Primary Prevention of Cardiovascular Disease with a Mediterranean Diet Supplemented with Extra-Virgin Olive Oil or Nuts.
Level 2 - randomized trial
Individual randomized controlled trial reanalyzed with propensity-score adjustments due to protocol deviations
PubMed 29897866 · doi:10.1056/NEJMoa1800389
What was done
In a multicenter trial in Spain, 7,447 participants (55 to 80 years of age, 57% women) at high cardiovascular risk without cardiovascular disease at baseline were assigned to one of three diets: a Mediterranean diet supplemented with extra-virgin olive oil, a Mediterranean diet supplemented with mixed nuts, or a control diet with advice to reduce dietary fat. Participants received quarterly educational sessions and dietary provisions (olive oil, nuts, or nonfood gifts). The primary endpoint was major cardiovascular events (myocardial infarction, stroke, or cardiovascular death) over a median follow-up of 4.8 years. Following the identification of protocol deviations in randomization at certain sites and among household members, effect estimates were revised using analyses adjusted for baseline characteristics and propensity scores, as well as sensitivity analyses omitting 1,588 participants with protocol deviations.
What was found
A primary endpoint event occurred in 288 participants: 96 in the olive oil group (3.8%), 83 in the nut group (3.4%), and 109 in the control group (4.4%). In the adjusted intention-to-treat analysis, the hazard ratio for major cardiovascular events compared with the control diet was 0.69 (95% CI, 0.53 to 0.91) for the Mediterranean diet with extra-virgin olive oil and 0.72 (95% CI, 0.54 to 0.95) for the Mediterranean diet with nuts. Results were similar after omitting 1,588 participants with known or suspected protocol departures.
Why it matters
This corrected reanalysis demonstrates that a Mediterranean diet supplemented with either extra-virgin olive oil or nuts significantly lowers the primary incidence of major cardiovascular events in older individuals at high cardiovascular risk.
Limits
Protocol deviations occurred during execution, including non-randomized enrollment of household members and inconsistent use of randomization tables at two study sites, necessitating observational-style propensity adjustments. The trial was stopped early after an interim analysis, and the cohort was limited to an older Spanish population at high cardiovascular risk, which may limit generalizability to lower-risk or non-Mediterranean populations.
Cited by
- supports In a randomized trial in Spain with over 7,500 participants (PREDIMED), the Mediterranean diet intervention was halted after roughly 5 years because the cardiovascular benefits were so pronounced that continuing the control diet was deemed unethical.