AMGEN and Repatha at ACC

Repatha® (evolocumab) reduced the LDL-C levels and
risk of MI, stroke, and coronary revascularization in
patients with established CVD1

FOURIER: LDL-C reductions and CV risk in patients with CVD

Further Cardiovascular OUtcomes Research With PCSK9 Inhibition in Subjects With Elevated Risk

FOURIER Study Design

FOURIER was a double-blind, randomized, placebo-controlled, event-driven trial in 27,564 adult patients with established CVD and with LDL-C ≥70 mg/dL and/or non–HDL-C ≥100 mg/dL despite moderate- or high-intensity statin therapy. Patients received either subcutaneous injections of Repatha® (140 mg every 2 weeks or 420 mg once monthly) or placebo. The median follow-up duration was 26 months.1

Repatha® added to a statin was evaluated in patients with established CVD who remained at risk despite high- or moderate-intensity statin therapy1

99%

99% of patients were receiving moderate- or high-intensity statin therapy2

70%

70% of patients in the Repatha® arm were on high-intensity statins2
Patients were ≥40 to ≤85 years
old with prior MI, stroke, or
symptomatic PAD2,*,†
92 mg/dL median baseline
LDL-C for enrolled patients2

*Symptomatic peripheral arterial disease (history of claudication with ABI <0.85 or previous revascularization or amputation).3

As well as additional characteristics that placed them at high CV risk.2

FOURIER efficacy

The addition of Repatha® resulted in a sustained and consistent LDL-C reduction1

  • 63% mean reduction in LDL-C from baseline at week 12 in the Repatha® + statin group1
  • 87% of patients achieved LDL-C ≤70 mg/dL with Repatha® added to a statin at 48 weeks2
  • Adding Repatha® to a statin can dramatically lower LDL-C in just 4 weeks2

Large CV outcomes trials like FOURIER influenced the latest ACC/AHA Guideline3

Repatha® (evolocumab) added to a statin was proven to reduce the risk
of composite CV events by 20%
in a median of only 2.2 years of follow-up,
and the benefit improved over time1,2

  • Primary composite endpoint of time to first occurrence of CV death, MI, hospitalization for unstable angina, stroke, or coronary revascularization: HR 0.85 (95% CI, 0.79–0.92; P < 0.0001)1
  • MI = 27% RRR1; Revascularization = 22% RRR1; Stroke = 21% RRR2
  • Key secondary composite endpoint of time to first occurence of CV death, MI, or stroke: HR 0.80 (95% CI, 0.73–0.88; P < 0.0001); ARR = 2.0%1,2
  • Relative risk reductions for the primary and secondary composite endpoints were driven by a reduction in the risk of MI: HR 0.73 (95% CI, 0.65–0.82); stroke: HR 0.79 (95% CI, 0.66–0.95); and coronary revascularization: HR 0.78 (95% CI, 0.71–0.86)1,*
  • *Not statistically significant.
  • Observed HR for CV death: 1.05 (95% CI, 0.88–1.25) and hospitalizations due to unstable angina: 0.99 (95% CI, 0.82–1.18)1

In adults with established CVD

Help prevent a future MI or stroke

Patients within 1 year of their most recent MI have
a higher CV risk4-6

In a FOURIER subanalysis, Repatha® + statin provided a greater ARR for patients who suffered an MI within 1 year compared to patients with a more distant MI4
Recent MI

Key secondary endpoint: Composite of CV death, MI, or stroke4

ARR = 3.2%

ARR = 1.3%

  • ARR of 2.0% in the overall Repatha® CV Outcomes Trial study population was evaluated at 36 months2

  • Analysis of 81% (N = 22,320) of patients in Repatha® CV Outcomes Trial with a prior MI2,4

  • 5,711 patients who experienced an MI within 1 to 12 months of randomization were compared to 16,609 patients with a more distant MI (more than 12 months prior to randomization)4

Repatha® in the acute setting for acs patients: LDL-C lowering data

EVACS TRIAL: Evidence for Repatha® (evolocumab)
administration within 24 hours of ACS hospital admission

EVolocumab in Acute Coronary Syndrome

In EVACS, Repatha® was administered in-hospital during the early post infarction period,
within 24 hours of hospitalization7

Repatha® added to statin therapy reduced LDL-C levels at 30-day follow-up more than a statin alone7

Change in mean LDL-C levels7
Achievement of LDL-C <70 mg/dL7

The EVACS trial was not designed to assess a correlation between LDL-C reduction and CV events.7

Study design: The EVACS trial was an investigator-sponsored study that enrolled patients with NSTEMI and troponin I of ≥5 ng/mL and randomly assigned them in a 1:1 ratio to a single dose of evolocumab SQ 420 mg or matching placebo within 24 hours of presentation. There were 57 patients enrolled in the study (30 Repatha® arm; 27 placebo arm). The primary endpoint was the change in LDL-C at 30 days. Other atherogenic lipid outcomes were also measured. All patients received high-intensity statin unless contraindicated and were treated in accordance with current ACS guidelines.7

In the EVACS trial, the number of Repatha® and placebo patients with any adverse event was 10 and 12, respectively,
and with a serious adverse event, 2 and 6, respectively7

EVOPACS TRIAL: Evidence for
Repatha® (evolocumab) administration
in-hospital during the acute phase of ACS

In the EVOPACS trial, when initiated in-hospital during
the acute phase of ACS, Repatha® added to a statin
reduced LDL-C at 8 weeks8

95% of patients on Repatha® added to a statin achieved the ACC/AHA
Guideline–recommended threshold of below 70 mg/dL vs 37% of patients
on placebo + statin3,8
% LDL-C reduction from baseline at week 88

Repatha® +
atorvastatin 40 mg

(Baseline LDL-C: 139 mg/dL)

n=155

-77%

Placebo +
atorvastatin 40 mg

(Baseline LDL-C: 132 mg/dL)

n=153

-35%

% of patients who reached LDL-C <55 mg/dL at week 89

Repatha® +
atorvastatin 40 mg

90%

Placebo +
atorvastatin 40 mg

11%

The EVOPACS trial was not designed to assess a correlation between LDL-C reduction and CV events.3

Study design: EVOPACS was a randomized, double-blind, placebo-controlled, multicenter, investigator-sponsored study conducted in Switzerland evaluating the safety and efficacy of Repatha® when administered in the acute phase of ACS (NSTEMI/UA <72 hours, STEMI <24 hours) typically within 72 hours of symptom onset. There were 308 patients enrolled in the study (155 Repatha® arm; 153 placebo arm). Patients presenting with ACS were included if their LDL-C levels were either ≥70 mg/dL despite high-intensity statin therapy, or ≥90 mg/dL despite low- or moderate-intensity statin, or ≥125 mg/dL in statin-naive patients or patients not on stable statin therapy. Patients were randomized to receive Repatha® 420 mg once monthly subcutaneously plus atorvastatin 40 mg or placebo plus atorvastatin 40 mg; 78.2% of patients were not on background statin therapy prior to randomization.8

In the EVOPACS trial, the safety and tolerability of Repatha® were consistent with previous trials8

ABI = ankle brachial index; ACC/AHA = American College of Cardiology/American Heart Association; ACS = acute coronary syndrome; ARR = absolute risk reduction; CI = confidence interval; CV = cardiovascular; CVD = cardiovascular disease; HDL-C = high-density lipoprotein cholesterol; HR = hazard ratio; KM = Kaplan-Meier; LDL-C = low-density lipoprotein cholesterol; MI = myocardial infarction; NSTEMI = non–ST-segment–elevation myocardial infarction; PAD = peripheral artery disease; RRR = relative risk ratio; SQ = subcutaneous; STEMI = ST-elevation myocardial infarction; UA = unstable angina.


References: 1. Repatha® (evolocumab) prescribing information, Amgen. 2. Sabatine MS, Giugliano RP, Keech AC, et al; FOURIER Steering Committee and Investigators. Evolocumab and clinical outcomes in patients with cardiovascular disease. N Engl J Med. 2017;376:1713-1722. 3. Grundy SM, Stone NJ, Bailey AL, et al. 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA guideline on the management of blood cholesterol: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol. 2019;73:e285-e350. 4. Gencer B, Mach F, Murphy SA, et al. Evolocumab and cardiovascular outcomes in patients with recent myocardial infarction: a prespecified secondary analysis from the FOURIER trial. JAMA Cardiol. 2020;5:952-957. 5. Jernberg T, Hasvold P, Henriksson M, Hjelm H, Thuresson M, Janzon M. Cardiovascular risk in post-myocardial infarction patients: nationwide real world data demonstrate the importance of a long-term perspective. Eur Heart J. 2015;36(19):1163-1170. 6. Wang Y, Li J, Zheng X, et al. Risk factors associated with major cardiovascular events 1 year after acute myocardial infarction. JAMA Netw Open. 2018;1:e181079. doi:10.1001/jamanetworkopen.2018.1079. 7. Leucker TM, Blaha MJ, Jones SR, et al. Effect of evolocumab on atherogenic lipoproteins during the peri- and early postinfarction period: a placebo-controlled, randomized trial. Circulation. 2020;142:419-421. 8. Koskinas KC, Windecker S, Pedrazzini G, et al. Evolocumab for early reduction of LDL cholesterol levels in patients with acute coronary syndromes (EVOPACS). J Am Coll Cardiol. 2019;74:2452-2462. 9. Koskinas KC. EVOlocumab for early reduction of LDL-cholesterol levels in Patients with Acute Coronary Syndromes (EVOPACS): a randomized, double-blind, placebo-controlled multicenter study. Presented at: ESC World Congress of Cardiology; August 31-September 4, 2019; Paris, France.  

IMPORTANT SAFETY INFORMATION
  • Contraindication: Repatha® is contraindicated in patients with a history of a serious hypersensitivity reaction to evolocumab or any of the excipients in Repatha®. Serious hypersensitivity reactions including angioedema have occurred in patients treated with Repatha®.
  • Hypersensitivity Reactions: Hypersensitivity reactions, including angioedema, have been reported in patients treated with Repatha®. If signs or symptoms of serious hypersensitivity reactions occur, discontinue treatment with Repatha®, treat according to the standard of care, and monitor until signs and symptoms resolve.

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