Magnitude Of Risk Reduction Research Articles

Efficacy of the ABC Pathway for Integrated Care Across Phenotypes of Patients with Atrial Fibrillation: A Latent-Class Analysis Report from the mAFA-II Clinical Trial

Abstract Background The mAFA-II cluster randomised trial demonstrated the efficacy of a mobile health-technology implemented ‘Atrial fibrillation Better Care’ (ABC) pathway (mAFA intervention) for integrated care management of patients with AF. Objective To evaluate the effect of mAFA intervention across phenotypes of patients with AF. Design We conducted a latent-class analysis (LCA) according to eight variables, including age and comorbidities. Participants The mAFA-II trial enrolled AF patients between June 2018 and August 2019 across 40 centres in China. Main Measures We evaluated the interaction between the groups identified through LCA, and the effect of mAFA intervention on the risk of the primary composite outcome of all-cause death, stroke/thromboembolism, and rehospitalisations. Results were expressed as adjusted hazard ratio (aHR) and 95% confidence intervals (95% CI). Key Results Across the 3324 patients included in the trial (mean age 68.5 ± 13.9 years, 38.0% females), we identified three phenotypes: (i) low morbidity phenotype (n = 1234, 37.1%), (ii) hypertensive/coronary artery disease (CAD) phenotype (n = 1534, 46.2%), and (iii) mixed morbidity phenotype (n = 556, 16.7%). The effect of mAFA intervention on the primary outcome appeared greater in the low morbidity phenotype (aHR, 0.08; 95% CI 0.02–0.33) compared to the hypertensive/CAD (aHR, 0.30; 95% CI 0.16–0.58) and the mixed morbidity phenotype (aHR, 0.68; 95% CI 0.37–1.24), with a statistically significant interaction (pint = 0.004). Conclusions In patients with AF, the ABC pathway improved prognosis across different comorbidity phenotypes, although with some differences in the magnitude of risk reduction. Patients with more complex phenotypes require further efforts to improve their outcomes, considering their high baseline risk of adverse events. Trial Registration WHO International Clinical Trials Registry Platform (ICTRP) Registration number: ChiCTR-OOC-17014138.

Вариация оценок готовности платить в зависимости от величины снижения риска смерти от загрязнения воздуха

The present study endeavors to elucidate the variability in estimates of willingness-to-pay (WTP) concerning the mitigation of mortality risk attributable to air pollution, contingent upon the extent of the corresponding risk reduction. Through the lens of air pollution control projects, the research seeks to discern fluctuations in WTP estimates, thereby shedding light on the intricacies of decision-making processes surrounding environmental management initiatives. The salience of this inquiry stems from the escalating prevalence of methodologies employing willingness-to-pay assessments as a yardstick for evaluating the value of human life across diverse spheres of societal activity, thereby informing policy deliberations by regulatory authorities. Central to the research quandary is the recognition that alterations in the magnitude of risk reduction can engender disproportional shifts in WTP values, holding all other variables constant. This phenomenon engenders a profound reliance on the methodological framework employed, thereby exerting a substantial influence on the resultant cost-of-living appraisals. Employing the contingent valuation method grounded in stated preferences within a double dichotomous choice framework, empirical findings reveal that WTP for reducing mortality risk from air pollution escalates by 43.8 %, ascending from 11 713 to 16 839 rubles, concomitant with a twofold increase in the reduction rate, from 2.5 to 5.0 per 10,000 inhabitants. This equates to a reduction in mortality rates from 100.0 to 97.5 and 100.0 to 95.0 per 10,000 inhabitants, respectively, all else being equal. The implications drawn from these conclusions are pivotal in guiding the formulation, execution, and interpretation of research endeavors pertaining to cost-of-living assessments across diverse contexts. Furthermore, they furnish critical insights for substantiating policy decisions within regulatory bodies, thereby enhancing the efficacy and integrity of environmental management initiatives.

Impact of remission from type 2 diabetes on long-term health outcomes: findings from the Look AHEAD study.

We examined the association of attainment of diabetes remission in the context of a 12 year intensive lifestyle intervention with subsequent incidence of chronic kidney disease (CKD) and CVD. The Look AHEAD study was a multi-centre RCT comparing the effect of a 12 year intensive lifestyle intervention with that of diabetes support and education on CVD and other long-term health conditions. We compared the incidence of CVD and CKD among 4402 and 4132 participants, respectively, based on achievement and duration of diabetes remission. Participants were 58% female, and had a mean age of 59 years, a duration of diabetes of 6 year and BMI of 35.8 kg/m2. We applied an epidemiological definition of remission: taking no diabetes medications and having HbA1c <48 mmol/mol (6.5%) at a single point in time. We defined high-risk or very high-risk CKD based on the Kidney Disease Improving Global Outcomes (KDIGO) criteria, and CVD incidence as any occurrence of non-fatal acute myocardial infarction, stroke, admission for angina or CVD death. Participants with evidence of any remission during follow-up had a 33% lower rate of CKD (HR 0.67; 95% CI 0.52, 0.87) and a 40% lower rate of the composite CVD measure (HR 0.60; 95% CI 0.47, 0.79) in multivariate analyses adjusting for HbA1c, BP, lipid levels, CVD history, diabetes duration and intervention arm, compared with participants without remission. The magnitude of risk reduction was greatest for participants with evidence of longer-term remission. Participants with type 2 diabetes with evidence of remission had a substantially lower incidence of CKD and CVD, respectively, compared with participants who did not achieve remission. This association may be affected by post-baseline improvements in weight, fitness, HbA1c and LDL-cholesterol. ClinicalTrials.gov NCT00017953 DATA AVAILABILITY: https://repository.niddk.nih.gov/studies/look-ahead/.

Abstract 14566: Long-Term Efficacy of Evolocumab in Patients With and Without Multivessel Coronary Artery Disease

Background: In FOURIER, the magnitude of reduction in risk of major adverse cardiovascular events (MACE) was larger in patients with multivessel disease (MVD) than in those without. However, the median follow-up was only 2.2 yrs. The open-label extension (FOURIER-OLE) allows for a better assessment of the long-term benefit of intensive lipid-lowering in these two subgroups. Methods: Patients with CAD at time of enrollment in the parent FOURIER trial were categorized based on the presence or absence of MVD (≥40% stenosis in ≥2 large vessels). Primary endpoint (PEP; CV death, MI, stroke, hospitalization for UA, or coronary revascularization) and key secondary endpoint (SEP; CV death, MI, or stroke) were assessed through FOURIER and FOURIER-OLE, during which all patients received evolocumab. Results: At enrollment in FOURIER, 23,674 patients had CAD, of whom 25% had MVD (N=6007). In the placebo arm, those with MVD had a higher risk of the PEP (HR 1.45 [95%CI 1.32-1.60], P&lt;0.0001) &amp; SEP (HR 1.37 [1.22-1.56], P&lt;0.0001) than those without MVD. The magnitude of the overall relative risk reduction in those initially randomized to evolocumab tended to be greater in patients with MVD than in those without (RRR 23% vs. 12% for PEP; 30% vs. 15% for SEP; P int 0.07 &amp; 0.04, respectively). The magnitude of benefit tended to grow over the first several years (Fig). This was especially true for CV death, in which for patients with MVD, initial randomization to evolocumab reduced the risk of CV death in the later years (HR 0.70 [0.51-0.97]; Fig bottom). Conclusion: Evolocumab reduced the rate of MACE in patients with and without MVD, with earlier and larger benefit seen in patients with MVD. The magnitude of benefit grew over time, supporting early initiation of intensive LDL-C lowering both in patients with and without MVD.

Metformin Reduces the Risk of Hearing Loss: A Retrospective Cohort Study.

To compare the risk of hearing loss with regard to metformin exposure. Retrospective cohort. Taiwan's National Health Insurance database. We enrolled 292,071 ever users and 18,200 never users of metformin with new-onset diabetes mellitus from1999 to 2005 and followed them for hearing loss from January 1, 2006, to December 31, 2011. Hazard ratios (HRs) weighted by propensity score were estimated. Hearing loss was newly diagnosed in 10,085 ever users and 1072 never users. Their respective incidence rates (per 100,000 person-years) were 738.09 and 1366.83. The HRcomparing ever-to-never users was 0.534 (95% confidence interval [CI]: 0.501-0.569]. The HR (95% CI) for the first (<27.07 months), second (27.07-59.13 months), and third (>59.13 months) tertiles of cumulative duration of metformin therapy were 0.912 (0.852-0.975), 0.544 (0.508-0.582), and 0.275 (0.255-0.295), respectively; and were 0.900 (0.841-0.962), 0.531 (0.496-0.569), and 0.293 (0.273-0.315), respectively, for the first (<796.70 g), second (796.70-2020.15 g), and third (>2020.15 g) tertiles of cumulative dose. The magnitude of risk reduction became more remarkable in corresponding to the increasing tertiles of the defined daily dose prescribed. Subtype analyses suggested that the risk reduction was more significant for sensorineural than conductive hearing loss. Findings derived from a propensity score-matched cohort did not substantially change the conclusions, and the risk reduction for mixed hearing loss was not statistically significant in the matched cohort as significantly observed in the unmatched cohort. The risk of hearing loss is reduced in a dose-response pattern in patients who use metformin.

Evaluating cannabis use risk reduction as an alternative clinical outcome for cannabis use disorder.

Abstinence is rarely achieved in clinical trials for cannabis use disorder (CUD). Cannabis reduction is associated with functional improvement, but reduction endpoints have not been established, indicating a need to identify and validate clinically meaningful reduction endpoints for assessing treatment efficacy. Data from a 12-week double-blind randomized placebo-controlled medication trial for cannabis cessation (NCT01675661) were analyzed. Participants (N = 225) were treatment-seeking adults, M = 30.6 (8.9) years old, 70.2% male, and 42.2% Non-White, with CUD who completed 12 weeks of treatment. Frequency (days of use per week) and quantity (grams per using day) were used to define high-, medium-, and low-risk levels. Anxiety and depression were assessed using the Hospital Anxiety and Depression Scale and cannabis-related problems were assessed using the Marijuana Problems Scale. General linear models for repeated measures tested associations between the magnitude of risk reduction and functional outcomes from baseline (BL) to end-of-treatment (EOT). Cannabis risk levels were sensitive to reductions in use from BL to EOT for frequency- (χ² = 19.35, p = .004) and quantity-based (χ² = 52.06, p < .001) metrics. Magnitude reduction in frequency-based risk level was associated with magnitude decrease in depression (F = 2.76, p = .043, ηp² = .04), anxiety (F = 3.70, p = .013, ηp² = .05), and cannabis-related problems (F = 8.95, p < .001, ηp² = .12). Magnitude reduction in quantity-based risk level was associated with magnitude decrease in anxiety (F = 3.02, p = .031, ηp² = .04) and cannabis-related problems (F = 3.24, p = .023, ηp² = .05). Cannabis use risk levels, as operationalized in this study, captured reductions in use during a clinical trial. Risk level reduction was associated with functional improvement suggesting that identifying risk levels and measuring the change in levels over time may be a viable and clinically meaningful endpoint for determining treatment efficacy. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Is Blood Pressure Lowering in the Very Elderly With Previous Stroke Associated With a Higher Risk of Adverse Events?

BackgroundWe investigated whether blood pressure lowering for secondary prevention is associated with a reduction in recurrent stroke risk and/or a higher risk of adverse events in very elderly compared with younger trial participants.Methods and ResultsThis is a random effects meta‐analysis of randomized controlled trials of blood pressure lowering for secondary stroke prevention to evaluate age‐stratified (<80, ≥80 years) risk of adverse events. Ovid‐MEDLINE was searched for trials between 1970 and 2020. Summary‐level data were acquired including outcomes of stroke, cardiovascular events, mortality, and adverse events. Seven trials were included comprising 38 596 participants, of whom 2336 (6.1%) were aged ≥80 years. There was an overall reduction in stroke risk in the intervention group compared with controls (risk ratio [RR], 0.90 [95% CI, 0.80, 0.98], I2=49%), and the magnitude of risk reduction did not differ by age subgroup (<80, ≥80 years). There was no increase in the risk of hypotensive symptoms in the intervention group for patients aged <80 years (RR, 1.19 [95% CI, 0.99], 1.44, I2=0%), but there was an increased risk in those ≥80 years (RR, 2.17 [95% CI, 1.22], 3.86, I2=0%). No increase was observed in the risk of falls, syncope, study withdrawal, or falls in either age subgroup.ConclusionsVery elderly people in secondary prevention trials of blood pressure lowering have an increased risk of hypotensive symptoms, but with no statistical increase in the risk of falls, syncope, or mortality. However, evidence is lacking for frail elderly with multiple comorbidities who may be more vulnerable to adverse effects of blood pressure lowering.

Leisure-time physical activity and incidence of objectively assessed hearing loss: The Niigata Wellness Study.

Previous cohort study reported that high physical activity was associated with a low risk of self-reported hearing loss in women. However, no studies have examined the association between physical activity and the development of hearing loss as measured using an objective assessment of hearing loss in men and women. Here, we used cohort data to examine the association between leisure-time physical activity and incidence of objectively assessed hearing loss in men and women. Participants included 27537Japanese adults aged 20-80years without hearing loss, who completed a self-administered physical activity questionnaire between April 2001 and March 2002. The participants were followed up for the development of hearing loss as measured by audiometry between April 2002 and March 2008. During follow-up, 3691 participants developed hearing loss. Compared with the none physical activity group, multivariable adjusted hazard ratios (HRs) for developing hearing loss were 0.93 (95% confidence interval (CI), 0.86-1.01) and 0.87 (0.81-0.95) for the medium (<525MET-min/week) and high (≥525MET-min/week) physical activity groups, respectively (p for trend=0.001). The magnitude of risk reduction was slightly greater in vigorous-intensity activity than in moderate-intensity activity (p for interaction=0.01). Analysis by sound frequency showed that the amount of physical activity was inversely associated with high frequency hearing loss development (p for trend <0.001), but not with low frequency hearing loss development (p for trend=0.19). Higher level of leisure-time physical activity was associated with lower incidence of hearing loss, particularly for vigorous-intensity activities and high sound frequencies.

Abstract 14325: Pooled Analysis of Bleeding, Major Adverse Cardiovascular Events and Mortality in Clinical Trials of Time-constrained Dual-antiplatelet Therapy After Percutaneous Coronary Intervention

Introduction: The net clinical benefit of dual antiplatelet therapy (DAPT) reflects the paradoxical effects of an increased risk of bleeding and a reduced risk of major adverse cardiovascular events (MACE). A time-constrained approach to DAPT has been recently investigated in five multicenter trials including GLOBAL LEADERS, STOP-DAPT2, SMART-CHOICE, TWIGHLIGHT and TICO. Methods: We undertook a pooled analysis of these trials to assess the overall associations between time-constrained P2Y12 inhibitor monotherapy (“aspirin free regimen”) for bleeding events, MACE and all-cause mortality as compared to standard care with DAPT for at least 12 months post-PCI. We implemented a DerSimonian and Laird random effects meta-analysis using the metafor package in R. Results: 32,361 randomized trial participants, including 16,898 (52.2%) with a history of ACS, underwent PCI and had outcome data available. P2Y12 inhibitor monotherapy from 1 - 3 months was associated with a reduced risk for bleeding (hazard ratio (HR) (95% confidence interval (CI)) 0.60 (0.45, 0.81); p=0.024), including in the ACS group in which the magnitude of risk reduction was greatest (HR (95% CI) 0.50 (0.41, 0.61). The estimates of the effect of P2Y12 inhibitor monotherapy on the hazard were also favorable for MACE (0.88 (0.77, 1.02)) and all-cause mortality (95% CI 0.85 (0.71, 1.03)). Conclusions: Compared with DAPT for 12 months post-PCI, P2Y12 inhibitor monotherapy from 1-3 months substantially reduces the risk of major and fatal bleeding and, in addition, potentially protective effects, for MACE and all-cause mortality. Considering patient safety, the results support a strategy of DAPT for 1-3 months followed by ‘aspirin free’ P2Y12 inhibitor monotherapy.

Pooled Analysis of Bleeding, Major Adverse Cardiovascular Events, and All-Cause Mortality in Clinical Trials of Time-Constrained Dual-Antiplatelet Therapy After Percutaneous Coronary Intervention.

BackgroundThe net clinical benefit of dual antiplatelet therapy (DAPT) reflects the paradoxical effects of an increased risk of bleeding and a reduced risk of major adverse cardiovascular events. A time‐constrained approach to DAPT has been recently investigated in 5 multicenter trials including GLOBAL LEADERS, STOPDAPT2 (Short and Optimal Duration of Dual Antiplatelet Therapy After Everolimus‐Eluting Cobalt‐Chromium Stent‐2), SMART‐CHOICE, TWILIGHT (Ticagrelor With Aspirin or Alone in High‐Risk Patients After Coronary Intervention), and TICO (Ticagrelor Monotherapy After 3 Months in the Patients Treated With New Generation Sirolimus Stent for Acute Coronary Syndrome).Methods and ResultsWe undertook a pooled analysis of these trials to assess the overall associations between time‐constrained P2Y12 inhibitor monotherapy (aspirin‐free regimen) for bleeding events, major adverse cardiovascular events, and all‐cause mortality as compared to standard care with DAPT for at least 12 months post‐percutaneous coronary intervention. We implemented a DerSimonian and Laird random effects meta‐analysis using the metafor package in R. 32 361 randomized trial participants, including 16 898 (52.2%) who had a history of acute coronary syndrome, underwent percutaneous coronary intervention, and had outcome data available. P2Y12 inhibitor monotherapy from 1 to 3 months was associated with a reduced risk for bleeding (hazard ratio [HR] 0.60; 95% CI, 0.45‐0.81), including in the acute coronary syndrome group in which the magnitude of risk reduction was greatest (HR 0.50; 95% CI, 0.41‐0.61). The estimates of the effect of P2Y12 inhibitor monotherapy on the HR were also favorable for major adverse cardiovascular events (0.88; 95% CI, 0.77‐1.02) and all‐cause mortality (0.85; 95% CI, 0.71‐1.03).ConclusionsCompared with DAPT for 12 months post‐percutaneous coronary intervention, P2Y12 inhibitor monotherapy from 1 to 3 months substantially reduces the risk of major and fatal bleeding and, in addition, confers potentially protective effects, for major adverse cardiovascular events and all‐cause mortality. Considering patient safety, the results support a strategy of DAPT for 1 to 3 months followed by aspirin‐free P2Y12 inhibitor monotherapy.

Magnitude of reduction in risk of second contralateral breast cancer with bilateral mastectomy in patients with breast cancer: Data from California, 1998 through 2015.

Increasingly, patients with breast cancer undergo bilateral mastectomy (BLM). To the authors' knowledge, the magnitude of benefit is unknown. The authors used data from the Surveillance, Epidemiology, and End Results (SEER) program regarding all women diagnosed with American Joint Committee on Cancer stage 0 to stage III unilateral breast cancer in California from 1998 through 2015 and treated with BLM versus breast-conserving therapy including surgery and radiotherapy (BCT) or unilateral mastectomy (ULM). The authors measured relative risks of second contralateral breast cancer (CBC) and breast cancer death using Fine and Gray multivariable regression modeling adjusted for the competing risk of death and death from another cause, respectively, and potential confounding factors. Absolute excess risk of CBC was measured as the observed minus expected number of breast cancers in the general population divided by 10,000 person-years at risk. Among 245,418 patients with a median follow-up of 6.7years, 7784 patients (3.2%) developed CBC. Relative risks were lower after BLM (hazard ratio [HR], 0.10; 95% CI, 0.07-0.14) and higher after ULM (HR, 1.07; 95% CI, 1.02-1.13) versus BCT. Absolute excess risks were higher after BCT and ULM (5.0 and 13.6 more cases, respectively) compared with BLM (28.6 fewer cases). BLM reduced risk more among older women (38.0 fewer cases for women aged ≥50years vs 17.9 fewer cases among women aged <50years) but provided similar risk reduction across categories of tumor grade and tumor hormone receptor status. Compared with BCT, the risk of breast cancer death was equivalent after BLM (HR, 1.03; 95% CI, 0.96-1.11) and higher after ULM (HR, 1.21; 95% CI, 1.17-1.25). BLM may reduce second breast cancer risk by 34 to 43 cases per 10,000 person-years compared with other surgical procedures, but is not associated with a lower risk of death. Second breast cancers are rare, and their reduction should be weighed against the harms associated with BLM.

Highlights from Selected Cardiovascular Disease Prevention Studies Presented at the 2019 European Society of Cardiology Congress.

This review intends to highlight selected cardiovascular disease (CVD) prevention studies presented at the 2019 European Society of Cardiology (ESC) Congress. Results from the Inclisiran for Subjects with ASCVD or ASCVD-risk Equivalent and Elevated Low-density Lipoprotein Cholesterol (ORION-11) trial validate inclisiran's ability to significantly lower low-density lipoprotein cholesterol (LDL-C) levels in at-risk individuals on a background of maximally tolerated statin therapy. The EVOlocumab for Early Reduction of LDL-cholesterol Levels in Patients With Acute Coronary Syndromes (EVOPACS) trial provide additional support that a PCSK9 inhibitor can be initiated safely and effectively early after an acute coronary syndrome. A sub-study of the Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab (ODYSSEY OUTCOMES) trial provides further support for stratification of secondary prevention patients to help define the magnitude of risk reduction associated with PCSK9 inhibitor therapy. A post hoc analysis from the Aspirin in Reducing Events in the Elderly (ASPREE) trial suggest that any benefits associated with aspirin utilizing a risk-based approach are overwhelmed by increased bleeding risk. In a large retrospective cohort study of patients with diabetes mellitus and obesity, the addition of metabolic (weight loss) surgery to standard care led to greater improvement in CVD outcomes, weight loss, and glycemic control. Results from the Prospective Urban Rural Epidemiology (PURE) study demonstrate that while hypertension and dyslipidemia exert additive lifelong effects on CVD risk, other less established risk factors such as low education, household pollution, and poor diet also have a strong impact on CVD outcomes, especially in middle- and low-income countries. Finally, in the Heart Outcomes Prevention and Evaluation (HOPE) 4 trial, a comprehensive model of care adapted to address multiple barriers of specific communities led to substantial improved blood pressure (BP) control, medication use, and adherence. A number of studies presented at the 2019 ESC Congress reinforced the value of preventative interventions in CVD risk reduction.

P4733Risk of myocardial infarction with coronary artery bypass grafting versus percutaneous coronary intervention: a systematic review and meta-analysis of fifteen randomised trials

Abstract Background It remains controversial whether coronary artery bypass grafting (CABG) or percutaneous coronary intervention (PCI) is more effective in the prevention of myocardial infarction (MI). MI has been evaluated only as a secondary endpoint without a focused systematic review in multiple meta-analyses. Purpose To compare the risk of MI at the latest follow-up available between CABG versus PCI with stents in patients with multivessel or left main coronary artery disease in a pairwise meta-analysis of randomised controlled trials (RCT). Methods We searched EMBASE, Cochrane, and Pubmed databases for articles comparing CABG versus PCI for the treatment of multivessel or left main disease. We utilised random-effects model to calculate pooled risk ratio (RR) and 95% confidence interval (CI). Fifteen trials with a total of 13,592 patients treated with either CABG (n=6,596) or PCI (n=6,996) were eligible and included. A multivariable random-effects meta-regression model, including variables such as age, sex, diabetes mellitus, publication year, follow-up duration, type of stent used, and type of coronary artery disease, was used to explore the source of potential heterogeneity of the primary result. Results After a weighted follow-up of 4.3 years, patients treated with CABG had a significantly lower risk of MI than patients treated with PCI (RR 0.75, 95% CI 0.58–0.96, P=0.024, I2=66%). The lower risk of MI with CABG as compared to PCI was more evident during a longer duration of follow-up (≥3 years, RR 0.69, 95% CI 0.52–0.91, P=0.008; ≥5 years, RR 0.64, 95% CI 0.48–0.86, P=0.003) and in diabetic population (RR 0.55, 95% CI 0.44–0.70, P&lt;0.001). There was a statistically meaningful trend toward fewer MIs with CABG with a similar magnitude of risk reduction across patients with left main disease (RR 0.74, 95% CI 0.47–1.15) and multivessel disease (RR 0.72, 95% CI 0.53–0.99). Moderate inter-study heterogeneity could not be explained by the clinical and trial-based variables tested in meta-regression, and is likely because of differences in definitions of MI, risk profile of enrolled patients, and procedural specifics. Forest plots Conclusions In patients undergoing revascularization for multivessel or left main disease, the risk of MI was lower with CABG compared to PCI. The quality assurance for MI definition and treatment-specific procedures should be emphasized for future RCTs.

More- Versus Less-Intensive Lipid-Lowering Therapy.

It has not been yet adequately addressed whether the addition of the nonstatin LDL-C (low-density lipoprotein cholesterol)-lowering agents on top of statins has the same magnitude of risk reduction in the cardiovascular events as compared with more-intensive statin therapy. We performed a systematic review and meta-analysis of RCTs (randomized controlled trials) comparing more- versus less-intensive lipid-lowering therapy (LLT) on clinical outcomes in patients with atherosclerotic cardiovascular risk. We included 23 studies involving 133 037 patients (more-intensive LLT: 67 691 patients and less-intensive LLT: 65 346 patients). We evaluated 3 types of more- versus less-intensive LLT including more versus less statins (57 672 patients), combination therapy of ezetimibe versus statins alone (20 688 patients), or a PCSK9 (proprotein convertase subtilisin-kexin type 9) inhibitor with statins versus statins alone (54 677 patients). The odds for major adverse cardiovascular events (MACE; equivalent to the composite of coronary heart death, nonfatal myocardial infarction, stroke, or coronary revascularization) were significantly lower in the more-intensive LLT group compared with the less-intensive LLT group in the entire study population (odds ratio, 0.84; 95% CI, 0.79-0.88; P<0.001), and in all the 3 categories of more-intensive LLT strategies (more-intensive statin therapy: odds ratio, 0.83; 95% CI, 0.76-0.90; P<0.001, ezetimibe: odds ratio, 0.90; 95% CI, 0.85-0.96; P<0.001, and PCSK9 inhibitors: odds ratio, 0.81; 95% CI, 0.73-0.90; P<0.001) with numerically greater relative odds reduction by more-intensive statin therapy and PCSK9 inhibitors than by ezetimibe. Odds reduction for MACE per 20 mg/dL LDL-C reduction was also different across the 3 types of more-intensive LLT (more-intensive statin therapy: 17.4%, ezetimibe: 11.0%, and PCSK9 inhibitors: 6.6%). In this meta-analysis, more-intensive LLT as compared with less-intensive LLT was associated with significant odds reduction for MACE in the entire study population and in all the 3 categories of more-intensive LLT such as more-intensive statin therapy, ezetimibe, and PCSK9 inhibitors. However, overall odds reduction for MACE and odds reduction for MACE per 20 mg/dL LDL-C reduction were different across the 3 types of more-intensive LLT. Registration: URLs: https://www.crd.york.ac.uk/PROSPERO/ and http://www.umin.ac.jp/ctr. Unique identifiers: PROSPERO: CRD42018081196, and UMIN-CTR: R000036229.

Gleason score and docetaxel response in advanced hormone-sensitive prostate cancer: The lower the better

Recently, three randomized controlled trials evaluated the addition of docetaxel to ADT in advanced hormone-sensitive prostate cancer (aHSPC). Interestingly, all trials showed a trend towards improved OS in the subgroup of patients with Gleason <8 tumors. We herein performed a meta-analysis of these trials to assess the OS benefit of docetaxel in different Gleason score groups (<8 vs ≥8). We searched the Pubmed and Medline databases and ASCO conference proceedings (through February 1st 2018) for relevant trials. For each study, median OS values and hazard ratios (HR) with 95% confidence intervals (CI) collected across different Gleason score groups. We combined the HRs from each of the three eligible trials in the meta-analysis using the random-effect model. Three eligible studies were included in the analyses (CHAARTED, GETUG-AFU-15, and STAMPEDE). In the meta-analysis of three studies, docetaxel-based chemotherapy plus ADT was associated with improved OS [HR: 0.74; 95% CI: 0.62-0.87; p<0.001]. Among patients with tumor Gleason score <8, addition of docetaxel to ADT significantly improved overall survival [HR: 0.66, 95% CI: 0.52–0.85, p=0.001]. Although there was a trend towards improved OS with docetaxel in patients with Gleason score of ≥8, the magnitude of risk reduction was lower and did not achieve statistical significance [HR: 0.81, 95% CI: 0.64–1.02, p=0.066]. In this meta-analysis, OS benefit with the addition of docetaxel to ADT was more prominent in Gleason score <8 tumors. We propose that Gleason score can be a useful criteria for treatment selection in patients with aHSPC.

Meta-Analysis Comparing the Risk of Myocardial Infarction Following Coronary Artery Bypass Grafting Versus Percutaneous Coronary Intervention in Patients With Multivessel or Left Main Coronary Artery Disease

There is insufficient data regarding the comparative efficacy of coronary artery bypass graft surgery (CABG) and percutaneous coronary intervention (PCI) regarding myocardial infarction (MI). Our systematic review included randomized controlled trials that compared CABG versus PCI with stents in patients with multivessel or left main coronary artery disease (CAD). Included trials should have had reported event number of MI and a clinical follow-up of one or more years. Data were pooled using a random-effects model. The primary end point was MI at the longest available follow-up in the intention-to-treat population. Fifteen trials with a total of 13,592 patients treated with either CABG (n = 6,596) or PCI (n = 6,996) were included. After a weighted follow-up of 4.5 years, patients treated with CABG had a significantly lower risk of MI than those treated with PCI (risk ratio [RR] 0.75, 95% confidence interval [CI] 0.58 to 0.96, p = 0.024). The lower risk of MI with CABG as compared with PCI was more evident during a longer duration of follow-up (≥3 years, RR 0.69, 95% CI 0.52 to 0.91, p = 0.008; ≥5 years, RR 0.64, 95% CI 0.48 to 0.86, p = 0.003) and in the diabetic population (RR 0.55, 95% CI 0.44 to 0.70, p <0.001). The magnitude of risk reduction was similar across patients with multivessel (RR 0.72, 95% CI 0.53 to 0.99) and left main CAD (RR 0.74, 95% CI 0.47 to 1.15). In conclusion, the present meta-analysis of studies involving patients with multivessel or left main CAD suggests a significant benefit of CABG over PCI concerning the risk of future MI.

Genetic risk of dementia mitigated by cognitive reserve: A cohort study.

ObjectiveWe investigated whether cognitive reserve modifies the risk of dementia attributable to apolipoprotein ε4 (APOE‐ε4), a well‐known genetic risk factor for dementia.MethodsWe followed 2,556 cognitively intact participants aged ≥60 years from the ongoing prospective community‐based Swedish National Study on Aging and Care in Kungsholmen (SNAC‐K). Dementia was ascertained through clinical and neuropsychological assessments and diagnosed according to Diagnostic and Statistical Manual of Mental Disorders, 4th edition criteria. Structural equation modeling was used to generate a cognitive reserve indicator from 4 previously validated contributors: early life education, midlife substantive work complexity, late life leisure activities, and late life social networks. Cox proportional hazard models estimated dementia risk in relation to cognitive reserve indicator. The interaction between the cognitive reserve indicator and APOE‐ε4 was assessed on multiplicative and additive scales.ResultsAfter an average of 6.3 years (range = 2.1–10.7) of follow‐up, 232 dementia cases were ascertained. Relative to individuals in the lowest tertile of cognitive reserve indicator, those with moderate and high reserve were at a reduced risk of dementia. There was no multiplicative interaction between APOE‐ε4 status and cognitive reserve indicator (p = 0.113). Additive interaction was statistically significant. Relative to APOE‐ε4 carriers with low cognitive reserve, ε4 carriers with high reserve had a reduced risk of dementia (hazard ratio [HR] = 0.28, 95% confidence interval [CI] = 0.13–0.59). The magnitude of risk reduction was similar in ε4 noncarriers with a high cognitive reserve indicator (HR = 0.24, 95% CI = 0.15–0.40).InterpretationLifelong engagement in reserve‐enhancing activities attenuates the risk of dementia attributable to APOE‐ε4. Promoting cognitive reserve might be especially effective in subpopulations with high genetic risk of dementia. ANN NEUROL 2019

PATTERNS OF STATIN ADHERENCE OVER LONG TERM FOLLOW UP IN AN INSURED SECONDARY PREVENTION POPULATION WITH ATHEROSCLEROTIC CARDIOVASCULAR DISEASE

Clinical trials have shown a consistent relationship between years of LDL-C reduction on statin therapy and magnitude of risk reduction. WOSCOPS found that 5 years of statins led to lifelong risk reduction, but little is known about real world persistence over this time frame. The objective of this

Reduced risk of emergency admission for colorectal cancer associated with the introduction of bowel cancer screening across England: a retrospective national cohort study.

We wanted to find out if roll-out of the bowel cancer screening programme (BCSP) across England was associated with a reduced risk of emergency hospital admission for people presenting with colorectal cancer (CRC) during this period. This is a retrospective cohort study of 27763 incident cases of CRC over a 1-year period during the roll-out of screening across parts of England. The primary outcome was the number of emergency (unplanned) hospital admissions during the diagnostic pathway. The primary exposure was to those living in an area where the BCSP was active at the time of diagnosis. Patients were categorized into three exposure groups: BCSP not active (reference group), BCSP active <6months or BCSP active ≥6months. The risk of emergency admission for CRC in England was associated with increasing age, female gender, comorbidity and social deprivation. After adjusting for these factors in logistic regression, the odds ratio (OR) for emergency admission in patients diagnosed ≥6months after the start-up of local screening was 0.83 (CI 0.76-0.90). The magnitude of risk reduction was greatest for cases of screening age (OR 0.75; CI 0.63-0.90) but this effect was apparent also for cases outside the 60-69-year age group (OR 0.85; CI 0.77-0.94). Living in an area with active BCSP conferred no reduction in risk of emergency admission for people diagnosed with oesophagogastric cancer during the same period. The start-up of bowel cancer screening in England was associated with a substantial reduction in the risk of emergency admission for CRC in people of all ages. This suggests that the roll-out of the programme had indirect benefits beyond those related directly to participation in screening.

Abstract 77: Intensity of Blood Pressure Reduction and Secondary Stroke Prevention: A Systematic Review and Meta-regression Analysis of Randomized Clinical Trials

Background &amp; Purpose: Current recommendations do not specifically address the optimal blood pressure (BP) cut-off for secondary stroke prevention in patients with previous cerebrovascular events. We conducted a systematic review and meta-regression analysis on the association of BP reduction with recurrent stroke and cardiovascular events using data from randomized-controlled clinical trials (RCTs) of secondary stroke prevention. Methods: For all reported events during each eligible study period we calculated the corresponding risk ratios (RRs) to express the comparison of event occurrence risk between patients randomized to antihypertensive treatment and those randomized to placebo. Based on the reported BP values, we performed univariate meta-regression analyses according to achieved BP values under the random-effects model (Method of Moments) for those outcome events reported in ≥10 total subgroups of included RCTs. Results: In pairwise meta-analyses of 14 RCTs comprising 42,736 patients antihypertensive treatment lowered the risk for recurrent stroke (RR=0.73, 95%CI: 0.62-0.87, p&lt;0.001), disabling or fatal stroke (RR=0.71, 95%CI: 0.59-0.85, p&lt;0.001) and cardiovascular death (RR=0.85, 95%CI: 0.75-0.96, p=0.010). In meta-regression analyses systolic BP reduction was linearly related to lower risk of recurrent stroke (p=0.049; Figure A), myocardial infarction (p=0.024), death from any cause (p=0.001) and cardiovascular death (p&lt;0.001). Similarly, diastolic BP reduction was linearly related to a lower risk of recurrent stroke (p=0.026; Figure B) and all-cause mortality (p=0.009). Funnel plot inspection and Egger’s statistical test revealed no evidence of publication bias. Conclusion: The extent of BP reduction is linearly associated with the magnitude of risk reduction in recurrent cerebro- and cardio-vascular events. Strict and aggressive BP control appears to be essential for effective secondary stroke prevention.