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Access to Prescribed PCSK9 Inhibitors and CV Outcomes
Study Questions:
Are acute coronary syndromes, coronary interventions, stroke, and cardiac arrest (composite cardiovascular [CV] events) more prevalent in patients with rejected (RJ) or abandoned (AB) proprotein convertase subtilisin kexin type 9 inhibitor (PCSK9i) prescriptions than for those with paid (PD) PCSK9i prescriptions?
Methods:
The authors utilized an electronic healthcare registry with over 221 million patients to identify 139,036 individuals aged ≥18 years who met the following three criteria: prescribed PCSK9i between August 2015 and December 2017, had claims history, and had an established date of exposure for paid, rejected, or abandoned status. To compare the effects of rejected or abandoned versus paid status, Cox regression analyses and incidence density rates for CV events were estimated on the propensity score (PS)-matched cohorts. Case-controlled PS matching without replacement was performed in a 1:1 ratio for RJ versus PD and AB versus PD cohorts and was tested to assess patient characteristics in the matched pairs. Date of the first prescription that qualified the patient for PD, RJ, or AB status was defined as the final adjudication status (FAS) date. Patients who received 168 or more days of paid PCSK9i medication within a 12-month period were defined as paid.
Results:
Average age was 66 years, 51% were females, 63% white, 7% black, 5% Hispanic, 2% other, and 23% unknown. Of the 139,036 patients prescribed a PCSK9i, 32,886 (24%) were in the paid group, 85,370 (61%) were rejected, and 20,780 (15%) were in the abandoned (AB) group. Also, among those prescribed PCSK9i, 88,770 (63.8%) had a history of atherosclerotic cardiovascular disease (ASCVD) before their FAS date, and 2,889 (2.1%) had a documented diagnosis of familial hypercholesterolemia (FH). Of those with FH, 1,944 (1.4%) also had a history of ASCVD before their FAS date. A total of 49,321 individuals (35%) had no diagnosis of FH or pre-FAS ASCVD. The hazard ratios for composite CV event outcomes in propensity score-matched analyses were 1.10 (95% confidence interval [CI], 1.01–1.19; p = 0.02) for rejected versus paid and 1.12 (95% CI, 1.01–1.24; p = 0.03) for abandoned versus paid. In a stricter analysis where paid patients were defined by receiving 338 or more days of therapy within 12 months, the hazard ratio was 1.16 (95% CI, 1.02–1.30; p = 0.04) for rejected versus paid and 1.21 (95% CI, 1.04–1.38; p = 0.03) for the abandoned versus paid status. Women, minorities, and those with lower education or lower income levels were less likely to receive approval for a PCSK9i prescription and were less likely to fill an approved prescription.
Conclusions:
Individuals in the rejected and abandoned cohorts had significantly increased risk of CV events compared with those in the paid cohort. Rejection, abandonment, and disparities related to PCSK9i prescriptions are related to higher CV outcome rates.
Perspective:
Most impressive is the hazard ratio for those whose indication was FH or ASCVD compared to those 35% with neither indication for PCSK9i. The hazard ratio was 2.8 (p < 0.001) for the FH cohort versus individuals who did not have a documented diagnosis of FH or ASCVD, 2.12 (p < 0.001) for ASCVD versus non-FH and non-ASCVD, 1.75 (p < 0.001) for FH+ASCVD versus ASCVD alone, 5.4 (p < 0.001) for FH+ASCVD versus non-FH and non-ASCVD, and no statistical difference in risk between primary prevention FH and secondary prevention ASCVD. These findings support the classic indications for PCSK9i being FH with or without ASCVD and ASCVD with inadequate lowering of low-density lipoprotein cholesterol (LDL-C). Amongst the limitations of the observational study include potential inaccuracy for diagnosis of ASCVD and FH, and lack of LDL-C levels at baseline and on-treatment. Fortunately, the majority of insurance carriers now recognize the value of PSCSK9i, and cost and co-pay are coming down.
Keywords: Acute Coronary Syndrome, Atherosclerosis, Cardiology Interventions, Cholesterol, LDL, Drug Costs, Heart Arrest, Hyperlipoproteinemia Type II, Outcome Assessment, Health Care, Primary Prevention, Risk, Secondary Prevention, Stroke, Subtilisins, Vascular Diseases
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