Background: Ischemic heart disease (IHD) has been considered the top cause of mortality globally. However, countries differ in their rates and there have been changes over time. Methods and Results: We analyzed mortality data submitted to the World Health Organization from 2005 to 2015 by individual countries. We explored patterns in relationships with age, sex, and income and calculated age-standardized mortality rates for each country in addition to crude death rates. In 5 illustrative countries which provided detailed data, we analyzed trends of mortality from IHD and 3 noncommunicable diseases (lung cancer, stroke, and chronic lower respiratory tract diseases) and examined the simultaneous trends in important cardiovascular risk factors. Russia, United States, and Ukraine had the largest absolute numbers of deaths among the countries that provided data. Among 5 illustrative countries (United Kingdom, United States, Brazil, Kazakhstan, and Ukraine), IHD was the top cause of death, but mortality from IHD has progressively decreased from 2005 to 2015. Age-standardized IHD mortality rates per 100 000 people per year were much higher in Ukraine (324) and Kazakhstan (97) than in United States (60), Brazil (54), and the United Kingdom (46), with much less difference in other causes of death. All 5 countries showed a progressive decline in IHD mortality, with a decline in smoking and hypertension and in all cases a rise in obesity and type II diabetes mellitus. Conclusions: IHD remains the single largest cause of death in countries of all income groups. Rates are different between countries and are falling in most countries, indicating great potential for further gains. On the horizon, future improvements may become curtailed by increasing hypertension in some developing countries and more importantly global growth in obesity.

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Objective To investigate whether discrepancies in trials of use of bone marrow stem cells in patients with heart disease account for the variation in reported effect size in improvement of left ventricular function.Design Identification and counting of factual discrepancies in trial reports, and sample size weighted regression against therapeutic effect size. Meta-analysis of trials that provided sufficient information. Data sources PubMed and Embase from inception to April 2013.Eligibility for selecting studies Randomised controlled trials evaluating the effect of autologous bone marrow stem cells for heart disease on mean left ventricular ejection fraction.Results There were over 600 discrepancies in 133 reports from 49 trials. There was a significant association between the number of discrepancies and the reported increment in EF with bone marrow stem cell therapy (Spearman's r=0.4, P=0.005). Trials with no discrepancies were a small minority (five trials) and showed a mean EF effect size of −0.4%. The 24 trials with 1-10 discrepancies showed a mean effect size of 2.1%. The 12 with 11-20 discrepancies showed a mean effect of size 3.0%. The three with 21-30 discrepancies showed a mean effect size of 5.7%. The high discrepancy group, comprising five trials with over 30 discrepancies each, showed a mean effect size of 7.7%.Conclusions Avoiding discrepancies is difficult but is important because discrepancy count is related to effect size. The mechanism is unknown but should be explored in the design of future trials because in the five trials without discrepancies the effect of bone marrow stem cell therapy on ejection fraction is zero.

BackgroundIschaemic heart disease (IHD) is the leading cause of death worldwide and its prevention is a public health priority.MethodWe analysed worldwide IHD mortality data from the World Health Organisation as of February 2014 by country, age and income. Age-standardised mortality rates by country were calculated. We constructed a cartogram which is an algorithmically transformed world map that conveys numbers of deaths in the form of spatial area.ResultsOf the countries that provided mortality data, Russia, the United States of America and Ukraine contributed the largest numbers of deaths. India and China were estimated to have even larger numbers of deaths. Death rates from IHD increase rapidly with age. Crude mortality rates appear to be stable whilst age-standardised mortality rates are falling. Over half of the world's countries (113/216) have provided IHD mortality data for 2008 or later. Of these, 13 countries provided data in 2012. No countries have yet provided 2013 data. Of the 103 remaining countries, 24 provided data in 2007 or earlier, and 79 have never provided data in the ICD9 or ICD10 format.ConclusionsIn the countries for which there are good longitudinal data, predominantly European countries, recent years have shown a continuing decline in age-standardised IHD mortality. However, the progressive aging of populations has kept crude IHD mortality high. It is not known whether the pattern is consistent globally because many countries have not provided regular annual data including wealthy countries such as the United Arab Emirates and large countries such as India and China.

Background Most people who begin statins abandon them, most commonly because of side effects. Objectives The purpose of this study was to assess daily symptom scores on statin, placebo, and no treatment in participants who had abandoned statins. Methods Participants received 12 1-month medication bottles, 4 containing atorvastatin 20 mg, 4 placebo, and 4 empty. We measured daily symptom intensity for each using an app (scale 1-100). We also measured the “nocebo” ratio: the ratio of symptoms induced by taking statin that was also induced by taking placebo. Results A total of 60 participants were randomized and 49 completed the 12-month protocol. Mean symptom score was 8.0 (95% CI: 4.7-11.3) in no-tablet months. It was higher in statin months (16.3; 95% CI: 13.0-19.6; P < 0.001), but also in placebo months (15.4; 95% CI: 12.1-18.7; P < 0.001), with no difference between the 2 (P = 0.388). The corresponding nocebo ratio was 0.90. In the individual-patient daily data, neither symptom intensity on starting (OR: 1.02; 95% CI: 0.98-1.06; P = 0.28) nor extent of symptom relief on stopping (OR: 1.01; 95% CI: 0.98-1.05; P = 0.48) distinguished between statin and placebo. Stopping was no more frequent for statin than placebo (P = 0.173), and subsequent symptom relief was similar between statin and placebo. At 6 months after the trial, 30 of 60 (50%) participants were back taking statins. Conclusions The majority of symptoms caused by statin tablets were nocebo. Clinicians should not interpret symptom intensity or timing of symptom onset or offset (on starting or stopping statin tablets) as indicating pharmacological causation, because the pattern is identical for placebo. (Self-Assessment Method for Statin Side-effects Or Nocebo [SAMSON]; NCT02668016 )

Aims This meta-analysis aims to quantify the association of reduced coronary flow with all-cause mortality and major adverse cardiovascular events (MACE) across a broad range of patient groups and pathologies. Methods and results We systematically identified all studies between 1 January 2000 and 1 August 2020, where coronary flow was measured and clinical outcomes were reported. The endpoints were all-cause mortality and MACE. Estimates of effect were calculated from published hazard ratios (HRs) using a random-effects model. Seventy-nine studies with a total of 59 740 subjects were included. Abnormal coronary flow reserve (CFR) was associated with a higher incidence of all-cause mortality [HR: 3.78, 95% confidence interval (CI): 2.39–5.97] and a higher incidence of MACE (HR 3.42, 95% CI: 2.92–3.99). Each 0.1 unit reduction in CFR was associated with a proportional increase in mortality (per 0.1 CFR unit HR: 1.16, 95% CI: 1.04–1.29) and MACE (per 0.1 CFR unit HR: 1.08, 95% CI: 1.04–1.11). In patients with isolated coronary microvascular dysfunction, an abnormal CFR was associated with a higher incidence of mortality (HR: 5.44, 95% CI: 3.78–7.83) and MACE (HR: 3.56, 95% CI: 2.14–5.90). Abnormal CFR was also associated with a higher incidence of MACE in patients with acute coronary syndromes (HR: 3.76, 95% CI: 2.35–6.00), heart failure (HR: 6.38, 95% CI: 1.95–20.90), heart transplant (HR: 3.32, 95% CI: 2.34–4.71), and diabetes mellitus (HR: 7.47, 95% CI: 3.37–16.55). Conclusion Reduced coronary flow is strongly associated with increased risk of all-cause mortality and MACE across a wide range of pathological processes. This finding supports recent recommendations that coronary flow should be measured more routinely in clinical practice, to target aggressive vascular risk modification for individuals at higher risk.

Background: In patients presenting with ST-segment–elevation myocardial infarction, percutaneous coronary intervention (PCI) reduces mortality when compared with fibrinolysis. In other forms of coronary artery disease (CAD), however, it has been controversial whether PCI reduces mortality. In this meta-analysis, we examine the benefits of PCI in (1) patients post–myocardial infarction (MI) who did not receive immediate revascularization; (2) patients who have undergone primary PCI for ST-segment–elevation myocardial infarction but have residual coronary lesions; (3) patients who have suffered a non–ST-segment–elevation acute coronary syndrome; and (4) patients with truly stable CAD with no recent infarct. This analysis includes data from the recently presented International Study of Comparative Health Effectiveness with Medical and Invasive Approaches (ISCHEMIA) and Complete versus Culprit-Only Revascularization Strategies to Treat Multivessel Disease after Early PCI for STEMI (COMPLETE) trials. Methods and Results: We systematically identified all randomized trials of PCI on a background of medical therapy for the treatment of CAD. The ISCHEMIA trial, presented in November 2019, was eligible for inclusion. Data were combined using a random-effects meta-analysis. The primary end point was all-cause mortality. Forty-six trials, including 37 757 patients, were eligible. In the 3 unstable scenarios, PCI had the following effects on mortality: unrevascularized post-MI relative risk (RR) 0.68 (95% CI, 0.45–1.03); P =0.07; multivessel disease following ST-segment–elevation myocardial infarction (RR, 0.84 [95% CI, 0.69–1.04]; P =0.11); non–ST-segment–elevation acute coronary syndrome (RR, 0.84 [95% CI, 0.72–0.97]; P =0.02). Overall, in these unstable scenarios PCI was associated with a significant reduction in mortality (RR, 0.84 [95% CI, 0.75–0.93]; P =0.02). In unstable CAD, PCI also reduced cardiac death (RR, 0.69 [95% CI, 0.53–0.90]; P =0.007) and MI (RR, 0.74 [95% CI, 0.62–0.90]; P =0.002). For stable CAD, PCI did not reduce mortality (RR, 0.98 [95% CI, 0.87–1.11]), cardiac death (RR, 0.89 [95% CI, 0.71–1.12]; P =0.33), or MI (RR, 0.96 [95% CI, 0.86–1.08]; P =0.54). Conclusions: PCI prevents death, cardiac death, and MI in patients with unstable CAD. For patients with stable CAD, PCI shows no evidence of an effect on any of these outcomes.

Discrepancies in drug trials between office and ambulatory blood pressure reductions disappear once double-blinded placebo control is implemented. Renal denervation trials may also undergo similar evolution. We predict that as denervation trial designs gradually improve in bias-resistance, office and ambulatory pressure drops will converge. We predict that it is the office drops that will move to match the ambulatory drops, that is, not 30, but nearer 13.