Larger early LDL-c lowering after MI associated with reduced CV outcomes in real-world setting
Low-density lipoprotein cholesterol reduction and statin intensity in myocardial infarction patients and major adverse outcomes: a Swedish nationwide cohort study
Literature - Schubert J, Lindahl B, Melhus H et al., - Eur Heart J 2021, 42:243-252, doi:10.1093/eurheartj/ehaa1011Introduction and methods
Clinical trial data suggest that acquired relative CV risk reduction per unit LDL-c reduction is consistent, regardless of baseline LDL-c [1]. Patients with higher baseline LDL-c though benefit most from LDL-c lowering therapy with a larger absolute LDL-c lowering and greatest reduction in mortality [2]. This has been studied in clinical trials enrolling patients with predefined characteristics, but data on the association between LDL-c lowering after myocardial infarction (MI) with long-term outcomes from real-life populations are limited.
Aim of this study was to investigate the association between early LDL-c changes and statin intensity with mortality and major adverse CV outcomes after an MI.
Data from the SWEDEHEART registry was used. This is a Swedish nationwide MI quality registry. Patients admitted with an MI to a coronary care unit in Sweden were included in the registry [3]. This study included 40,607 patients 30-75 years, admitted for MI between Jan 2006 and Dec 2016, who were alive at a follow-up visit within cardiac rehabilitation (CR), 6-10 weeks after discharge. Outcomes included all-cause mortality, CV mortality, MI, ischemic stroke, hospitalization for heart failure, coronary artery revascularization, and a composite of CV mortality, MI, ischemic stroke and coronary artery revascularization (major vascular event). Median follow-up was 3.8 years (Q1-Q3:1.9-6.5).
Main results
- Median LDL-c at time of index event was 3.1 (2.3-3.9) mmol/L and median change was 1.2 mmol/L reduction. Largest mean reduction was achieved in statin naïve patients with a high-intensity statin. Ezetimibe was used by 1% of patients at the index event and 7% at the follow-up visit.
- 27% of patients had LDL-c reduction ≥50%, 57% had LDL-c reduction of <50% and 16% had no reduction or increase in LDL-c.
- A stepwise lower risk of all outcomes with quartiles of larger LDL-reduction was observed. Patients in the 75th percentile of LDL-c reduction (1.85 mmol/L) had a lower hazard of outcomes compared with patients in the 25th percentile (0.36 mmol/L) (for the composite of CV mortality, MI and ischemic stroke: HR 0.77, 95%CI: 0.70-0.84; for all-cause mortality: HR 0.71, 95%CI: 0.63-0.80; for CV mortality: HR 0.68, 95%CI; 0.57-0.81; for MI: HR 0.81, 95%CI: 0.73-0.91; for ischemic stroke: HR 0.76, 95%CI: 0.62-0.93; for heart failure hospitalization: HR 0.73, 95%CI: 0.63-0.85; for coronary artery revascularization: HR 0.86, 95%CI: 0.79-0.94).
- Magnitude of LDL-c reduction was related to the event rates of MACE, all-cause mortality and major vascular event.
- Among patients with ≥50% reduction in LDL-c, those with a high-intensity statin after the CR visit had lower incidence of all outcomes compared with patients with a low-or medium-intensity statin.
- Patients with LDL-c increase or no reduction had higher event rates and increased risk of all outcomes compared to patients with any LDL-c reduction.
- For every 1 mmol/L reduction in LDL-c was an ~25% relative event rate reduction for major vascular events. Similar results were obtained for outcomes of MACE, all-cause mortality, MI and a larger reduction in event rate for hospitalization for heart failure.
Conclusion
In real-world patients in the SWEDEHEART registry, early LDL-c reduction after an MI was associated with lower incidence and reduced adjusted risk of MACE, all-cause mortality, CV mortality, MI, ischemic stroke, hospitalization for HF and coronary revascularization.
The authors write: ‘The relationship between LDL-c reduction and event rate decline was linear and comparable to the CTTC meta-analysis of statin treatment trials’ [1].
Editorial comment
In his editorial comment [4], Ray KR lists the lessons learnt from this study that could inform future practice.
First, 77% of the patients in this study were statin naïve at the time of MI, indicating that identification and treatment of those at risk of MI in the primary prevention setting must be improved.
Second, patients who were statin naïve before their MI were very different from those who were on statins prior to their MI with regard to clinical characteristics, LDL-c management which will likely have an impact on outcomes. Prior statin use likely identifies sicker patients with multiple comorbidities with a higher risk of prior ASCVD, who will derive greater absolute benefit from additional non-statin lipid-lowering therapy.
Third, the findings of this study suggest that there is insufficient intensification of treatment in those prior on statins.
Last, cardiac rehabilitation (CR) is greatly undervalued and this study demonstrated the importance of CR in the long-term management of post-MI patients by assessing and reinforcing lifestyle, medication adherence and personalizing care. Ray states: ‘The strength of real-world data is their ability to highlight at scale the shortfalls in public health/implementation, helping to shape future practice, by forcing us to ask ourselves the basic question: is what we are doing sensible and good enough?’
In the end Ray writes that statins, ezetimibe, PCSK9 inhibitor and newer therapies such as bempedoic acid and inclisiran offer an opportunity to improve implementation of guidelines to bring the population-mean LDL-c closer to 1.4 mmol/L. He proposes a pragmatic personalized approach to intensive LDL-c lowering, from a high-intensity statin based approach for all to a high-intensity lipid-lowering therapy approach.
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