily pill fatigue and a drop-off in patient adherence frequently capped our ability to keep those levels stable over time."
Lee Yong-jun added, "The VICTORION-INCEPTION trial provides the first concrete evidence of rapid LDL-C reduction that stays locked in through day 330 for a recent ACS patient population. An intervention that turns down PCSK9 production with just two maintenance doses a year stands to fundamentally reshape how we manage high-risk individuals."
Naturally, safety remains a critical variable alongside clinical efficacy. In day-to-day practice, medical professionals must closely monitor for minor localized injection-site reactions, track patient comorbidities, and carefully calibrate combination plans with existing lipid-lowering drugs. Because every patient's cardiovascular landscape is unique, specific target metrics and timelines must be customized.
For individuals who have stared down a heart attack or unstable angina, controlling cholesterol is no longer an abstract exercise in numbers. It is a vital shield against re-blockage, and medical attention is intensely focused on how this RNA-silencing platform will redefine rapid, durable secondary prevention for high-risk patients.
