A higher dose of pitavastatin can benefit Japanese patients with stable coronary artery disease (CAD) compared with a low-dose pitavastatin, even though cardiovascular (CV) event incidence is known to be lower in Asian than Western patients, according to the REAL-CAD study presented at the AHA Scientific Sessions 2017.

“High-intensity statins are not widely used in daily clinical practice, particularly in Asia,” said Dr Hiroaki Shimokawa of Tohoku University Graduate School of Medicine in Sendai, Japan. “No clear evidence regarding [the benefits of high-intensity statins] … has been established in Asian populations.”

The multicentre, prospective, open-label trial randomized 13,054 patients (mean age 68 years, 83 percent males) with stable CAD and who achieved LDL-C of <120 mg/dL during a 4-week run-in period to receive high-dose (4 mg/day) or low-dose (1 mg/day) pitavastatin in a 1:1 ratio. [AHA 2017, abstract LBS.02] 

At 5-year follow-up, the composite primary endpoint of CV death, nonfatal ischaemic stroke, nonfatal myocardial infarction, and unstable angina occurred at a lower rate in the high-dose vs the low-dose pitavastatin arms (4.3 percent vs 5.4 percent, hazard ratio [HR], 0.81; p=0.01). The number needed to treat (NNT) to prevent one occurrence of the primary endpoint was 63.

The risk of the primary endpoint plus coronary revascularization (ie, secondary endpoint) was also reduced in the high-dose compared with the low-dose pitavastatin arms (7.9 percent vs 9.7 percent, HR, 0.83; p=0.002), with an NNT of 41.

“Considering the limitations of the open-label trial design, the primary endpoint was defined as not including coronary revascularization procedures,” explained Shimokawa.

Other secondary endpoint that were significantly reduced with high-dose vs low-dose pitavastatin included all-cause mortality (p=0.03), myocardial infarction (p=0.004), coronary revascularization (p=0.008), and nontarget lesion revascularization (p=0.003).

The high-dose pitavastatin was well tolerated, with muscle complaints being the only safety outcome that was significantly more common in the high-dose vs the low-dose groups (1.9 percent vs 0.7 percent; p<0.001). Other commonly reported adverse events included new onset diabetes mellitus (4.5 percent vs 4.3 percent; p=0.76) and elevated levels of ALT, AST, or both (2.9 percent vs 2.7 percent; p=0.46), although the difference was not significant between the groups.

Nonetheless, the reduction in LDL-C levels with both doses of pitavastatin was less than expected, noted invited discussant Dr Karol Watson, codirector of the University of California, Los Angeles Program in Preventive Cardiology in Los Angeles, California, US: pitavastatin 4 mg/day reduced LDL-C by about 15 percent from 87.7 mg/dL to 76.6 mg/dL at 3 years, while pitavastatin 1 mg/day did not reduce LDL-C in the trial (88.1 mg/dL to 91 mg/dL at 3 years).

“What would have happened if we got [a] greater LDL-C reduction?” she asked. “Would outcomes have been improved with greater LDL-C reduction?”  

While the findings are encouraging, several questions remained to be addressed, Watson pointed out. In particular, if a higher-potency and -intensity statin therapy would improve the outcomes, and whether high-intensity therapy would be as tolerable in Asians? She also wondered if the study results translate to other statins. “There are some things we still don't know,” she said.

Nonetheless, noting the substantial reluctance to use higher dose statins in Asians, Watson said, “This trial should give us a lot of comfort that this strategy is safe, well tolerated, and beneficial.”