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Expert Opinion on Pharmacotherapy May 2018In 2017, Schmidt et al. conducted a Cochrane systematic review and meta-analysis to evaluate the effect of using proprotein convertase subtilisin/kexin type 9 (PCSK9)... (Meta-Analysis)
Meta-Analysis Review
In 2017, Schmidt et al. conducted a Cochrane systematic review and meta-analysis to evaluate the effect of using proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors to reduce low-density-lipoprotein- cholesterol (LDL-C) and cardiovascular disease (CVD). The Cochrane review was a systematic review and meta-analysis of 20 randomized, double-blinded trials that compared the use of PCSK9 inhibitors with statins/ezetimibe, ezetimibe, or placebo for a treatment duration of at least 24 weeks. The use of PCSK9 inhibitors lowered the risk for CVD (OR 0.86 (0.80 to 0.92)) but not mortality (OR 1.02 (0.91 to 1.14)) when compared to placebo. Areas covered: The following article evaluates the recently published Cochrane review and clarifies the efficacy of PCSK9 inhibitors for improving cardiovascular morbidity and mortality. Expert opinion: The Cochrane review discussed suggests that PCSK9 inhibitors are effective in lowering LDL-C and the risk of CVD but not the risk of mortality. The higher price of PCSK9 inhibitors is a further deterrent for using them as a substitute for statins - cholesterol lowering medications with history showing they lower mortality. Statins should remain the gold-standard cholesterol-lowering drug class until PCSK9 inhibitors become more affordable and demonstrate consistent efficacy for reducing CVD and mortality.
Topics: Cardiovascular Diseases; History, 21st Century; Humans; Middle Aged; PCSK9 Inhibitors
PubMed: 29667439
DOI: 10.1080/14656566.2018.1464558 -
Endocrine Journal Jun 2021This review evaluated the risk of rheumatoid arthritis in patients with type 2 diabetes treated with dipeptidyl peptidase-4 inhibitors (Dpp-4i). The MEDLINE (via... (Meta-Analysis)
Meta-Analysis
This review evaluated the risk of rheumatoid arthritis in patients with type 2 diabetes treated with dipeptidyl peptidase-4 inhibitors (Dpp-4i). The MEDLINE (via PubMed), Embase, the Cochrane Library databases and web of science were used to search the effects of Dpp-4i on rheumatoid arthritis in patients with type 2 diabetes from inception to 7 September, 2020. We included studies that met the following criteria:(i) A randomized controlled trial (RCT), prospective or retrospective cohort study examining the relationship between Dpp-4i and rheumatoid arthritis. Exclusion criteria included the following: Reviews and researches related to other diseases or subjects; and studies without data on the prevalence of rheumatoid arthritis were excluded. Risk of Bias table contained in Review Manager 5.3 and Newcastle-Ottawa scale (NOS) were used for quality assessment of included RCT and observational studies separately. Meta-analysis was used to estimate the risk of disease. We conducted a subgroup analysis of duration of follow-up, adjusted (adjusted RR or unadjusted RR), sample size and study design. A total of 10 independent studies assessing 1,420,414 patients were included in this analysis. In this meta-analysis, we found that there was nonsignificant increase of rheumatoid arthritis with Dpp-4 inhibitor exposure (RR 0.96, 95%CI (0.69-1.32)). Our results revealed that Dpp-4 inhibitors do not seem to increase the risk of rheumatoid arthritis. Long-term follow-up monitoring is necessary.
Topics: Arthritis, Rheumatoid; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Humans; Hypoglycemic Agents
PubMed: 33642418
DOI: 10.1507/endocrj.EJ20-0647 -
The American Journal of Cardiology Feb 2024In patients with stable atherosclerotic cardiovascular disease, proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9is) have shown a 50% to 60% reduction in... (Meta-Analysis)
Meta-Analysis
In patients with stable atherosclerotic cardiovascular disease, proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9is) have shown a 50% to 60% reduction in low-density lipoprotein cholesterol (LDL-C) from baseline when added to high-intensity statin therapy. However, less is known about the impact of PCSK9is in the setting of an acute coronary syndrome (ACS). Therefore, we performed a systematic review and meta-analysis comparing PCSK9is with placebo in the setting of ACS added to guideline-directed high-intensity or maximally tolerated statin therapy. We included randomized controlled trials with initiation of a PCSK9i or placebo within 1 week of presentation or percutaneous coronary intervention for ACS. PubMed, EMBASE, and Cochrane Central were searched. This study followed the Cochrane and Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) recommendations. A total of 6 randomized controlled trials were included, with a total of 996 patients, of whom 503 (50.5%) received PCSK9is. The mean follow-up ranged from 4 to 52 weeks. The LDL-C (mean difference [MD] -44.0 mg/100 ml, CI -54.3 to -33.8, p <0.001) and lipoprotein (a) levels (MD -24.0 nmol/L, confidence interval [CI] -43.0 to -4.9, p = 0.01) were significantly lower at follow-up with PCSK9is. Similarly, the total cholesterol (MD -49.2 mg/100 ml, CI -59.0 to -39.3), triglycerides (MD -19.0 mg/100 ml, CI -29.9 to -8.2), and apolipoprotein B (MD -33.3 mg/100 ml, CI -44.4 to -22.1) were significantly reduced with PCSK9is. In conclusion, in patients with ACS, early initiation of PCSK9i added to statin significantly reduces LDL-C and lipoprotein (a) levels compared with placebo. Whether the differences in these atherogenic lipoproteins translate into a reduction in clinical end points is yet to be determined.
Topics: Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Cholesterol, LDL; Proprotein Convertase 9; PCSK9 Inhibitors; Acute Coronary Syndrome; Atherosclerosis; Lipoprotein(a); Anticholesteremic Agents
PubMed: 37875235
DOI: 10.1016/j.amjcard.2023.10.043 -
American Journal of Therapeutics 2018The approval of the oral direct thrombin inhibitor, dabigatran etexilate, gave patients an alternative to oral anticoagulation with warfarin. Like all anticoagulants,... (Review)
Review
BACKGROUND
The approval of the oral direct thrombin inhibitor, dabigatran etexilate, gave patients an alternative to oral anticoagulation with warfarin. Like all anticoagulants, the primary adverse event (AE) associated with dabigatran is bleeding. Until the FDA approval of idarucizumab, there had been no reversal agent for dabigatran-induced anticoagulation in patients with life-threatening or uncontrollable bleeding, or those requiring emergent procedures.
AREAS OF UNCERTAINTY
The primary purpose of this review is to summarize the safety and efficacy of idarucizumab, a monoclonal antibody fragment, and its use as a reversal agent for dabigatran.
DATA SOURCES
A literature search was conducted through MEDLINE (1946 to November week 1 2015) and Embase (1980-2015 week 46) using the search term idarucizumab. Clinicaltrials.gov was consulted for a comprehensive list of ongoing and completed studies. Additional studies were identified through bibliographical citations. Clinical trials in animals and humans published in English evaluating the safety and efficacy of idarucizumab for reversal of anticoagulant treatment with dabigatran were included for review.
RESULTS
Idarucizumab has been shown to significantly reverse the anticoagulant effects of dabigatran in both healthy volunteers and patients requiring a reversal agent because of either overt bleeding or an emergency surgery or invasive procedure. The most common AEs were headache, nasopharyngitis, back pain, skin irritation, hypokalemia, delirium, constipation, pyrexia, and pneumonia. Deaths reported in idarucizumab studies were attributed to either the index event or a preexisting comorbidity. Most adverse effects were minor, but 21 serious AEs have been reported in the published data including thrombotic events.
CONCLUSIONS
Given the increased use of direct oral anticoagulants, such as dabigatran, a need for specific reversal agents exists. Idarucizumab has been shown to be safe and effective in the reversal of dabigatran-induced anticoagulation in patients requiring emergent or urgent surgery or in patients with severe bleeding.
Topics: Antibodies, Monoclonal, Humanized; Antithrombins; Blood Coagulation; Dabigatran; Hemorrhage; Humans; Treatment Outcome
PubMed: 27175894
DOI: 10.1097/MJT.0000000000000460 -
Giornale Italiano Di Dermatologia E... Apr 2020Treatment with antihypertensive drugs may be associated with different dermatological adverse reactions.
INTRODUCTION
Treatment with antihypertensive drugs may be associated with different dermatological adverse reactions.
EVIDENCE ACQUISITION
We systematically reviewed the literature available on the MEDLINE (PubMED) databases, up to July 2018. We searched for the terms "calcium-channel blockers" or "angiotensin-converting enzyme inhibitors" or "angiotensin II receptors blockers" or "diuretics" or "beta blockers" AND "dermatological effects" or "skin disease."
EVIDENCE SYNTHESIS
The most important cutaneous events occurring during treatment with calcium-channel blockers are represented by pedal edema and photosensitivity with consequent increased risk of skin cancer. Moreover, other adverse reactions are eczematous and psoriasiform dermatitis, subacute cutaneous lupus erythematosus, and rarely toxic epidermal necrolysis. In patients taking angiotensin-converting enzyme inhibitors or angiotensin II receptors blockers, angioedema, psoriasis and pemphigus can be exacerbated. Furthermore, some authors associated the use of these medications with the onset of skin neoplasms. As for diuretics, the most relevant cutaneous reactions are represented by subacute cutaneous lupus erythematosus and leukocytoclastic vasculitis. Photosensitivity is another important event related to diuretics use. Eventually, itching is often related to the use of thiazides, particularly in elderly patients. With regards to beta blockers, we should remember a significant association with psoriasis, lichen planus, subacute cutaneous lupus erythematosus, and an increased risk of skin cancer.
CONCLUSIONS
During antihypertensive treatment, several dermatological reactions may occur. Clinicians should inform their patients of the increased risk of cutaneous lesions associated with the use of these drugs, and perform periodic examination of the skin.
Topics: Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Drug Eruptions; Humans
PubMed: 31195782
DOI: 10.23736/S0392-0488.19.06360-0 -
The Canadian Journal of Cardiology Mar 2015Atrial fibrillation (AF) increases the risk of stroke and thromboembolic events. Recently, biomarkers have been proposed as a practical tool to predict adverse outcomes... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Atrial fibrillation (AF) increases the risk of stroke and thromboembolic events. Recently, biomarkers have been proposed as a practical tool to predict adverse outcomes in patients with AF. The prognostic value of inflammatory and hemostatic markers in AF has been widely studied; however, the results of previous studies have been inconclusive.
METHODS
We conducted a systematic review and meta-analysis to evaluate the association of inflammatory and hemostatic markers with stroke and thromboembolic events in patients with AF.
RESULTS
A total of 27 studies including 22,176 participants met our inclusion criteria for the systematic review. Our meta-analysis determined that elevated circulating plasminogen activator inhibitor-1 (PAI-1) and thrombin-antithrombin (TAT) were significantly associated with increased risk of stroke in patients with AF (standardized mean difference [SMD], 0.89; 95% confidence interval [CI], 0.20-1.59 and 1.43; 95% CI, 0.40-2.47, respectively). Higher levels of D-dimer were associated with increased subsequent thromboembolic event risk with a pooled hazard ratio of 2.90 (95% CI, 1.22-6.90) for cohort studies and an SMD of 0.93 (95% CI, 0.36-1.50) for case-control studies. There was also very limited evidence indicating that other biomarkers-such as interleukin-6, von Willebrand factor, P-selectin, and mean platelet volume-could predict adverse outcomes in AF.
CONCLUSIONS
In conclusion, increased circulating PAI-1 and TAT levels were significantly associated with subsequent stroke in patients with AF, and high levels of D-dimer were associated with thromboembolic events in AF. Further epidemiologic studies are needed to accumulate more evidence on the prognostic role of inflammatory and hemostatic markers in AF.
Topics: Anticoagulants; Antifibrinolytic Agents; Antithrombin III; Atrial Fibrillation; Biomarkers; Fibrin Fibrinogen Degradation Products; Humans; Interleukin-6; Mean Platelet Volume; Peptide Hydrolases; Plasminogen Activator Inhibitor 1; Predictive Value of Tests; Prognosis; Selectins; Sensitivity and Specificity; Serine Proteinase Inhibitors; Stroke; Thromboembolism; von Willebrand Factor
PubMed: 25746020
DOI: 10.1016/j.cjca.2014.12.002 -
Cancer Causes & Control : CCC Sep 2015We aim to investigate the association between angiotensin-converting enzyme inhibitors (ACEIs)/angiotensin receptor blockers (ARBs) therapy and colorectal cancer (CRC)... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
We aim to investigate the association between angiotensin-converting enzyme inhibitors (ACEIs)/angiotensin receptor blockers (ARBs) therapy and colorectal cancer (CRC) by conducting a systematic review with meta-analysis.
METHODS
Literature was searched on PubMed, Scopus, and the Cochrane library to identify relevant studies evaluating ACEIs/ARBs therapy and risk of CRC incidence or survival of CRC patients. Pooled risk ratio (RR) with 95% confidence intervals was calculated for the association between ACEIs/ARBs and CRC risk and mortality.
RESULTS
Eleven observational studies were included in the systematic review. A meta-analysis of six studies totaling 113,048 individuals indicated a 6% decreased risk of CRC in ACEIs/ARBs users compared to non-users (95% CI 0.89-0.98). In the four case-control studies, individuals using ACEIs/ARBs were associated with a 6% decreased risk of CRC (95% CI 0.90-0.99). The meta-analysis of three studies investigating the relationship between ACEIs/ARBs and survival of CRC did not show a significantly decreased mortality in ACEIs/ARBs users (RR 0.81, 95% CI 0.60-1.09). Seven studies evaluated the dose-response relationship between ACEIs/ARBs therapy and CRC, and two of them showed that the association was related to longer duration and higher dose.
CONCLUSIONS
CEIs/ARBs therapy might be associated with a reduce risk of CRC development, but whether use of these medications improves the outcomes of CRC remains unknown. Large-scale and more robust studies are needed to further explore this association.
Topics: Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Colorectal Neoplasms; Humans; Hypertension; Incidence; Risk
PubMed: 26081426
DOI: 10.1007/s10552-015-0617-1 -
Journal of Clinical Pharmacy and... Apr 2016Many trials have indicated that interventions by pharmacists resulted in beneficial outcomes with positive effects on cardiovascular diseases. The interventions through... (Meta-Analysis)
Meta-Analysis Review
WHAT IS KNOWN AND OBJECTIVE
Many trials have indicated that interventions by pharmacists resulted in beneficial outcomes with positive effects on cardiovascular diseases. The interventions through pharmacist-involved pharmaceutical care in patients with heart failure (HF) and acute coronary syndrome (ACS) were reviewed systemically and examined.
METHODS
A systematic literature search was conducted to identify relevant articles describing pharmacist interventions in HF and ACS. Most studies were evaluated qualitatively, and the strength of evidence was graded according to the Agency for Healthcare Research and Quality (AHRQ) guidelines. Some of the studies were also assessed by a meta-analysis.
RESULTS
A total of 26 studies containing data on 9415 patients were identified. For all studies, the strength of the body of evidence was reviewed and graded, and 14 studies among them were meta-analysed. The evidence was not strong enough to determine the effects of pharmaceutical care on major and patient-centred outcomes, except the prescription rates of angiotensin-converting-enzyme inhibitors (ACEI) with a high strength of evidence. In the meta-analysis, all-cause hospitalization [odds ratio (OR), 0·74; 95% confidence interval (CI), 0·58-0·94] was reduced and the prescription rates of angiotensin-converting-enzyme inhibitors (ACEI; OR 1·43; 95% CI, 1·07-1·91) and beta-blockers (OR 1·92; 95% CI, 1·24-2·96) were significantly higher in the pharmaceutical care group compared with the usual care group.
WHAT IS NEW AND CONCLUSIONS
All-cause hospitalization showed improvement in the pharmaceutical care group. However, the strength of evidence for the majority of outcomes with pharmaceutical care, except direct performance measures such as prescription rates, was either insufficient or low. This could be explained by the presence of imprecision and inconsistency derived from the diversity of pharmaceutical care, the heterogeneity of patient populations or clinical settings. Moreover, it may indicate the necessity for homogeneous applicable criteria for assessment. A standardized consensus of the guidelines for pharmaceutical care service should be considered to improve homogeneity.
Topics: Acute Coronary Syndrome; Adrenergic beta-Antagonists; Angiotensin-Converting Enzyme Inhibitors; Heart Failure; Hospitalization; Humans; Pharmaceutical Services; Pharmacists
PubMed: 26954666
DOI: 10.1111/jcpt.12367 -
Clinical Infectious Diseases : An... Jul 2016Previous studies suggest that nonnucleoside reverse-transcriptase inhibitors (NNRTIs) cause faster virologic suppression, while ritonavir-boosted protease inhibitors... (Meta-Analysis)
Meta-Analysis Review
Nonnucleoside Reverse-transcriptase Inhibitor- vs Ritonavir-boosted Protease Inhibitor-based Regimens for Initial Treatment of HIV Infection: A Systematic Review and Metaanalysis of Randomized Trials.
BACKGROUND
Previous studies suggest that nonnucleoside reverse-transcriptase inhibitors (NNRTIs) cause faster virologic suppression, while ritonavir-boosted protease inhibitors (PI/r) recover more CD4 cells. However, individual trials have not been powered to compare clinical outcomes.
METHODS
We searched databases to identify randomized trials that compared NNRTI- vs PI/r-based initial therapy. A metaanalysis calculated risk ratios (RRs) or mean differences (MDs), as appropriate. Primary outcome was death or progression to AIDS. Secondary outcomes were death, progression to AIDS, and treatment discontinuation. We calculated RR of virologic suppression and MD for an increase in CD4 cells at week 48.
RESULTS
We included 29 trials with 9047 participants. Death or progression to AIDS occurred in 226 participants in the NNRTI arm and in 221 in the PI/r arm (RR, 1.03; 95% confidence interval, .87-1.22; 12 trials; n = 3825), death in 205 participants in the NNRTI arm vs 198 in the PI/r arm (1.04; 0.86-1.25; 22 trials; n = 8311), and progression to AIDS in 140 participants in the NNRTI arm vs 144 in the PI/r arm (1.00; 0.80-1.25; 13 trials; n = 4740). Overall treatment discontinuation (1.12; 0.93-1.35; 24 trials; n = 8249) and from toxicity (1.21; 0.87-1.68; 21 trials; n = 6195) were comparable, but discontinuation due to virologic failure was more common with NNRTI (1.58; 0.91-2.74; 17 trials; n = 5371). At week 48, there was no difference between NNRTI and PI/r in virologic suppression (RR, 1.03; 0.98-1.09) or CD4(+) recovery (MD, -4.7 cells; -14.2 to 4.8).
CONCLUSIONS
We found no difference in clinical and viro-immunologic outcomes between NNRTI- and PI/r-based therapy.
Topics: Anti-HIV Agents; Drug Therapy, Combination; HIV Infections; HIV Protease Inhibitors; Humans; Reverse Transcriptase Inhibitors; Ritonavir
PubMed: 27090986
DOI: 10.1093/cid/ciw236 -
Frontiers in Endocrinology 2022The dipeptidyl peptidase-4 inhibitor (DPP-4i) drugs, such as evogliptin, as the second-line drugs for type 2 diabetes mellitus (T2DM) treatment have been reported to... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
The dipeptidyl peptidase-4 inhibitor (DPP-4i) drugs, such as evogliptin, as the second-line drugs for type 2 diabetes mellitus (T2DM) treatment have been reported to facilitate insulin secretion by reducing glucagon and inhibiting glucagon like peptides. With a vague consensus, the advantageous and non-inferior effects of evogliptin relative to other DPP-4i drugs were recently demonstrated on hemoglobin A1c (HbA1c) levels and overall adverse events in T2DM patients. Thus, the aim was to evaluate the overall influence of evogliptin on HbA1c levels and the adverse events in T2DM patients compared to sitagliptin and linagliptin.
METHODS
Complying with PRISMA guidelines, we conducted a systematic literature search in databases and a meta-analysis. Data about HbA1c levels and the adverse events of T2DM patients were collected and analyzed.
RESULTS
From 1,397 studies, we found five matched studies involving 845 subjects (mean age: 54.7 ± 3 years). The meta-analysis revealed that evogliptin was non-inferior to sitagliptin/linagliptin with a mean difference of 0.062 (95% CI: -0.092 to 0.215. I: 0%. = 0.431) regarding the HbA1c level reduction, and the risk ratio was -0.006 (95% CI: -0.272 to 0.260. I: 1.7%. = 0.966) regarding the adverse effects, indicating no significant difference between evogliptin and linagliptin or sitagliptin in affecting the HbA1c level and adverse effects.
CONCLUSION
The study provides preliminary evidence regarding the similarity in the efficacy of evogliptin compared to other DPP-4i drugs, including sitagliptin and linagliptin, for managing HbA1c levels and adverse events.
Topics: Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Linagliptin; Middle Aged; Piperazines; Sitagliptin Phosphate
PubMed: 36060938
DOI: 10.3389/fendo.2022.962385