Risk of cardiovascular outcomes with bempedoic acid in high-risk statin intolerant patients: a systematic review and meta analysis

Probably not a substantial claim: may not pass S3 (load-bearing).

The mean age of the patients ranged from 62.2 years to 68 years.

“The mean age of the pa tien ts ranged from 62.2 years to 68 years.”

Probably not a substantial claim: may not pass S3 (load-bearing).

Among those receiving primary interventions, 4,307 were men and 3,823 were women.

“Among those receiving primary in terven tions, 4307 were men and 3823 w er e w omen.”

Probably not a substantial claim: may not pass S3 (load-bearing).

The study by Ballantyne et al., 2018 was included in analyzing adverse events because it reported side effects with bempedoic acid.

“How ev er, the study was included in analyzing the adverse events as it reported side effects with bempedoic acid.”

Probably not a substantial claim: may not pass S3 (load-bearing).

All included studies had a uniform dosage of bempedoic acid (180 mg/day as a single dose).

“All the studies had a uniform dosage of bempedoic acid (180 mg/day as a single dose).”

The quote only partly states this claim.

There is no significant difference in the incidence of serious adverse events between bempedoic acid and placebo (RR 1.02; 95% CI [0.96, 1.08]; p = 0.49).

“no significant difference was observed in serious adverse events”

Probably not a substantial claim: may not pass S3 (load-bearing).

The online search yielded 1,016 articles from the three databases.

“The online search yielded 1016 articles from the three databases.”

May combine two claims.

The review included six randomized controlled trials with a total of 17,844 patients.

“Only six randomized controlled trials were used in final analysis consisting of 17,844 pa tien ts.”

• Also stated in: § 3. Results · plain

  “only 6 articles w er e used in the analysis”

• Also stated in: § 3.1. Characteristics of the included studies · plain

  “The total number of pa tien ts included in the trials was 17,844”

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

The six included trials were multicenter clinical trials conducted in different sites in one or more countries, including the USA, Canada, Netherlands, United Kingdom, and Poland.

“All the studies w er e multi-c ent er clinical trials c onduct ed in different sites in either one country or different countries including United states of America (USA), Canada, Netherlands, United Kingdom and Poland just to name a few”

Probably not a substantial claim: may not pass S3 (load-bearing).

Most of the included trials compared bempedoic acid to placebo.

“Most of the trials compared bempedoic acid t o plac ebo apart from NCT03337308”

Probably not a substantial claim: may not pass S3 (load-bearing).

After screening and eligibility assessment, only six articles were used in the analysis.

“Aft er careful analy sis based on the elig ibility crit eria outlined in our PICOS format, only 6 articles w er e used in the analysis.”

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

Of the 17,844 patients included in the trials, 8,130 were involved in the primary intervention and 9,714 in the secondary intervention.

“The total number of pa tien ts included in the trials was 17,844 of which 8,130 w er e inv olv ed in primar y inter vention and 9,714 in the secondary in terven tion.”

May combine two claims.

Risk reductions for stroke, revascularization, and cardiac mortality with bempedoic acid were not statistically significant.

“However, other studies also show a decrease in other risk of stroke, rev asculariza tion and cardiac mortality with bempedoic acid which was inc onsist ent with our findings as risk reduction for these events were not significant [ 27 , 28 ].”

May combine two claims.

Bempedoic acid is still favorable since no major adverse events were increasingly reported in the bempedoic acid group.

“Based on these results, bempedoic acid is still favorable since no major adverse ev ents w er e incr easingly r eported in the bempedoic acid group.”

Probably not a substantial claim: may not pass S3 (load-bearing).

Three independent reviewers conducted the study selection in different phases.

“Thr ee independent r eview ers c onduct ed the study selection in different phases.”

Probably not a substantial claim: may not pass S3 (load-bearing).

Statins cannot achieve desired lipid levels unless combined with other lipid lowering drugs.

“Although statins as mentioned above are the current standard drug for hyperlipidemia but cannot achieve the desir ed lev els unless combined with other lipid low ering drugs [ 29 , 30 ].”

• cites [29]Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

• cites [30]Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

Probably not a substantial claim: may not pass S3 (load-bearing).

Ballantyne et al., 2020 showed concerns in two domains: bias due to missing outcome data and bias in selection of reported result.

“study Ballantyne et al., 2020 also showed c onc erns in two domains i.e., bias due to missing out c ome data and bias in selection of reported result [ 10 ].”

• cites [10]Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

PCSK9 inhibitors are considered second line of management alongside ezetimibe due to being less cost effective and potential of causing neurocognitive impairments.

“Among new drugs, Pr opr ot ein c onvertase subtilisin/kexin type 9 (PCSK9) inhibitors are also being studied , how ev er they ar e consider ed as a part of second line of management alongside ezetimibe due to being less cost effective, and the potential of causing neuroc og nitive impairments [ 31 ].”

• cites [31]Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

Probably not a substantial claim: may not pass S3 (load-bearing).

Bempedoic acid could be placed above statins in terms of patient compliance.

“This outcome could be due to the reason that bempedoic acid being a prodrug needs an enzyme to activ a te it which is not present in muscles and thus could well place bempedoic acid above statins in terms of patient c omplianc e as with the use of statins which may lead to muscle problems such as pain and weakness, the c omplianc e may be reduced in addition to intolerance [ 14 , 34 ].”

• cites [14]Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

• cites [34]Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

• AssumptionRests on an assumption: Bempedoic acid being a prodrug needs an enzyme to activate it which is not present in muscles.

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

The literature search was done using two search strategies for all articles published until March 2024.

“The literature search was done using two search strat eg ies for all articles published until March 2024.”

Classified as probably not a substantial claim. May combine two claims.

Heterogeneity was evaluated using I2, with low heterogeneity assigned for I2 < 25%, moderate for I2 = 25-50%, and high for I2 > 50%.

“ensuring ev alua tion of the heterogeneity of the various studies using the I 2 .A low heterogeneity was assigned for I 2 < 25%, moderate het erogeneity t o I 2 = 25-50%, high het erogeneity t o I 2 > 50%.”

Probably not a substantial claim: may not pass S3 (load-bearing).

Reviewers manually analyzed the reference lists of selected articles to identify relevant articles that may have been missed in the database search.

“the r eview ers in this study took use of another r esear ch strategy, which inv olv ed manually analyzing the r efer ence list of the selected articles to single out the r esear ches that may not have been included or may have been missed in the first attempt”

Probably not a substantial claim: may not pass S3 (load-bearing).

This review did not focus on other outcomes such as lipid profile changes, so possible associations between lipid profile changes and other outcomes may have been missed.

“Sec ond, sinc e the study focused on the cardiovascular out c omes of patients receiving bempedoic acid therapy, the other out c omes such as lipid profile changes w er e not focused on and thus possible associations between lipid profile changes and other out c ome ma y ha v e been missed out.”

May combine two claims.

Bempedoic acid has a favorable safety profile and can be used safely in high-risk statin-intolerant patients.

“Lastly, our analysis showed that the safety profile of bempedoic acid is favorable and can thus be used safely in highrisk statin intolerant patients.”

• Also stated in: § 6. Future p ersp ective · plain

  “Mor eov er, our analysis also shows that the safety profile of bempedoic acid is satisfactory how ev er it incr eases the risk of trea tmen t rela ted adverse effects.”

Probably not a substantial claim: may not pass S3 (load-bearing).

Three reviewers used data extraction forms to independently extract all relevant data from the included studies.

“three reviewers used data ex trac tion forms to independently ex trac t all the relevant data from the included studies”

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

A random effects model was selected for the meta-analysis considering expectations for high heterogeneity of the included studies; a fixed effects model was used when heterogeneity was low.

“A random effects model was selected for the meta-analysis considering the expectations for high heterogeneity of the studies included.However, in the cases where the heterogeneity was low, the fixed effects model was used in the analysis.”

Probably not a substantial claim: may not pass S3 (load-bearing).

The review's protocol was registered on PROSPERO (CRD42024536827).

“This r eview's pr ot oc ol was reg ist ered on PR OSPER O (CRD42024536827).”

Probably not a substantial claim: may not pass S3 (load-bearing).

Risk of bias of the included studies was assessed using the ROB2 assessment scale provided by the Cochrane Collaboration.

“The risk of bias (ROB) of the various studies was performed using the ROB2 assessment scale provided by the Cochrane Collaboration [ 13 ].”

• cites [13]Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

May combine two claims.

The number of studies included in this review was limited, and hence the findings are not strongly supported.

“First of all, the number of studies included although had a large number of participants, they w er e limited in number and hence the findings are not strongly support ed.”

May combine two claims.

Bempedoic acid is a possible and efficacious alternative therapy in high-risk patients who are intolerant to statin therapy.

“Based on the results of this review, we conclude that bempedoic acid is a possible and efficacious alternative therapy in high-risk pa tien ts who are in toleran t to statin therapy as it is beneficial in reducing the risk of developing MACE.”

• Also stated in: § 4. Discussion · hedged

  “Bempedoic acid could be a good alt ernative t o other lipid lowering drugs in statin intolerant high-risk patients.”

• Also stated in: § Additional information · plain

  “Bempedoic acid, an ATP-citrate lyase inhibitor, is an effective alt ernative t o sta tins in high-risk pa tien ts who are in toleran t to statins.”

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

Statins have been widely applied in prevention of MACE especially by lowering LDL-C, and their efficacy has been established in various settings and combinations.

“and statins have been widely applied in the prevention of development of MACE especially b y lo wering LDL-C.The efficacy of these agents in the pr ev ention of MACE has been widely established in various settings and in different combinations which are statin-based therapies [ 24 ].”

• cites [24]Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

Probably not a substantial claim: may not pass S3 (load-bearing).

Publication bias across studies was assessed using funnel plots at 95% CI.

“the publication bias across studies was also assessed using funnel plots at 95% CI.”

Probably not a substantial claim: may not pass S3 (load-bearing).

The PRISMA 2020 guidelines were used as the basis for conducting this meta-analysis and systematic review.

“The guidelines of the PRISMA 2020 (Preferred Reporting It ems for Sy st ematic Review s and Meta-Analy ses) w er e used as the basis for conducting this meta-analysis”

• cites [12]Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

May combine two claims.

The incidence of MACE is reduced in patients receiving bempedoic acid although not consistent across all components of MACE.

“We can ther efor e establish that the incidence of M ACE is reduced in pa tien ts receiving bempedoic acid although not c onsist ent across all the c omponen ts of MACE .”

Probably not a substantial claim: may not pass S3 (load-bearing).

The search utilized three databases: Google Scholar, Science Direct, and PubMed.

“The search utilized three databases: Google S cholar, S cience Direct and PubMed .”

May combine two claims.

Bempedoic acid is a safe and effective alternative to statins in high-risk statin-intolerant patients, decreasing the risk of MACE.

“Bempedoic acid is a safe and effective alternative to statins in high-risk patients in toleran t to statins, decreasing the risk of MACE.”

• Also stated in: § Abstract · plain

  “Bempedoic acid is a safe and effective trea tmen t tha t can be given to pa tien ts who cannot t olerat e statins or develop side effects to it, as it reduces the risk of heart-related adv erse ev ents.”

• AssumptionRests on an assumption: The MACE definitions used across the included trials are sufficiently comparable to be pooled in a single meta-analysis.
• AssumptionRests on an assumption: The populations of the included trials are sufficiently similar to combine for the pooled cardiovascular outcome analyses.

Probably not a substantial claim: may not pass S3 (load-bearing).

Due to the limited number of studies, a detailed subgroup analysis to determine factors affecting efficacy of bempedoic acid could not be conducted.

“Furthermor e, due to the limited number of studies, a detailed subgroup analy sis t o det ermine the fact ors affecting efficacy of bempedoic acid such as adjuv an t therapies, baseline lipid profiles and drug history use could not be conducted.”

Probably not a substantial claim: may not pass S3 (load-bearing).

Nissen et al., 2023 showed some concerns in the domain of bias in measurement of the outcome.

“with study by Nissen et al., 2023 also showing some c onc erns in the domain of bias in measurement of the out c ome [ 2 , 16 , 17 ].”

• cites [2]Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

• cites [16]Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

• cites [17]Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

May combine two claims.

Some studies observed elevation in liver enzymes and hyperuricemia in patients taking bempedoic acid, but these effects were minimal and liver enzyme levels were self-resolving.

“How ev er, some studies did observe an elev a tion in liver enzymes and hyperuricemia in pa tien ts taking bempedoic acid but these effects w er e minimal and liver enzymes levels were found to be self-resolving [ 35 , 36 ].”

• cites [35]Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

• cites [36]Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.