Heart disease: The forgotten pandemic.

Over the past 10 years cholesterol levels have been falling while the number of Americans dying of heart disease has been steadily climbing. This apparent paradox compels us to question whether lowering cholesterol is the best way to prevent coronary heart disease. A number of recent studies suggest that cholesterol, specifically LDL-C, may not be a primary risk factor for coronary heart disease and other markers, such as insulin resistance or remnant cholesterol, may be much more important. Furthermore, therapies designed to prevent coronary heart disease by lowering cholesterol with drugs or diet have yielded inconsistent results. Despite the widespread utilization of cholesterol-lowering statins in Europe, observational studies indicate that there has been no accompanying decline in coronary heart disease deaths. This new evidence should give us pause as we try to understand why the campaign to prevent heart disease by lowering cholesterol has not achieved its goals.

Statin wars: have we been misled about the evidence? A narrative review.

Statins are the most widely prescribed, cholesterol-lowering drugs in the world. Despite the expiration of their patents, revenue for statins is expected to rise, with total sales on track to reach an estimated US$1 trillion by 2020. A bitter dispute has erupted among doctors over suggestions that statins should be prescribed to millions of healthy people at low risk of heart disease. There are concerns that the benefits have been exaggerated and the risks have been underplayed. Also, the raw data on the efficacy and safety of statins are being kept secret and have not been subjected to scrutiny by other scientists. This lack of transparency has led to an erosion of public confidence. Doctors and patients are being misled about the true benefits and harms of statins, and it is now a matter of urgency that the raw data from the clinical trials are released.

Interventions to help patients withdraw from depression drugs: A systematic review.

BACKGROUND: Depression drugs can be difficult to come off due to withdrawal symptoms. Gradual tapering with tapering support is needed to help patients withdraw safely. OBJECTIVE: To review the withdrawal success rates, using any intervention, and the effects on relapse/recurrence rates, symptom severity, quality of life, and withdrawal symptoms. METHODS: Systematic review based on PubMed and Embase searches (last search 4 October 2022) of randomised trials with one or more treatment arms aimed at helping patients withdraw from a depression drug, regardless of indication for treatment. We calculated the mean and median success rates and the risk difference of depressive relapse when discontinuing or continuing depression drugs. RESULTS: We included 13 studies (2085 participants). Three compared two withdrawal interventions and ten compared drug discontinuation vs. continuation. The success rates varied hugely between the trials (9% to 80%), with a weighted mean of 47% (95% confidence interval 38% to 57%) and a median of 50% (interquartile range 29% to 65%). A meta-regression showed that the length of taper was highly predictive for the risk of relapse (P = 0.00001). All the studies we reviewed confounded withdrawal symptoms with relapse; did not use hyperbolic tapering; withdrew the depression drug too fast in a linear fashion; and stopped it entirely when receptor occupancy was still high. CONCLUSION: The true proportion of patients on depression drugs who can stop safely without relapse is likely considerably higher than the 50% we found.

Evaluating the Association Between Low-Density Lipoprotein Cholesterol Reduction and Relative and Absolute Effects of Statin Treatment: A Systematic Review and Meta-analysis.

Importance: The association between statin-induced reduction in low-density lipoprotein cholesterol (LDL-C) levels and the absolute risk reduction of individual, rather than composite, outcomes, such as all-cause mortality, myocardial infarction, or stroke, is unclear. Objective: To assess the association between absolute reductions in LDL-C levels with treatment with statin therapy and all-cause mortality, myocardial infarction, and stroke to facilitate shared decision-making between clinicians and patients and inform clinical guidelines and policy. Data Sources: PubMed and Embase were searched to identify eligible trials from January 1987 to June 2021. Study Selection: Large randomized clinical trials that examined the effectiveness of statins in reducing total mortality and cardiovascular outcomes with a planned duration of 2 or more years and that reported absolute changes in LDL-C levels. Interventions were treatment with statins (3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors) vs placebo or usual care. Participants were men and women older than 18 years. Data Extraction and Synthesis: Three independent reviewers extracted data and/or assessed the methodological quality and certainty of the evidence using the risk of bias 2 tool and Grading of Recommendations, Assessment, Development and Evaluation. Any differences in opinion were resolved by consensus. Meta-analyses and a meta-regression were undertaken. Main Outcomes and Measures: Primary outcome: all-cause mortality. Secondary outcomes: myocardial infarction, stroke. Findings: Twenty-one trials were included in the analysis. Meta-analyses showed reductions in the absolute risk of 0.8% (95% CI, 0.4%-1.2%) for all-cause mortality, 1.3% (95% CI, 0.9%-1.7%) for myocardial infarction, and 0.4% (95% CI, 0.2%-0.6%) for stroke in those randomized to treatment with statins, with associated relative risk reductions of 9% (95% CI, 5%-14%), 29% (95% CI, 22%-34%), and 14% (95% CI, 5%-22%) respectively. A meta-regression exploring the potential mediating association of the magnitude of statin-induced LDL-C reduction with outcomes was inconclusive. Conclusions and Relevance: The results of this meta-analysis suggest that the absolute risk reductions of treatment with statins in terms of all-cause mortality, myocardial infarction, and stroke are modest compared with the relative risk reductions, and the presence of significant heterogeneity reduces the certainty of the evidence. A conclusive association between absolute reductions in LDL-C levels and individual clinical outcomes was not established, and these findings underscore the importance of discussing absolute risk reductions when making informed clinical decisions with individual patients.

Presentation of benefits and harms of antidepressants on websites: A cross-sectional study.

BACKGROUND: Many people use the Internet for obtaining information about their medications. OBJECTIVE: To investigate whether information about antidepressants on popular websites reflects the scientific evidence and enables people to make informed choices. METHODS: Cross-sectional study using a checklist with 14 predefined criteria of 39 websites from 10 countries. RESULTS: All 39 websites mentioned the benefits of antidepressants. Twenty-nine (74%) websites attributed depression to a "chemical imbalance" or claimed they could fix an imbalance. Sexual dysfunction was mentioned as a harmful effect on 23 (59%) websites while five (13%) mentioned emotional numbing. Twenty-five (64%) stated that antidepressants may cause increased suicidal ideation, but 23 (92%) of them contained incorrect information, and only two (5%) websites noted that the suicide risk is increased in people of all ages. Twenty-eight websites (72%) warned patients about withdrawal effects but only one stated that antidepressants can be addictive. CONCLUSIONS: None of the websites met our predefined criteria. The information was generally inaccurate and unhelpful and has potential to lead to inappropriate use and overuse of antidepressants and reduce the likelihood that people will seek better options for depression like psychotherapy.

Statins for primary prevention: what is the regulator's role?

Globally, drug regulators have approved statins for the prevention of cardiovascular disease (CVD), although their use in primary prevention has been controversial. A highly publicised debate has ensued over whether the benefits outweigh the harms. Drug regulators, which are legally required to make independent judgements on drug approvals, have remained silent during the debate. Our aim was to navigate the decision-making processes of European drug regulators and ultimately request the data upon which statins were approved. Our findings revealed a system of fragmented regulation in which many countries licensed statins but did not analyse the data themselves. There is no easily accessible archive containing information about the licensing approval of statins or a central location for holding the trial data. This is an unsustainable model and serves neither the general public, nor researchers.

COVID-19 and Substance Use Disorders: Recommendations to a Comprehensive Healthcare Response. An International Society of Addiction Medicine Practice and Policy Interest Group Position Paper.

Coronavirus Disease 2019 (COVID-19) is escalating all over the world and has higher morbidities and mortalities in certain vulnerable populations. People Who Use Drugs (PWUD) are a marginalized and stigmatized group with weaker immunity responses, vulnerability to stress, poor health conditions, high-risk behaviors, and lower access to health care services. These conditions put them at a higher risk of COVID-19 infection and its complications. In this paper, an international group of experts on addiction medicine, infectious diseases, and disaster psychiatry explore the possible raised concerns in this issue and provide recommendations to manage the comorbidity of COVID-19 and Substance Use Disorder (SUD).

Endothelial cell COX-2 expression and activity in hypoxia.

The clinical experience with selective cyclooxygenase (COX)-2 inhibitors reveals there are important protective roles for COX-2 in the cardiovascular system. This study examined the response to hypoxia of endothelial cell eicosanoid synthesis with respect to the role of COX-2 and its molecular regulation in hypoxia. Human umbilical vein endothelial cells (HUVEC) were exposed to hypoxia and the effects on COX-2, prostacyclin (PGI(2)) and thromboxane (TXA(2)) synthesis were examined. COX-2 promoter constructs were used to examine the role of Hypoxia Inducible Factors (HIFs) in COX-2 responses to hypoxia. Hypoxia caused an increase in PGI(2) synthesis, but not TXA(2) synthesis. PGI(2), but not TXA(2) synthesis, was absolutely dependent on upregulation of COX-2 by hypoxia. Mutations of transcription factor binding sites in the promoter showed a lack of involvement of NFkappaB in the response to hypoxia, but suggested involvement of HIFs. Transfection of HUVEC with HIF expression vectors increased activity of the promoter construct and increased native COX-2 expression in normoxia. EMSA showed HIF binding in nuclear extracts of hypoxic HUVEC to a region of the COX-2 promoter. The endothelial cell response to hypoxia involves increased production of the anti-thrombotic eicosanoid, PGI(2), which is dependent on COX-2 upregulation by a HIF-mediated process.