Effects of pharmacist interventions on cardiovascular risk factors and outcomes: An umbrella review of meta-analysis of randomized controlled trials.

AIMS: To grade the evidence from published meta-analyses of randomized controlled trials (RCTs) that assessed effects of pharmacist intervention on cardiovascular risk factors and cardiovascular outcomes. METHODS: MEDLINE, Embase, and the Cochrane Library were searched from database inception to July 2021. Meta-analyses of RCTs were eligible. Quality of evidence were assessed by GRADE approach. RESULTS: From 9308 publications, 149 full-text articles were evaluated for eligibility, and 24 studies with 85 unique meta-analyses that assessed effects of pharmacist intervention on cardiovascular risk factors and cardiovascular outcomes were selected. Overall, 71.7% (61/85) of unique meta-analyses showed significant impacts of pharmacist intervention. For the quality of evidence, 63.4% of meta-analyses had large heterogeneity (I2 > 50%) while 1.2, 16.5, 32.9 and 49.4% of meta-analyses were graded as high, moderate, low and very low quality based on GRADE approach, respectively. Among meta-analyses with moderate quality, pharmacist interventions significantly mitigated risk factors (including 6/3 mmHg reduction of blood pressure, increased the rate of lipid control, glucose control and smoking cessation (pooled odds ratio, [95% confidence interval] 1.91 [1.55, 2.35], 3.11 [2.3, 4.3] and 2.3 [1.33, 3.97], respectively) and improved medication adherence (1.67 [1.38, 2.02]). Furthermore, pharmacist interventions significantly reduced all-cause mortality (0.72 [0.58, 0.89]) and improved quality of life in patients suffering from chronic heart failure. CONCLUSION: This umbrella review found convincing evidence that pharmacist intervention can provide a wide range of benefits in cardiovascular disease management, ranging from risk factor control, improvement in medication adherence and, in some settings, reduction in morbidity and mortality.

Effect of tomato, lycopene and related products on blood pressure: A systematic review and network meta-analysis.

BACKGROUND: A number of randomized controlled trials (RCTs) have been conducted to evaluate the hypotensive effects of tomato, lycopene, and related products. However, the findings were conflicting, partly due to differences in the types of products investigated. Therefore, this study aimed to assess and compare the hypotensive effects of different tomato-related preparations through a network meta-analysis based on randomized controlled trials. STUDY DESIGN: A systematic review and network meta-analysis. METHODS: A network meta-analysis based on a systematic review of RCTs comparing the effect of various tomato, lycopene and related products versus placebo on blood pressure in adults was performed. PubMed, EMBASE, SCOPUS, and Clinicaltrial.gov databases were searched up to October 2020 without language restrictions. The primary outcomes were systolic and diastolic blood pressure. Mean differences (MDs) along with 95% confidence intervals (CIs) were estimated and pooled using a random-effects model. Heterogeneity was assessed using the global inconsistency test. RESULTS: A total of 11 studies including six forms of tomato, lycopene and related products met the inclusion criteria. Among these trials, eight (N = 617) and seven trials (N = 501) were included in the analysis of systolic (SBP) and diastolic blood pressure (DBP) outcomes, respectively. The standardized tomato extract (STE) significantly decreased SBP compared to placebo, with a pooled MD (95% CI) of -5.89 (-9.13 to -2.64) mmHg. The effect on DBP was not significant, with a pooled MD (95% CI) of -3.51 (-7.39 to 0.38) mmHg. Subgroup analysis in hypertensive patients showed that STE significantly reduced both SBP and DBP with pooled MDs (95% CIs) of -8.09 (-11.52 to -4.67) and -4.25 (-6.97 to -1.53) mmHg, respectively, compared to placebo. Other forms of tomato, including other dose ranges of standardized tomato extract, tomato-containing diet, lycopene-free preparation, and synthetic lycopene, did not show consistent and significant effects on either SBP or DBP in all analyses. CONCLUSION: Standardized tomato extract (STE) significantly decreased SBP compared to placebo in a mixed population of healthy volunteers and hypertensive patients. The BP-lowering effect was more pronounced among hypertensive patients. No significant BP effects were seen with other forms of tomato, lycopene and related products in the overall population or any subgroup of the population.

Prescriber compliance to direct oral anticoagulant labels and impact on outcomes in Thailand.

AIMS: This study aimed to evaluate the prescriber compliance to the approved labels of direct oral anticoagulants (DOACs) and impact of appropriateness of dosing on clinical outcomes. METHODS: A retrospective study was conducted using simple-stratified random sampling of adult patients receiving ≥6 months of DOACs for various indications during 2013-2017 in 10 tertiary care hospitals. Patients were classified into 3 dosing groups including approved dose, underdosing and overdosing based on the Thai Food and Drug Administration-approved labels. Cox proportional hazard models were used to evaluate the impact of different dosings on thromboembolic and bleeding events. RESULTS: From 1200 patients included in the data analysis, prescribing of DOACs was consistent with the approved indications in 1130 cases (94.2%) while 70 patients (5.8%) received DOACs despite having contraindications or with off-label usage. Among 1026 cases of dosing evaluation cohort, 688 patients (67.1%) received approved doses. There were 227 (21.9%) and 110 (10.7%) cases of underdosing and overdosing, respectively. Multivariate analysis showed that underdosing was associated with an increased risk of thromboembolism 3.023 (95% confidence interval [CI]: 1.291-7.080; P = .011) while overdosing was associated with an increased risk of bleeding requiring hospitalization (adjusted hazard ratio, 3.045; 95% CI, 1.501-6.178; P = .002) and Bleeding Academic Research Consortium type 2 or more (adjusted hazard ratio, 2.196; 95% CI, 1.083-4.452; P = .029). CONCLUSION: Prescribers' compliance to approved indications were high. However, 1/3 of DOAC prescriptions were inconsistent with approved dosing. Dosing deviation was associated with an increase in adverse clinical outcomes.

Effects of Non-statin Lipid-Modifying Agents on Cardiovascular Morbidity and Mortality Among Statin-Treated Patients: A Systematic Review and Network Meta-Analysis.

Background: Currently, there is a lack of information on the comparative efficacy and safety of non-statin lipid-lowering agents (NST) in cardiovascular (CV) disease risk reduction when added to background statin therapy (ST). This study determine the relative treatment effects of NST on fatal and non-fatal CV events among statin-treated patients. Methods: A network meta-analysis based on a systematic review of randomized controlled trials (RCTs) comparing non-statin lipid-modifying agents among statin-treated patients was performed. PubMed, EMBASE, CENTRAL, and Clinicaltrial.gov were searched up to April 10, 2018. The primary outcomes were CV and all-cause mortalities. Secondary CV outcomes were coronary heart disease (CHD) death, non-fatal myocardial infarction (MI), any stroke, and coronary revascularization. Risks of discontinuations were secondary safety outcomes. Results: Sixty-seven RCTs including 259,429 participants with eight interventions were analyzed. No intervention had significant effects on the primary outcomes (CV mortality and all-cause mortality). For secondary endpoints, proprotein convertase subtilisin/kexin type 9 inhibitor (PCSK) plus statin (PCSK/ST) significantly reduced the risk of non-fatal MI (RR 0.82, 95% CI 0.72-0.93, p = 0.003), stroke (RR 0.74, 95% CI 0.65-0.85, p < 0.001), coronary revascularization (RR 0.84, 95% CI 0.75-0.94, p = 0.003) compared to ST. Combinations of ST and all NST except PCSK and ezetimibe showed higher rate of discontinuation due to adverse events compared to ST. Conclusions: None of NST significantly reduced CV or all-cause death when added to ST. PCSKs and to a lesser extent, ezetimibe may help reduce cardiovascular events with acceptable tolerability profile among broad range of patients.

Cost-Effectiveness Analysis of Non-Statin Lipid-Modifying Agents for Secondary Cardiovascular Disease Prevention Among Statin-Treated Patients in Thailand.

BACKGROUND: Using non-statin lipid-modifying agents in combination with statin therapy provides additional benefits for cardiovascular disease (CVD) risk reduction, but their value for money has only been evaluated in high-income countries (HICs). Furthermore, studies mainly derive effectiveness data from a single trial or older meta-analyses. OBJECTIVES: Our study used data from the most recent network meta-analysis (NMA) and local parameters to assess the cost effectiveness of non-statin agents in statin-treated patients with a history of CVD. METHODS: A published Markov model was adopted to investigate lifetime outcomes: (1) number of recurrent CVD events prevented, (2) quality-adjusted life-years (QALYs) gained, (3) costs and (4) incremental cost-effectiveness ratios (ICERs) of proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) and ezetimibe added to statin therapy. Event rates and effectiveness inputs were obtained from the NMA. Cost and utility data were gathered from published studies conducted in Thailand. A series of sensitivity analyses were performed. RESULTS: Patients receiving PCSK9i and ezetimibe experienced fewer recurrent CVD events (number needed to treat [NNT] 17 and 30) and more QALYs (0.168 and 0.096 QALYs gained per person). However, under the societal perspective and at current acquisition costs in 2018, ICERs of both agents were $US1,223,995 and 27,361 per QALY gained, respectively. Based on threshold analyses, the costs need to be reduced by 97 and 85%, respectively, for PCSK9i and ezetimibe to be cost-effective. CONCLUSIONS: Despite the proven effectiveness of PCSK9i and ezetimibe, the costs of these agents need to reduce to a much greater extent than in HICs to be cost-effective in Thailand.