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High-dose pitavastatin benefits Japanese population with CAD
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ANAHEIM, Calif. — High-dose pitavastatin, compared with a low dose, significantly reduced CV events and was well-tolerated in Japanese adults with stable CAD enrolled in the REAL-CAD study.
The prospective, randomized, open-label trial included 13,054 patients who received pitavastatin (Livalo, Kowa Pharmaceutical Co. Ltd.) 1 mg per day for an initial run-in period of at least 1 month, followed by random assignment to the continued daily 1-mg dose or a 4-mg dose. Median follow-up duration was 3.9 years in both groups.
High-dose pitavastatin significantly reduced the primary endpoint, a composite of CV death, nonfatal MI, nonfatal ischemic stroke or unstable angina requiring emergency hospitalization, with a relative risk reduction of 19% (HR = 0.81; 95% CI, 0.69-0.95). The 4-year cumulative incidence of the primary endpoint was 4.6% in the high-dose group vs. 5.6% in the low-dose group. The number needed to treat was 63 for the primary endpoint at 5 years, Hiroaki Shimokawa, MD, PhD, from Tohoku University Graduate School of Medicine, Japan, said during the late-breaking clinical trial presentation.
The 4-mg dose also significantly reduced a secondary composite endpoint including coronary revascularization, with a relative risk reduction of 17% (HR = 0.83; 95% CI, 0.73-0.93). The 4-year cumulative incidence of the secondary composite endpoint was 8.5% in the high-dose group vs. 10.4% in the low-dose group. The number needed to treat was 41 for the secondary composite endpoint at 5 years, according to Shimokawa.
Pitavastatin treatment was also associated with improvements in lipid parameters and high-sensitivity C-reactive protein, with greater improvements observed with the 4-mg dose. LDL was lowered by about 15 mg/dL in the 4-mg group compared with the 1-mg group, triglycerides were lowered by about 7 mg/dL and non-HDL was increased by about 0.6 mg/dL. High-sensitivity CRP was low and not different in either group, he said.
In terms of safety, high-dose pitavastatin was generally well tolerated. Rates of rhabdomyolysis, new-onset diabetes and creatine kinase were low and similar in both treatment groups. Muscle-related complaints were higher in the 4-mg group (1.9% vs. 0.7%; P < .001).
“The present study provides support for the notion that administration of higher doses of statins within the range of local approval would be the preferred statin therapy in patients with established CAD regardless of the baseline LDL levels,” Shimokawa said. “This study provides important insight into statin therapy in the Japanese population.”
During a discussion of the trial, Karol E. Watson, MD, PhD, FNLA, FACC, FAHA, co-director of the UCLA Program in Preventive Cardiology and a Cardiology Today Editorial Board Member, noted that there has been “substantial reluctance to use higher-dose statins in Asian patients.”
According to Shimokawa, “high-intensity statins are not widely used in daily clinical practice, particularly in Asia. No clear evidence regarding ‘more vs. less statins’ has been established in Asian populations. Most of the doses of high-intensity statin therapy defined in the American College of Cardiology/American Heart Association guidelines are not approved in Japan.” He also noted that the incidence of CV events is generally lower in Asian patients compared with patients in Western countries.
“This trial should give comfort that this strategy is safe, well tolerated and beneficial,” Watson said. – by Katie Kalvaitis
Reference:
Shimokawa H, et al. LBS.02 – Late-Breaking Science in Prevention. Presented at: American Heart Association Scientific Sessions; Nov. 11-15, 2017; Anaheim, California.
Disclosures: Shimokawa reports relationships with Kowa Pharmaceutical Co. Ltd. And Public Health Research Foundation. Watson reports she has received research grants from the NIH, serves on the speakers bureau for Boehringer Ingelheim, and consults for Amgen and Boehringer Ingelheim.
Perspective
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Sripal Bangalore, MD, MHA, FACC, FAHA, FSCAI
For most of the world, it is not a surprise that a higher-intensity statin showed significant CV benefits. We have known this for a long time and a number of clinical trials have proven it. For whatever reason, the Asian countries have been hesitant about starting patients on high-intensity statins. This is an important trial in that respect. While pitavastatin (at the dose tested in the trial) is more of a moderate-intensity statin, it was well-tolerated and offered a significant benefit. The study ought to convince Asian patients that there are not any safety concerns and there are significant benefits — which are along the lines with what we’ve seen in other clinical trials — with statins.
Perspective
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Martha Gulati, MD, MS, FACC, FAHA, FASPC
This was a study of a Japanese population in whom the authors note that it is relatively infrequent that high-intensity statins are used. I have to admit, I am unclear why high-intensity statins are used less frequently in Japan compared with the United States. In this particular population, the researchers looked at people who already had coronary disease, so, translating it to the United States, these are patients who should already be on a high-intensity statin, according to current guidelines. The study evaluated use of pitavastatin and showed a reduction in CV events with the high-intensity statin in this Japanese population. Of note, this statin is still not a generic in the United States; I am a cost-concerned cardiologist. In my opinion, the findings were expected, considering use of a high-intensity statin. One flaw of this study is that the authors did not have data on 17% of patients after almost 5 years of follow-up. There was some therapy discontinuation, as one would expect with a high-intensity statin. It would be interesting to know the outcomes in that 17% of patients. Overall, these findings confirm the results demonstrated in prior studies of the positive effects of high-intensity statins.
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