Icosapent ethyl reduces myocardial infarction events in patients treated with statins | Latest news for doctors, nurses and pharmacists
In the REDUCE-IT STEMI trial, icosapent ethyl (IPE) reduced MI events overall and across a range of MI subtypes in statin-treated patients at cardiovascular risk (CV ) increased.
“Across all MI analyzes (which includes fatal, non-fatal, STEMI, NSTEMI*), we found a relative risk reduction (RR) of 31% which is statistically significant,” said Professor Deepak Bhatt of the Harvard Medical School and
Brigham and Women’s Hospital, Boston, Massachusetts, USA, at ESC 2022.
The the event rate in the IPE arm was 8.6% versus 12.0% in the placebo arm (relative risk [HR], 0.69; p=0.000005). [ESC 2022, Late-Breaking Science Session]
The benefit was seen early and became significant at 26 months, Bhatt noted. “Therefore, after about 2 years, the reduction in MI became statistically significant; so, it takes about as much time for this end point to be influenced.
When assessed separately, STEMI and NSTEMI events were lower with PEI compared to placebo (2.7% vs. 3.9%; HR, 0.60; p=0.0008 [STEMI] and 5.9% versus 7.8%; HR, 0.73; p=0.001 [NSTEMI]).
The results consistently favored PEI over placebo when assessing other subtypes of MI, such as nonfatal MI (HR, 0.70) and spontaneous MI (HR, 0 .67), MI defined by clinical presentation (HR, 0.66), biomarker elevations (HR, 0.67) and electrocardiography. changes (HR, 0.64) and MI type 1, which constituted the majority of MIs in this trial (HR, 0.67; p
Other subtypes of MI that were markedly reduced with PEI compared to placebo were fatal (HR, 0.55; p=0.048), resuscitated (HR, 0.34; p=0.006) and related MI to PCI** (HR, 0.25; p = 0.06), as well as MI leading to cardiac arrest (HR, 0.49; p = 0.01).
Assessment of MIs by size showed a consistent and significant reduction – from relatively smaller MIs (≥1 x ULN***; HR, 0.67; p=0.0005) to larger MIs (≥100 x ULN ;HR, 0.54; p=0.004). “[T]he bigger mi [appear to have] lower HR or larger effect size with PEI compared to placebo than smaller MIs,” Bhatt noted. “[There was] indeed a statistically significant trend (p=0.000008), suggesting that there is, in fact, an even greater benefit with PEI compared to placebo on large MIs. Bhatt was quick to point out that despite these results, that doesn’t mean “the little ones don’t matter.”
Response to exposure to EPA
In the placebo arm, there was no significant change in EPA# level. When examining the association between higher EPA levels and lower MI rates, the relationship was significant but relatively attenuated (p-value of the Cox-Stuart trend test for slope, 0.008) . “[The] EPA levels are not affected by the placebo but rather are determined by genetics, diet, and other factors that [we have yet to] understand,” Bhatt noted.
In the IPE arm, there was a 400% increase in EPA level. The relationship between higher levels of EPA achieved during treatment and lower rates of MI was more robust (p-value of Cox-Stuart trend test for slope,
“The overall tolerability and adverse event patterns with PEI and placebo in patients who developed STEMI or NSTEMI were consistent with the full study,” Bhatt said.
Non-serious bleeding events, although numerically higher with PEI compared to placebo, were not significantly different between arms (19% vs 14%; p=0.41 [STEMI] and 24% versus 18%; p=0.23 [NSTEMI]). These effects were observed regardless of background antithrombotic treatment.
Consistent with key findings
In REDUCE-IT, all 8,179 participants had mildly elevated triglyceride levels (135 to 500 mg/dL), received dietary advice, and required statin therapy. They were randomized 1:1 to receive either IPE 2g BID or placebo and were followed for up to 6.2 years.
Current results reinforce initial findings of significant reductions in primary composite## (HR, 0.75; p=0.00000001) and secondary key### endpoints (HR, 0.74; p=0.0000006) and in the first and subsequent events (RR, 0.69; p=0.0000000004), with IPE vs. placebo. [N Engl J Med 2019;380:11-22;
J Am Coll Cardiol 2019;73:2791-2802]
Taken together, the results continue to be underline
the CV benefit of PEI in this patient setting.