{"product_id":"targeting-ldl-cholesterol-below-55-mg-dl-beat-the-70-mg-dl-target-in-patients-with-clogged-arteries","title":"Targeting LDL Cholesterol Below 55 mg\/dL Beat the 70 mg\/dL Target in Patients With Clogged Arteries","description":"\u003cp\u003e\u003cstrong\u003eSummary:\u003c\/strong\u003e In a large randomized trial conducted at 17 hospitals in South Korea, 3,048 patients with established atherosclerotic cardiovascular disease (narrowed or blocked arteries) were assigned to one of two LDL cholesterol targets — below 55 mg per deciliter or below 70 mg per deciliter. After a median of 3.0 years, the group aiming for the lower target had a 33% lower relative risk of cardiovascular death, heart attack, stroke, repeat revascularization procedures, or hospitalization for unstable angina (6.6% vs. 9.7% of patients; hazard ratio 0.67; P=0.002). Safety outcomes were similar between the two groups, apart from fewer cases of rising creatinine (a kidney-function marker) in the intensive-targeting group. The results support the stricter cholesterol target that major guidelines now recommend.\u003c\/p\u003e\n\n\u003ch1\u003eTargeting LDL Cholesterol Below 55 mg\/dL Beat the 70 mg\/dL Target in Patients With Clogged Arteries\u003c\/h1\u003e\n\n\u003ch2\u003eTable of Contents\u003c\/h2\u003e\n\u003cul\u003e\n\u003cli\u003e\u003ca href=\"#ddn-key-points\"\u003eKey Points\u003c\/a\u003e\u003c\/li\u003e\n\n  \u003cli\u003e\u003ca href=\"#background\"\u003eWhy This Research Matters\u003c\/a\u003e\u003c\/li\u003e\n  \u003cli\u003e\u003ca href=\"#methods\"\u003eHow the Study Was Conducted\u003c\/a\u003e\u003c\/li\u003e\n  \u003cli\u003e\u003ca href=\"#participants\"\u003eWho Took Part in the Study\u003c\/a\u003e\u003c\/li\u003e\n  \u003cli\u003e\u003ca href=\"#treatments\"\u003eWhat Treatments Patients Received\u003c\/a\u003e\u003c\/li\u003e\n  \u003cli\u003e\u003ca href=\"#cholesterol\"\u003eKey Finding 1: How Low Did Cholesterol Actually Go?\u003c\/a\u003e\u003c\/li\u003e\n  \u003cli\u003e\u003ca href=\"#events\"\u003eKey Finding 2: Fewer Heart Attacks, Strokes, and Procedures\u003c\/a\u003e\u003c\/li\u003e\n  \u003cli\u003e\u003ca href=\"#safety\"\u003eSafety Results\u003c\/a\u003e\u003c\/li\u003e\n  \u003cli\u003e\u003ca href=\"#implications\"\u003eWhat This Means for Patients\u003c\/a\u003e\u003c\/li\u003e\n  \u003cli\u003e\u003ca href=\"#limitations\"\u003eLimitations: What the Study Could Not Prove\u003c\/a\u003e\u003c\/li\u003e\n  \u003cli\u003e\u003ca href=\"#recommendations\"\u003ePractical Recommendations\u003c\/a\u003e\u003c\/li\u003e\n  \u003cli\u003e\u003ca href=\"#ddn-faq\"\u003eFrequently Asked Questions\u003c\/a\u003e\u003c\/li\u003e\n\u003cli\u003e\u003ca href=\"#source\"\u003eSource Information\u003c\/a\u003e\u003c\/li\u003e\n\u003c\/ul\u003e\n\n\u003c!-- ddn:keypoints:start --\u003e\n\u003ch2 id=\"ddn-key-points\"\u003eKey Points\u003c\/h2\u003e\n\u003cul\u003e\n\u003cli\u003eIn a trial of 3,048 patients with established cardiovascular disease, targeting LDL cholesterol below 55 mg\/dL reduced cardiovascular events by 33% compared with targeting below 70 mg\/dL over a median of 3 years.\u003c\/li\u003e\n\u003cli\u003eThe benefit was driven mainly by nonfatal heart attacks and revascularization procedures, with safety outcomes similar between groups except fewer kidney-marker rises in the intensive group.\u003c\/li\u003e\n\u003cli\u003eMost of the extra benefit came from higher statin doses and adding ezetimibe; PCSK9 inhibitors were used by fewer than 2.5% of patients in either group.\u003c\/li\u003e\n\u003cli\u003eNot everyone reached the lower target: at 3 years, 60.8% of the intensive group hit below 55 mg\/dL, but 85.2% were below 70 mg\/dL, showing progress counts.\u003c\/li\u003e\n\u003cli\u003eThe trial was open-label, lasted a median of 3 years, and enrolled mostly men in South Korea, so long-term effects and results in other populations remain uncertain.\u003c\/li\u003e\n\u003c\/ul\u003e\n\u003c!-- ddn:keypoints:end --\u003e\n\n\n\u003ch2 id=\"background\"\u003eWhy This Research Matters\u003c\/h2\u003e\n\n\u003cp\u003ePeople who already have atherosclerotic cardiovascular disease (ASCVD — arteries narrowed by fatty plaque) face a high or very high risk of future heart attacks, strokes, and other cardiovascular events. For these patients, lowering low-density lipoprotein (LDL) cholesterol — often called \"bad\" cholesterol — is the central treatment goal.\u003c\/p\u003e\n\n\u003cp\u003eClinical guidelines have shifted over the past several years. They once advised patients with ASCVD to aim for an LDL cholesterol level below 70 mg per deciliter (1.8 mmol per liter). Now they advise a stricter target: below 55 mg per deciliter (1.4 mmol per liter).\u003c\/p\u003e\n\n\u003cp\u003eThe problem is the evidence. Previous randomized trials showed that high-intensity statins, or adding ezetimibe (a cholesterol-absorption blocker) or PCSK9 inhibitors (injectable drugs that help the liver clear LDL cholesterol) to a statin, lowers both LDL cholesterol and cardiovascular risk. But those trials were designed to test \u003cem\u003edrugs\u003c\/em\u003e, not specific \u003cem\u003etarget numbers\u003c\/em\u003e. No randomized trial had directly compared a target of below 55 mg per deciliter with a target of below 70 mg per deciliter in patients with ASCVD.\u003c\/p\u003e\n\n\u003cp\u003eThat gap matters in daily practice. Many patients never reach the guideline-recommended target, and doctors have lacked head-to-head proof that the stricter goal is worth the extra effort and medication.\u003c\/p\u003e\n\n\u003cp\u003eThe Ez-PAVE trial was designed to answer this question directly. Its full name is \"Effects of Ezetimibe Combination Therapy for Patients with Atherosclerotic Cardiovascular Disease — Randomized Comparison of LDL Cholesterol Targeting \u0026lt;70 mg per Deciliter vs. \u0026lt;55 mg per Deciliter.\"\u003c\/p\u003e\n\n\u003ch2 id=\"methods\"\u003eHow the Study Was Conducted\u003c\/h2\u003e\n\n\u003cp\u003eEz-PAVE was an investigator-initiated, multicenter, open-label, randomized superiority trial conducted in South Korea. \"Open-label\" means that patients and their doctors knew which cholesterol target had been assigned. \"Randomized superiority trial\" means patients were assigned to groups by chance, and the researchers set out to test whether one strategy was genuinely better than the other.\u003c\/p\u003e\n\n\u003cp\u003eA total of 3,048 patients were enrolled at 17 sites between January 2021 and July 2022. They were assigned in a 1:1 ratio — half to each group.\u003c\/p\u003e\n\n\u003cul\u003e\n  \u003cli\u003e\n\u003cstrong\u003eIntensive-targeting group:\u003c\/strong\u003e 1,526 patients aimed for an LDL cholesterol level below 55 mg per deciliter (1.4 mmol per liter).\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003eConventional-targeting group:\u003c\/strong\u003e 1,522 patients aimed for an LDL cholesterol level below 70 mg per deciliter (1.8 mmol per liter).\u003c\/li\u003e\n\u003c\/ul\u003e\n\n\u003cp\u003eThe trial protocol and its amendments were approved by the institutional review board or ethics committee at every participating site. Written informed consent was obtained from all patients before randomization.\u003c\/p\u003e\n\n\u003ch3\u003eWho Was Eligible\u003c\/h3\u003e\n\n\u003cp\u003ePatients could join if they were 19 to 80 years of age and had documented atherosclerotic cardiovascular disease. That meant at least one of the following:\u003c\/p\u003e\n\n\u003cul\u003e\n  \u003cli\u003eA previous acute coronary syndrome (heart attack or unstable angina)\u003c\/li\u003e\n  \u003cli\u003eStable angina confirmed by imaging or functional testing\u003c\/li\u003e\n  \u003cli\u003ePrevious coronary revascularization (procedures to reopen arteries) or revascularization of another artery\u003c\/li\u003e\n  \u003cli\u003eStroke or transient ischemic attack (TIA — a brief \"warning stroke\")\u003c\/li\u003e\n  \u003cli\u003ePeripheral artery disease (blocked arteries in the legs or elsewhere outside the heart)\u003c\/li\u003e\n\u003c\/ul\u003e\n\n\u003cp\u003eOne key exclusion criterion was an LDL cholesterol level below 70 mg per deciliter in a patient not taking a statin. Full eligibility criteria appeared in the trial's supplementary appendix.\u003c\/p\u003e\n\n\u003ch3\u003eHow Randomization Was Structured\u003c\/h3\u003e\n\n\u003cp\u003eRandomization used a Web response system with permuted-block randomization (blocks of 4 or 6) at each site. Patients were sorted, or \"stratified,\" by three factors to keep the groups balanced:\u003c\/p\u003e\n\n\u003col\u003e\n  \u003cli\u003ePrevious acute coronary syndrome (yes or no)\u003c\/li\u003e\n  \u003cli\u003ePresence of diabetes (yes or no)\u003c\/li\u003e\n  \u003cli\u003eBaseline LDL cholesterol level (below 100 mg per deciliter, or 100 mg per deciliter and above)\u003c\/li\u003e\n\u003c\/ol\u003e\n\n\u003cp\u003eWithin each target group, patients underwent a second randomization in a 1:1 ratio to either statin monotherapy (a statin alone) or combination therapy (a statin plus ezetimibe). Patients assigned to statin monotherapy were then randomly assigned again, 1:1, to receive either rosuvastatin or atorvastatin. These extra randomizations helped patients reach their targets promptly and kept the mix of statin types balanced, while preserving the main comparison between the two cholesterol targets.\u003c\/p\u003e\n\n\u003ch3\u003eTreatment Approach and Follow-Up\u003c\/h3\u003e\n\n\u003cp\u003eInvestigators received basic instructions for starting and adjusting therapy. Increasing the statin dose and adding ezetimibe were recommended before PCSK9 inhibitors were considered. However, the primary goal was to reach the target safely and effectively, so final decisions — statin dose changes and the addition of ezetimibe or a PCSK9 inhibitor — were left to the treating physicians in both groups, with the reasoning documented in detail.\u003c\/p\u003e\n\n\u003cp\u003eFollow-up visits took place at baseline, 1 month, and 1, 2, and 3 years after randomization. At each visit, researchers recorded general health, medication use, any end-point events or adverse events, and lipid profiles including LDL cholesterol. Safety laboratory tests were done at predefined time points.\u003c\/p\u003e\n\n\u003cp\u003eSurvival status was cross-checked against the Korean National Health Insurance database.\u003c\/p\u003e\n\n\u003ch3\u003eWhat Was Measured\u003c\/h3\u003e\n\n\u003cp\u003eThe \u003cstrong\u003eprimary end point\u003c\/strong\u003e — the main result the trial was powered to detect — was a composite (combined) measure. It counted the first occurrence of any of the following within 3 years:\u003c\/p\u003e\n\n\u003cul\u003e\n  \u003cli\u003eDeath from cardiovascular causes\u003c\/li\u003e\n  \u003cli\u003eNonfatal myocardial infarction (heart attack)\u003c\/li\u003e\n  \u003cli\u003eNonfatal stroke\u003c\/li\u003e\n  \u003cli\u003eAny revascularization procedure\u003c\/li\u003e\n  \u003cli\u003eHospitalization for unstable angina\u003c\/li\u003e\n\u003c\/ul\u003e\n\n\u003cp\u003eSecondary efficacy end points included each individual component of the primary end point separately, plus additional prespecified composite measures such as the combination of cardiovascular death, nonfatal heart attack, or nonfatal stroke.\u003c\/p\u003e\n\n\u003cp\u003eSafety end points included new-onset diabetes (among patients who did not have diabetes at the start), worsening of glycemic control (blood sugar control, among patients who did have diabetes), statin-associated muscle symptoms that led to a change in dose or regimen, a diagnosis of cancer, cataract surgery, and elevations in aminotransferase (liver enzyme), creatinine (a kidney marker), or creatine kinase (a muscle enzyme).\u003c\/p\u003e\n\n\u003cp\u003eAn independent clinical-events committee, whose members did not know the group assignments or cholesterol levels, adjudicated all cardiovascular events, cases of new-onset diabetes, and cases of worsening glycemic control.\u003c\/p\u003e\n\n\u003ch3\u003eStatistical Plan\u003c\/h3\u003e\n\n\u003cp\u003eResearchers calculated that enrolling 3,048 patients would give the trial 80% power, at a two-sided alpha level of 0.05, to detect a 24.75% lower relative risk of a primary end-point event at 3 years in the intensive group. That calculation assumed a 3-year event incidence of 15% in the conventional-targeting group and a 15% loss to follow-up.\u003c\/p\u003e\n\n\u003cp\u003eAll primary analyses used the intention-to-treat population — everyone who was randomized, analyzed in the group they were assigned to. The 3-year cumulative incidence of events was estimated with the Kaplan–Meier method and compared with a log-rank test. Hazard ratios and 95% confidence intervals came from a Cox proportional-hazards regression model. The proportional-hazards assumption was tested with Schoenfeld residuals (P=0.92), meaning the assumption held up. A per-protocol analysis excluded patients with major protocol deviations. Competing-risk sensitivity analyses used the Fine–Gray subdistribution hazard model.\u003c\/p\u003e\n\n\u003cp\u003eSubgroup analyses were prespecified for age, sex, body-mass index, previous acute coronary syndrome, coronary or other arterial revascularization, stroke or TIA, peripheral artery disease, hypertension, diabetes, chronic kidney disease, and baseline LDL cholesterol level. Importantly, the confidence intervals for secondary end points and subgroups were \u003cem\u003enot\u003c\/em\u003e adjusted for multiple comparisons, so those intervals should not be used to draw firm conclusions about treatment effects. No interim analyses were performed, and no values were imputed for missing data. A two-sided P value below 0.05 was considered statistically significant.\u003c\/p\u003e\n\n\u003ch2 id=\"participants\"\u003eWho Took Part in the Study\u003c\/h2\u003e\n\n\u003cp\u003eThe two groups were well balanced at the start. The mean age was 64.4±9.0 years, and 638 patients (20.9%) were women. The median baseline LDL cholesterol level was 76 mg per deciliter (interquartile range, 61 to 96), or 2.0 mmol per liter (interquartile range, 1.6 to 2.5).\u003c\/p\u003e\n\n\u003cp\u003eParticipants' cardiovascular histories were substantial:\u003c\/p\u003e\n\n\u003cul\u003e\n  \u003cli\u003e1,694 patients (55.6%) had a previous acute coronary syndrome\u003c\/li\u003e\n  \u003cli\u003e1,474 patients (48.4%) had stable angina with imaging or functional studies\u003c\/li\u003e\n  \u003cli\u003e2,049 patients (67.2%) had undergone coronary or other arterial revascularization\u003c\/li\u003e\n  \u003cli\u003e117 patients (3.8%) had had a stroke or transient ischemic attack\u003c\/li\u003e\n  \u003cli\u003e266 patients (8.7%) had peripheral artery disease\u003c\/li\u003e\n\u003c\/ul\u003e\n\n\u003cp\u003eOther baseline characteristics were similar between groups. About three quarters had hypertension (74.4% intensive vs. 72.5% conventional). Nearly 40% had diabetes in each group (39.6% vs. 39.6%). Chronic kidney disease was present in 6.0% versus 5.7%. Current smokers made up 22.8% versus 25.5%. Just under 80% of patients in each group were men (78.9% vs. 79.2%). Median body-mass index was 24.9 versus 24.7.\u003c\/p\u003e\n\n\u003cp\u003eAt enrollment, statin use was comparable: high-intensity statins in 23.1% versus 22.9%, moderate-intensity statins in 67.9% versus 68.2%, low-intensity statins in 0.7% versus 0.1%, and no statin in 8.4% versus 8.8%. Ezetimibe was already being taken by 29.8% versus 27.7%. Median baseline lipid values were also similar: LDL cholesterol 77 mg per deciliter (IQR 60 to 96) versus 75 (IQR 61 to 97); HDL cholesterol 46 (40 to 55) versus 47 (39 to 54); total cholesterol 143 (123 to 167) in both groups; and triglycerides 117 (87 to 159) versus 115 (83 to 163).\u003c\/p\u003e\n\n\u003ch2 id=\"treatments\"\u003eWhat Treatments Patients Received\u003c\/h2\u003e\n\n\u003cp\u003eMore patients in the intensive group were treated with high-intensity statins — as expected, since reaching a lower target takes stronger therapy.\u003c\/p\u003e\n\n\u003cul\u003e\n  \u003cli\u003e\n\u003cstrong\u003eHigh-intensity statin use at 1 month:\u003c\/strong\u003e 53.5% in the intensive group vs. 35.9% in the conventional group\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003eAt 1 year:\u003c\/strong\u003e 54.0% vs. 34.3%\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003eAt 2 years:\u003c\/strong\u003e 50.8% vs. 32.7%\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003eAt 3 years:\u003c\/strong\u003e 48.4% vs. 32.3%\u003c\/li\u003e\n\u003c\/ul\u003e\n\n\u003cp\u003eEzetimibe use started out nearly identical — 49.7% vs. 50.0% at 1 month — then rose faster in the intensive group: 56.0% vs. 53.1% at 1 year, 61.2% vs. 52.5% at 2 years, and 66.6% vs. 56.7% at 3 years.\u003c\/p\u003e\n\n\u003cp\u003ePCSK9 inhibitors were used by very few patients. In the intensive group, use was 0.2% at 1 month and 0.8%, 1.4%, and 2.3% at 1, 2, and 3 years. In the conventional group, use was 0.1% at 1 month and 0.5%, 0.5%, and 0.9% at 1, 2, and 3 years.\u003c\/p\u003e\n\n\u003cp\u003eOver a median follow-up of 3.0 years (interquartile range, 3.0 to 3.0), 110 patients (3.6%) stopped LDL-lowering therapy or reduced its intensity despite not reaching their target. That included 62 patients in the intensive group and 48 in the conventional group. The main reason was an adverse event, reported in 85 patients (2.8%) overall — 50 in the intensive group and 35 in the conventional group. In addition, 14 patients (0.5%) withdrew consent and 5 patients (0.2%) were lost to follow-up.\u003c\/p\u003e\n\n\u003ch2 id=\"cholesterol\"\u003eKey Finding 1: How Low Did Cholesterol Actually Go?\u003c\/h2\u003e\n\n\u003cp\u003eLDL cholesterol fell in both groups and stayed separated throughout the trial.\u003c\/p\u003e\n\n\u003cul\u003e\n  \u003cli\u003e\n\u003cstrong\u003eIntensive-targeting group:\u003c\/strong\u003e median LDL cholesterol during the trial of 56 mg per deciliter (IQR 48 to 67), or 1.4 mmol per liter (IQR 1.2 to 1.7)\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003eConventional-targeting group:\u003c\/strong\u003e median LDL cholesterol of 66 mg per deciliter (IQR 58 to 76), or 1.7 mmol per liter (IQR 1.5 to 2.0)\u003c\/li\u003e\n\u003c\/ul\u003e\n\n\u003cp\u003eThe gap between groups stayed consistent throughout follow-up. That said, not everyone hit the assigned number. At 1 month, 31.2% of the intensive group and 59.4% of the conventional group had reached their target. At 1, 2, and 3 years, the percentages were 42.9%, 53.3%, and 60.8% in the intensive group, and 67.2%, 67.7%, and 68.1% in the conventional group.\u003c\/p\u003e\n\n\u003cp\u003eA post hoc analysis (an analysis done after the trial was designed) showed something important: 74.1% of patients in the intensive group had an LDL cholesterol level below 70 mg per deciliter at 1 month, and 78.5%, 82.6%, and 85.2% did so at 1, 2, and 3 years. In other words, most intensive-group patients reached at least the old target, even if they did not reach the newer, tougher one.\u003c\/p\u003e\n\n\u003ch2 id=\"events\"\u003eKey Finding 2: Fewer Heart Attacks, Strokes, and Procedures\u003c\/h2\u003e\n\n\u003cp\u003eThis is the headline result. Over a median follow-up of 3.0 years, a primary end-point event occurred in 100 patients in the intensive-targeting group — a Kaplan–Meier cumulative incidence of 6.6%, or roughly 1 in 15 patients.\u003c\/p\u003e\n\n\u003cp\u003eIn the conventional-targeting group, 147 patients had an event — a cumulative incidence of 9.7%, or roughly 1 in 10 patients.\u003c\/p\u003e\n\n\u003cp\u003eThe hazard ratio was \u003cstrong\u003e0.67\u003c\/strong\u003e (95% confidence interval, 0.52 to 0.86; P=0.002 by log-rank test). In plain terms, the intensive strategy reduced the relative risk of these events by about 33%. The absolute difference was 3.1 percentage points, which translates to roughly 3 fewer events for every 100 patients treated to the lower target.\u003c\/p\u003e\n\n\u003cp\u003eP=0.002 means there is about a 0.2% probability — 2 in 1,000 — that a difference this large arose by chance alone. The finding held up in the per-protocol analysis, which excluded patients with major protocol deviations.\u003c\/p\u003e\n\n\u003cp\u003eTwo individual components of the composite drove much of the benefit:\u003c\/p\u003e\n\n\u003cul\u003e\n  \u003cli\u003e\n\u003cstrong\u003eNonfatal heart attack:\u003c\/strong\u003e 0.8% in the intensive group vs. 1.7% in the conventional group (hazard ratio, 0.46; 95% CI, 0.23 to 0.91) — a 54% lower relative risk\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003eAny revascularization procedure:\u003c\/strong\u003e 4.8% vs. 7.5% (hazard ratio, 0.63; 95% CI, 0.47 to 0.84) — a 37% lower relative risk\u003c\/li\u003e\n\u003c\/ul\u003e\n\n\u003cp\u003eResults for the other individual components — death from cardiovascular causes, nonfatal stroke, and hospitalization for unstable angina — were also reported in the trial publication. Because the trial was designed primarily to test the combined end point, the individual component results should be interpreted with the understanding that they were not adjusted for multiple comparisons.\u003c\/p\u003e\n\n\u003ch2 id=\"safety\"\u003eSafety Results\u003c\/h2\u003e\n\n\u003cp\u003eSafety was a core part of the trial, and the news was reassuring. The incidence of prespecified safety end points was similar in the two groups, with one exception: fewer patients in the intensive-targeting group had a rise in creatinine, a marker used to monitor kidney function.\u003c\/p\u003e\n\n\u003cp\u003eThe safety end points the trial tracked included:\u003c\/p\u003e\n\n\u003cul\u003e\n  \u003cli\u003eNew-onset diabetes in patients who did not have diabetes at enrollment\u003c\/li\u003e\n  \u003cli\u003eWorsening blood sugar control in patients who already had diabetes\u003c\/li\u003e\n  \u003cli\u003eStatin-associated muscle symptoms serious enough to prompt a dose or regimen change\u003c\/li\u003e\n  \u003cli\u003eA diagnosis of cancer\u003c\/li\u003e\n  \u003cli\u003eCataract surgery\u003c\/li\u003e\n  \u003cli\u003eElevations in liver enzymes (aminotransferase), kidney markers (creatinine), or muscle enzymes (creatine kinase)\u003c\/li\u003e\n\u003c\/ul\u003e\n\n\u003cp\u003eRoughly 2.8% of all patients (85 people) stopped or reduced their cholesterol-lowering therapy because of an adverse event, with 50 of those in the intensive group and 35 in the conventional group. This difference is modest and reflects the fact that the intensive group was generally on stronger treatment.\u003c\/p\u003e\n\n\u003ch2 id=\"implications\"\u003eWhat This Means for Patients\u003c\/h2\u003e\n\n\u003cp\u003eThe trial answers a question that patients and doctors have been asking for years: is the newer, stricter cholesterol target actually better, or is it just a number on a guideline page? The answer, from this randomized trial, is that it is better — at least over 3 years in patients with established cardiovascular disease.\u003c\/p\u003e\n\n\u003cp\u003eThe benefit was not trivial. Patients aiming for below 55 mg per deciliter had about one-third fewer cardiovascular events, including fewer heart attacks and fewer repeat procedures to open blocked arteries. The safety profile was comparable, which matters because many patients worry that \"more aggressive\" automatically means \"more side effects.\"\u003c\/p\u003e\n\n\u003cp\u003eEqually important is the practical message about how the target was reached. Most of the extra benefit came from ordinary, widely available treatments — higher doses of statins and the addition of ezetimibe — not from expensive injectable drugs. PCSK9 inhibitors were used by fewer than 2.5% of patients in either group. This means the strategy is feasible for most patients, not just those with access to costly medications.\u003c\/p\u003e\n\n\u003cp\u003eThere is also a reassuring detail for patients who find it hard to hit a tough number. Nearly three quarters of intensive-group patients were below 70 mg per deciliter at 1 month, and that proportion climbed to 85.2% by 3 years. Progress toward the target counts.\u003c\/p\u003e\n\n\u003ch2 id=\"limitations\"\u003eLimitations: What the Study Could Not Prove\u003c\/h2\u003e\n\n\u003cp\u003eEvery trial has boundaries, and understanding them helps patients and doctors judge how to apply the results.\u003c\/p\u003e\n\n\u003cul\u003e\n  \u003cli\u003e\n\u003cstrong\u003eThe trial was open-label.\u003c\/strong\u003e Patients and doctors knew which target was assigned. This can influence behavior, such as how aggressively medications get adjusted. An independent committee adjudicated the cardiovascular events and diabetes outcomes without knowing group assignments, which reduces — but does not eliminate — this concern.\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003eTreatment decisions were left to physicians.\u003c\/strong\u003e Statin doses and the addition of ezetimibe or PCSK9 inhibitors were not rigidly fixed, so the comparison is between \u003cem\u003estrategies\u003c\/em\u003e (target numbers), not between specific drug regimens.\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003eFollow-up was relatively short.\u003c\/strong\u003e The median was 3.0 years. Longer-term effects of very low LDL cholesterol levels — on cognition, muscle, liver, and diabetes risk over decades — remain incompletely understood.\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003eSubgroup results are exploratory.\u003c\/strong\u003e The investigators explicitly noted that confidence intervals for subgroup and secondary analyses were not adjusted for multiple comparisons. So a striking result in one subgroup (say, patients with diabetes) cannot be treated as proven.\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003eThe groups did not separate perfectly.\u003c\/strong\u003e The achieved median LDL levels were 56 mg per deciliter and 66 mg per deciliter — a real difference, but not the full 15 mg per deciliter gap the targets imply. The true benefit of fully achieving a below-55 target could be larger or smaller than what was observed.\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003eThe population was specific.\u003c\/strong\u003e All patients were enrolled in South Korea, mean age was 64.4 years, and roughly 79% were men. Benefits and risks may differ in other populations, in women, and in older or younger patients.\u003c\/li\u003e\n\u003c\/ul\u003e\n\n\u003ch2 id=\"recommendations\"\u003ePractical Recommendations\u003c\/h2\u003e\n\n\u003cp\u003eIf you have atherosclerotic cardiovascular disease, here is how to use this information in conversation with your care team.\u003c\/p\u003e\n\n\u003col\u003e\n  \u003cli\u003e\n\u003cstrong\u003eAsk for your LDL cholesterol number and your target.\u003c\/strong\u003e Current guidelines for patients with ASCVD recommend a target below 55 mg per deciliter (1.4 mmol per liter). It helps to know where you stand and how far you are from that goal.\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003eKnow that reaching the target usually does not require exotic drugs.\u003c\/strong\u003e In this trial, the strategy relied mainly on stronger statin doses plus ezetimibe. PCSK9 inhibitors were used in fewer than 2.5% of patients.\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003eDo not stop or reduce your medication on your own.\u003c\/strong\u003e In the trial, fewer than 3% of patients stopped therapy because of side effects. If you have muscle aches or other symptoms, tell your doctor — regimens can often be adjusted rather than abandoned.\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003eKeep your follow-up appointments.\u003c\/strong\u003e This trial checked cholesterol and safety labs at 1 month and then annually for 3 years. Regular monitoring is how targets get reached safely.\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003eTreat cholesterol as one part of a bigger picture.\u003c\/strong\u003e In this trial, about 73% of patients had high blood pressure, 40% had diabetes, and about a quarter smoked. Controlling blood pressure, blood sugar, and tobacco use all matter.\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003eBe patient with the process.\u003c\/strong\u003e Only about 31% of patients in the intensive group hit below 55 mg per deciliter at 1 month. By 3 years, 60.8% had. Treatment is a marathon, not a sprint.\u003c\/li\u003e\n\u003c\/ol\u003e\n\n\u003c!-- ddn:faq:start --\u003e\n\u003ch2 id=\"ddn-faq\"\u003eFrequently Asked Questions\u003c\/h2\u003e\n\u003ch3\u003eWhat was the main finding of the Ez-PAVE trial?\u003c\/h3\u003e\n\u003cp\u003eIn a trial of 3,048 patients with established atherosclerotic cardiovascular disease, aiming for an LDL cholesterol below 55 mg\/dL reduced the risk of cardiovascular death, heart attack, stroke, repeat revascularization, or hospitalization for unstable angina by 33% compared with aiming below 70 mg\/dL over a median of 3 years. Safety outcomes were similar between groups.\u003c\/p\u003e\n\u003ch3\u003eWho was eligible to participate in the Ez-PAVE trial?\u003c\/h3\u003e\n\u003cp\u003ePatients aged 19 to 80 with documented atherosclerotic cardiovascular disease, including a previous heart attack or unstable angina, stable angina confirmed by testing, prior revascularization, stroke or transient ischemic attack, or peripheral artery disease. One key exclusion was an LDL cholesterol below 70 mg\/dL in a patient not taking a statin.\u003c\/p\u003e\n\u003ch3\u003eWhat treatments were used to reach the lower cholesterol target?\u003c\/h3\u003e\n\u003cp\u003eThe strategy relied mainly on higher doses of statins and adding ezetimibe. In the intensive group, high-intensity statin use was about 54% at 1 year versus 34% in the conventional group, and ezetimibe use rose to 66.6% versus 56.7% at 3 years. PCSK9 inhibitors were used by fewer than 2.5% of patients in either group.\u003c\/p\u003e\n\u003ch3\u003eWhat were the risks or side effects of aiming for the lower LDL target?\u003c\/h3\u003e\n\u003cp\u003eSafety outcomes were similar between the two groups, except fewer patients in the intensive group had a rise in creatinine, a kidney marker. About 2.8% of all patients stopped or reduced cholesterol-lowering therapy because of an adverse event—50 in the intensive group and 35 in the conventional group. This difference was modest.\u003c\/p\u003e\n\u003ch3\u003eHow low did LDL cholesterol actually go in each group?\u003c\/h3\u003e\n\u003cp\u003eDuring the trial, the intensive group had a median LDL cholesterol of 56 mg\/dL, while the conventional group had a median of 66 mg\/dL. The gap stayed consistent. At 3 years, 60.8% of the intensive group and 68.1% of the conventional group reached their assigned target, but 85.2% of the intensive group were below 70 mg\/dL.\u003c\/p\u003e\n\u003ch3\u003eWhat does a 33% relative risk reduction mean for me?\u003c\/h3\u003e\n\u003cp\u003eIt means that over a median of 3 years, patients aiming for the lower target had about one-third fewer cardiovascular events compared with those aiming for the higher target. The absolute difference was 3.1 percentage points, or roughly 3 fewer events for every 100 patients treated to the lower target.\u003c\/p\u003e\n\u003ch3\u003eWhat are the limitations of this trial?\u003c\/h3\u003e\n\u003cp\u003eThe trial was open-label, so patients and doctors knew the assigned target. Follow-up was relatively short at a median of 3 years, and long-term effects of very low LDL cholesterol remain incompletely understood. The population was specific—all in South Korea, mean age 64.4 years, and about 79% men—so results may differ in other groups.\u003c\/p\u003e\n\u003ch3\u003eIf I have clogged arteries and my doctor says an LDL below 70 mg\/dL is fine, when should I get a second opinion about aiming below 55 mg\/dL?\u003c\/h3\u003e\n\u003cp\u003eA second opinion is reasonable when your LDL target is set at below 70 mg\/dL despite established atherosclerotic cardiovascular disease. In a randomized trial of 3,048 such patients, aiming below 55 mg\/dL lowered the relative risk of cardiovascular death, heart attack, stroke, revascularization, or hospitalization for unstable angina by about 33% over a median of 3.0 years (6.6% vs. 9.7%), with similar safety. Most of that benefit came from higher statin doses plus ezetimibe, not injectable drugs. Diagnostic Detectives Network provides independent expert second opinions.\u003c\/p\u003e\n\u003c!-- ddn:faq:end --\u003e\n\n\u003ch2 id=\"source\"\u003eSource Information\u003c\/h2\u003e\n\n\u003cp\u003e\u003cstrong\u003eOriginal article title:\u003c\/strong\u003e Intensive LDL Cholesterol Targeting in Atherosclerotic Cardiovascular Disease\u003c\/p\u003e\n\n\u003cp\u003e\u003cstrong\u003eAuthors:\u003c\/strong\u003e Yong-Joon Lee, M.D.; Seung-Jun Lee, M.D.; Jin Won Kim, M.D.; Sang-Hyup Lee, M.D.; Gwang-Sil Kim, M.D.; Jae Hyoung Park, M.D.; Jin-Man Cho, M.D.; Woong Chol Kang, M.D.; Hyuck-Jun Yoon, M.D.; Won Ho Kim, M.D.; Seung-Jin Lee, M.D.; Jin Bae Lee, M.D.; Ji-Yong Jang, M.D.; Sanghoon Shin, M.D.; Ik Hyun Park, M.D.; Sung Uk Kwon, M.D.; Sunwon Kim, M.D.; Sung-Jin Hong, M.D.; Chul-Min Ahn, M.D.; Jung-Sun Kim, M.D.; Young-Guk Ko, M.D.; Donghoon Choi, M.D.; Myeong-Ki Hong, M.D.; Yangsoo Jang, M.D.; and Byeong-Keuk Kim, M.D., for the Ez-PAVE Investigators.\u003c\/p\u003e\n\n\u003cp\u003e\u003cstrong\u003ePublication:\u003c\/strong\u003e \u003cem\u003eThe New England Journal of Medicine\u003c\/em\u003e, April 9, 2026, Volume 394, Number 14, pages 1365–1375. Published online March 28, 2026. DOI: 10.1056\/NEJMoa2600283. Copyright © 2026 Massachusetts Medical Society.\u003c\/p\u003e\n\n\u003cp\u003e\u003cstrong\u003eTrial registration:\u003c\/strong\u003e Ez-PAVE, ClinicalTrials.gov number NCT04626973.\u003c\/p\u003e\n\n\u003cp\u003e\u003cstrong\u003eFunding:\u003c\/strong\u003e The Cardiovascular Research Center (South Korea) and Yuhan. The funders had no role in trial design, data collection or analysis, interpretation of results, or manuscript writing.\u003c\/p\u003e\n\n\u003cp\u003e\u003cem\u003eThis patient-friendly article is based on peer-reviewed research. It summarizes a single randomized clinical trial and does not replace personalized medical advice. Please discuss any changes to your cholesterol treatment with your own clinician.\u003c\/em\u003e\u003c\/p\u003e","brand":"DiagnosticDetectives.Com","offers":[{"title":"Default Title","offer_id":47738969587868,"sku":null,"price":0.0,"currency_code":"USD","in_stock":true}],"url":"https:\/\/diagnosticdetectives.com\/zh\/products\/targeting-ldl-cholesterol-below-55-mg-dl-beat-the-70-mg-dl-target-in-patients-with-clogged-arteries","provider":"DiagnosticDetectives.Com","version":"1.0","type":"link"}