EARLY: Educational Intervention to Improve Patient Awareness on Early LDL-C Lowering in Secondary Prevention (EARLY)

Educational Intervention for Patient's Awareness on eaRly LDL-C Lowering Using Novel Pharmacological Strategies in secondarY Prevention (EARLY)

Cluster Randomized Trial to test the effectiveness of a patient level delivered educational intervention to improve the awareness on the relevance of obtaining LDL cholesterol recommended goals in patients admitted for an acute coronary syndrome, as compared to usual care. Overall, 24 sites (Coronary Care Units) will be included in the study, 12 randomized to the intervention and 12 to usual care. Overall, 240 patients will be enrolled during an acute coronary syndrome hospitalization.

Study Overview

• Status: Not yet recruiting
• Conditions: Acute Coronary Syndromes; Chronic Coronary Syndromes
• Intervention / Treatment: Other: Patient-oriented educational intervention

Detailed Description

Elevated LDL cholesterol levels are associated with an increased risk of adverse events after an acute coronary syndrome. The higher the LDL cholesterol level at patients' admission for acute coronary syndrome, the greater the intensity of lipid-lowering treatment to be adopted to obtain the greatest benefits in terms of reduction of all-cause and cardiovascular mortality.

Despite European Society of Cardiology guideline recommendations to achieve low LDL cholesterol targets in patients with acute coronary syndrome (halving of baseline LDL cholesterol values and reaching LDL cholesterol values < 55 mg/dl or < 40 mg/dl in the case of a second event within two years of the first), this is unlikely to happen in clinical practice. Recent observational studies, such as the Da Vinci and Santorini, provide important insights into the practical management of lipid-lowering therapy in post-ACS patients in daily clinical practice, showing that only about 20% of high- or very-high-risk patients achieve guideline-recommended targets.

On the other hand, aggressive control of modifiable risk factors could prevent up to 80% of premature deaths related to cardiovascular disease. This underscores the importance of healthcare professionals in maximizing prevention efforts. Improvements in community health could prevent millions of serious cardiovascular events each year if properly implemented.

New therapies, such as PCSK9 inhibitors (monoclonal antibodies) or siRNA (inclisiran), offer an option for further and faster LDL cholesterol reduction during the peri- and post-acute coronary syndrome period, associated with a marked improvement in prognosis.

However, the use of these pharmacological strategies is currently quite limited in clinical practice. Several conditions account for the reduced "adherence" of clinicians and patients to the recommended therapies. Health disparities due to socioeconomic status, age, race, gender and cost, limited access to healthcare, perceived side effects associated with lipid-lowering therapies, health literacy and the presence of comorbidities, are all factors contributing to the suboptimal use of proposed therapies. Furthermore, clinical factors, including failure to identify patients requiring LDL cholesterol reassessment, insufficient monitoring, and clinical inertia have been associated with an insufficient use of lipid-lowering therapies.

Recently, the Italian Association of Hospital Cardiologists published a position paper on the treatment of hypercholesterolemia in patients with acute coronary syndrome. In the document, aimed at achieving the lipid targets outlined in the ESC/EAS 2019 guidelines more quickly than those currently recommended (from 8 weeks of the guidelines to 4 weeks of the Italian Association of Hospital Cardiologists document with a progressive and sustainable approach) and including new therapeutic options to reduce LDL cholesterol levels, a personalized therapeutic intervention based on LDL cholesterol levels at the time of hospital admission was proposed.

As a consequence, implementing lipid-lowering treatments early according to patients' clinical risk and the pharmacological options available to clinicians, while improving patients' awareness of cardiovascular risk, remains one of the primary objectives of the clinical cardiologist in secondary prevention.

Technology can effectively serve as an essential aid in achieving therapeutic targets. The introduction of dedicated applications could facilitate doctor-patient communication. On the basis of this evidence, the investigators designed the present study with the aim to evaluate if an educational intervention to improve the awareness on the relevance of obtaining LDL cholesterol recommended goals in patients with confirmed diagnosis of acute coronary syndrome, as compared to usual care can increase the proportion of patients at LDL cholesterol goal as suggested by 2019 ESC/EAS guidelines.

• Study Type: Interventional
• Enrollment (Estimated): 240
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Leonardo De Luca, MD; Phone Number: +390555101355; Email: early@heartcarefoundation.it

Study Locations

• Italy
  • Acquaviva delle Fonti, Italy, 70021
    • Ospedale Miulli - U.O.C. CARDIOLOGIA - UTIC
    • Contact: Nicola Vitulano, MD; Phone Number: +39 0803054357; Email: n.vitulano@miulli.it
    • Principal Investigator: Nicola Vitulano, MD
  • Ancona, Italy, 60122
    • A.O.U. delle Marche - Cardiologia Ospedaliera e UTIC
    • Contact: Matilda Shkoza, MD; Phone Number: +39 071 5965320; Email: matilda.shkoza@ospedaliriuniti.marche.it
    • Principal Investigator: Matilda Shkoza, MD
  • Arzignano, Italy, 36071
    • Ospedale Civile - U.O.C. Di Cardiologia
    • Contact: Claudio Bilato, MD; Phone Number: + 39 0444 479191-479106; Email: claudio.bilato@aulss8.veneto.it
    • Principal Investigator: Claudio Bilato, MD
  • Benevento, Italy, 82100
    • Azienda Ospedaliera San Pio-PO G. Rummo - Cardiologia Interventistica e UTIC
    • Contact: Marino Scherillo, MD; Phone Number: +39 0824 57679; Email: marino.scherillo@gmail.com
    • Principal Investigator: Marino Scherillo, MD
  • Cagliari, Italy, 09134
    • Arnas G. Brotzu - Cardiologia Con Utic
    • Contact: Giulio Binaghi, MD; Phone Number: +39 070 539512; Email: giulio.binaghi@aob.it
    • Principal Investigator: Giulio Binaghi, MD
  • Caserta, Italy, 81100
    • Azienda Ospedaliera S. Anna E S. Sebastiano - U.O. Cardiologia D'Emergenza Con Utic
    • Principal Investigator: Paolo Calabrò, MD
    • Contact: Paolo Calabrò, MD; Phone Number: +39 0823 232352; Email: paolo.calabro@unicampania.it
  • Catania, Italy, 95126
    • Azienda Ospedaliera Cannizzaro - Uoc Cardiologia
    • Contact: Simona Giubilato, MD; Phone Number: +39 095 7264739; Email: simogiub@hotmail.com
    • Principal Investigator: Simona Giubilato, MD
  • Crema, Italy, 26013
    • Ospedale Maggiore - U.O. Cardiologia E Utic
    • Contact: Sabato D'Amore, MD; Phone Number: +39 0373 280033-280097; Email: sabato.damore@asst-crema.it
    • Principal Investigator: Sabato D'Amore, MD
  • Erice, Italy, 91016
    • Po S. Antonio Abate Di Trapani - U.O.C. Di Cardiologia, Utic Ed Emodinamica
    • Contact: Giovanna Geraci, MD; Phone Number: +39 0923 809317; Email: giovannageraci68@icloud.com
    • Principal Investigator: Giovanna Geraci, MD
  • Genova, Italy, 16100
    • Ospedale Padre Antero Micone - Sc Cardiologia - Utic
    • Contact: Kevin Pisani, MD; Phone Number: +39 010 8498401-8498341; Email: kevin.pisani@asl3.liguria.it
    • Principal Investigator: Kevin Pisani, MD
  • Genova, Italy, 16149
    • Ospedale Villa Scassi - Asl 3 Ligure - Sc Cardiologia Utic
    • Contact: Luisiana Pastorino, MD; Phone Number: +39 010 8492351; Email: luisiana.pastorino@asl3.liguria.it
    • Principal Investigator: Luisiana Pastorino, MD
  • Livorno, Italy, 57124
    • Ospedali Riuniti - U.O.C. Cardiologia E Utic
    • Contact: Emilio Maria Pasanisi, MD; Phone Number: +39 0586 223387; Email: emiliomariagiovanni.pasanisi@uslnordovest.toscana.it
    • Principal Investigator: Emilio Maria Pasanisi, MD
  • Milan, Italy, 20162
    • Asst Ospedale Metropolitano Niguarda - Cardiologia 1 - Emodinamica
    • Contact: Giovanna Viola, MD; Phone Number: +39 02 64441-64442308-2565; Email: giovanna.viola@ospedaleniguarda.it
    • Principal Investigator: Giovanna Viola, MD
  • Monza, Italy, 20900
    • Fondazione Irccs San Gerardo Dei Tintori - Ospedale San Gerardo - U.O.C. Cardiologia
    • Contact: Andrea Mauro, MD; Phone Number: +39 039 2333304; Email: andrea.mauro@irccs-sangerardo.it
    • Principal Investigator: Andrea Mauro, MD
  • Napoli, Italy, 80131
    • Aorn Cardarelli - U.O. Cardiologia Con Utic
    • Contact: Ciro Mauro, MD; Phone Number: +39 0817472808; Email: ciro.mauro@aocardarelli.it
    • Principal Investigator: Ciro Mauro, MD
  • Palermo, Italy, 90146
    • Aor Villa Sofia-Cervello P.O. Cervello - U.O. Cardiologia - Cervello
    • Contact: Vincenzo Polizzi, MD; Phone Number: +39 091 7802692; Email: v.polizzi@villasofia.it
    • Principal Investigator: Vincenzo Polizzi, MD
  • Palermo, Italy, 90146
    • AOR Villa Sofia-Cervello PO Villa Sofia - UOC Cardiologia e UTIC e Emodinamica-Villa Sofia
    • Contact: Maria Stella Scaccianoce, MD; Phone Number: +39 091 7808096; Email: stellascaccia@gmail.com
    • Principal Investigator: Maria Stella Scaccianoce, MD
  • Pavia, Italy, 27100
    • FONDAZIONE IRCCS POLICLINICO SAN MATTEO - UOC Cardiologia
    • Principal Investigator: Leonardo De Luca, MD
    • Contact: Leonardo De Luca, MD; Phone Number: +39 0382 503157; Email: l.deluca@smatteo.pv.it
  • Pescara, Italy, 65124
    • Ospedale Santo Spirito - Cardiologia Con Utic
    • Contact: Massimo Di Marco, MD; Phone Number: +39 085 4252526; Email: massimo.dimarco@asl.pe.it
    • Principal Investigator: Massimo Di Marco, MD
  • Piacenza, Italy, 29100
    • Ospedale Civile Guglielmo da Saliceto - UOC Cardiologia e UTIC
    • Contact: Daniela Aschieri, MD; Phone Number: +39 0523 303209-303215; Email: d.aschieri@ausl.pc.it
    • Principal Investigator: Daniela Aschieri, MD
  • Prato, Italy, 59100
    • Ospedale Santo Stefano - U.O. Cardiologia
    • Contact: Emilio Di Vincenzo, MD; Phone Number: +39 0574 803762; Email: emilio.divincenzo@uslcentro.toscana.it
    • Principal Investigator: Emilio Di Vincenzo, MD
  • Reggio Emilia, Italy, 42100
    • Po Santa Maria Nuova - Ausl Re Irccs - Soc Cardiologia Ospedaliera
    • Contact: Alessandro Navazio, MD; Phone Number: +39 0522 296429; Email: alessandro.navazio@ausl.re.it
    • Principal Investigator: Alessandro Navazio, MD
  • Roma, Italy, 00135
    • P.O. San Filippo Neri - Asl Roma 1 - Cardiologia Clinica E Riabilitativa
    • Contact: Furio Colivicchi, MD; Phone Number: +39 06 33062429; Email: furio.colivicchi@aslroma1.it
    • Principal Investigator: Furio Colivicchi, MD
  • Roma, Italy, 00152
    • Ospedale San Camillo - Uoc Cardiologia
    • Contact: Domenico Gabrielli, MD; Phone Number: +39 0658704419; Email: dgabrielli@scamilloforlanini.rm.it
    • Principal Investigator: Domenico Gabrielli, MD
  • Roma, Italy, 00169
    • Policlinico Casilino - U.O.C. Cardiologia
    • Contact: Germana Panattoni, MD; Phone Number: +39 06 23188205; Email: gpanattoni@policlinicocasilino.it
    • Principal Investigator: Germana Panattoni, MD
  • Salerno, Italy, 84131
    • Aou S. Giovanni Di Dio-Ruggi D'Aragona - Ssd Utic
    • Contact: Amelia Ravera, MD; Phone Number: +39 089 673136; Email: amelia.ravera@sangiovannieruggi.it
    • Principal Investigator: Amelia Ravera, MD
  • Sassari, Italy, 07100
    • Ospedale Ss. Annunziata - Cardiologia Clinica Ed Interventistica
    • Contact: Gavino Casu, MD; Phone Number: +39 079 2646120; Email: gavino.casu@aouss.it
    • Principal Investigator: Gavino Casu, MD
  • Viterbo, Italy, 01100
    • Ospedale Belcolle - Uosd Utic Polo
    • Contact: Francesco Serra, MD; Phone Number: +39 0761 339435; Email: francesco.serra@asl.vt.it
    • Principal Investigator: Francesco Serra, MD
  • TO
    • Orbassano, TO, Italy, 10043
      • Aou San Luigi Gonzaga - S.C.D.O. Cardiologia
      • Contact: Carloalberto Biolè, MD; Phone Number: +39 011 9026701-9026706; Email: c.biole@sanluigi.piemonte.it
      • Principal Investigator: Carloalberto Biolè, MD
    • Torino, TO, Italy, 10128
      • Ospedale Mauriziano Umberto I - Sc Cardiologia
      • Contact: Giuseppe Musumeci, MD; Phone Number: +39 011 5081111-5082515-2525; Email: gmusumeci@mauriziano.it
      • Principal Investigator: Giuseppe Musumeci, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age ≥18 and <80 years old.
2. Males and females at birth.

3. Baseline LDL-Cholesterol:

   • ≥ 130 mg/dl (in statin-naïve patients or who have not followed a stable (unchanged) statin regimen for at least 4 weeks prior to enrollment) or
   • ≥110 mg/dl (in patients who have received stable moderate-intensity or low-intensity statin treatment in the 4 weeks prior to enrollment) or
   • ≥100 mg/dl (in patients who have received stable treatment with high-intensity statins in the 4 weeks prior to enrollment)
4. Discharged at home
5. Ability to understand the requirements of the study and to provide informed consent

Exclusion Criteria:

1. Patients who have previously received or currently treated with PCSK9i (evolocumab or alirocumab) or siRNA (inclisiran)
2. Unstable clinical status (hemodynamic or electrical instability)
3. Uncontrolled cardiac arrhythmias, defined as recurrent, symptomatic ventricular tachycardia or atrial fibrillation or flutter with rapid ventricular response
4. Severe renal dysfunction, defined by eGFR < 30 mL/min/1.73 m2
5. Active liver disease or liver dysfunction, reported in the medical record or defined by AST or ALT levels > 3 times the upper limit of normal.
6. Reported intolerance to statins defined by the following criteria: inability to tolerate at least two different statins; intolerance associated with confirmed and intolerable statin-related adverse effects or significant biomarker abnormalities; improvement/resolution of symptoms or biomarkers following dose decrease or discontinuation; symptoms or changes in biomarkers not attributable to established predispositions.
7. Treatment with systemic steroids or systemic cyclosporine within the past 3 months (e.g., intravenously, intramuscularly, or orally)
8. Known active infection or severe hematologic, metabolic, or endocrine dysfunction as judged by the Investigator.
9. Current inclusion in other pharmacological and non-pharmacological experimental studies.
10. Pregnancy. For women of childbearing potential (age < 50 years and last menses <12 months prior to screening) who have not undergone tubal ligation, oophorectomy, or hysterectomy, pregnancy will be excluded from a pregnancy test prior to inclusion in the study.
11. Active neoplasia or very severe disease compromising short-medium term life expectancy.

Only for sites randomized to the interventional group:

• Patients without a device suitable for App use (eg. Smartphone or tablet) or patients that do not consent to receive push notifications by the App.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Quality-improvement educational intervention; Patients included in the interventional arm will be guided to download a smartphone App which will allow them: To see a 3-minute animated video aimed at explaining in layman terminology the benefits of intensifying LDL cholesterol reduction therapy, gaps in prescribing, reasons for clinical inertia, and motivations for patients to achieve recommended targets.; To see a check-list intended to propose a conscious way of managing dyslipidemia by the patient in relation to the targets to be achieved.; To include the ongoing lipid lowering therapy and enter the control LDL cholesterol value evaluated during hospitalization and that patient will perform in the days preceding the all the follow-up visits showing if goal has been achieved.	Other: Patient-oriented educational intervention; APP support
No Intervention: Usual care; Patients followed in the centers randomized to the control arm will be managed by usual care in accordance with local clinical guidance.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of patients achieving Guideline recommended LDL-Cholesterol goal	To compare the rate of patients with acute coronary syndrome who achieve the 2019 European Society of Cardiology/European Atherosclerosis Society guideline recommended LDL-Cholesterol goal (<55 mg/dl or <40 mg/dl in patients with recurrent events in the previous 24 months despite maximal lipid lowering treatment) at 12 months in sites following the interventional education protocol versus those receiving usual care.	12 month

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
LDL-Cholesterol variation	Change in LDL-Cholesterol from baseline.	12 months
Use of Injective Lipid Lowering Therapy	Rate of patients who received PCSK9i inhibitors (monoclonal antibodies) or inclisiran during hospitalization (very fast track)	1 month
Use of Injective Lipid Lowering Therapy	Rate of patients who received PCSK9i inhibitors (monoclonal antibodies) or inclisiran during hospitalization (very fast track)	6 month
Number of participants with lipid lowering treatments related adverse events	In the eCRF at the 6-month follow-up visit discontinuation of lipid-lowering treatments will be recorded together with side effects most frequently associated with these treatments (e.g., arthralgia, limb pain, flu-like symptoms/malaise, myalgia, back pain, and elevated transaminases).	6 months
Number of participants with lipid lowering treatments related adverse events	In the eCRF at the 12-month follow-up visit discontinuation of lipid-lowering treatments will be recorded together with side effects most frequently associated with these treatments (e.g., arthralgia, limb pain, flu-like symptoms/malaise, myalgia, back pain, and elevated transaminases).	12 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cardiovascular death (explorative objective)	Assess the rate of cardiovascular deaths	12 month
New hospitalizations for atherothrombotic events (explorative objective)	Assess the rate of new hospitalizations for atherothrombotic events.	12 month
All-cause mortality (explorative objective)	Assess the rate of all-cause mortality	12 month
All-cause hospitalizations (explorative objective)	Assess the rate of all-cause hospitalizations	12 month

Collaborators and Investigators

• Sponsor: Heart Care Foundation
• Collaborators: Novartis Farma S.p.A.

Publications and helpful links

General Publications

• Ray KK, Molemans B, Schoonen WM, Giovas P, Bray S, Kiru G, Murphy J, Banach M, De Servi S, Gaita D, Gouni-Berthold I, Hovingh GK, Jozwiak JJ, Jukema JW, Kiss RG, Kownator S, Iversen HK, Maher V, Masana L, Parkhomenko A, Peeters A, Clifford P, Raslova K, Siostrzonek P, Romeo S, Tousoulis D, Vlachopoulos C, Vrablik M, Catapano AL, Poulter NR; DA VINCI study. EU-Wide Cross-Sectional Observational Study of Lipid-Modifying Therapy Use in Secondary and Primary Care: the DA VINCI study. Eur J Prev Cardiol. 2021 Sep 20;28(11):1279-1289. doi: 10.1093/eurjpc/zwaa047.
• Byrne RA, Rossello X, Coughlan JJ, Barbato E, Berry C, Chieffo A, Claeys MJ, Dan GA, Dweck MR, Galbraith M, Gilard M, Hinterbuchner L, Jankowska EA, Juni P, Kimura T, Kunadian V, Leosdottir M, Lorusso R, Pedretti RFE, Rigopoulos AG, Rubini Gimenez M, Thiele H, Vranckx P, Wassmann S, Wenger NK, Ibanez B; ESC Scientific Document Group. 2023 ESC Guidelines for the management of acute coronary syndromes. Eur Heart J. 2023 Oct 12;44(38):3720-3826. doi: 10.1093/eurheartj/ehad191. No abstract available.
• Mach F, Baigent C, Catapano AL, Koskinas KC, Casula M, Badimon L, Chapman MJ, De Backer GG, Delgado V, Ference BA, Graham IM, Halliday A, Landmesser U, Mihaylova B, Pedersen TR, Riccardi G, Richter DJ, Sabatine MS, Taskinen MR, Tokgozoglu L, Wiklund O; ESC Scientific Document Group. 2019 ESC/EAS Guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk. Eur Heart J. 2020 Jan 1;41(1):111-188. doi: 10.1093/eurheartj/ehz455. No abstract available.
• De Luca L, Riccio C, Navazio A, Valente S, Cipriani M, Corda M, De Nardo A, Francese GM, Napoletano C, Tizzani E, Roncon L, Caldarola P, Gulizia MM, Gabrielli D, Oliva F, Colivicchi F. ANMCO position paper on the management of hypercholesterolaemia in patients with acute coronary syndrome. Eur Heart J Suppl. 2023 May 18;25(Suppl D):D312-D322. doi: 10.1093/eurheartjsupp/suad100. eCollection 2023 May.
• Ray KK, Haq I, Bilitou A, Manu MC, Burden A, Aguiar C, Arca M, Connolly DL, Eriksson M, Ferrieres J, Laufs U, Mostaza JM, Nanchen D, Rietzschel E, Strandberg T, Toplak H, Visseren FLJ, Catapano AL; SANTORINI Study Investigators. Treatment gaps in the implementation of LDL cholesterol control among high- and very high-risk patients in Europe between 2020 and 2021: the multinational observational SANTORINI study. Lancet Reg Health Eur. 2023 Apr 5;29:100624. doi: 10.1016/j.lanepe.2023.100624. eCollection 2023 Jun.

Study record dates

Study Major Dates

• Study Start (Estimated): December 11, 2025
• Primary Completion (Estimated): August 11, 2027
• Study Completion (Estimated): August 11, 2027

Study Registration Dates

• First Submitted: November 14, 2025
• First Submitted That Met QC Criteria: November 19, 2025
• First Posted (Actual): November 26, 2025

Study Record Updates

• Last Update Posted (Actual): November 26, 2025
• Last Update Submitted That Met QC Criteria: November 19, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Keywords: Acute Coronary Syndrome; LDL cholesterol; educational intervention; Lipid lowering drugs; Patient awareness
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Heart Diseases; Myocardial Ischemia; Acute Coronary Syndrome
• Other Study ID Numbers: K28

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No