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3rd November 2022
Elevated levels of both C-reactive protein (CRP) levels and lipoprotein A (LpA) in those with coronary heart disease undergoing a percutaneous coronary intervention (PCI) result in a greater risk of major adverse cardiovascular and cerebrovascular events according to the results of a study by Chinese researchers.
The risk of a recurrent vascular event in patients with established cardiovascular disease remains even in those with optimal treatment. For example, one study has found that when risk factors are modified to achieve guideline recommended targets, the residual 10-year risk while < 10% in 47% of patients is >30% in 9%. One factor associated with this residual risk is inflammation and it has been found that patients who have low CRP levels after statin therapy, had better clinical outcomes than those with higher CRP levels, regardless of the resultant level of LDL cholesterol. Furthermore, clinical and genetic research studies have also shown that lipoprotein A has a crucial role in the pathogenesis of cardiovascular disease. In fact, it has been found that elevated LpA levels during treatment of cardiovascular disease are related to cardiovascular-related death when CRP levels are > 2 mg/L. Nevertheless, much less is known about the relationship between CRP and LpA levels in patients undergoing PCI.
For the present study, the Chinese team set out to examine the joint and independent association between LpA and CRP levels among patients with coronary artery disease who underwent a PCI. The researchers used data from a prospective, observational cohort at a national tertiary care centre and identified patients undergoing PCI and where LpA and CRP levels had been measured. Patients were followed-up for 5 years after discharge and the team set the primary endpoint as major adverse cardiac and cerebrovascular events (MACCE), which was a composite of all-cause mortality, myocardial infarction, unplanned revascularisation and ischaemic stroke.
C-reactive protein and lipoprotein A levels and MACCE
A total of 10,424 patients with a mean age of 58.4 years (77.2% male) were included in the analysis. The median level of LpA was 18.53 mg/dL and CRP 1.62 mg/L. After 5 years of follow-up, the primary endpoint (MACCE) occurred in 20.5% of participants.
Multivariable analysis showed that when LpA levels were > 30 mg/dL there was a higher risk of MACCE (Hazard ratio, HR = 1.14, 95% CI 1.05 – 1.25, p < 0.05) compared to levels below 30 mg/dL. Similarly, CRP levels above 2 mg/L were also significantly associated with a greater risk of MACCE (HR = 1.10, 95% CI 1.01 – 1.20, p < 0.05).
But when both LpA and CRP were higher than 30 mg/dL and 2 mg/L respectively, in fully adjusted models, there was a 22% higher risk of MACCE (HR = 1.22, 95% CI 1.07 – 1.39, p < 0.05).
The authors concluded that elevated LpA levels were associated with a higher risk of adverse cardiovascular events and that this risk was even higher when C-reactive protein levels were above 2 mg/L. They suggested that measuring levels of both could help identify high-risk individuals and who might benefit from further therapeutic interventions.
Yuan D et al. Lipoprotein(a), high-sensitivity C-reactive protein, and cardiovascular risk in patients undergoing percutaneous coronary intervention Atherosclerosis 2022
10th October 2022
Dual anti-platelet therapy for longer than 12 months following coronary stenting compared with aspirin therapy alone, has been shown to significantly reduce the risks of stent thrombosis and major adverse cardiovascular and cerebrovascular events but was associated with an increased risk of bleeding. Consequently, there is a move away from dual towards P2Y12 inhibitor (P2Y12I) mono-therapy and in a recent meta-analysis of 6 trials of coronary revascularisation following acute coronary syndrome, the authors concluded that mono-therapy was associated with a similar risk of death, myocardial infarction, or stroke and a lower bleeding risk compared with dual therapy. Although a recent, randomised trial found that P2Y12I mono-therapy with clopidogrel during the chronic maintenance period after percutaneous coronary intervention (PCI) with dual-eluting stents significantly reduced the risk of the composite of all-cause death major bleeding, there remains uncertainty over the clinical outcomes of long-term P2Y12I mono-therapy compared to dual therapy following a percutaneous coronary intervention (PCI).
As a result, in the present study, a team of Korean researchers examined the long-term comparative safety and efficacy of P2Y12I mono-therapy following three months of dual therapy to continued dual therapy for 12 months or longer in patients following a PCI. In this open-label follow-up of a randomised trial SMART-CHOICE, participants were randomised 1:1 to P2Y12I mono-therapy (after 3 months of dual therapy) or prolonged dual therapy. Treatment in the dual therapy arm was aspirin 100 mg daily and the P2Y12 inhibitors, clopidogrel 75 mg or prasugrel 10 mg daily or ticagrelor 90 mg twice daily. In those assigned to continued P2Y12I mono-therapy, the aspirin was stopped after 3 months. The primary endpoint was major adverse cardiac and cerebrovascular events and which the researchers defined as a composite of all-cause death, myocardial infarction or stroke up to 3 years after the PCI procedure. The team set several secondary endpoints including bleeding (BARC types 2 – 5) and major bleeding (BARC types 3 – 5).
P2Y12 inhibitor mono-therapy and cardiovascular outcomes
A total of 2,993 patients with a mean age of 64.6 years (74.2% male) were included and randomised between the two interventions.
After 3 years of follow-up, the primary endpoint occurred in 6.3% of those assigned to P2Y12I mono-therapy and 6.1% the dual therapy which was non-significant (hazard ratio, HR = 1.06, 95% CI 0.79 – 1.44, p = 0.69). Moreover, there were also no significant differences in all-cause mortality, myocardial infarction or stroke.
In contrast, mono-therapy significantly reduced the risk of BARC types 2 – 5 bleeding (HR = 0.39, 95% CI 0.28 – 0.55, p < 0.001) as well as major bleeding (HR = 0.56, 95% CI 0.31 – 0.99, p = 0.048) compared to dual therapy.
The authors concluded that P2Y12I mono-therapy was associated with a significantly lower risk of bleeding following PCI despite no differences in ischaemic cardiovascular events.
Choi KI et al. Long-term Effects of P2Y12 Inhibitor Monotherapy After Percutaneous Coronary Intervention: 3-Year Follow-up of the SMART-CHOICE Randomized Clinical Trial JAMA Cardiol 2022
25th January 2022
Colchicine use in patients with coronary artery disease undergoing a percutaneous intervention, significantly reduced the incidence of major adverse cardiovascular events (MACE) according to a meta-analysis by a team from the University of Oxford, UK.
Coronary artery disease is characterised by atherosclerotic plaque accumulation in the epicardial arteries and can be managed with various interventions including lifestyle modification, pharmacological therapies and invasive interventions, all of which are designed to achieve disease stabilisation or regression. One particular intervention is percutaneous coronary intervention (PCI) and defined as a non-surgical, invasive procedure which seeks to relieve the narrowing or occlusion of the coronary artery and improve blood supply to the ischaemic tissue.
The importance of inflammation in the pathogenesis of coronary artery disease was established many years ago and during PCI, damage to the endothelial layer after stent implantation can also lead to a further inflammatory response. Moreover, the presence of residual inflammation can increase the risk of subsequent complications such as a myocardial infarction therefore highlighting the importance of minimising inflammation to improve patient outcomes.
Colchicine use represents a low cost anti-inflammatory agent and there is evidence that they drug has beneficial effects as a secondary preventative measure, especially after a myocardial infarction. Nevertheless, the value of colchicine use as an adjunctive intervention to PCI to prevent cardiovascular events remains unclear and was the objective of the current analysis.
The team undertook a systematic review and meta-analysis for studies that compared the efficacy of colchicine use to either no use or placebo in patients undergoing PCI and which reported on MACE. The primary outcome measures were the MACE and which included outcomes including in-stent restenosis (ISR), repeat vessel revascularisation, stent thrombosis, stroke and all cause mortality.
A total of 7 trials including 6660 participants with a mean age of 60.9 years (3347 assigned to colchicine use) and a follow-up time ranging from 3 days to 22.6 months were analysed.
The incidence of MACE was 7.08% in those assigned to colchicine use and 9.15% in the control arm, leading to a significant reduction in MACE (risk ratio, RR = 0.73, 95% CI 0.61 – 0.87, p = 0.0003) and with little evidence of heterogeneity across the analysis.
Use of colchicine was associated with a significant reduction in stent thrombosis (RR = 0.50), repeat vessel revascularisation (RR = 0.47) and stroke (RR = 0.50). However, there was no significant difference in all-cause mortality (RR = 1.12, 95% CI 0.49 – 2.58, p = 0.79).
The authors calculated the number needed to treat with colchicine to prevent one episode of MACE to be 41. They concluded that colchicine use significantly reduced the risk of MACE in patients with coronary artery disease undergoing PCI and called for future trials to further evaluate the value of colchicine with different types of stents and alternative dosing regimes.
Aw KL et al. Colchicine for symptomatic coronary artery disease after percutaneous coronary intervention Open Heart 2022