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Reproductive Sciences (Thousand Oaks,... Feb 2024Pregnant women are encouraged to reduce sitting time and replace it with physical activity. Complications arising during pregnancy include gestational hypertension,... (Review)
Review
Pregnant women are encouraged to reduce sitting time and replace it with physical activity. Complications arising during pregnancy include gestational hypertension, preeclampsia, gestational diabetes mellitus (GDM), and prenatal and postpartum depression. In this systematic review, we examined effects of sedentary behavior on the health of pregnant women. We conducted a systematic review with PubMed from year 2000 to identify the relationship between a sedentary lifestyle and psychological effects, occurrence of GDM, gestational hypertension, and preeclampsia. Data extracted included sedentary time of pregnant women, psychological effects, occurrence of GDM, gestational hypertension, and preeclampsia as outcomes. Among the 200 studies retrieved, 11 were finally included after screening. The mean age of eligible pregnant women ranged from 28.5 to 32.9 years. Five studies were extracted with outcomes of psychological effects on the mother, five with GDM, and one with gestational hypertension/preeclampsia. Longer sedentary time was associated with increased risks of prepartum/postpartum depression in three of five studies and GDM in three of five studies. No association was found between sedentary behavior and the risk for gestational hypertension/preeclampsia. Higher sedentary behavior in the second trimester of pregnancy was likely to be associated with postpartum depression. Longer sitting time may increase the risk of prenatal or postnatal depression and GDM, but no relationship was proven for gestational hypertension and preeclampsia in one study. High sedentary behavior in the second trimester may have psychological impacts. The number of studies was small and further research is needed to statistically evaluate impacts of sedentary behavior during pregnancy.
Topics: Pregnancy; Female; Humans; Adult; Sedentary Behavior; Pregnant Women; Pre-Eclampsia; Depression, Postpartum; Hypertension, Pregnancy-Induced; Diabetes, Gestational
PubMed: 37644379
DOI: 10.1007/s43032-023-01321-w -
BJOG : An International Journal of... May 2024Treatment with vaginal progesterone reduces the risk of miscarriage and preterm birth in selected high-risk women. The hypothesis that vaginal progesterone can reduce... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Treatment with vaginal progesterone reduces the risk of miscarriage and preterm birth in selected high-risk women. The hypothesis that vaginal progesterone can reduce the risk of hypertensive disorders of pregnancy (HDP) is unexplored.
OBJECTIVES
To summarise the evidence on the effectiveness of vaginal progesterone to reduce the risk of HDP.
SEARCH STRATEGY
We searched Embase (OVID), MEDLINE (OVID), PubMed, CENTRAL and clinicaltrials.gov from inception until 20 June 2023.
SELECTION CRITERIA
We included placebo-controlled randomised trials (RCTs) of vaginal progesterone for the prevention or treatment of any pregnancy complications.
DATA COLLECTION AND ANALYSIS
We extracted absolute event numbers for HDP and pre-eclampsia in women receiving vaginal progesterone or placebo, and meta-analysed the data with a random effects model. We appraised the certainty of the evidence using GRADE methodology.
MAIN RESULTS
The quantitative synthesis included 11 RCTs, of which three initiated vaginal progesterone in the first trimester, and eight in the second or third trimesters. Vaginal progesterone started in the first trimester of pregnancy lowered the risk of any HDP (risk ratio [RR] 0.71, 95% confidence interval [CI] 0.53-0.93, 2 RCTs, n = 4431 women, I = 0%; moderate-certainty evidence) and pre-eclampsia (RR 0.61, 95% CI 0.41-0.92, 3 RCTs, n = 5267 women, I = 0%; moderate-certainty evidence) when compared with placebo. Vaginal progesterone started in the second or third trimesters was not associated with a reduction in HDP (RR 1.19, 95% CI 0.67-2.12, 3 RCTs, n = 1602 women, I = 9%; low-certainty evidence) or pre-eclampsia (RR 0.97, 95% CI 0.71-1.31, 5 RCTs, n = 4274 women, I = 0%; low-certainty evidence).
CONCLUSIONS
Our systematic review found first-trimester initiated vaginal micronised progesterone may reduce the risk of HDP and pre-eclampsia.
Topics: Pregnancy; Infant, Newborn; Female; Humans; Progesterone; Pre-Eclampsia; Hypertension, Pregnancy-Induced; Premature Birth; Pregnancy Complications
PubMed: 37941309
DOI: 10.1111/1471-0528.17705 -
The Science of the Total Environment Mar 2024A growing body of literature demonstrated an association between exposure to ambient air pollution and maternal health outcomes with mixed findings. The objective of... (Review)
Review
A growing body of literature demonstrated an association between exposure to ambient air pollution and maternal health outcomes with mixed findings. The objective of this umbrella review was to systematically summarize the global evidence on the effects of air pollutants on maternal health outcomes. We adopted the Joanna Briggs Institute (JBI) methodology and Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) reporting standards for this umbrella review. We conducted a comprehensive search across six major electronic databases and other sources to identify relevant systematic reviews and meta-analyses (SRMAs) published from the inception of these databases up to June 30, 2023. Out of 2399 records, 20 citations matched all pre-determined eligibility criteria that include SRMAs focusing on exposure to air pollution and its impact on maternal health, reported quantitative measures or summary effects, and published in peer-reviewed journals in the English language. The risk of bias of included SRMAs was evaluated based on the JBI critical appraisal checklist. All SRMAs reported significant positive associations between ambient air pollution and several maternal health outcomes. Specifically, particulate matter (PM), SO, and NO demonstrated positive associations with gestational diabetes mellitus (GDM). Moreover, PM and NO showed a consistent positive relationship with hypertensive disorder of pregnancy (HDP) and preeclampsia (PE). Although limited, available evidence highlighted a positive correlation between PM and gestational hypertension (GH) and spontaneous abortion (SAB). Only one meta-analysis reported the effects of air pollution on maternal postpartum depression (PPD) where only PM showed a significant positive relationship. Limited studies were identified from low- and middle-income countries (LMICs), suggesting evidence gap from the global south. This review necessitates further research on underrepresented regions and communities to strengthen evidence on this critical issue. Lastly, interdisciplinary policymaking and multilevel interventions are needed to alleviate ambient air pollution and associated maternal health disparities.
Topics: Female; Humans; Pregnancy; Air Pollutants; Air Pollution; Environmental Exposure; Outcome Assessment, Health Care; Particulate Matter; Pre-Eclampsia; Systematic Reviews as Topic
PubMed: 38199356
DOI: 10.1016/j.scitotenv.2023.169792 -
IJID Regions Sep 2023To determine the prevalence of long COVID, its most common symptoms, comorbidities, and pathophysiological mechanisms in African populations. (Review)
Review
OBJECTIVES
To determine the prevalence of long COVID, its most common symptoms, comorbidities, and pathophysiological mechanisms in African populations.
METHODS
A systematic review of long COVID in African populations was conducted. The random effects model was used to calculate the pooled prevalence rates (95% CI). A narrative synthesis was also performed.
RESULTS
We included 14 studies from seven African countries, totaling 6030 previously SARS-CoV-2 infected participants and 2954 long COVID patients. Long COVID had a pooled prevalence of 41% (26-56%). Fatigue, dyspnea, and confusion or lack of concentration were the most common symptoms, with prevalence rates (95% CI) of 41% (26-56%), 25% (12-38%), and 40% (12-68%), respectively. Long COVID was mainly associated with advanced age, being female, more than three long COVID symptoms in the acute phase, initial fatigue and dyspnea, COVID-19 severity, pre-existing obesity, hypertension, diabetes mellitus, and the presence of any chronic illness ( ≤0.05). High microclot and platelet-poor plasma viscosity explained the pathophysiology of long COVID.
CONCLUSION
Long COVID prevalence in Africa was comparable to the global prevalence. The most common symptoms were higher in Africa. Comorbidities associated with long COVID may lead to additional complications in African populations due to hypercoagulation and thrombosis.Systematic review registration: PROSPERO CRD42023430024.
PubMed: 37674565
DOI: 10.1016/j.ijregi.2023.08.004 -
Archives of Gynecology and Obstetrics Apr 2024To show the impact of Sjögren's syndrome (SS) on maternal and fetal outcomes following pregnancy. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To show the impact of Sjögren's syndrome (SS) on maternal and fetal outcomes following pregnancy.
METHODS
We performed a literature search based on PubMed, Web of science, Wan fang, China National Knowledge Infrastructure and ProQuest databases from 1 January 2007 to 6 November 2022. Grading of Recommendations, Assessment, Development, and Evaluations approach was used to assess the certainty of the evidence. Systematic reviews and meta-analyses were performed using RevMan 5.3 software. Pooled odds ratio (OR) and 95% confidence interval (CI) were calculated using a random-effect, generic inverse variance method of DerSimonian and Laird. Trial sequential analyses were performed by TSA 0.9.
RESULTS
Nine studies with 2341 patients and 2472 pregnancies with SS were included in our analysis. This current analysis showed pregnancy hypertension and preeclampsia/eclampsia to be significantly higher in pregnant women with SS compared to pregnant women without SS (OR: 1.65, 95% CI: 1.04-2.63; P = 0.03), (OR: 2.06, 95% CI: 1.16-3.65; P = 0.01) respectively. Cesarean section, thromboembolic disease, premature rupture of membranes, and spontaneous abortion were also significantly higher in the SS women with OR: 2.07, 95% CI: 1.48-2.88; P < 0.0001, OR: 9.45, 95% CI: 1.99-44.87; P = 0.005, OR: 1.36, 95% CI: 1.13-1.64; P = 0.001, OR: 9.30, 95% CI: 4.13-20.93; P < 0.00001, respectively. Significantly higher premature births were observed with infants who were born from SS mothers (OR: 2.19, 95% CI: 1.54-3.12; P < 0.0001). Infants defined as 'small for gestational age/intrauterine growth restriction' and 'weighing < 2500 g' were also significantly higher in patients suffering from SS (OR: 2.26, 95% CI: 1.38-3.70; P = 0.001), (OR: 3.84, 95% CI: 1.39-10.61; P = 0.009) respectively. In addition, live birth significantly favored infants who were born from mothers without SS (OR: 21.53, 95% CI: 8.36-55.44; P < 0.00001). Subgroup analysis by sample size revealed that pregnancy hypertension risk has significantly increased in small cohort (OR: 2.74, 95%CI: 1.45-5.18), and a slight increase was found in population-based studies (OR: 1.14, 95%CI: 0.91-1.43). In both small cohorts and population-based researches, cesarean section was significantly higher in SS (OR: 2.13, 95% CI: 1.29, 3.52; OR: 1.85, 95% CI: 1.29-2.64, respectively). The number of infants with intrauterine growth restriction did not grow in the population-based researches (OR: 2.07, 95%CI: 0.92-4.66) although there has been an increase in small reports (OR: 2.53, 95%CI: 1.16-5.51). Subgroup analysis was conducted on the basis of study location (not Asian vs. Asian countries) indicated that cesarean section was significantly higher in SS in both countries (OR: 1.69, 95% CI: 1.31-2.18; OR: 3.37, 95% CI: 2.39-4.77, respectively).
CONCLUSION
This meta-analysis has shown SS to have a high impact on maternal and fetal outcomes following pregnancy.
Topics: Infant; Pregnancy; Female; Humans; Pregnancy Outcome; Fetal Growth Retardation; Cesarean Section; Sjogren's Syndrome; Premature Birth; Pre-Eclampsia; Hypertension
PubMed: 37921880
DOI: 10.1007/s00404-023-07259-3 -
The Cochrane Database of Systematic... Oct 2023Gestational diabetes mellitus (GDM) has major short- and long-term implications for both the mother and her baby. GDM is defined as a carbohydrate intolerance resulting... (Review)
Review
BACKGROUND
Gestational diabetes mellitus (GDM) has major short- and long-term implications for both the mother and her baby. GDM is defined as a carbohydrate intolerance resulting in hyperglycaemia or any degree of glucose intolerance with onset or first recognition during pregnancy from 24 weeks' gestation onwards and which resolves following the birth of the baby. Rates for GDM can be as high as 25% depending on the population and diagnostic criteria used, and overall rates are increasing globally. There is wide variation internationally in glycaemic treatment target recommendations for women with GDM that are based on consensus rather than high-quality trials.
OBJECTIVES
To assess the effect of different intensities of glycaemic control in pregnant women with GDM on maternal and infant health outcomes.
SEARCH METHODS
We searched the Cochrane Pregnancy and Childbirth Group's Trials Register, ClinicalTrials.gov, the World Health Organization International Clinical Trials Registry Platform (26 September 2022), and reference lists of the retrieved studies.
SELECTION CRITERIA
We included randomised controlled trials (RCTs), cluster-RCTs, and quasi-RCTs. Trials were eligible for inclusion if women were diagnosed with GDM during pregnancy and the trial compared tighter and less-tight glycaemic targets during management. We defined tighter glycaemic targets as lower numerical glycaemic concentrations, and less-tight glycaemic targets as higher numerical glycaemic concentrations.
DATA COLLECTION AND ANALYSIS
We used standard Cochrane methods for carrying out data collection, assessing risk of bias, and analysing results. Two review authors independently assessed trial eligibility for inclusion, evaluated risk of bias, and extracted data for the four included studies. We assessed the certainty of evidence for selected outcomes using the GRADE approach. Primary maternal outcomes included hypertensive disorders of pregnancy and subsequent development of type 2 diabetes. Primary infant outcomes included perinatal mortality, large-for-gestational-age, composite of mortality or serious morbidity, and neurosensory disability.
MAIN RESULTS
This was an update of a previous review completed in 2016. We included four RCTs (reporting on 1731 women) that compared a tighter glycaemic control with less-tight glycaemic control in women diagnosed with GDM. Three studies were parallel RCTs, and one study was a stepped-wedged cluster-RCT. The trials took place in Canada, New Zealand, Russia, and the USA. We judged the overall risk of bias to be unclear. Two trials were only published in abstract form. Tight glycaemic targets used in the trials ranged between ≤ 5.0 and 5.1 mmol/L for fasting plasma glucose and ≤ 6.7 and 7.4 mmol/L postprandial. Less-tight targets for glycaemic control used in the included trials ranged between < 5.3 and 5.8 mmol/L for fasting plasma glucose and < 7.8 and 8.0 mmol/L postprandial. For the maternal outcomes, compared with less-tight glycaemic control, the evidence suggests a possible increase in hypertensive disorders of pregnancy with tighter glycaemic control (risk ratio (RR) 1.16, 95% confidence interval (CI) 0.80 to 1.69, 2 trials, 1491 women; low certainty evidence); however, the 95% CI is compatible with a wide range of effects that encompass both benefit and harm. Tighter glycaemic control likely results in little to no difference in caesarean section rates (RR 0.98, 95% CI 0.82 to 1.17, 3 studies, 1662 women; moderate certainty evidence) or induction of labour rates (RR 0.96, 95% CI 0.78 to 1.18, 1 study, 1096 women; moderate certainty evidence) compared with less-tight control. No data were reported for the outcomes of subsequent development of type 2 diabetes, perineal trauma, return to pre-pregnancy weight, and postnatal depression. For the infant outcomes, it was difficult to determine if there was a difference in perinatal mortality (RR not estimable, 2 studies, 1499 infants; low certainty evidence), and there was likely no difference in being large-for-gestational-age (RR 0.96, 95% CI 0.72 to 1.29, 3 studies, 1556 infants; moderate certainty evidence). The evidence suggests a possible reduction in the composite of mortality or serious morbidity with tighter glycaemic control (RR 0.84, 95% CI 0.55 to 1.29, 3 trials, 1559 infants; low certainty evidence); however, the 95% CI is compatible with a wide range of effects that encompass both benefit and harm. There is probably little difference between groups in infant hypoglycaemia (RR 0.92, 95% CI 0.72 to 1.18, 3 studies, 1556 infants; moderate certainty evidence). Tighter glycaemic control may not reduce adiposity in infants of women with GDM compared with less-tight control (mean difference -0.62%, 95% CI -3.23 to 1.99, 1 study, 60 infants; low certainty evidence), but the wide CI suggests significant uncertainty. We found no data for the long-term outcomes of diabetes or neurosensory disability. Women assigned to tighter glycaemic control experienced an increase in the use of pharmacological therapy compared with women assigned to less-tight glycaemic control (RR 1.37, 95% CI 1.17 to 1.59, 4 trials, 1718 women). Tighter glycaemic control reducedadherence with treatment compared with less-tight glycaemic control (RR 0.41, 95% CI 0.32 to 0.51, 1 trial, 395 women). Overall the certainty of evidence assessed using GRADE ranged from low to moderate, downgraded primarily due to risk of bias and imprecision.
AUTHORS' CONCLUSIONS
This review is based on four trials (1731 women) with an overall unclear risk of bias. The trials provided data on most primary outcomes and suggest that tighter glycaemic control may increase the risk of hypertensive disorders of pregnancy. The risk of birth of a large-for-gestational-age infant and perinatal mortality may be similar between groups, and tighter glycaemic targets may result in a possible reduction in composite of death or severe infant morbidity. However, the CIs for these outcomes are wide, suggesting both benefit and harm. There remains limited evidence regarding the benefit of different glycaemic targets for women with GDM to minimise adverse effects on maternal and infant health. Glycaemic target recommendations from international professional organisations vary widely and are currently reliant on consensus given the lack of high-certainty evidence. Further high-quality trials are needed, and these should assess both short- and long-term health outcomes for women and their babies; include women's experiences; and assess health services costs in order to confirm the current findings. Two trials are ongoing.
Topics: Humans; Pregnancy; Infant; Female; Diabetes, Gestational; Blood Glucose; Glycemic Control; Hypertension, Pregnancy-Induced; Diabetes Mellitus, Type 2
PubMed: 37815094
DOI: 10.1002/14651858.CD011624.pub3 -
Archives of Gynecology and Obstetrics Mar 2024Hypertensive disorders during pregnancy are a significant cause of maternal and perinatal mortality and morbidity worldwide. White coat hypertension (WCH) is a... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
Hypertensive disorders during pregnancy are a significant cause of maternal and perinatal mortality and morbidity worldwide. White coat hypertension (WCH) is a hypertensive disease characterized by an increased clinic blood pressure but normal home or workplace blood pressure. Due to variable prevalence, a subset of women with WCH may be incorrectly diagnosed with chronic hypertension, highlighting the need for accurate diagnosis. Little is known about the role of WCH in pregnancy, but a meta-analysis aims to determine whether WCH increases the likelihood of developing preeclampsia.
METHODS
A systematic review and meta-analysis was conducted to determine whether there is an association between WCH and the incidence of preeclampsia in pregnant women. The search included PubMed, Embase, and Scopus databases until February 2023, using PRISMA guidelines. Pregnant women with apparent office hypertension throughout pregnancy who underwent 24-hour ambulatory blood pressure monitoring or home blood pressure monitoring were included. Meta-analysis was performed using RevMan.
RESULTS
This study included 12 studies with a total of 4,672 pregnant women and found that women with WCH have a higher risk of developing preeclampsia compared to normotensive women (RR: 2.29, 95% CI [1.18,4.43], P = 0.01). However, when compared with pregnant women with gestational hypertension or chronic hypertension, women with WCH had a significantly lower risk of developing preeclampsia ((RR: 0.39, [0.20,0.80], p=0.009) and (RR: 0.41, [0.27,0.62], P<0.001), respectively).
CONCLUSION
The study recommends incorporating 24-hour ABPM into clinical practice to differentiate between chronic hypertension and WCH in early pregnancy and focus on special management for those who need it. The findings may guide future research on ABPM's role in diagnosing WCH and its effects on pregnancy outcomes.
Topics: Female; Humans; Pregnancy; White Coat Hypertension; Pre-Eclampsia; Blood Pressure Monitoring, Ambulatory; Pregnant Women; Hypertension; Blood Pressure; Pregnancy Outcome; Hypertension, Pregnancy-Induced
PubMed: 37792010
DOI: 10.1007/s00404-023-07247-7 -
Vascular Dec 2023This study aims to assess prevalence and prognostic implications of pre-existing peripheral artery disease (PAD) in patients infected by the SARS-CoV-2 by means of a... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
This study aims to assess prevalence and prognostic implications of pre-existing peripheral artery disease (PAD) in patients infected by the SARS-CoV-2 by means of a systematic review and meta-analysis.
MATERIAL AND METHODS
We searched MEDLINE and Scopus to locate all the articles published up to 10 December 2021, reporting data on pre-existing PAD among COVID-19 survivors (S) and non survivors (NS). The pooled prevalence of pre-existing PAD in COVID-19 patients was calculated using a random effects model and presenting the related 95% confidence interval (CI), while the mortality risk was estimated using the Mantel-Haenszel random effects models with odds ratio (OR) and related 95% CI. Statistical heterogeneity was measured using the Higgins I statistic.
RESULTS
Eight investigations, enrolling 13,776 COVID-19 patients (mean age: 67.1 years, 3.863 males), met the inclusion criteria and were included in the final analysis. The pooled prevalence of pre-existing PAD was 5.7% of cases (95% CI: 3.8-8.4%, < 0.0001), with high heterogeneity (I = 84.5%), which was directly correlated with age ( < 0.0001), previous hypertension ( = 0.003), and dyslipidaemia ( = 0.02) as demonstrated by the meta-regression. Moreover, pre-existing PAD was significantly associated with higher risk of short-term death in patients with SARS-CoV-2 infection (OR: 2.78, 95% CI: 2.37-3.27, < 0.0001 I = 0%); the sensitivity analysis confirmed yielded results.
CONCLUSIONS
Pre-existing PAD represents a comorbidity in about 1 out of 6 COVID-19 patients, but it is associated with a twofold higher risk of short-term mortality.
Topics: Male; Humans; Aged; Prevalence; COVID-19; SARS-CoV-2; Peripheral Arterial Disease; Arteries
PubMed: 35593210
DOI: 10.1177/17085381221100380 -
Hypertension in Pregnancy Dec 2023To systematically review the literature on hypertensive disorders of pregnancy (HDP) after multifetal pregnancy reduction (MFPR). (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To systematically review the literature on hypertensive disorders of pregnancy (HDP) after multifetal pregnancy reduction (MFPR).
METHODS
A comprehensive search in PubMed, Embase, Web of Science, and Scopus was performed. Prospective or retrospective studies reporting on MFPR from triplet or higher-order to twin compared to ongoing (i.e., non-reduced) triplets and/or twins were included. A meta-analysis of the primary outcome HDP was carried out using a random-effects model. Subgroup analyses of gestational hypertension (GH) and preeclampsia (PE) were performed. Risk of bias was assessed using the Newcastle-Ottawa Quality Assessment Scale.
RESULTS
Thirty studies with a total of 9,811 women were included. MFPR from triplet to twin was associated with a lower risk for HDP compared to ongoing triplets (OR 0.55, 95% CI, 0.37-0.83; = 0.004). In a subgroup analysis, the decreased risk of HDP was driven by GH, and PE was no longer significant (OR 0.34, 95% CI, 0.17-0.70; = 0.004 and OR 0.64, 95% CI, 0.38-1.09; = 0.10, respectively). HDP was also significantly lower after MFPR from all higher-order (including triplets) to twin compared to ongoing triplets (OR 0.55, 95% CI, 0.38-0.79; = 0.001). In a subgroup analysis, the decreased risk of HDP was driven by PE, and GH was no longer significant (OR 0.55, 95% CI 0.32-0.92; = 0.02 and OR 0.55, 95% CI 0.28-1.06; = 0.08, respectively). No significant differences in HDP were found in MFPR from triplet or higher-order to twin versus ongoing twins.
CONCLUSIONS
MFPR in women with triplet and higher-order multifetal pregnancies decreases the risk of HDP. Twelve women should undergo MFPR to prevent one event of HDP. These data can be used in the decision-making process of MFPR, in which the individual risk factors of HDP can be taken into account.
Topics: Pregnancy; Female; Humans; Pregnancy Reduction, Multifetal; Hypertension, Pregnancy-Induced; Retrospective Studies; Prospective Studies; Pregnancy Outcome; Pre-Eclampsia; Pregnancy, Twin
PubMed: 37337887
DOI: 10.1080/10641955.2023.2225597 -
Cancer Medicine Mar 2024Due to encouraging pre-clinical data and supportive observational studies, there has been growing interest in applying cardiovascular drugs (including aspirin,... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Due to encouraging pre-clinical data and supportive observational studies, there has been growing interest in applying cardiovascular drugs (including aspirin, angiotensin-converting enzyme [ACE] inhibitors, statins, and metformin) approved to treat diseases such as hypertension, hyperlipidemia, and diabetes mellitus to the field of oncology. Moreover, given growing costs with cancer care, these medications have offered a potentially more affordable avenue to treat or prevent recurrence of cancer. We sought to investigate the anti-cancer effects of drugs repurposed from cardiology or anti-inflammatories to treat cancer. We specifically evaluated the following drug classes: HMG-CoA reductase inhibitors (statins), cyclo-oxygenase inhibitors, aspirin, metformin, and both angiotensin receptor blockers (ARBs) and angiotensin-converting enzyme inhibitors. We also included non-steroidal anti-inflammatory drugs (NSAIDs) because they exert a similar mechanism to aspirin by blocking prostaglandins and reducing inflammation that is thought to promote the development of cancer.
METHODS
We performed a systematic literature review using PubMed and Web of Science with search terms including "aspirin," "NSAID," "statin" (including specific statin drug names), "metformin," "ACE inhibitors," and "ARBs" (including specific anti-hypertensive drug names) in combination with "cancer." Searches were limited to human studies published between 2000 and 2023.
MAIN OUTCOMES AND MEASURES
The number and percentage of studies reported positive results and pooled estimates of overall survival, progression-free survival, response, and disease-free survival.
RESULTS
We reviewed 3094 titles and included 67 randomized clinical trials. The most common drugs that were tested were metformin (n = 21; 30.9%), celecoxib (n = 20; 29.4%), and simvastatin (n = 8; 11.8%). There was only one study that tested cardiac glycosides and none that studied ACE inhibitors. The most common tumor types were non-small-cell lung cancer (n = 19; 27.9%); breast (n = 8; 20.6%), colorectal (n = 7; 10.3%), and hepatocellular (n = 6; 8.8%). Most studies were conducted in a phase II trial (n = 38; 55.9%). Most studies were tested in metastatic cancers (n = 49; 72.1%) and in the first-line setting (n = 36; 521.9%). Four studies (5.9%) were stopped early because of difficulty with accrual. The majority of studies did not demonstrate an improvement in either progression-free survival (86.1% of studies testing progression-free survival) or in overall survival (94.3% of studies testing overall survival). Progression-free survival was improved in five studies (7.4%), and overall survival was improved in three studies (4.4%). Overall survival was significantly worse in two studies (3.8% of studies testing overall survival), and progression-free survival was worse in one study (2.8% of studies testing progression-free survival).
CONCLUSIONS AND RELEVANCE
Despite promising pre-clinical and population-based data, cardiovascular drugs and anti-inflammatory medications have overall not demonstrated benefit in the treatment or preventing recurrence of cancer. These findings may help guide future potential clinical trials involving these medications when applied in oncology.
Topics: Humans; Angiotensin-Converting Enzyme Inhibitors; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Carcinoma, Non-Small-Cell Lung; Angiotensin Receptor Antagonists; Lung Neoplasms; Randomized Controlled Trials as Topic; Anti-Inflammatory Agents, Non-Steroidal; Anti-Inflammatory Agents; Aspirin; Antihypertensive Agents; Metformin
PubMed: 38491813
DOI: 10.1002/cam4.7049