Incidence of major adverse cardiovascular events decreases with greater adherence to both Mediterranean and low-fat dietary patterns in secondary prevention patients: a randomized controlled trial
In people with prior coronary disease, stronger long-term adherence to either a Mediterranean-style or low-fat diet was linked to fewer major heart and stroke events.
*Randomized controlled trial with adherence subgroup analysis; Level 1b (OCEBM).
*Randomized controlled trial with adherence subgroup analysis; Level 1b (OCEBM).
Citation
Delgado-Lista J, Alcala-Diaz JF, Torres-Peña JD, et al; CORDIOPREV Investigators. Incidence of major adverse cardiovascular events decreases with greater adherence to both Mediterranean and low-fat dietary patterns in secondary prevention patients: a randomized controlled trial. European Journal of Internal Medicine. 2026;147:106733. doi:10.1016/j.ejim.2026.106733
Background
Healthy eating is recommended after coronary disease, but it is unclear how much “sticking with the diet” over years changes future risk. This trial examined whether higher measured adherence predicted fewer repeat events.
Patients
1002 adults (age 20–75) in Spain with established coronary heart disease; no coronary events in prior 6 months; excluded severe illness/limited life expectancy.
Intervention
Mediterranean-style diet program; adherence measured repeatedly with a Mediterranean diet score (0–14).
Control
Low-fat diet program; adherence measured repeatedly with a low-fat diet score (0–9).
Outcome
Major adverse cardiovascular events (composite): heart attack, coronary revascularization, ischemic stroke, peripheral artery disease, or cardiovascular death.
Follow-up Period
7 years
Results
| Finding | Event rate | Adjusted relative risk |
|---|---|---|
| Mediterranean diet: highest vs lowest adherence | 10.81% vs 44.44% | Hazard ratio ~0.14–0.15 (highest vs lowest) |
| Low-fat diet: highest vs lowest adherence | 9.09% vs 35.71% | Hazard ratio ~0.13–0.14 (highest vs lowest) |
| Exploratory: Mediterranean vs low-fat after removing least-adherent groups | — | Hazard ratio 0.71 (95% confidence interval 0.52–0.95) |
Adjusted models included age, sex, high blood pressure, low-density lipoprotein cholesterol target status, body mass index, smoking, statin intensity, and diabetes.
Limitations
Adherence level was not randomized; excluding low-adherence participants breaks random assignment and may select more motivated/healthier people. Single-country setting with intensive dietitian follow-up and free foods may limit general use. Composite outcomes can be driven by specific components.
Funding
Spanish foundations and government grants; European Union; funders had no study-role.
Clinical Application
For secondary prevention, prioritize sustained, measurable adherence to a Mediterranean-style or low-fat diet, using repeated check-ins; the “dose” of adherence appears crucial.
Discussion
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In this 7-year randomized controlled trial of Mediterranean vs low-fat diet in CHD patients, higher adherence within the Mediterranean arm was associated with lower MACE (e.g., MEDAS >12: 10.81% vs MEDAS <9: 44.44%; HR 0.162). Because adherence is post-randomization, how much should this influence practice vs reflect confounding/healthy-adherer bias? The authors compared outcomes after excluding the least-adherent participants (e.g., removing MEDAS <9 or low-fat score <4), and the Mediterranean diet then appeared better (HR 0.707). What is the main validity concern with this type of analysis in a randomized trial?
validity concern: people's behaviors confound results/some of the effect can be explained by different health behaviors overall rather than the diet alone.