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. 2024 Mar 8;103(10):e37416. doi: 10.1097/MD.0000000000037416

In-hospital initiation of a PCSK9 inhibitor in patients with acute coronary syndrome: A systematic review and meta-analysis of randomized controlled trials

Wenhai Shi a,*, Yong Xu a, Lin Zhou a, Wuwan Wang b, Wei Huang c, Bo Zhou c
PMCID: PMC10919517  PMID: 38457555

Abstract

Background:

Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors have been shown to be effective and safe in patients with stable angina and previous myocardial infarction. However, evidence for initiating their use in patients hospitalized with acute coronary syndrome (ACS) is limited. This systematic review and meta-analysis was performed to provide more clinical evidence.

Methods:

PubMed, Embase, OVID, Cochrane Library and ClinicalTrials.gov were systematically searched for eligible randomized controlled trials up to March 20, 2023. The risk ratios, standardized mean differences and 95% confidence intervals were calculated for primary and secondary outcomes. The bias risk of the included studies was assessed using the Cochrane RoB 2 criteria.

Results:

About 8 randomized controlled trials involving 1255 inpatients with ACS were included. PCSK9 inhibitor treatment significantly reduced low-density lipoprotein cholesterol (LDL-C) (SMD −1.28, 95% CI −1.76 to −0.8, P = .001), triglycerides (TG) (SMD −0.93, 95% CI −1.82 to −0.05, P = .03), total cholesterol (SMD −1.36, 95% CI −2.01 to −0.71, P = .001), and apolipoprotein B (Apo B) (SMD −0.81, 95% CI −1.09 to −0.52, P = .001) within approximately 1 month. PCSK9 inhibitor treatment significantly reduced the total atheroma volume (TAV) (SMD −0.33, 95% CI −0.59 to −0.07, P = .012). It also significantly increased minimum fibrous cap thickness (FCT) (SMD 0.41, 95% CI 0.22–0.59, P = .001) in long-term follow-up (>6 months). PCSK9 inhibitor treatment significantly reduced the risk of readmission for unstable angina (RR 0.32, 95% CI 0.12–0.91, P = .032) in short-term follow-up (<6 months). There were no significant differences in all-cause mortality, cardiovascular death, myocardial infarction, ischemic stroke, coronary revascularization or heart failure. Only nasopharyngitis (RR 1.71, 95% CI 1.01–2.91, P = .047) adverse events were significantly observed in the PCSK9 inhibitor group.

Conclusion:

Application of a PCSK9 inhibitor in hospitalized patients with ACS reduced lipid profiles and plaque burdens and was well tolerated with few adverse events.

Keywords: acute coronary syndrome, alirocumab, evolocumab, PCSK9 inhibitors

1. Introduction

Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors have been demonstrated to effectively reduce serum low-density lipoprotein cholesterol (LDL-C) and the number of clinical events in patients after acute coronary syndrome (ACS).[1,2] However, there is limited evidence on the initiation of PCSK9 inhibitors before hospital discharge in patients with ACS.[3] Therefore, we conducted a systematic review and meta-analysis to assess the efficacy and safety of PCSK9 inhibitors in such patients (PROSPERO registration number: CRD 42019135934).

2. Methods

2.1. Search strategy

In accordance with the 2020 PRISMA guidelines,[4] we systematically searched PubMed, Embase, the Cochrane Library, OVID and Clinical Trials.gov up to March 20, 2023 with no start date restriction. The search terms were as follows: PCSK9 inhibitor, alirocumab, evolocumab, AMG145, REGN727, SAR236553, JS002, tafolecimab, recaticimab, SHR-1209, lerodalcibep, AZD8233, CVI-LM001. The full electronic search strategy is presented in Supplemental Figure S1, http://links.lww.com/MD/L848. The Human Research Committee of Chongqing Medical University approved this study and waived the requirement for informed consent.

3. Study selection

Studies were selected if they met the following inclusion criteria: randomized controlled trial (RCT) design; in-hospital initiation of a PCSK9 inhibitor in patients with ACS; a report of clinical outcomes or adverse events in text or supplementary materials; and language restricted to English. The reference lists of the original studies, review articles and meta-analyses were analyzed for potentially eligible studies. We also directly contacted authors through e-mail for additional information if necessary. The exclusion criteria were as follows: patients without ACS; patients who did not initiate PCSK9 inhibitor treatment during hospitalization; clinical outcomes were not provided; and observational studies and nonRCTs.

4. Data extraction

Two reviewers (Wuwan Wang and Bo Zhou) independently extracted the data from original studies and cross-checked each other’s findings. All necessary data were directly extracted from the publications and supplemental materials on the website rather than by analyzing graphs using scanning or conversion. The extracted information included the trial name/authors, sample size, follow-up time, intervention and control methods, type of PCSK9 inhibitors, characteristics of the patients, lipid level, and clinical and coronary imaging outcomes.

5. Definition of outcomes

The primary outcome was the change in lipid profiles, including LDL-C, high-density lipoprotein cholesterol (HDL-C), total cholesterol (TC), triglycerides (TG), lipoprotein (a) (Lp (a)) and apolipoprotein B (Apo B). Secondary outcomes were coronary imaging endpoints including total atheroma volume (TAV) and fibrous cap thickness (FCT) between baseline and follow-up; event endpoints, including all-cause mortality, cardiovascular death, myocardial infarction (MI), ischemic stroke, coronary revascularization, heart failure, readmission for unstable angina (UA); adverse events, including myalgia, poor blood glucose control or new-onset diabetes mellitus, local injection reaction, neurocognitive event, alanine aminotransferase (ALT) increase > 3 × upper limit of normal and nasopharyngitis. A follow-up period of at least 24 weeks was defined as “long-term.”

6. Risk of bias assessment

Two reviewers (Yong Xu and Lin Zhou) independently assessed the quality of each study and resolved any disagreements by consulting a third reviewer (Wei Huang). The revised Cochrane risk-of-bias tool for randomized trials (RoB 2), which is a domain-based evaluation system composed of 5 principles—bias arising from the randomization process, bias due to deviations from intended interventions, bias due to missing outcome data, bias in measurement of the outcome, and bias in selection of the reported result—was used to evaluate the quality of the original literature. Each item was evaluated as “low risk of bias,” “some concerns” or “high risk of bias.”[5]

7. Statistical analysis

We used Stata 12.0 (Stata Corporation, College Station, TX) to calculate the risk ratios, standardized mean differences and 95% confidence intervals for the pooled analysis. standard deviations were calculated from the standard errors or confidence intervals if not reported in the original article. 2-tailed P values < .05 indicated statistical significance. Heterogeneity was examined by Cochran Q-statistic and the I2 statistic. I2 values > 50% or P values < .01 of Cochran Q-statistic were considered to indicate high levels of heterogeneity among studies. We used the random-effects model for analyses since all trials were performed independently. The potential sources of heterogeneity between trials, such as the follow-up period, were solved by subgroup analysis and meta-regression. A sensitivity analysis was conducted to assess the robustness of the synthesized results if necessary.

8. Evidence quality assessment

Two reviewers (Wenhai Shi and Bo Zhou) independently used the grading of recommendations assessment, development and evaluation (GRADE) approach to assess the quality of evidence and any disagreements by consulting a third reviewer (Wei Huang). The GRADE approach classifies evidence as “high,” “moderate,” “low” and “very low.”[6]

9. Results

9.1. Study and patient characteristics

A total of 14,485 relevant articles were identified, of which 6636 duplicate articles were excluded. After reviewing the title and abstract, we excluded 7818 articles, including reviews, guidelines, animal experiments, case reports, and expert opinions. The full texts of 31 articles were assessed for meeting the eligibility criteria. A further 23 articles were excluded according to our exclusion criteria. Finally, 8 studies were included in the present meta-analysis.[7–14] (Fig. 1)

Figure 1.

Figure 1.

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Study selection according to the PRISMA 2020 flow diagram.

Our meta-analysis included a total of 1255 patients involving 8 randomized controlled trials (RCTs), of which 4 used alirocumab as the intervention group and 4 used evolocumab.[7–14] 3 studies reported optical coherence tomography or intravascular ultrasound (IVUS) outcomes.[10,11,14] There were 4 studies with follow-up times >24 weeks.[7,10,11,14] The patients were mainly male, with an age range of 57 to 63. Hypertension was common in all studies. The mean range for LDL-C was 2.4 to 4.0 mmol/L at baseline on statins or ezetimibe treatment. The general characteristics of the included studies and patients are shown in Tables 1 and 2.

Table 1.

Characteristics of the included trials.

Trials Yr Sample size Type of ACS and amount of patients (n) Time to initiate a PCSK9 inhibitor therapy Intervention Control *Intensive statin use (I/C) (%) Ezetimibe use (I/C) (%) Coronary imaging method Follow-up (wk)
Raber et al[11] 2022 300 NSTEMI (142) <24 h after PCI Alirocumab 150 mg Q2W Placebo 88.5/94.8 1.5/2.2 OCT/IVUS 52
STEMI (158)
Nicholls et al[10] 2022 161 NSTEMI (161) 6.5 d after index NSTEMI Evolocumab 420 mg monthly Placebo 78.8/82.7 1.3/2.5 OCT/IVUS 52
Mehta et al[12] 2022 68 STEMI (68) Before primary PCI Alirocumab 150 mg Q2W Sham control 97.3/100 5.2/3.3 / 6
Hao et al[8] 2020 136 NSTMI (65) 48 h after PCI Evolocumab 140 mg Q2W No PCSK9 inhibitors 100/100 100/100 / 12
STEMI (55)
UA (16)
Abdelnabi et al[7] 2022 80 NSTEMI (50) After index ACS Evolocumab 420 mg monthly No PCSK9 inhibitors 100/100 100/100 / 24
STEMI (50)
Koskinas et al[9] 2019 308 NSTE-ACS (195) Before or after PCI Evolocumab 420 mg monthly Placebo 88.6/89.1 2.8/3 / 8
STEMI (113)
Ako et al[14] 2019 182 NSTEMI (28) <4 wk after ACS diagnosis Alirocumab 75~150 mg Q2W No PCSK9 inhibitors 45.2/48.3 7.5/7.9 IVUS 36
STEMI (102)
UA (52)
Trankle et al[13] 2019 20 NSTEMI (20) <24 h after presenting ACS Single dose of alirocumab 150 mg Placebo 100/100 0/0 / 2
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ACS = acute coronary syndrome, I/C = intervention vs. control, IVUS = intravascular ultrasonography, NSTEMI = non-ST-elevation myocardial infarction, OCT = optical coherence tomography, PCI = percutaneous coronary intervention, PCSK9 = proprotein convertase subtilisin/kexin type 9, STEMI = ST-elevation myocardial infarction, UA = unstable angina

*

Intensive statin therapy was defined as daily use of atorvastatin ≥ 40 mg, rosuvastatin ≥ 20 mg or simvastatin 80 mg after randomization

Table 2.

Characteristics of patients.

Trial Raber et al[11] Nicholls et al[10] Mehta et al[12] Hao et al[8] Abdelnabi et al[7] (total patients) Koskinas et al[9] Ako et al[14] Trankle et al[13]
Age, mean (yr) 58.4/58.6 60.9/60.2 61.3/63.6 62.2/62.2 59 60.5/61.0 61.8/60.5 57.6/57.1
Female (%) 16.2/21.1 25/32.1 29/6.7 33.9/29.5 33.4 27/20 20.4/19.1 40/90
BMI mean 27.3/28.2 28.2/28 NR 26.2/25.7 NR 26.9/27.8 25.2/25 NR
Smoking (%) 52/42.8 58.8/59.3 NR 48.5/52.9 58.8 41/30 NR NR
Hypertension (%) 40.5/46.1 56.3/40.7 44.7/43.3 70.5/60.2 65.0 51/56 68.8/70.8 70/90
Diabetes mellitus (%) 8.1/12.5 16.3/17.3 13.1/3.3 39.7/33.8 26.3 15/16 29/34.8 50/40
Previous MI (%) 1.4/3.3 6.3/11.1 7.8/10 NR 50 15/12 NR NR
Previous PCI (%) 1.4/3.3 11.3/14.8 NR NR NR 16/15 NR NR
Stroke (%) NR NR 2.6/0 5.8/4.4 NR 1/0 5.4/3.4 NR
PAD (%) 1.4/2.6 NR NR NR NR 3/3 1.1/0 NR
ACE inhibitor 8.1/7.9 73.8/71.6 NR 83.8/91.1 NR NR NR NR
LDL-C (mmol/L) 4.0/3.9 3.6/3.7 2.9/2.8 3.5/3.5 3.9/3.7 3.6/3.4 2.5/2.4 2.6/2.9
HDL-C (mmol/L) 1.1/1.1 1.1/1.0 0.9/1.0 1.1/1.1 NR 1.1/1.1 1.1/1.2 NR
TC (mmol/L) 5.3/5.2 4.5/4.5 4.7/4.5 4.8/4.9 NR 5.5/5.3 4.3/4.4 NR
TG (mmol/L) 1.2/1.2 1.6/1.7 1.2/0.8 2.0/1.7 NR 1.8/1.6 1.3/1.2 NR
Apo B (mg/dL) 115.4/113.6 91/92.9 88.0/83.0 100/106 NR 117/112 90.9/90.6 NR
Lp (a) (mg/dL) 30.9/34.5 38.4/34.3 6.8/10.1 19.8/22.1 NR 26.3/22.5 18/17 NR
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Intervention group/control group

ACE = angiotensin converting enzyme, Apo B = apolipoprotein B, BMI = body mass index, HDL-C = high-density lipoprotein cholesterol, LDL-C = low-density lipoprotein cholesterol, Lp (a) = lipoprotein (a), MI = myocardial infarction, NR = not reported, PAD = peripheral arterial disease, PCI = percutaneous coronary intervention, TC = total cholesterol, TG = triglycerides

The risk of bias assessments for each study are displayed in Supplemental Figure S2, http://links.lww.com/MD/L849 and half of these studies had a “low risk of bias.” Blinding is an important part of bias evaluation, and unsuccessful blinding leads to subjective tendencies of participants, trial investigators or assessors in RCTs.[15] In the EPIC-STEMI trial, an alirocumab training pen without an internal needle was used in the sham-control group. It is possible that some patients could have been unblinded, and this could have affected follow-up.[12] In the ODYSSEY J-IVUS trial, investigators were able to alter background lipid-lowering therapy in the control group, which may have confounded the results.[14] The evidence quality of the 8 studies assessed by the GRADE approach was high (see Supplemental Figure S3, http://links.lww.com/MD/L850).

10. Primary outcome

10.1. Lipid profiles

PCSK9 inhibitors were significantly associated with a decrease in LDL-C (SMD −1.28 95% CI −1.76 to −0.8, P = .001), TG (SMD −0.93 95% CI −1.82 to −0.05, P = .03), TC (SMD −1.36 95% CI −2.01 to −0.71, P = .001), Apo B (SMD −0.81 95% CI −1.09 to −0.52, P = .001) and Lp (a) (SMD −0.8 95% CI −1.36 to −0.23, P = .006) compared with no PCSK9 inhibitor treatment within 6 weeks (Fig. 2). The meta-regression was conducted from 3 aspects, including age, body mass index and duration of coronary artery disease. The results were not significantly altered throughout this process (see Supplemental File S1, http://links.lww.com/MD/L857).

Figure 2.

Figure 2.

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Pooled analysis for lipid results at 1 month.

11. Secondary outcomes

11.1. Coronary imaging endpoints

11.1.1. Change in TAV.

Three RCTs reported PCSK9 inhibitor treatment and absolute changes in TAV.[10,11,14] The heterogeneity of the 3 RCTs was slightly high (P = .12, I2 = 52.2%). PCSK9 inhibitors were significantly associated with a decrease in TAV within 1 year (SMD −0.33 95% CI −0.59 to −0.07, P = .012) (Fig. 3A). Subgroup analysis showed that neither alirocumab nor evolocumab reduced TAV (see Supplemental Figure S4, http://links.lww.com/MD/L851).

Figure 3.

Figure 3.

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Pooled analysis for coronary imaging endpoints. (A) Change in total atheroma volume. (B) Minimal fibrous cap thickness.

11.1.2. Minimal FCT.

Two RCTs reported PCSK9 inhibitor treatment and minimal FCT.[10,11] No significant heterogeneity was found (P = .68, I2 = 0%). PCSK9 inhibitors were significantly associated with an increase in minimal FCT within 1 year (SMD 0.41 95% CI 0.22–0.59, P = .001) (Fig. 3B).

11.2. Event endpoints

11.2.1. All-cause mortality.

Two RCTs reported PCSK9 inhibitor treatment and short-term all-cause mortality.[9,12] No significant heterogeneity was found (P = .36, I2 = 0%). PCSK9 inhibitors were not associated with a decrease in all-cause mortality within 8 weeks (RR 1.18 95% CI 0.07–20.65, P = .90). 2 RCTs reported PCSK9 inhibitor treatment and long-term all-cause mortality.[11,14] The heterogeneity of the 2 RCTs was moderate (P = .19, I2 = 41.3%). PCSK9 inhibitors were not associated with a decrease in all-cause mortality within 1 year (RR 1.06 95% CI 0.16–7.18, P = .95) (Fig. 4A).

Figure 4.

Figure 4.

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Pooled analysis for event endpoints. (A) All-cause mortality. (B) Cardiovascular death. (C) Readmission for unstable angina. (D) Myocardial infarction. (E) Ischemic stroke. (F) Coronary revascularization. (G) Heart failure.

11.2.2. Cardiovascular death.

Two RCTs reported PCSK9 inhibitor treatment and short-term cardiovascular death.[8,9] No significant heterogeneity was found (P = .78, I2 = 0%). PCSK9 inhibitors were not associated with a decrease in cardiovascular death within 12 weeks (RR 3.69 95% CI 0.41–33.09, P = .24). 3 RCTs reported PCSK9 inhibitor treatment and long-term cardiovascular death.[7,10,11] The heterogeneity of the 3 RCTs was moderate (P = .31, I2 = 12.8%). PCSK9 inhibitors were not associated with a decrease in cardiovascular death within 1 year (RR 0.71 95% CI 0.13–3.86, P = .69) (Fig. 4B). Subgroup analysis showed that neither alirocumab nor evolocumab reduced cardiovascular death (see Supplemental Figure S5, http://links.lww.com/MD/L852).

11.2.3. Readmission for UA.

Three RCTs reported PCSK9 inhibitor treatment and short-term readmission for UA.[8,9,13] No significant heterogeneity was found (P = .82, I2 = 0%). PCSK9 inhibitors were significantly associated with a decrease in readmission for UA within 12 weeks (RR 0.32 95% CI 0.12–0.91, P = .03). Only one study reported PCSK9 inhibitor treatment and long-term readmission for UA.[14] No significant decrease in readmission for UA was found compared with no PCSK9 inhibitor treatment at half a year (RR 2.48 95% CI 0.49–12.47, P = .27) (Fig. 4C).

11.2.4. MI.

Two RCTs reported PCSK9 inhibitor treatment and short-term MI.[8,9] The heterogeneity of the 2 RCTs was moderate (P = .18, I2 = 42.4%). PCSK9 inhibitors were not associated with a decrease in MI within 12 weeks (RR 1.36 95% CI 0.22–8.50, P = .73). 3 RCTs reported PCSK9 inhibitor treatment and long-term MI.[7,10,11] No significant heterogeneity was found (P = .64, I2 = 0%). PCSK9 inhibitors were not associated with a decrease in MI within 1 year (RR 0.54 95% CI 0.17–1.68, P = .28) (Fig. 4D). Subgroup analysis showed that neither alirocumab nor evolocumab reduced MI (see Supplemental Figure S6, http://links.lww.com/MD/L853).

11.2.5. Ischemic stroke.

Three RCTs reported PCSK9 inhibitor treatment and short-term stroke.[8,9,13] The heterogeneity of the 3 RCTs was moderate (P = .34, I2 = 7.2%). PCSK9 inhibitors were not associated with a decrease in stroke within 12 weeks (RR 1.11 95% CI 0.17–7.13, P = .91). 2 RCTs reported PCSK9 inhibitor treatment and long-term stroke.[11,14] The heterogeneity of the 2 RCTs was moderate (P = .23, I2 = 29.5%). PCSK9 inhibitors were not associated with a decrease in stroke within 1 year (RR 1.37 95% CI 0.1–18.75, P = .81) (Fig. 4E). Subgroup analysis showed that neither alirocumab nor evolocumab reduced stroke (see Supplemental Figure S7, http://links.lww.com/MD/L854).

11.2.6. Coronary revascularization.

Only one study reported PCSK9 inhibitor treatment and short-term coronary revascularization.[9] No significant decrease in coronary revascularization was found compared with no PCSK9 inhibitor treatment at 8 weeks (RR 0.88 95% CI 0.59–1.33, P = .90). About 2 RCTs reported PCSK9 inhibitor treatment and long-term coronary revascularization.[11,14] The heterogeneity of the 2 RCTs was slightly high (P = .10, I2 = 63%). PCSK9 inhibitors were not associated with a decrease in coronary revascularization within 1 year (RR 0.76 95% CI 0.18–3.13, P = .71) (Fig. 4F).

11.2.7. Heart failure.

Two RCTs reported PCSK9 inhibitor treatment and short-term heart failure.[12,13] No significant heterogeneity was found (P = .86, I2 = 0%). PCSK9 inhibitors were not associated with a decrease in heart failure within 8 weeks (RR 5.99 95% CI 0.77–46.42, P = .08). Only one study reported PCSK9 inhibitor treatment and long-term heart failure.[7] No significant decrease in heart failure was found compared with no PCSK9 inhibitor treatment at half a year (RR 3.00 95% CI 0.13–71.51, P = .49) (Fig. 4G).

12. Adverse events

Myalgia, local injection reaction and biochemical adverse events were analyzed. PCSK9 inhibitors slightly increased the risk of nasopharyngitis (RR 1.71 95% CI 1.01–2.91, P = .04) (see Supplemental Figure S8, http://links.lww.com/MD/L855).

13. Sensitivity analysis

Considering that the first dose of the study drug after index ACS onset in the ODYSSEY J-IVUS trial was delayed compared to other studies,[14] we performed sensitivity analyses by eliminating the trial to identify the efficacy of PCSK9 inhibitors in TAV, but the pooled effect was not disturbed, indicating that the result was stable (see Supplemental Figure S9, http://links.lww.com/MD/L856).

14. Discussion

The present meta-analysis revealed that in-hospital initiation of a PCSK9 inhibitor in patients with ACS reduced lipid profiles in 1 month. In a previous study, a significantly higher concentration of PCSK9 was observed in patients with ACS.[16] Alirocumab and evolocumab bind to PCSK9 in serum, which prevents PCSK9 from binding to LDL receptors. Thus, many LDL receptors accumulate on the surface of hepatocytes, accelerating the degradation of LDL-C.[17] The ODYSSEY COMBO I, ODYSSEY LONG TERM and ODYSSEY JAPAN trials have demonstrated that PCSK9 inhibitors reduce LDL-C, TG, TC, Apo B and Lp (a) with a background statin therapy.[18–20] A recent network meta-analysis revealed that PCSK9 inhibitors enabled patients to rapidly achieve the recommended LDL-C target.[21,22]

A subgroup analysis of the FOURIER trial revealed that treatment with evolocumab reduced the primary endpoint (the composite of cardiovascular death, MI, stroke, coronary revascularization, or hospitalization for UA) by 20% in those with a more recent MI (<2 years).[23] The ODYSSEY OUTCOMES trial compared treatment with alirocumab or placebo in patients who experienced ACS within a median of 2.6 months prior to randomization. A composite primary endpoint event (the composite of cardiovascular death, MI, ischemic stroke, or hospitalization for UA) occurred in 9.5% of patients assigned to alirocumab, compared to 11.1% of those assigned to placebo (HR 0.85, 95% CI 0.78–0.93, P < .001).[2] Our meta-analysis showed that initiating PCSK9 inhibitor treatment during hospitalization significantly reduced rehospitalization for UA, which might be related to plaque regression, but due to the small number of trials included, this requires further validation in large-scale clinical trials.[24,25]

Our meta-analysis found an important reduction in TAV in patients who received a PCSK9 inhibitor, which was consistent with the findings of the GLAGOV trial, demonstrating a favorable effect on the progression of atherosclerotic plaques.[26] Our meta-analysis also found that a PCSK9 inhibitor significantly augmented minimal FCT. Early studies have confirmed that a thin fibrous cap is a marker of vulnerable plaques.[27,28] Moreover, the CLIMA study showed that minimal FCT < 75 μm was the strongest factor to predict clinical prognosis.[29] Recently, 2 meta-analyses demonstrated that treatment with PCSK9 inhibitors in patients with atherosclerotic cardiovascular disease reduced plaque burdens and did not increase serious adverse events, which was consistent with our findings.[30,31]

Our study is characterized by several innovations. First, the present meta-analysis adds new evidence regarding the efficacy and safety of PCSK9 inhibitors in patients with ACS. Second, the quality of evidence of original articles was assessed rigorously using the GRADE approach. Third, we conducted a sensitivity analysis to demonstrate the robustness of the outcomes.

This meta-analysis has some limitations. First, amalgamation of aggregate patient data in meta-analyses has well-known limitations. In the study of Hao et al[8], the dose of evolocumab (140 mg Q2 W) was different from other studies (420 mg Q4 W), which may amplify the positive outcomes, as an every 2-week regimen seems more effective in reducing LDL-C than an every 4-week regimen in the LAPLACE-TIMI 57 trial[32] Second, due to the short follow-up time and small sample size of the included trials, our study did not demonstrate that PCSK9 inhibitors reduce all-cause mortality, cardiovascular death or other clinical endpoints. Therefore, whether in-hospital initiation of a PCSK9 inhibitor in patients with ACS provides incremental clinical benefit over subsequent initiation in the outpatient setting in a longer follow-up period requires further research.

15. Conclusion

Application of a PCSK9 inhibitor in hospitalized patients with ACS reduced plaque burden and lipid profiles and was well tolerated with few adverse events.

Author contributions

Writing – original draft: Wenhai Shi.

Methodology: Yong Xu, Lin Zhou, Wuwan Wang, Wei Huang.

Writing – review and editing: Yong Xu, Lin Zhou, Wuwan Wang, Wei Huang.

Data curation: Wuwan Wang.

Resources: Wuwan Wang.

Formal analysis: Bo Zhou.

Software: Bo Zhou.

Supplementary Material

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Abbreviations:

ACS
acute coronary syndrome
ALT
alanine aminotransferase
Apo B
apolipoprotein B
BMI
body mass index
CI
confidence interval
FCT
fibrous cap thickness
GRADE
grading of recommendations assessment, development and evaluation
HDL-C
high-density lipoprotein cholesterol
IVUS
intravascular ultrasound
LDL-C
low-density lipoprotein cholesterol
Lp (a)
lipoprotein (a)
MI
myocardial infarction
OCT
optical coherence
PCSK9
proprotein convertase subtilisin/kexin type 9
RCT
randomized controlled trial
RR
risk ratio
SMD
standardized mean difference
TAV
atheroma volume
TC
total cholesterol
TG
triglycerides
UA
unstable angina
ULN
upper limit of normal.

The authors have no conflicts of interest to disclose.

The work was supported by the National Natural Science Foundation of China [grant number 30971212].

All data generated or analyzed during this study are included in this published article [and its supplementary information files].

Supplemental Digital Content is available for this article.

How to cite this article: Shi W, Xu Y, Zhou L, Wang W, Huang W, Zhou B. In-hospital initiation of a PCSK9 inhibitor in patients with acute coronary syndrome: A systematic review and meta-analysis of randomized controlled trials. Medicine 2024;103:10(e37416).

Contributor Information

Yong Xu, Email: xuyong000015@sina.com.

Lin Zhou, Email: 419870406@qq.com.

Wuwan Wang, Email: www_0505@163.com.

Wei Huang, Email: 15828554938@163.com.

Bo Zhou, Email: 419870406@qq.com.

References

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