Characteristics and Cardiovascular Disease Event Rates among African Americans and Whites Who Meet the Further Cardiovascular Outcomes Research with PCSK9 Inhibition in Subjects with Elevated Risk (FOURIER) Trial Inclusion Criteria

Abstract

Purpose: Determine the risk for cardiovascular disease (CVD) events among adults with clinically evident CVD who meet the inclusion criteria for the FOURIER clinical trial on PCSK9 inhibition in a real-world database.

Methods: We analyzed data from 2072 African American and 2972 white REasons for Geographic And Racial Differences in Stroke (REGARDS) study participants 45-85 years of age with clinically evident CVD. Study participants meeting the FOURIER inclusion criteria (one major or two minor cardiovascular risk factors, fasting LDL cholesterol ≥ 70 mg/dL or non-HDL cholesterol ≥ 100 mg/dL, triglycerides ≤ 400 mg/dL, and taking statin) were followed for CVD events (myocardial infarction, stroke, coronary revascularization, and CVD death) from baseline in 2003-2007 through 2014.

Results: Overall, 771 (37.2%) African Americans and 1200 (40.4%) whites met the FOURIER inclusion criteria. The CVD event rate per 1000 person years was 60.6 (95% CI 53.6-67.6) among African Americans and 63.5 (95% CI 57.7-69.3) among whites. The risk for CVD events among adults meeting the FOURIER inclusion criteria was higher for those with a history of multiple cardiovascular events (hazard ratios among African Americans and whites 1.34 [95% CI 1.05-1.71] and 1.34 [1.10-1.63], respectively), a prior coronary revascularization (1.44 [1.13-1.84] and 1.23 [1.00-1.52], respectively), diabetes (1.38 [1.08-1.76] and 1.41 [1.15-1.72], respectively), reduced glomerular filtration rate (1.63 [1.26-2.11] and 1.29 [1.03-1.62], respectively), and albuminuria (1.77 [1.37-2.27] and 1.33 [1.07-1.65], respectively).

Conclusions: The CVD event rate is high among African Americans and whites meeting the FOURIER inclusion criteria. Characteristics associated with a higher CVD risk may inform the decision to initiate PCSK9 inhibition.

Keywords: African Americans; Cardiovascular diseases; Continental population groups; Epidemiology; Evolocumab; Mortality.

Conflict of interest statement

Conflict of interest: KLM, KEM and LY are employed by Amgen, Inc. KLM and LY also are stockholders of Amgen, Inc. MMS has no potential conflicts of interest to report. RSR, TMB, MEF and PM receive research support from Amgen, Inc. RSR also receives research support from Akcea, Astra Zeneca, Medicines Company, Regeneron and Sanofi, serves on Advisory Boards for Akcea, Amgen, Inc., CVS Caremark, Easy Vitals, Regeneron and Sanofi, receives consulting fees and honoraria from Amgen, Regeneron, C5, CVS Caremark, Kowa and Pfizer, and receives royalties from UpToDate. TMB also receives research support from Astra Zeneca. PM also has received an honorarium from Amgen, Inc. LDC and GH have no disclosures.

Figures

Figure 1.

Inclusion criteria for the FOURIER trial among REGARDS study participants with clinically evident cardiovascular disease. FOURIER: Further cardiovascular OUtcomes Research with proprotein convertase subtilisin/kexin type 9 Inhibition in subjects with Elevated Risk; HDL: high-density lipoprotein; LDL: low-density lipoprotein; REGARDS: REasons for Geographic And Racial Differences in Stroke. Inclusion criteria for the FOURIER trial were applied sequentially and include:

1. Having one major or two minor cardiovascular risk factors (as defined in Supplemental Table 2).

2. Fasting LDL cholesterol ≥70 mg/dL or non-HDL cholesterol ≥100 mg/dL.

3. Triglycerides ≤400 mg/dL.

4. Statin use.

Figure 2.

Cumulative incidence for outcomes among REGARDS study participants with clinically evident cardiovascular disease who met the FOURIER inclusion criteria. FOURIER: Further cardiovascular OUtcomes Research with proprotein convertase subtilisin/kexin type 9 Inhibition in subjects with Elevated Risk; REGARDS: REasons for Geographic And Racial Differences in Stroke. a Includes cardiovascular death, stroke, myocardial infarction or coronary revascularization. b Also includes hospitalization for unstable angina. c Includes cardiovascular death, stroke or myocardial infarction.The cumulative incidence of cardiovascular outcomes at 2.2 years among FOURIER trial participants were adapted from Sabatine et al. [1].

Figure 3.

Hazard ratios for the primary outcome associated with participant characteristics among African Americans and whites who met the FOURIER inclusion criteria. ACR: albumin-to-creatinine ratio; eGFR: estimated glomerular filtration rate; FOURIER: Further cardiovascular OUtcomes Research with proprotein convertase subtilisin/kexin type 9 Inhibition in subjects with Elevated Risk; HDL: high-density lipoprotein; hsCRP: high-sensitivity C reactive protein; LDL: low-density lipoprotein; RAAS: renin-angiotensin-aldosterone system. Hazard ratios adjust for age, gender, geographic region of residence, income and education. a Multiple cardiovascular events is defined by a history of ≥2 myocardial infarction and/or stroke events, or peripheral artery disease in addition to a history of myocardial infarction or stroke. b Metabolic syndrome is defined by having ≥3 of the following components:

1. Elevated blood pressure, defined as systolic blood pressure ≥130 mmHg or diastolic blood pressure ≥85 mmHg, or self-reported use of antihypertensive medication.

2. Abdominal obesity, defined as waist circumference ≥88 cm among women and ≥102 cm among men.

3. Impaired glucose, defined by a fasting serum glucose ≥100 mg/dL (or non-fasting serum glucose ≥140 mg/dL), or self-report of a prior diagnosis of diabetes with current use of insulin or oral hypoglycemic medications.

4. Low HDL cholesterol, defined as <40 mg/dL among men and <50 mg/dL among women.

5. High triglycerides, defined as fasting triglycerides ≥150 mg/dL.

cP-values comparing the hazard ratio among African Americans versus whites. The primary outcome includes cardiovascular death, stroke, myocardial infarction or coronary revascularization.