Are there any outcome trials with pitavastatin?

Pitavastatin Outcome Trials

Yes, pitavastatin has demonstrated cardiovascular benefit in outcome trials, most notably the REAL-CAD trial in Japanese patients with stable coronary artery disease and the REPRIEVE trial in patients with HIV infection.

Major Cardiovascular Outcome Trials

REAL-CAD Trial (Japanese Population)

• The REAL-CAD trial provided the first evidence that high-dose statin therapy has cardiovascular outcomes benefits in an Asian population, comparing pitavastatin 4 mg/day versus 1 mg/day in 13,054 Japanese patients with stable coronary artery disease 1.
• High-dose pitavastatin (4 mg/day) significantly reduced cardiovascular events compared with low-dose (1 mg/day) in this secondary prevention population 1.
• This trial established that moderate-intensity doses of pitavastatin benefit Japanese patients with coronary artery disease 1.
• The study was designed as a prospective, multicenter, randomized, open-label, blinded-endpoint trial with an average follow-up of 5 years 2.

REPRIEVE Trial (HIV Population)

• In the REPRIEVE trial of 7,769 participants with HIV infection receiving antiretroviral therapy, pitavastatin calcium 4 mg significantly reduced major adverse cardiovascular events (MACE) by 35% 1, 3.
• After 5.1 years of follow-up, the incidence of MACE was 4.81/1000 person-years in the pitavastatin group versus 7.32/1000 person-years in placebo (HR 0.65; 95% CI 0.48–0.90; p = 0.002) 1.
• This trial demonstrated cardiovascular benefit in a low-to-moderate cardiovascular risk population with HIV infection 1.
• Muscle-related symptoms occurred in only 2.3% of pitavastatin-treated patients 1.

Supporting Evidence from Other Studies

LIVES Study (Japanese Post-Marketing Surveillance)

• The 5-year LIVES extension study (N = 6,582) showed that on-treatment levels of both HDL-C and LDL-C were significant predictors for cardiovascular and cerebrovascular risk 4.
• Multivariate analysis demonstrated that the greatest reduction in cardiovascular and cerebrovascular risk was achieved by patients reaching both their LDL-C and HDL-C targets 4.
• Long-term pitavastatin treatment was well tolerated with maintained LDL-C reduction and continued HDL-C elevation over 5 years 4.

Comparative Outcome Study

• A randomized trial comparing pitavastatin 2 mg/day versus atorvastatin 10 mg/day in 664 high-risk hypercholesterolemic patients (76% with diabetes, 74% primary prevention) over 240 weeks showed pitavastatin significantly reduced the primary composite endpoint by 63% (2.9% vs 8.1%, HR 0.366; 95% CI 0.170-0.787; P = 0.01) 5.
• The secondary endpoint (primary endpoint plus coronary revascularization) was reduced by 65% with pitavastatin (4.5% vs 12.9%, HR 0.350; 95% CI 0.189-0.645, P = 0.001) 5.
• These benefits occurred despite similar LDL-C lowering between both statins 5.

Clinical Context and Implications

Unique Properties Supporting Outcomes

• Pitavastatin's glucose-neutral profile through phosphatidylinositol 3-kinase (PI3K) inhibition may contribute to cardiovascular benefit, particularly in patients with metabolic disturbances 1, 3.
• The drug does not increase lipoprotein(a) levels, unlike many other statins, which may provide additional cardiovascular protection 3.
• Pitavastatin demonstrates intolerance rates similar to placebo, supporting long-term adherence necessary for outcome benefits 1, 3.

Guideline Recognition

• International lipid expert panels recommend pitavastatin as a rational treatment choice in patients with metabolic disturbances, diabetes/risk of diabetes, and pre-diabetes based on outcome trial evidence 1.
• The 2018 ACC/AHA cholesterol guideline specifically cites the REAL-CAD trial as evidence for pitavastatin's cardiovascular benefit in secondary prevention 1.

Important Caveats

• Most outcome trial data for pitavastatin comes from Asian populations (particularly Japanese) and patients with HIV infection, which may limit generalizability to other populations 1.
• While pitavastatin has demonstrated cardiovascular benefit, rosuvastatin and atorvastatin have more extensive outcome data across broader populations 3.
• The REAL-CAD trial used moderate-intensity doses (4 mg) that may give results similar to higher intensities in non-Japanese patients due to potential ethnic differences in statin sensitivity 1.