Table 10Mortality and Non-Fatal Events — ITT Population

OutcomesaREDUCE-IT

Icosapent ethyl

N = 4,089

Placebo

N = 4,090

Primary composite outcome (composite of CV death, non-fatal MI [including silent MI], non-fatal stroke, coronary revascularization, and unstable angina requiring hospitalization)
n (%)705 (17.2)901 (22.0)
HR (95% CI)0.752 (0.682 to 0.830)
P value0.00000001
Components contributing to composite outcome, n (%)b
 CV deathc137 (3.4)149 (3.6)
 Non-fatal MId205 (5.0)280 (6.8)
 Non-fatal stroke80 (2.0)105 (2.6)
 Coronary revascularization189 (4.6)244 (6.0)
 Hospitalization for unstable angina94 (2.3)123 (3.0)
Key secondary composite outcome (composite of CV death, non-fatal MI [including silent MI], and non-fatal stroke)
n (%)459 (11.2)606 (14.8)
HR (95% CI)0.735 (0.651 to 0.830)
P value0.0000006
Components contributing to composite outcome, n (%)b
 CV deathc149 (3.6)167 (4.1)
 Non-fatal MId230 (5.6)325 (7.9)
 Non-fatal stroke80 (2.0)114 (2.8)
CV death or non-fatal MI
 n (%)392 (9.6)507 (12.4)
 HR (95% CI)0.753 (0.660 to 0.859)
 P value< 0.001
Fatal or non-fatal MI
 n (%)250 (6.1)355 (8.7)
 HR (95% CI)0.688 (0.585 to 0.808)
 P value< 0.001
 Fatal MI, n (%)16 (0.4)29 (0.7)
  HR (95% CI)0.546 (0.297 to 1.005)
  P value0.0484
 Non-fatal MI, n (%)237 (5.8)332 (8.1)
  HR (95% CI)0.697 (0.590 to 0.823)
  P value< 0.0001
Urgent or emergency revascularization
 n (%)216 (5.3)321 (7.8)
 HR (95% CI)0.653 (0.550 to 0.776)
 P value< 0.001
CV death
 n (%)174 (4.3)213 (5.2)
 HR (95% CI)0.803 (0.657 to 0.981)
 P value0.0315
Hospitalization for unstable angina
 n (%)108 (2.6)157 (3.8)
 HR (95% CI)0.679 (0.531 to 0.868)
 P value0.0018
Fatal or non-fatal stroke
 n (%)98 (2.4)134 (3.3)
 HR (95% CI)0.720 (0.555 to 0.934)
 P value0.0129
 Fatal stroke, n (%)14 (0.3)18 (0.4)
  HR (95% CI)0.767 (0.382 to 1.543)
  P value0.4564
 Non-fatal stroke, n (%)85 (2.1)118 (2.9)
  HR (95% CI)0.708 (0.536 to 0.936)
  P value0.0149
Death from any cause, non-fatal MI, or non-fatal stroke
 n (%)549 (13.4)690 (16.9)
 HR (95% CI)0.772 (0.690 to 0.864)
 P value< 0.001
Death from any cause
 n (%)274 (6.7)310 (7.6)
 HR (95% CI)0.870 (0.739 to 1.023)
 P value0.0915e
Outcomes outside the hierarchy
 Coronary revascularization
 n (%)376 (9.2)544 (13.3)
 HR (95% CI)0.664 (0.583 to 0.758)
 P value0.0013
 Hospitalization for arrhythmias
 n (%)188 (4.6)154 (3.8)
 HR (95% CI)1.21 (0.97 to 1.49)
 P value0.0856
 Hospitalization for congestive heart failure
 n (%)141 (3.4)144 (3.5)
 HR (95% CI)0.97 (0.77 to 1.22)
 P value0.781

CI = confidence interval; CV = cardiovascular; HR = hazard ratio; ITT = intention-to-treat; MI = myocardial infarction.

a

Hazard ratio and 95% CI are reported from a Cox proportional hazard model with treatment as the covariate, and stratified by geographic region, CV risk category, and use of ezetimibe.

b

Based on a patient’s first post-randomization occurrence of the event contributing to the primary end point.

c

CV death includes adjudicated CV deaths and deaths of undetermined causality.

d

Non-fatal MI includes silent MI, which was assumed to occur on the date of the first post-randomization electrocardiogram tracing indicative of a silent MI.

e

Death from any cause was the only comparison not meeting statistical significance during the hierarchical evaluation. After this, all tertiary outcomes, such as heart failure and arrhythmias, were considered exploratory.

Source: Clinical Study Report for the REDUCE-IT1 study.

From: Clinical Evidence

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Clinical Review Report: Icosapent Ethyl (Vascepa): (HLS Therapeutics Inc.): Indication: Prevention of cardiovascular events in statin-treated patients [Internet].
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