High-Dose Versus Low-Dose Pitavastatin in Japanese Patients With Stable Coronary Artery Disease (REAL-CAD): A Randomized Superiority Trial.
Level 2 - randomized trial
Large multicenter randomized controlled trial with blinded endpoint evaluation
PubMed 29735587 · doi:10.1161/CIRCULATIONAHA.117.032615
What was done
In a prospective, multicenter, open-label, blinded endpoint randomized trial (REAL-CAD), 13,054 Japanese patients with stable coronary artery disease (mean age 68 years, 83% male) who achieved LDL-C <120 mg/dL during a run-in period on pitavastatin 1 mg/day were randomized 1:1 to high-dose pitavastatin (4 mg/day; n=6,526) or low-dose pitavastatin (1 mg/day; n=6,528). The primary outcome was a composite of cardiovascular death, nonfatal myocardial infarction, nonfatal ischemic stroke, or unstable angina requiring emergency hospitalization, followed for a median of 3.9 years.
What was found
During follow-up, LDL-C was 14.7 mg/dL lower in the high-dose group than in the low-dose group (P < 0.001). High-dose pitavastatin significantly reduced the primary composite endpoint compared to low-dose therapy (4.3% [266/6,526] vs 5.4% [334/6,528]; HR 0.81; 95% CI 0.69–0.95; P = 0.01). The secondary composite endpoint was also significantly reduced (7.9% [489 patients] vs 9.7% [600 patients]; HR 0.83; 95% CI 0.73–0.93; P = 0.002), along with significant reductions in all-cause death, myocardial infarction, and clinically indicated coronary revascularization. Serious adverse event rates were low in both groups.
Why it matters
This trial establishes that high-dose statin therapy provides superior cardiovascular risk reduction compared with low-dose therapy in an East Asian population with stable coronary artery disease.
Limits
The trial used an open-label design (mitigated by blinded endpoint evaluation), enrolled exclusively Japanese patients with stable coronary artery disease, and had a high proportion of male participants (83%).
Cited by
- contradicts Low doses of statins are sufficient to impact vascular inflammation, lower CRP, improve endothelial function, and stabilize arterial plaque without needing high or moderate doses.