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Real-World Risk of Recurrent Cardiovascular Events in Atherosclerotic Cardiovascular Disease Patients with LDL-C
Erin S Mackinnon1, Lawrence A Leiter2,3, Rajvi J Wani4
1Amgen Canada Inc., 6775 Financial Dr #300, Mississauga, ON, L5N 0A4, Canada. emackinn@amgen.com.
Insights
High LDL-C in patients with atherosclerotic cardiovascular disease (ASCVD) on statins leads to significant recurrent cardiovascular events. Intensifying lipid-lowering therapy is crucial for reducing risk in these high-risk individuals.
Area of Science:
- Cardiology
- Public Health
- Pharmacology
Background:
- Canadian Cardiovascular Society (CCS) guidelines recommend intensive low-density lipoprotein cholesterol (LDL-C) reduction for patients with atherosclerotic cardiovascular disease (ASCVD).
- For patients on maximally tolerated statins with LDL-C above threshold, adding ezetimibe or PCSK9 inhibitors (PCSK9i) is advised.
- This study investigated cardiovascular (CV) events in real-world ASCVD patients on statins with elevated LDL-C.
Purpose of the Study:
- To examine the incidence of cardiovascular events in patients with ASCVD on statins who have LDL-C levels exceeding current guideline thresholds.
- To identify specific high-risk subgroups experiencing a greater burden of recurrent CV events.
Main Methods:
- A population-based study using administrative health data from Alberta, Canada (April 2010–March 2016).
- Included patients with myocardial infarction (MI), ischemic stroke (IS), or peripheral artery disease with LDL-C > 1.8 mmol/L on statins.
- Calculated frequencies and rates of primary (MI, IS, unstable angina hospitalization, coronary revascularization, CV death) and secondary (MI, IS, CV death) composite CV events.
Main Results:
- The study included 32,984 patients with a mean follow-up of 40.8 months.
- Overall, 17.7% experienced a primary outcome and 15.6% a secondary outcome.
- Patients with acute coronary syndrome (ACS) or recent MI had notably high primary outcome rates (49.4% and 54.0%, respectively).
Conclusions:
- Real-world data confirm substantial recurrent CV events in high-risk ASCVD patients on statins with above-threshold LDL-C.
- Findings support intensifying lipid-lowering therapy to below-guideline thresholds to effectively reduce CV risk in these populations.
Introduction:
The 2021 Canadian Cardiovascular Society (CCS) guidelines recommend intensive low-density lipoprotein cholesterol (LDL-C) reduction for patients with atherosclerotic cardiovascular disease (ASCVD). For patients above LDL-C threshold on maximally tolerated statins, adding ezetimibe and/or a proprotein convertase subtilisin/kexin type 9 inhibitor (PCSK9i) is recommended. This population-based, real-world study examined cardiovascular (CV) events in patients with ASCVD who are on statins and above current guideline threshold LDL-C levels.
Methods:
Using administrative health data in Alberta, Canada, we identified patients with myocardial infarction (MI), ischemic stroke (IS), or peripheral artery disease with LDL-C > 1.8 mmol/L on statins between April 1, 2010 and March 31, 2016. Exploratory subgroups included very high-risk patients with ASCVD shown to derive the most benefit from PCSK9i intensification as identified by the CCS guidelines, including those with acute coronary syndrome (ACS) or recent MI. Frequencies and rates of individual and composite CV events (primary outcome: MI, IS, hospitalization for unstable angina, coronary revascularization, cardiovascular death; secondary outcome: MI, IS, CV death) were calculated over follow-up.
Results:
The study included 32,984 patients with a mean (standard deviation) follow-up of 40.8 (21.0) months. Overall, 17.7% and 15.6% experienced a primary and secondary outcome, respectively, with rates of 5.58 and 4.83 per 100 patient-years, respectively. CV death and MI were the most common events. Subgroups with recurrent MI and comorbid diabetes exhibited higher CV event rates (23.6% and 22.2% had a primary outcome, respectively). Rates of CV events were notably high in patients with ACS or recent MI (49.4% and 54.0% had a primary outcome, respectively).
Conclusion:
This real-world study confirms that statin-treated high-risk patients with ASCVD and above-threshold LDL-C levels have substantial incidence of recurrent CV events. These findings reinforce the opportunity for lipid-lowering therapy intensification in high-risk patients to levels below guideline-recommended threshold in order to reduce CV risk.
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