BACKGROUND: Recent clinical trials suggest that treating patients with hypertension to lower blood pressure (BP) targets improves cardiovascular outcomes.PURPOSE: To summarize the effects of intensive (or targeted) systolic BP (SBP) and diastolic BP (DBP) lowering with pharmacologic treatment on cardiovascular outcomes and harms in adults with hypertension.DATA SOURCES: Multiple databases, including MEDLINE and EMBASE, were searched for relevant systematic reviews (SRs) published in English from 15 December 2013 through 25 March 2019, with updated targeted searches through 8 January 2020.STUDY SELECTION: 8 SRs of randomized controlled trials examining either a standardized SBP target of -10 mm Hg (1 SR) or BP lowering below a target threshold (7 SRs).DATA EXTRACTION: One investigator abstracted data, assessed study quality, and performed GRADE assessments; a second investigator checked abstractions and assessments.DATA SYNTHESIS: The main outcome of interest was reduction in composite cardiovascular outcomes. High-strength evidence showed benefit of a 10-mm Hg reduction in SBP for cardiovascular outcomes among patients with hypertension in the general population, patients with chronic kidney disease, and patients with heart failure. Evidence on reducing SBP for cardiovascular outcomes in patients with a history of cardiovascular disease (moderate strength) or diabetes mellitus (high strength) to a lower SBP target was mixed. Low-strength evidence supported intensive lowering to a 10-mm Hg reduction in SBP for cardiovascular outcomes in patients with a history of stroke. All reported harms were considered, including general adverse events, serious adverse events, cognitive impairment, fractures, falls, syncope, hypotension, withdrawals due to adverse events, and acute kidney injury. Safety results were mixed or inconclusive.Limitations: This was a qualitative synthesis of new evidence with existing meta-analyses. Data were sparse for outcomes related to treating DBP to a lower target or for patients older than 60 years.CONCLUSION: Overall, current clinical literature supports intensive BP lowering in patients with hypertension for improving cardiovascular outcomes. In most subpopulations, intensive lowering was favored over less-intensive lowering, but the data were less clear for patients with diabetes mellitus or cardiovascular disease.Primary Funding Source: U.S. Department of Veterans Affairs, Veterans Health Administration.
BACKGROUND: Beta-blockers are widely used for many cardiovascular conditions; however, their efficacy in contemporary clinical practice remains uncertain.
METHODS: We performed a prospectively designed, umbrella review of meta-analyses of randomised controlled trials (RCTs) investigating the evidence of beta-blockers in the contemporary management of coronary artery disease (CAD), heart failure (HF), patients undergoing surgery or hypertension (registration: PROSPERO CRD42016038375). We searched MEDLINE, EMBASE and the Cochrane Library from inception until December 2018. Outcomes were analysed as beta-blockers versus control for all-cause mortality, myocardial infarction (MI), incident HF or stroke. Two independent investigators abstracted the data, assessed the quality of the evidence and rated the certainty of evidence.
RESULTS: We identified 98 meta-analyses, including 284 unique RCTs and 1,617,523 patient-years of follow-up. In CAD, 12 meta-analyses (93 RCTs, 103,481 patients) showed that beta-blockers reduced mortality in analyses before routine reperfusion, but there was a lack of benefit in contemporary studies where ≥ 50% of patients received thrombolytics or intervention. Beta-blockers reduced incident MI at the expense of increased HF. In HF with reduced ejection fraction, 34 meta-analyses (66 RCTs, 35,383 patients) demonstrated a reduction in mortality and HF hospitalisation with beta-blockers in sinus rhythm, but not in atrial fibrillation. In patients undergoing surgery, 23 meta-analyses (89 RCTs, 19,211 patients) showed no effect of beta-blockers on mortality for cardiac surgery, but increased mortality in non-cardiac surgery. In non-cardiac surgery, beta-blockers reduced MI after surgery but increased the risk of stroke. In hypertension, 27 meta-analyses (36 RCTs, 260,549 patients) identified no benefit versus placebo, but beta-blockers were inferior to other agents for preventing mortality and stroke.
CONCLUSIONS: Beta-blockers substantially reduce mortality in HF patients in sinus rhythm, but for other conditions, clinicians need to weigh up both benefit and potential risk.
DESCRIPTION: The American College of Physicians (ACP) and the American Academy of Family Physicians (AAFP) jointly developed this guideline to present the evidence and provide clinical recommendations based on the benefits and harms of higher versus lower blood pressure targets for the treatment of hypertension in adults aged 60 years or older.
METHODS: This guideline is based on a systematic review of published randomized, controlled trials for primary outcomes and observational studies for harms only (identified through EMBASE, the Cochrane Database of Systematic Reviews, MEDLINE, and ClinicalTrials.gov), from database inception through January 2015. The MEDLINE search was updated through September 2016. Evaluated outcomes included all-cause mortality, morbidity and mortality related to stroke, major cardiac events (fatal and nonfatal myocardial infarction and sudden cardiac death), and harms. This guideline grades the evidence and recommendations using the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) method.
TARGET AUDIENCE AND PATIENT POPULATION: The target audience for this guideline includes all clinicians, and the target patient population includes all adults aged 60 years or older with hypertension.
RECOMMENDATION 1: ACP and AAFP recommend that clinicians initiate treatment in adults aged 60 years or older with systolic blood pressure persistently at or above 150 mm Hg to achieve a target systolic blood pressure of less than 150 mm Hg to reduce the risk for mortality, stroke, and cardiac events. (Grade: strong recommendation, high-quality evidence). ACP and AAFP recommend that clinicians select the treatment goals for adults aged 60 years or older based on a periodic discussion of the benefits and harms of specific blood pressure targets with the patient.
RECOMMENDATION 2: ACP and AAFP recommend that clinicians consider initiating or intensifying pharmacologic treatment in adults aged 60 years or older with a history of stroke or transient ischemic attack to achieve a target systolic blood pressure of less than 140 mm Hg to reduce the risk for recurrent stroke. (Grade: weak recommendation, moderate-quality evidence). ACP and AAFP recommend that clinicians select the treatment goals for adults aged 60 years or older based on a periodic discussion of the benefits and harms of specific blood pressure targets with the patient.
RECOMMENDATION 3: ACP and AAFP recommend that clinicians consider initiating or intensifying pharmacologic treatment in some adults aged 60 years or older at high cardiovascular risk, based on individualized assessment, to achieve a target systolic blood pressure of less than 140 mm Hg to reduce the risk for stroke or cardiac events. (Grade: weak recommendation, low-quality evidence). ACP and AAFP recommend that clinicians select the treatment goals for adults aged 60 years or older based on a periodic discussion of the benefits and harms of specific blood pressure targets with the patient.
BACKGROUND: Colorectal cancer is a common and often fatal malignancy. Currently, the modifications that alter disease outcome include early symptom recognition, population screening as well as improved surgical and adjuvant treatments. Preventative strategies have been limited with little evidence that lifestyle changes significantly alter risk. There is however a growing awareness of a potential role for chemoprevention in some patient groups. This study aimed to review the literature associated with chemoprevention in colorectal cancer.
METHODS: An electronic literature search of MEDLINE and Embase databases was performed on PubMed for studies detailing the use of chemoprevention agents in colon and rectal cancer. The search was limited to clinical trials on adult humans (>16 years of age) published in English since 1990.
RESULTS: The strongest evidence is for non-steroidal anti-inflammatory drugs slowing polyp progression, notably Sulindac and aspirin in patients with familial adenomatous polyposis and hereditary nonpolyposis colorectal cancer, respectively. There is also increasing evidence that continuing use of low-dose aspirin reduces long-term incidence of colorectal cancers. Cyclooxygenase 2 inhibitors also have a potential role but cardiac toxicity currently limits their use. Folic acid, statins, antioxidants, calcium and 5-aminosalicylic acid lack evidence to support their use at present.
CONCLUSIONS: Currently, there is not enough evidence to support the implementation of a chemopreventative agent for general use. However, there appears to be a role for aspirin in selected subgroups.
OBJECTIVE: Multiple systematic reviews address the effect of antihypertensive treatment in people with diabetes. Here, we summarize current systematic reviews concerning antihypertensive treatment effect at different blood pressure (BP) levels, and relative treatment effect of different antihypertensive agents.
METHODS: We searched MEDLINE, BIOSIS, DARE and CDSR during years 2005-2016. Eligibility criteria, number of trials and participants, outcomes analysed, statistical methods used for data synthesis, and principal results were extracted for each review. Review quality was assessed using the assessment of multiple systematic reviews tool.
RESULTS: We found four reviews concerning BP treatment level. These consistently showed that the effect of antihypertensive treatment on mortality, cardiovascular disease and coronary heart disease was attenuated at lower BP levels. If SBP was more than 140 mmHg, treatment reduced all-cause and cardiovascular mortality, cardiovascular disease, stroke, myocardial infarction and heart failure. If SBP was less than 140 mmHg, treatment increased the risk of cardiovascular death. We found eight reviews concerning choice of agent. We found no difference between angiotensin-converting enzyme inhibitors, angotensin receptor blockers, beta-blockers, calcium channel blockers and diuretics in preventing all-cause or cardiovascular mortality, combined cardiovascular disease, coronary heart disease and end-stage renal disease. Minor differences exist for stroke and heart failure. Data were limited on people with type 1 diabetes and very elderly patients with type 2 diabetes. None of the reviews concerning choice of agent included all relevant trials.
CONCLUSION: The available evidence supports treatment in people with type 2 diabetes and SBP more than 140 mmHg, using any of the major antihypertensive drug classes.
BACKGROUND: We update recommendations on 12 topics that were in the 9th edition of these guidelines, and address 3 new topics.
METHODS: We generate strong (Grade 1) and weak (Grade 2) recommendations based on high- (Grade A), moderate- (Grade B), and low- (Grade C) quality evidence.
RESULTS: For VTE and no cancer, as long-term anticoagulant therapy, we suggest dabigatran (Grade 2B), rivaroxaban (Grade 2B), apixaban (Grade 2B), or edoxaban (Grade 2B) over vitamin K antagonist (VKA) therapy, and suggest VKA therapy over low-molecular-weight heparin (LMWH; Grade 2C). For VTE and cancer, we suggest LMWH over VKA (Grade 2B), dabigatran (Grade 2C), rivaroxaban (Grade 2C), apixaban (Grade 2C), or edoxaban (Grade 2C). We have not changed recommendations for who should stop anticoagulation at 3 months or receive extended therapy. For VTE treated with anticoagulants, we recommend against an inferior vena cava filter (Grade 1B). For DVT, we suggest not using compression stockings routinely to prevent PTS (Grade 2B). For subsegmental pulmonary embolism and no proximal DVT, we suggest clinical surveillance over anticoagulation with a low risk of recurrent VTE (Grade 2C), and anticoagulation over clinical surveillance with a high risk (Grade 2C). We suggest thrombolytic therapy for pulmonary embolism with hypotension (Grade 2B), and systemic therapy over catheter-directed thrombolysis (Grade 2C). For recurrent VTE on a non-LMWH anticoagulant, we suggest LMWH (Grade 2C); for recurrent VTE on LMWH, we suggest increasing the LMWH dose (Grade 2C).
CONCLUSIONS: Of 54 recommendations included in the 30 statements, 20 were strong and none was based on high-quality evidence, highlighting the need for further research.
Since 2008, the direct-acting oral anticoagulants (DOACs) have expanded the therapeutic options of cardiovascular diseases with recognized clinical and epidemiological impact, such as non-valvular atrial fibrillation (NVAF) and venous thromboembolism (VTE), and also in the preventive setting of orthopedic surgical patients. The large body of evidence, not only from pivotal clinical trials but also from ‘real-world’ postmarketing observational findings (e.g. analytical epidemiological studies and registry data) gathered to date allow for a first attempt at verifying a posteriori whether or not the pharmacological advantages of the DOACs actually translate into therapeutic innovation, with relevant implications for clinicians, regulators and patients. This review aims to synthesize the risk–benefit profile of DOACs in the aforementioned consolidated indications through an ‘evidence summary’ approach gathering the existent evidence-based data, particularly systematic reviews with meta-analyses of randomized controlled trials, as well as observational studies, comparing DOACs with vitamin K antagonists. Clinical evidence will be discussed and compared with major international guidelines to identify whether an update is needed. Controversial clinically relevant safety issues will be also examined in order to highlight current challenges and unsettled questions (e.g. actual bleeding risk in susceptible populations). It is anticipated that the large number of publications on NVAF or VTE (44 systematic reviews with meta-analyses and 12 observational studies retained in our analysis) suggests the potential existence of overlapping studies and calls for common criteria to qualitatively and quantitatively assess discordances, thus guiding future research.
AIM: To review the evidence on the association between specific colon adenoma features and the risk of future colonic neoplasia [adenomas and colorectal cancer (CRC)].
METHODS: We performed a literature search using the National Library of Medicine through PubMed from 1/1/2003 to 5/30/2015. Specific Medical Subject Headings terms (colon, colon polyps, adenomatous polyps, epidemiology, natural history, growth, cancer screening, colonoscopy, CRC) were used in conjunction with subject headings/key words (surveillance, adenoma surveillance, polypectomy surveillance, and serrated adenoma). We defined non-advanced adenomas as 1-2 adenomas each < 10 mm in size and advanced adenomas as any adenoma ≥ 10 mm size or with > 25% villous histology or high-grade dysplasia. A combined endpoint of advanced neoplasia included advanced adenomas and invasive CRC.
RESULTS: Our search strategy identified 592 candidate articles of which 8 met inclusion criteria and were relevant for assessment of histology (low grade vs high grade dysplasia, villous features) and adenoma size. Six of these studies met the accepted quality indicator threshold for overall adenoma detection rate > 25% among study patients. We found 254 articles of which 7 met inclusion criteria for the evaluation of multiple adenomas. Lastly, our search revealed 222 candidate articles of which 6 met inclusion criteria for evaluation of serrated polyps. Our review found that villous features, high grade dysplasia, larger adenoma size, and having ≥ 3 adenomas at baseline are associated with an increased risk of future colonic neoplasia in some but not all studies. Serrated polyps in the proximal colon are associated with an increased risk of future colonic neoplasia, comparable to having a baseline advanced adenoma.
CONCLUSION: Data on adenoma features and risk of future adenomas and CRC are compelling yet modest in absolute effect size. Future research should refine this risk stratification.
Objectives To critically appraise published network meta-analyses (NMAs) evaluating the efficacy or safety of the new oral anticogulants (NOACs) dabigatran, rivaroxaban, and apixaban for the prevention of stroke in patients with nonvalvular atrial fibrillation (AF). Methods A systematic literature review was performed to identify the relevant NMAs using MEDLINE, EMBASE, Cochrane Library, Database of Abstracts of Reviews of Effects, and Health Technology Assessment. The synthesis studies were evaluated using the "Questionnaire to assess the relevance and credibility of the NMA." Results Eleven NMAs evaluating NOACs among adults with nonvalvular AF were identified. Most NMAs included three large phase III randomized controlled trials, comparing NOACs to adjusted-dose warfarin (Randomized Evaluation of Long-Term Anticoagulation Therapy [RE-LY], Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared With Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation [ROCKET-AF], and Apixaban for Reduction of Stroke and Other Thromboembolic Events in Atrial Fibrillation [ARISTOTLE]). The main differences identified related to potential treatment effect modifiers regarding the mean time spent in therapeutic range (TTR) in the warfarin arm, the risk of stroke or systemic embolism across the trials (mean CHADS2 score: C = congestive heart failure, H = hypertension, A = older than age 75 years, D = diabetes mellitus, S2 = prior stroke or history of transient ischemic attack) or primary versus secondary prevention, and type of populations used in the analysis. Kansal et al. [Kansal AR, Sharma M, Bradley-Kennedy C, et al. Dabigatran versus rivaroxaban for the prevention of stroke and systemic embolism in atrial fibrillation in Canada: comparative efficacy and cost-effectiveness. Thromb Haemost 2012;108:672-82] appropriately adjusted the ROCKET-AF TTR to match the RE-LY population on the basis of individual patient data. Meta-regressions are not expected to minimize confounding bias given limited data, whereas subgroup analyses had some impact on the point estimates for the treatment comparisons. Conclusions Results of the synthesis studies were generally comparable and suggested that the NOACs had similar efficacy, although some differences were identified depending on the outcome. The extent to which differences in the distribution of TTR, CHADS2 score, or primary versus secondary prevention biased the results remains unclear.
Idiopathic thromboembolic disease presents a high risk of recurrence. There is controversy about the effects of aspirin in reducing this risk after the completion of anticoagulant treatment. Searching in Epistemonikos database, which screens 30 databases, we identified four systematic reviews that together include two randomized trials. We combined the evidence using meta-analysis and generated a summary of findings table following the GRADE approach. We concluded that aspirin administered after having completed anticoagulation reduces the risk of recurrence, probably without importantly increasing the risk of hemorrhage.
Recent clinical trials suggest that treating patients with hypertension to lower blood pressure (BP) targets improves cardiovascular outcomes.
PURPOSE:
To summarize the effects of intensive (or targeted) systolic BP (SBP) and diastolic BP (DBP) lowering with pharmacologic treatment on cardiovascular outcomes and harms in adults with hypertension.
DATA SOURCES:
Multiple databases, including MEDLINE and EMBASE, were searched for relevant systematic reviews (SRs) published in English from 15 December 2013 through 25 March 2019, with updated targeted searches through 8 January 2020.
STUDY SELECTION:
8 SRs of randomized controlled trials examining either a standardized SBP target of -10 mm Hg (1 SR) or BP lowering below a target threshold (7 SRs).
DATA EXTRACTION:
One investigator abstracted data, assessed study quality, and performed GRADE assessments; a second investigator checked abstractions and assessments.
DATA SYNTHESIS:
The main outcome of interest was reduction in composite cardiovascular outcomes. High-strength evidence showed benefit of a 10-mm Hg reduction in SBP for cardiovascular outcomes among patients with hypertension in the general population, patients with chronic kidney disease, and patients with heart failure. Evidence on reducing SBP for cardiovascular outcomes in patients with a history of cardiovascular disease (moderate strength) or diabetes mellitus (high strength) to a lower SBP target was mixed. Low-strength evidence supported intensive lowering to a 10-mm Hg reduction in SBP for cardiovascular outcomes in patients with a history of stroke. All reported harms were considered, including general adverse events, serious adverse events, cognitive impairment, fractures, falls, syncope, hypotension, withdrawals due to adverse events, and acute kidney injury. Safety results were mixed or inconclusive.Limitations: This was a qualitative synthesis of new evidence with existing meta-analyses. Data were sparse for outcomes related to treating DBP to a lower target or for patients older than 60 years.
CONCLUSION:
Overall, current clinical literature supports intensive BP lowering in patients with hypertension for improving cardiovascular outcomes. In most subpopulations, intensive lowering was favored over less-intensive lowering, but the data were less clear for patients with diabetes mellitus or cardiovascular disease.Primary Funding Source: U.S. Department of Veterans Affairs, Veterans Health Administration.
