Amarin Beyond LDL: Focused Insights High Triglycerides, Very High Triglycerides and CV Residual Risks December 2017

Methodology The purpose of this survey is to better understand cardiologists and CV Team members who are managing high triglyceride patients and incorporating the new evidence more aggressively, and to identify what they think of the associated CV risk. Online survey distributed to random sample of active US cardiologists and CV Team members. Survey live from October 25 to December 7. Two reminder emails were sent to CV Team. Three reminder emails were sent to cardiologists and 1 reminder email was sent to cardiologist oversample. A total of 348 respondents participated in the survey, resulting in a response rate of 9%; 305 (156 cardiologist members and 149 CV Team members) respondents met the inclusion criteria of treating patients with dyslipidemia or hypertriglyceridemia and completed the full questionnaire.

Descriptors Gender Cardiologist CV Team Male 87% 13% Female 7% 67% Missing 6% 19% Practice setting Cardiologist CV Team CV Group 45% Government Hospital 1% 6% Non-Government Hospital 2% 9% Industry/Pharma Device 0% Insurance Company Med School 13% 11% Multi Specialty 4% Other 3% Retired -- Solo 5% Missing 24% 20% Age Cardiologist CV Team 30 & under 0% 6% 31-40 years 21% 41-50 years 20% 23% 51-60 years 38% 28% 61-70 years 33% 15% 71+ years 7% Missing 1% Member Type AACC -- 16% Associate Fellow 3% 84% FACC 97% Tenure Cardiologist Physician 8-14 years 17% Physician 15-21 years 27% Physician 22+ years 56%

Descriptors (Cont’d) Board Cardiologist CV Disease 94% EP 9% Interventional 22% Nuclear Medicine 1% General surgery Pediatric cardiology 2% Heart failure/Transplant No Board certification 3% Specialty Cardiologist CV Team Adult congenital cardiology 1% Clinical cardiology/General cardiology 14% 16% Adult cardiology 74% 38% Surgery 0% Vascular surgery/medicine 3% Echocardiology 19% EP 9% 6% Geriatrics Heart failure/Transplant 7% Invasive cardiology 5% Interventional cardiology 21% Nuclear cardiology 12% Non-invasive cardiology 4% Pediatric cardiology 2% Preventative cardiology No specialty 34% Other

Key Findings Overall, cardiologists and CV Team members are similar in their view points of hypertriglyceridemia. They classify the risk level for future CV events and risk factors when diagnosing hypertriglyceridemia similarly. Their recommendations for lifestyle changes are similar. The majority of both groups would like to expand their knowledge in hypertriglyceridemia. They are both split on their satisfaction with medication options for treating hypertriglyceridemia with one quarter saying that they are very satisfied while one third say they are very dissatisfied with the Rx options. They are similar in hypertriglyceridemia treatment approaches when LDL is controlled. Both groups find acute coronary syndrome and high triglycerides and high LDL-C the highest risk for CV risk. The top statements that both agree on are “Optimizing LDL independent of triglyceride levels is still most important” and “More investigation is needed to determine magnitude of triglycerides and CV risk.” Their understanding of omega-3 fish oil is similar. Cardiologists name CV outcomes trials as the top challenge in treating hypertriglyceridemia while CV Team members cite patient adherence. CV team members are also more likely to see challenges in costs of medication, education, insurance denials, adherence monitoring, underdiagnoses and patient preference. Cardiologists express confidence in their knowledge and treatment of hypertriglyceridemia and are more likely to be aware of treatment options such as Fibrates and Niacin . Overall, cardiologists are more familiar with clinical trials than their CV team counterparts. Cardiologists are most familiar with PROVE-IT with over half reporting stronger familiarity. Of note, familiarity with these trials is significantly lower than other clinical trials evaluated like SPRINT. CV Team members find all the triglyceride management tools more useful compared to cardiologists. The top useful tools for both groups are patient education materials and patient assessment tool.

Number of Dyslipidemia Patients Seen Cardiologists and CV Team members are similar in the number of dyslipidemia patients they see in a typical week. Mean=40.4 patients per week* Mean=34.4 patients per week* *Midpoint of each range was taken to calculate mean. More than 100 was assigned 105.5. Q1: To begin, approximately how many patients do you see in a typical week for all types of dyslipidemia?

Percentage of Patients with Hypertriglyceridemia Over three quarters (76%) of cardiologists mention that 1-30% of their patients have hypertriglyceridemia compared to three-fifths (59%) of CV Team members. Mean=22.1%* Mean=30.8%* *Midpoint of each range was taken to calculate mean. Q2: Approximately what percentage of your patients have hypertriglyceridemia (>200 mg/dL)?

Risk Level for Future CV Events Cardiologist and CV Team members are similar in the way they classify the risk level for future CV events for the below types of patients except multiple CV risk factors such as diabetes, hypertension, smoking or obesity, with controlled LDL-C (with medication) and hypertriglyceridemia. CAD with prior MI and CAD without prior MI has the highest risk for future CV events followed by multiple CV risk factors. Mean* 2.73 2.76 2.65 2.76 2.38 2.46 2.34 2.43 1.46 1.43 1.46 1.49 *High risk=3; Moderate risk=2; Low risk=1; Excluded not sure and no answer from mean Q3: How would you classify the risk level for future CV events for each of the following types of patients?

Risk Factors When Diagnosing Hypertriglyceridemia Cardiologist and CV Team members are similar in the way they diagnose risk factors for hypertriglyceridemia except cholesterol levels of LDL and HDL. Medical history is the top risk factor followed by diet and alcohol consumption. Q4: What are the risk factors when diagnosing hypertriglyceridemia?

When to Start Treating Hypertriglyceridemia Two-fifths (42%) of cardiologists start treating hypertriglyceridemia when fasting triglyceride levels are more than 500mg/dL and another 45% when the levels reach >200mg/dL. About 3 out of 10 CV Team members (29%) start treatment at >500mg/dL, while 46% would start treatment at >200mg/dL and 1 out of 5 (20%) would even start it at >150mg/dL. Q5: When do you start treating hypertriglyceridemia? When fasting triglyceride levels are:

Treatment for Patients with Co-Morbidities If the patient has 1 or more co-morbidities or risk factors, then seven out of ten cardiologists (70%) start treatment at 200mg/dL or more, while about half of CV Team members (52%) would start treatment at >200mg/dL. Q6: If the patient has 1 or more co-morbidities or risk factors, at what level of fasting triglycerides do you start treatment?

Current Challenges in Treating Hypertriglyceridemia Cardiologists find lack of CV outcomes trials (54%) to be a top challenge where only three tenths (28%) of CV team members find it a challenge. CV team members are more likely to see challenges in patient adherence, costs of medication, education, insurance denials, adherence monitoring, underdiagnoses and patient preference. Q7: What would you consider to be the current challenges in treating patients with hypertriglyceridemia?

Confidence in Diagnosis and Treatment of Hypertriglyceridemia Not surprisingly, cardiologists are more confident in their knowledge concerning diagnosing and treatment of hypertriglyceridemia (49%) than CV Team members (36%). Cardiologists are less confident in hypertriglyceridemia compared to Afib and FH while CV team members tend to report more confidence in knowledge of hypertriglyceridemia than FH. 36% 49% Q8: How confident are you in your knowledge concerning the diagnosis and treatment of hypertriglyceridemia?

Hypertriglyceridemia – An Area to Expand Knowledge The majority of cardiologists (82%) and CV Team members (88%) would like to expand their knowledge in hypertriglyceridemia. Q9: Is hypertriglyceridemia an area where you would like to expand your knowledge?

Familiarity with Medical Therapies Cardiologists are very familiar with Fibrates (79%) and Niacin (74%) compared to other medical therapies. CV Team members’ familiarity with all four medical therapies are about the same. Q10: Now turning to some specific medical therapies for hypertriglyceridemia…Please rate your familiarity with each of the following medical therapies.

Satisfaction with Medication Options Low Cardiologists and CV Team members are split on their satisfaction with medication options for treating hypertriglyceridemia with one quarter saying that they are very satisfied while one third say they are very dissatisfied with the Rx options. 27% 23% Q11: How satisfied are you with the medication options for treating hypertriglyceridemia?

Treating Hypertriglyceridemia when LDL is Controlled Cardiologist and CV Team members are similar in the way they ranked the ways to treat hypertriglyceridemia when LDL is controlled. Fibrates are the preferred first line treatment followed by prescription omega 3. Q12: Please rank the following based on most preferable when treating hypertriglyceridemia when LDL is controlled.

Conditions in Terms of CV Risk Both cardiologists and CV Team members find acute coronary syndrome and high triglycerides and high LDL-C the highest risk for CV risk. Almost half (46%) of CV Team find low HDL-C to be the lowest risk compared to one fifth (22%) of cardiologists. Q13: Please rank the following conditions from highest to lowest risk in terms of CV risk. 1=highest risk 7=lowest

Familiarity with Clinical Trials Cardiologists’ familiarity with ongoing clinical trials are higher for most trials than CV Team members especially PROVE-IT and AIM-HIGH. Their familiarity with STRENGTH and PROMINENT are about the same as CV Team members. Cardiologists are most familiar with PROVE-IT with over half reporting stronger familiarity. Of note, familiarity with these trials is significantly lower than other clinical trials evaluated like SPRINT. Q14: Please rate your familiarity with the following completed or ongoing clinical trials.

Statements about Triglycerides The top statements that both cardiologists and CV Team members agree on are “Optimizing LDL independent of triglyceride levels is still most important” and “More investigation is needed to determine magnitude of triglycerides and CV risk.” Less than half of cardiologists agree on the role of triglyceride level and CV risk. Q15: Below are some statements made about Triglycerides.  Please select the statements with which you agree.

Understanding of Omega-3 Fish Oil in US Cardiologists and CV Team members’ understanding of omega-3 fish oil is similar with the exception of DHA in fish oil supplements increasing LDL-C about which CV team members are less likely to have an opinion. Over half of cardiologists and CV Team members do not know that content analysis of leading supplement fish oil dietary brands showed that the fish oil contained more saturated fat than active ingredients. Q16: What is your understanding of Omega-3 fish oil in the US? .

Lifestyle Change Recommendations Cardiologists and CV Team members are similar in their recommendations for lifestyle changes for patients with hypertriglyceridemia. Diet and weight loss are the top recommendations from both groups. Q17: What lifestyle changes do you recommend for your patients with hypertriglyceridemia?

Triglyceride Management Tools CV Team members find all the triglyceride management tools more useful compared to cardiologists. The top useful tools for both groups are patient education materials (both brochures about high triglycerides and how to manage and comparing prescription Omega-3 vs. dietary supplements) and patient assessment tool. Q18: Below please find descriptions of some proposed triglyceride management tools. Please rate the usefulness of each tool to your practice.