Heart and circulation
Does it prevent an actual heart attack?
The hardest endpoint in this entire catalogue and the rarest. A trial that counted events is worth more than a hundred that counted markers.
178,846
people in trials
54
human studies
3
compounds, animal or cell only
9
trials found nothing
Measured in people
Ranked by how many people, which is a fact about the evidence and not a judgement about the compound. The one at the top is the most studied, which is not the same as the best. Counts are never added across compounds, because the same person can appear in more than one trial.
- 23,347 people4 human studies1 found nothing
found nothingEMPA-REG OUTCOME. 7,020 people with type 2 diabetes at high cardiovascular risk, median observation 3.1 years. The primary composite of cardiovascular death, nonfatal myocardial infarction or nonfatal stroke occurred in 10.5 percent on empagliflozin against 12.1 percent on placebo (hazard ratio 0.86, P = 0.04). Death from any cause was 5.7 percent against 8.3 percent, a 32 percent relative risk reduction. There was no significant difference in rates of myocardial infarction or stroke, and genital infection was more common on the drug.
New England Journal of Medicine, 2015 · 7,020 people
EMPA-KIDNEY. 6,609 people with chronic kidney disease, median 2.0 years. Kidney disease progression or cardiovascular death occurred in 13.1 percent against 16.9 percent (hazard ratio 0.72). Notably for anyone reading the drug as a mortality intervention, death from any cause was 4.5 percent against 5.1 percent and was not a significant difference in this trial.
New England Journal of Medicine, 2023 · 6,609 people
EMPEROR-Preserved. 5,988 people with class II to IV heart failure and an ejection fraction above 40 percent, median 26.2 months. Cardiovascular death or heart failure hospitalisation occurred in 13.8 percent against 17.1 percent (hazard ratio 0.79). The authors state the effect was mainly driven by fewer heart failure hospitalisations rather than fewer deaths.
New England Journal of Medicine, 2021 · 5,988 people
EMPEROR-Reduced. 3,730 people with class II to IV heart failure and an ejection fraction of 40 percent or less, median 16 months. Cardiovascular death or heart failure hospitalisation occurred in 19.4 percent against 24.7 percent on placebo (hazard ratio 0.75). Estimated glomerular filtration rate fell by 0.55 against 2.28 ml per minute per 1.73 square metres per year. The effect held regardless of diabetes status.
New England Journal of Medicine, 2020 · 3,730 people
- 17,604 people1 human study
17,604 adults with cardiovascular disease and BMI 27 or higher but no diabetes: semaglutide 2.4 mg cut major adverse cardiovascular events 20% (6.5% vs 8.0%; HR 0.80) over a mean 39.8 months.
New England Journal of Medicine, 2023 · 17,604 people
- 14,752 people1 human study1 found nothing
found nothing14,752 patients, median 3.2 years: MACE in 11.4% on weekly exenatide vs 12.2% on placebo (HR 0.91, 95% CI 0.83 to 1.00), noninferior for safety but not statistically superior.
New England Journal of Medicine, 2017 · 14,752 people
- 13,299 people1 human study
13,299 patients with type 2 diabetes and atherosclerotic disease: primary MACE in 12.2% on tirzepatide vs 13.1% on dulaglutide (HR 0.92), meeting noninferiority against an active comparator with proven benefit; basis of the August 2026 cardiovascular indication.
New England Journal of Medicine, 2025 · 13,299 people
- 9,901 people1 human study
9,901 participants (only about a third with prior cardiovascular disease), median 5.4 years: MACE in 12.0% on dulaglutide vs 13.4% on placebo (HR 0.88; p=0.026).
The Lancet, 2019 · 9,901 people
- 9,503 people2 human studies1 found nothing
found nothingThe historical result that kept niacin in the guidelines for thirty years, and it is weaker than its reputation. In the Coronary Drug Project, 8,341 men aged 30 to 64 with a previous myocardial infarction were treated between 1966 and 1975. Niacin modestly reduced definite non-fatal recurrent myocardial infarction but did not reduce total mortality during the trial. At a mean follow-up of 15 years, nearly 9 years after the drug was stopped, all-cause mortality was 52.0 percent on niacin versus 58.2 percent on placebo, 11 percent lower, P=0.0004. This is a post-trial observational mortality difference in a pre-statin population, not a result obtained on top of modern therapy, and both AIM-HIGH and HPS2-THRIVE tested niacin on top of modern therapy and found nothing.
Journal of the American College of Cardiology, 1986 · 8,341 people
Observational metabolomics rather than a trial, and it proposes a mechanism for why more niacin might be actively unhelpful. In a discovery cohort of 1,162 stable cardiac patients and validation cohorts of 2,331 US and 832 European patients, serum levels of the terminal metabolites of excess niacin, 2PY and 4PY, were associated with increased 3-year risk of major adverse cardiovascular events: for 4PY, adjusted hazard ratios of 1.89 (95 percent CI 1.26 to 2.84) and 1.99 (1.26 to 3.14). A genetic variant associated with both metabolites was also associated with soluble VCAM-1 in a meta-analysis of about 106,000 people. This is association plus a mechanistic hypothesis, not causal proof in humans.
Nature Medicine, 2024 · 1,162 people
- 9,463 people1 human study
9,463 adults aged 40 and over with type 2 diabetes and cardiovascular disease, 610 sites, 28 countries, randomised 1:1 to albiglutide 30 to 50 mg weekly or placebo, median follow-up 1.6 years. Primary composite (cardiovascular death, myocardial infarction, stroke): 338 of 4,731 (7 percent) against 428 of 4,732 (9 percent), hazard ratio 0.78 (95 percent CI 0.68 to 0.90), superiority P equals 0.0006. Pancreatitis 10 against 7, pancreatic cancer 6 against 5, medullary thyroid carcinoma 0 against 0. Funded by GlaxoSmithKline.
Lancet, 2018 · 9,463 people
- 9,340 people1 human study
9,340 patients with type 2 diabetes at high cardiovascular risk, median 3.8 years: primary MACE in 13.0% on liraglutide vs 14.9% on placebo (HR 0.87, a 13% relative reduction; P=0.01 for superiority).
New England Journal of Medicine, 2016 · 9,340 people
- 7,706 people3 human studies2 found nothing
found nothingRELAX-AHF-2, the confirmatory trial, and it failed. 6,545 patients in the intention to treat analysis, same drug, dose, 48 hour infusion and entry criteria as RELAX-AHF. Death from cardiovascular causes at 180 days occurred in 285 of 3,274 patients (8.7 percent) on serelaxin and 290 of 3,271 (8.9 percent) on placebo, hazard ratio 0.98 (0.83 to 1.15), p = 0.77. Worsening heart failure at day 5 occurred in 6.9 percent against 7.7 percent, hazard ratio 0.89 (0.75 to 1.07), p = 0.19. No significant difference in all-cause death at 180 days, in cardiovascular death or rehospitalisation, or in length of the index hospital stay. Adverse event rates were similar. Funded by Novartis. Registered as NCT01870778.
New England Journal of Medicine, 2019 · 6,545 people
found nothing1,161 patients hospitalised with acute heart failure randomised 1:1 to a 48 hour infusion of serelaxin at 30 micrograms per kilogram per day or placebo within 16 hours of presentation. Serelaxin improved the visual analogue scale dyspnoea endpoint by 448 mm times hours (95 percent CI 120 to 775, p = 0.007) but had no effect on the co-primary Likert endpoint (27 percent against 26 percent, p = 0.70). There was no effect on cardiovascular death or readmission at 60 days (hazard ratio 1.02, 0.74 to 1.41) or on days alive out of hospital. Among prespecified additional endpoints, 42 deaths occurred by day 180 on serelaxin against 65 on placebo, hazard ratio 0.63 (0.42 to 0.93, p = 0.019). Funded by Corthera, a Novartis affiliate company. Registered as NCT00520806.
The Lancet, 2013 · 1,161 people
An adjudicated analysis of every death in RELAX-AHF-2, run specifically to understand why the two trials disagreed. By 180 days 11.5 percent of patients had died, 38 percent of those deaths from heart failure. Unlike in RELAX-AHF, there was no apparent effect of serelaxin on any category of cause of death. Patients aged 75 or over died more often (14.2 percent against 8.8 percent) and more often from non-cardiovascular causes. Patients with preserved ejection fraction had less heart failure mortality (30 percent against 40 percent) and more non-cardiovascular mortality (36 percent against 20 percent).
JACC: Heart Failure, 2020 · no headcount in the line
- 7,141 people1 human study
ASCEND-HF: 7,141 people hospitalised with acute heart failure randomised to nesiritide or placebo for 24 to 168 hours on top of standard care. Dyspnoea improvement 44.5 versus 42.1 percent at 6 hours and 68.2 versus 66.1 percent at 24 hours, neither meeting the prespecified threshold. Rehospitalisation or death within 30 days 9.4 versus 10.1 percent (difference -0.7 percentage points, 95 percent confidence interval -2.1 to 0.7). No excess worsening renal function; more hypotension. Funded by Scios, the manufacturer.
New England Journal of Medicine, 2011 · 7,141 people
- 7,050 people3 human studies1 found nothing
found nothing4,228 asymptomatic people with ejection fraction 0.35 or below, mean follow-up 37.4 months. Total mortality 313 versus 334 deaths, risk reduction 8 percent (95 percent CI -8 to 21, p = 0.30), not significant. Death or development of heart failure 630 versus 818 (29 percent reduction, p < 0.001). The null mortality result in people without symptoms is the relevant one for anyone reading enalapril as a longevity drug.
New England Journal of Medicine, 1992 · 4,228 people
2,569 patients with symptomatic heart failure and ejection fraction 0.35 or below, enalapril 2.5 to 20 mg a day or placebo, mean follow-up 41.4 months. Deaths 452 (35.2 percent) versus 510 (39.7 percent), risk reduction 16 percent (95 percent CI 5 to 26, p = 0.0036); death or heart failure hospitalisation 613 versus 736 (26 percent reduction). Run by the US National Heart, Lung, and Blood Institute.
New England Journal of Medicine, 1991 · 2,569 people
253 patients with NYHA class IV heart failure, double-blind, enalapril 2.5 to 40 mg a day or placebo on top of conventional therapy. Six-month mortality 26 versus 44 percent (40 percent reduction, p = 0.002); one-year 31 percent reduction; 50 versus 68 deaths overall (27 percent). Entire benefit in progressive heart failure deaths, none in sudden death. Hypotension withdrawals 7 versus 0. Funding not stated in the abstract retrieved.
New England Journal of Medicine, 1987 · 253 people
- 6,800 people1 human study1 found nothing
found nothing6,800 patients with heart failure and ejection fraction 0.45 or less randomised to digoxin or placebo, average follow-up 37 months. Mortality unchanged: 1,181 deaths (34.8 percent) versus 1,194 (35.1 percent), risk ratio 0.99, 95 percent confidence interval 0.91 to 1.07. Hospitalisation for worsening heart failure fell from 34.7 to 26.8 percent, risk ratio 0.72. This is cardiology evidence and says nothing about senescence.
New England Journal of Medicine, 1997 · 6,800 people
- 6,068 people1 human study
6,068 patients: primary MACE hazard ratio 1.02, showing noninferiority to placebo but no cardiovascular benefit.
New England Journal of Medicine, 2015 · 6,068 people
- 5,650 people2 human studies
UKPDS post-trial monitoring of 4,209 randomised participants. Glycaemic differences disappeared within a year of the trial ending, yet at 10 years the sulfonylurea-insulin group retained reductions in any diabetes-related endpoint (9 percent, p = 0.04), microvascular disease (24 percent, p = 0.001), myocardial infarction (15 percent, p = 0.01) and death from any cause (13 percent, p = 0.007). The metformin group showed larger reductions in myocardial infarction (33 percent) and death (27 percent).
New England Journal of Medicine, 2008 · 4,209 people
DCCT/EDIC: 1,441 people with type 1 diabetes randomised to intensive or conventional insulin therapy for a mean 6.5 years, then followed observationally. Over a mean 17 years, intensive treatment reduced any cardiovascular event by 42 percent (95 percent confidence interval 9 to 63, p = 0.02) and non-fatal myocardial infarction, stroke or cardiovascular death by 57 percent (12 to 79, p = 0.02).
New England Journal of Medicine, 2005 · 1,441 people
- 5,470 people2 human studies
TREAT: 4,038 people with type 2 diabetes, chronic kidney disease and anaemia randomised to darbepoetin alfa targeting 13 g/dL or to placebo with rescue below 9 g/dL. Death or a cardiovascular event, hazard ratio 1.05 (0.94 to 1.17); death or end-stage renal disease, hazard ratio 1.06 (0.95 to 1.19). Fatal or non-fatal stroke 101 versus 53, hazard ratio 1.92, 95 percent confidence interval 1.38 to 2.68, p < 0.001. Fewer transfusions (297 versus 496) and only a modest improvement in fatigue. Sponsor Amgen.
New England Journal of Medicine, 2009 · 4,038 people
CHOIR: 1,432 people with chronic kidney disease randomised open-label to a haemoglobin target of 13.5 or 11.3 g/dL, median 16 months. The composite of death, myocardial infarction, heart failure hospitalisation and stroke occurred 125 times in the high-target group and 97 times in the low-target group, hazard ratio 1.34, 95 percent confidence interval 1.03 to 1.74, p = 0.03, with no improvement in quality of life. Registry status TERMINATED; sponsor Johnson and Johnson Pharmaceutical Research and Development.
New England Journal of Medicine, 2006 · 1,432 people
- 5,246 people1 human study
TRAVERSE. 5,246 men aged 45 to 80 with preexisting or high risk of cardiovascular disease, symptoms of hypogonadism and two fasting testosterone levels below 300 ng/dL, randomised double-blind to transdermal testosterone gel titrated to 350 to 750 ng/dL or placebo. Mean treatment 21.7 months, mean follow-up 33.0 months. Primary composite of cardiovascular death, non-fatal myocardial infarction or non-fatal stroke occurred in 182 (7.0%) on testosterone and 190 (7.3%) on placebo, hazard ratio 0.96 (95% CI 0.78 to 1.17), p < 0.001 for non-inferiority.
New England Journal of Medicine, 2023 · 5,246 people
- 5,246 people1 human study
TRAVERSE, 5,246 men, no excess of cardiovascular death, heart attack or stroke against placebo. Included because it is the safety context for any testosterone ester, with the qualifier that TRAVERSE used a transdermal gel titrated to a defined range rather than an injectable.
New England Journal of Medicine, 2023 · 5,246 people
- 4,444 people1 human study
4,444 people with angina or previous myocardial infarction, randomised double-blind, median follow-up 5.4 years. 256 placebo patients (12 percent) died against 182 on simvastatin (8 percent), relative risk of death 0.70 (95 percent CI 0.58 to 0.85, p equals 0.0003). Coronary deaths fell from 189 to 111. Major coronary events occurred in 28 percent on placebo and 19 percent on simvastatin.
Lancet, 1994 · 4,444 people
- 4,076 people1 human study
4,076 high-risk patients: MACE hazard ratio 0.73 and composite renal outcome hazard ratio 0.68 versus placebo.
New England Journal of Medicine, 2021 · 4,076 people
- 3,080 people1 human study
3,080 patients randomised at 300 sites before the trial was stopped for futility. The composite of death, non-fatal stroke or severe left ventricular dysfunction through day 28 occurred in 5.1% on acadesine against 5.0% on placebo (odds ratio 1.01). An earlier 1997 meta-analysis of five smaller trials had been positive; this trial is why the drug went no further.
JAMA, 2012 · 3,080 people
- 2,619 people4 human studies1 found nothing
Pooled analysis of two Japanese cohorts, 2,435 patients with acute decompensated heart failure split by carperitide dose. Cardiovascular and all-cause mortality within 1 year were lower in the low-dose group (at or above 0.02 micrograms per kilogram per minute) than in the no-carperitide and very-low-dose groups. This observational result points in the opposite direction to the propensity-matched in-hospital analyses and is reported here alongside them, not instead of them.
ESC Heart Failure, 2022 · 2,435 people
109 hospitalised patients randomised to tolvaptan or carperitide. Symptoms and plasma BNP improved similarly in both groups. Blood pressure was lower after carperitide, and fewer adverse events such as worsening heart failure and hypotension requiring discontinuation occurred with tolvaptan (p = 0.027).
Journal of Clinical Pharmacology, 2013 · 109 people
75 patients with acute heart failure given 0.0125 micrograms per kilogram per minute of carperitide for 6 hours. Lower baseline plasma ANP (r = -0.35, p = 0.002) and lower vasopressin (r = -0.54, p < 0.001) predicted a larger diuretic response; baseline blood pressure, renal function and prior loop diuretic use did not.
ESC Heart Failure, 2022 · 75 people
found nothingPost-hoc analysis of a multicentre prospective cohort, 162 patients with acute heart failure given intravenous carperitide. Serum sodium was unchanged over 48 hours; serum potassium fell from 4.32 to 4.08 mEq/L with carperitide alone (p = 0.004). Hypokalaemia at 24 hours was uncommon unless 20 mg or more of furosemide was added (12.5 versus 2.8 percent, p = 0.039).
Journal of Cardiology, 2021 · no headcount in the line
- 420 people1 human study
420 patients with moderate to severe chronic heart failure, 100 mg three times daily, two years. Major adverse cardiovascular events 15% against 26%, hazard ratio 0.50 (95% CI 0.32 to 0.80, p = 0.003). Cardiovascular mortality 9% against 16% (p = 0.026) and all-cause mortality 10% against 18% (p = 0.018). The short-term 16-week endpoints were null.
JACC Heart Failure, 2014 · 420 people
- 123 people1 human study
123 elderly hip-fracture patients: gait speed improved and IGF-1 rose, but most functional measures did not, and the trial was terminated early over a congestive heart failure safety signal.
Archives of Gerontology and Geriatrics, 2011 · 123 people
- 110 people1 human study
Russian clinical study of 110 post-stroke patients: Semax courses raised plasma BDNF and were associated with faster Barthel index improvement; not a blinded placebo-controlled trial.
Zhurnal Nevrologii i Psikhiatrii imeni S.S. Korsakova, 2018 · 110 people
- 110 people1 human study
110 patients after ischemic stroke, split by early and late rehabilitation and by whether they received semax at 6,000 micrograms per day in two ten-day courses. Semax raised plasma BDNF and improved Barthel index recovery. This is the unmodified parent peptide in a Russian clinical trial, not the acetylated amidated analog sold online.
Zhurnal Nevrologii i Psikhiatrii imeni S.S. Korsakova, 2018 · 110 people
Also measured, in animals or cells
Proteomic evidence of a protective effect for the parent heptapeptide after experimental stroke in rats. Again the parent compound: no published pharmacokinetic or efficacy study of the N-acetyl amidate form has been located.
- 110 people1 human study
Russian clinical study of 110 post-stroke patients. Semax courses raised plasma BDNF and were associated with faster Barthel index improvement. This was not a blinded placebo-controlled trial, and no Selank was given.
Zhurnal Nevrologii i Psikhiatrii imeni S.S. Korsakova, 2018 · 110 people
- 39 people1 human study
Adverse event analysis of that same 2,000-woman trial. Myocardial infarction in 39 women on placebo against 24 on zoledronate (hazard ratio 0.60, 95 percent CI 0.36 to 1.00). Total cancers reduced, hazard ratio 0.67 (0.51 to 0.89). Hazard ratio for death 0.65 (0.40 to 1.06, p equals 0.08), and 0.51 (0.30 to 0.87) in women without an incident fragility fracture. The authors state these apparent effects justify further appropriately powered trials with these nonskeletal conditions as primary endpoints.
Journal of Bone and Mineral Research, 2020 · 39 people
- 36 people1 human study
The cost side, in a different indication. 36 patients with acquired aplastic anaemia on danazol monotherapy at 10 mg per kg per day capped at 600 mg. After 6 months HDL cholesterol fell 30 percent and LDL rose 11 percent, with significant changes in left ventricular mass, ejection fraction and diastolic indices. The authors conclude that danazol causes profound dyslipidaemia and potential cardiac dysfunction.
Blood Cells, Molecules and Diseases, 2025 · 36 people
- 24 people1 human study
24 evaluable patients with advanced AML, 8 to 32 mg/m2 twice weekly. Maximum tolerated dose 24 mg/m2; cardiac dose-limiting toxicities at 32 mg/m2 (troponin elevation, myocardial infarction). Complete remission with incomplete count recovery in 3 of 17 evaluable. Company sponsored (Kosan).
Leukemia, 2010 · 24 people
- 18 people2 human studies
18 patients with NYHA II to III heart failure, 6 at coronary angiography and 26 healthy volunteers in randomised double-blind placebo-controlled studies. Forearm vasodilatation to apelin was preserved in heart failure (p 0.3) while the acetylcholine response was attenuated (p 0.01); intracoronary apelin-36 increased coronary flow and left ventricular dP/dt max and lowered filling pressures; systemic (Pyr1)apelin-13 at 30 to 300 nmol/min raised cardiac index and lowered mean arterial pressure and vascular resistance in both groups, raising heart rate only in controls. Non-US government funded.
Circulation, 2010 · 18 people
Novartis, phase 2, 26 enrolled, APJ receptor agonist CLR325 versus placebo in chronic stable heart failure, primary outcome adverse events, serious adverse events and death. Completed January 2019, results posted March 2020. The only industry trial of an APJ agonist in patients that has reported.
ClinicalTrials.gov, 2016 · no headcount in the line
- 18 people1 human study
18 patients with probable mild to moderate Alzheimer disease at Stanford, mean age 74.2 years, 12 women. Nine randomised in a double-blind crossover to four weekly infusions of one unit of young fresh frozen plasma from male donors aged 18 to 30 or 250 mL saline; nine received open-label plasma after an amendment. Primary outcomes were safety, tolerability and feasibility. No related serious adverse events. One withdrawal for urticaria, one for an unrelated stroke. Visit adherence 86 percent. NIH funded.
JAMA Neurology, 2019 · 18 people
- 18 people1 human study
18 adults with advanced solid tumours received escalating subcutaneous doses daily for 5 days on a 3 week cycle. Dose-limiting toxicities at 700 micrograms per kilogram were a grade 4 stroke and a grade 3 reversible cranial neuropathy. One patient had a 19 percent tumour reduction and 3 more had disease stabilisation beyond 3 months. Recommended phase 2 dose 400 micrograms per kilogram.
Clinical Cancer Research, 2009 · 18 people
- 8 people1 human study
Forearm plethysmography studies: in 8 healthy volunteers the antagonist B9340 blocked vasodilation to infused bradykinin without changing resting blood flow. In 17 patients with NYHA class II to IV heart failure on chronic ACE inhibitors, B9340 caused dose-dependent vasoconstriction (p = 0.01), which disappeared after the ACE inhibitor was withdrawn and returned when it was restarted.
Circulation, 2001 · 8 people
- 7 people1 human study1 found nothing
found nothing7 heart failure patients on a left ventricular assist device given oral clenbuterol up-titrated to 720 micrograms a day for 3 months. No serious adverse events or arrhythmias, creatine phosphokinase rose in 4 patients. Ejection fraction did not improve and end-diastolic dimension increased; body weight and lean mass rose and quadriceps maximal voluntary contraction improved from 37.0 to 45.8 kg. Cardiac function did not improve.
The Journal of Heart and Lung Transplantation, 2006 · 7 people
- no headcount stated1 human study
Acute IV hexarelin raised ejection fraction in ischemic cardiomyopathy patients but not in dilated cardiomyopathy, despite similar GH release; small study.
European Journal of Heart Failure, 2002 · no headcount in the line
- no headcount stated1 human study
12,064 myocardial infarction survivors randomised double blind to 2 mg folic acid plus 1 mg vitamin B12 daily or placebo, followed 6.7 years. Homocysteine fell by a mean 3.8 micromol/L, 28 percent. Major vascular events occurred in 1,537 of 6,033 on treatment (25.5 percent) against 1,493 of 6,031 on placebo (24.8 percent), risk ratio 1.04 (95 percent CI 0.97 to 1.12, p = 0.28). The marker moved and the outcome did not. This trial used B vitamins rather than betaine, which is the point: it tests the premise, not the product.
JAMA, 2010 · no headcount in the line
- no headcount stated1 human study
Randomised, open-label, in men with prostate cancer and known atherosclerotic cardiovascular disease. Enrolment stopped early at 545 of a planned 900 patients across 113 sites in 12 countries. Major adverse cardiovascular events at 12 months: 15 (5.5 percent) on degarelix versus 11 (4.1 percent) on leuprolide, hazard ratio 1.28 (95 percent CI 0.59 to 2.79), P equal to 0.53. The authors conclude that the relative cardiovascular safety of GnRH antagonists and agonists remains unresolved.
Circulation, 2021 · no headcount in the line
- no headcount stated1 human study
Tennessee Medicaid cohort. During five days of azithromycin, compared with no antibiotics, risk of cardiovascular death rose (hazard ratio 2.88, 95 percent CI 1.79 to 4.63) and of death from any cause (1.85, 1.25 to 2.75). Amoxicillin showed no such increase. Estimated 47 additional cardiovascular deaths per million courses, and 245 per million in the highest cardiovascular risk decile. An observational cohort, not a randomised trial, and the absolute risk is small.
New England Journal of Medicine, 2012 · no headcount in the line
- no headcount stated1 human study
The null half. A high-dose omega-3 against a corn oil placebo in a comparable high-risk statin-treated population produced no reduction in major adverse cardiovascular events. The trial was stopped for futility.
JAMA, 2020 · no headcount in the line
- no headcount stated1 human study
Population-based cohort of older adults. In those free of cardiovascular disease, the association with all-cause mortality was U-shaped: hazard ratio 0.81 per SD up to 12.4 mg/L, then 1.19 per SD (95 percent CI 1.12 to 1.27) above it. No association in those with cardiovascular disease alone; in heart failure or atrial fibrillation, higher adiponectin meant higher mortality, hazard ratio 1.31 (1.15 to 1.50) after adjustment. Results were similar for high molecular weight adiponectin and cardiovascular death. NIH funded.
Circulation, 2012 · no headcount in the line
Measured in animals or cells, not yet in people
These are separated from the trials above rather than ranked against them, because they answer a different question. A result in a rat is a real result and a reason somebody ran the study; it is not a measurement of what happens in you. Where the human work is missing, the reason is usually money rather than failure, and that is set out at the bottom of this page.
- 1 preclinical study
Measured in animals or cells
Animal. FGF17 acted on neuronal survival and oligodendrogenesis together to restore deficits in a stroke model, extending the oligodendrocyte finding beyond normal ageing into injury.
Neurotherapeutics, 2026 · animal
- 1 preclinical study
Measured in animals or cells
Mouse atherosclerosis models, with 25-hydroxycholesterol and CH25H expression also measured in human lesions. Macrophage-derived 25-hydroxycholesterol promoted vascular inflammation and lesion remodelling, a harm direction in the same organ system as the aortic stiffness study.
Circulation, 2023 · animal
- 1 preclinical study
Measured in animals or cells
Mice lacking the ketogenesis enzyme HMGCS2 died early, which a 1,3-butanediol diet prevented. In normal mice the same diet started early in life increased midlife mortality, while started in aged mice it extended lifespan and prevented atherosclerosis deaths in ApoE-deficient mice. An ad libitum ketogenic diet markedly increased mortality. Independent Japanese group.
Aging Cell, 2023 · animal
Why the trial record looks like this
A missing trial is usually a missing sponsor. Nobody runs a nine-figure programme on a molecule they cannot own, so the compounds with the thinnest human records are often the oldest and most freely available ones rather than the weakest. Taking FGF17 as the example, because it states the problem most clearly:
FGF17 is the cleanest example in this batch of a factor whose human literature exists, is good, and is about something else. Anyone searching for FGF17 in humans will find the hypogonadotropic hypogonadism genetics, which is a well-conducted study in 386 affected individuals, and it would be easy to read that as human validation of an ageing target. It is not. It is evidence that FGF17 matters during development of the GnRH and olfactory systems.
The delivery problem is the other honest obstacle. The 2022 experiment infused young cerebrospinal fluid, and then FGF17, directly into the brain. A systemic protein that has to reach the hippocampus is a different pharmaceutical problem from an intracerebroventricular infusion in a mouse, and no work has addressed it. That is a reason the field has produced no registered trial rather than a reason the biology is wrong.
The 2026 stroke paper is worth noting because it is the first extension of this finding into an injury model with a clearer clinical endpoint than normal cognitive ageing. It remains animal work.
A compound appears here only when a citation on its own page states this outcome and reports a result for it; naming it is not enough. Human, animal and cell work are counted separately and never merged. Participant counts are read from the study lines and deliberately undercount. Nothing here is advice, and nothing here is a recommendation to take or to avoid anything.