*For medical professionals only
The American Heart Association/American College of Cardiology (AHA/ACC) guidelines and the European Society of Cardiology/European Atherosclerosis Society (ESC/EAS) guidelines both recommend the use of statins As a first-line drug for cardiovascular risk reduction; ezetimibe is used as a second-line therapy for patients who are statin-intolerant or unable to achieve ideal LDL-C reduction despite maximally tolerated statin therapy. If further LDL-C lowering is required, escalation therapy with a PCSK9 inhibitor is recommended.
The evidence for the recommendation for PCSK9 inhibitors comes from the FOURIER and ODYSSEY trials. These two trials showed that the addition of a PCSK9 inhibitor to statin therapy (with or without ezetimibe) further reduced LDL-C levels and improved cardiovascular outcomes in patients with recent acute coronary syndrome .
However, a cost-benefit analysis shows that the cost of PCSK9 inhibitors is substantially greater than their clinical value; in individuals using maximally tolerated statins or statin-intolerant individuals, there is currently no There are large trials or meta-analyses evaluating the potential absolute incremental effect of ezetimibe or PCSK9 inhibitors alone, or both, estimating the absolute cardiovascular risk reduction of these therapies in patients with different cardiovascular risk degree.
The BMJ recently published a systematic review and network meta-analysis comparing ezetimibe in adults taking maximally tolerated doses of statin or statin-intolerant and PCSK9 inhibitors on cardiovascular outcomes, filling this knowledge gap. Let’s take a look together.
Study Design
Design: A Network Meta-Analysis.
Data sources: Medline, EMBASE and Cochrane databases as of December 31, 2020.
Criteria for selection of studies: randomized controlled trials of ezetimibe and PCSK9 inhibitors, the number of patients is ≥ 500, and the follow-up time is ≥ 6 months.
Primary endpoints: included relative risk (RR) and non-fatal myocardial infarction (MI), non-fatal stroke, all-cause death and cardiovascular disease per 1000 patients treated for 5 years absolute risk of death.
Conduct frequent fixed-effects network meta-analyses and GRADE (Grading of Recommendations, Assessments, Development, and Evaluation) to Assess the certainty of the evidence.
Assuming constant RR across baseline therapies and cardiovascular risk thresholds (estimated by network meta-analysis), absolute risk differences were estimated; primary prevention and Cardiovascular risk in secondary prevention.
Patients were classified as low to very high cardiovascular risk. The guideline panel and systematic review authors identified a minimally important difference (MID) of 12‰ for MI and 10‰ for stroke.
Findings
This meta-analysis identified 14 assessments of ezetimibe and PCSK9 inhibitors (83 660 statin-treated adults).
Ezetimibe added to statins
Reduces MI and stroke, but not all-cause or cardiovascular mortality:
MI: RR 0.87, 95% confidence interval [CI] (0.80-0.94);
Stroke: RR 0.82, 95% CI (0.71-0.96);
All-cause mortality: RR 0.99, 95%CI (0.92-1.06)
Cardiovascular mortality: RR 0.97, 95 %CI (0.87-1.09).
In addition to statins, PCSK9 inhibitors were added< /strong>
Reduces MI and stroke, but not all-cause or cardiovascular mortality:
MI: RR 0.81, 95%CI (0.76-0.87);
Stroke: RR 0.74, 95%CI (0.64-0.85);
All-cause mortality: RR 0.95, 95%CI (0.87-1.03);
Cardiovascular mortality: RR 0.95, 95%CI (0.87) -1.03).
In adults at very high cardiovascular risk, add a PCSK9 inhibitor span>
May reduce MI (16/1000) and stroke (21/1000) (moderate to high certainty); p>
In adults at very high cardiovascular risk, add ezetimibe
Possibly reduced stroke (14/1000), but reduction in MI (11/1000) (moderately certain) did not reach MID.
in PCSK9 inhibitor and statin-basedOn the basis of the addition of ezetimibe,
may reduce stroke (11/1000) but MI (9/1000) (Low certainty) MID not reached.
A PCSK9 inhibitor was added to statins and ezetimibe, < /p>
may reduce MI (14/1000) and stroke (17/1000) (low certainty).
In adults at high cardiovascular risk, add a PCSK9 inhibitor span>
May reduce MI (12/1000) and stroke (16/1000) (moderately certain);
In adults at high cardiovascular risk, the addition of ezetimibe
may Strokes were reduced (11/1000), but MI was not reduced to MID (8/1000) (moderately certain).
Ezetimibe added to PCSK9 inhibitors and statins< span>, did not reduce the results over MID,
in addition to ezetimibe and statins, adding a PCSK9 inhibitor span>, may reduce stroke (13/1000).
These effects were consistent in statin-intolerant patients.
Adding a PCSK9 inhibitor or ezetimibe to a statin had little benefit for MI and stroke in the intermediate and low cardiovascular risk groups.
Study Conclusions
In patients receiving maximum tolerated doses of statins Ezetimibe or PCSK9 inhibitors reduce non-fatal MI and stroke in adults with very high or high cardiovascular risk in patients treated or intolerant to statins, but not in those with intermediate and low cardiovascular risk Not so in China.
Review Highlights
Current Knowledge
Statins are recommended as first-line drugs to reduce cardiovascular risk;
if the patient needs to further reduce cardiovascular risk risk, ezetimibe and a PCSK9 inhibitor are recommended as add-on therapy.
Ezetimibe alone or in combination with a PCSK9 inhibitor compared The absolute effect of cardiovascular outcomes is uncertain.
What’s new in this study
< p>Ezetimibe or PCSK9 inhibitors reduce non-fatal mortality in adults at very high or high cardiovascular risk in adults taking maximally tolerated doses of statins or statin-intolerant Myocardial infarction and stroke. However, these benefits were not shown in moderate and low cardiovascular risk populations.
Adding ezetimibe or a PCSK9 inhibitor as add-on therapy, or in statin-intolerant populations, had no effect on all-cause or cardiovascular mortality. Significantly affected.
Prescribing these lipid-lowering drugs should be considered in populations at high or very high cardiovascular risk to obtain the expected cardiovascular benefit.
Source:
PCSK9 inhibitors and ezetimibe with or without statin therapy for cardiovascular risk reduction: a systematic review and network meta-analysis. BMJ. 2022 May 4;377:e069116. doi: 10.1136/bmj-2021-069116.
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