Clinical Trials

Front 1

LIFE

Back 1

2002 multicentre RCT that compared atenolol and losartan for hypertension. Diuretics could be added as needed, ad they ensured that people would reach their BP targets. They found that losartan reduced cardiovascular morbidity and mortality and had less side effects than atenolol, and less cases of new onset diabetes. However, only 10% finished on monotherapy, many patients crossed over drugs, many drugs were used as active controls and it was manufacturer-sponsored.

Front 2

ALL-HAT

Back 2

2002 multicentre RCT that compared thiazide diuretic, CCB, ACE inhibitor and alpha blocker for hypertension. They looked at reduction in heart attacks. But they had to stop using the alpha blocker because of side effects and alpha blockers aren't used for hypertension anyway. They found that thiazide like diuretics are better than ACE inhibitors and CCBs. However, they didn't achieve their primary outcome - no difference in heart attacks in different classes so they just looked at side effects, and thiazide like diuretics were only better in a small group of people.

Front 3

ASCOT-BPLA

Back 3

2004 multicentre RCT that compared lipid lowering and BP lowering drugs (atenolol + thiazide vs. amlodipine + perindopril) for hypertension. They found that A+P reduced major cardiovascular events and induced less cases of new onset diabetes. But the study was underpowered due to early termination (not enough patients to see a statistically significant effect even at the beginning of the study), 26% crossed over to other drugs and it was manufacturer sponsored.

Front 4

RECOVER

Back 4

2009 multicentre, double blind, non-inferiority trial for haemostasis/thrombosis, that compared dabigtran to warfarin for acute venous thromboembolism. They found that dabigatran was as effective as warfarin and had a similar safety profile, and doesn't require lab monitoring. Warfarin has many DDIs and its pro/anticoagulant balance is affected by diet and is inconsistent hence needs freq. lab monitoring. However, it was a manufacturer sponsored trial and lots of safety data was hidden e.g. on internal bleeding effects.

Front 5

CAPRIE

Back 5

1996 multicentre, double blind, non-inferiority trial for haemostasis/thrombosis. It compared clopidogrel and aspirin for stroke, myocardial infarction or vascular death. They found clopidogrel was more effective than aspirin and has less side effects. However, although it was only statistically powered to detect an effect on the whole cohort, they compared at 3 sub-outcomes. They found that there was no difference between aspirin and clopidogrel for stroke, clopidogrel was slightly worse for myocardial infarction and much better for preventing vascular death - then they averaged it out and said it was better.

Front 6

IST-3

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2012 multicentre RCT (open trial) for hypertension that compared alteplase vs control for ischemia within 6 hrs onset. They found more deaths within 7 days but fewer deaths between 7 days and 6 months, and they just averaged out and said alteplase was better. This is because there are 2 types of stroke: ischaemic & haemorrhagic, and alteplase shifts the balance to haemorrhagic. However, the study was underpowered, there was no real difference, the effect was only significant in people >80 yrs old, didn't mention what the control was, had an antiplatelet confounder and was manufacturer sponsored.

Front 7

Seven countries study

Back 7

Atherosclerosis study that found that in developed countries, as total serum cholesterol increased, death from CHD also increased.

Front 8

Interheart study

Back 8

Atherosclerosis study that looked at the association between many risk factors (diabetes, hypertension, risks combined, etc.) and acute myocardial infarction. They said if you have more/all the risk factors, 330x more chance of MI, although that's a bit extreme.

Front 9

4S study

Back 9

Atherosclerosis trial that looked at simvastatin in 4444 patients with CHD/raised LDL-cholesterol. They showed that simvastatin lowered mortality and morbidity in people at high risk for CHD.

Front 10

ASCOT-LLA

Back 10

Atherosclerosis trial that looked at patients with CHD, low or average LDL cholesterol. They found that atorvastatin lowered total serum cholesterol slightly.

Front 11

CARE, LIPID

Back 11

Atherosclerosis trial that looked at pravastatin in patients with CHD and average LDL-cholesterol. They found that pravastatin lowered LDL-cholesterol.

Front 12

VA-HIT

Back 12

Atherosclerosis trial that looked at gemfibrozil, and found there was a significant reduction in combined incidence of fatal and non-fatal coronary events, but there was no significant reduction in coronary deaths. There was also a slight increase in LDL-cholesterol and large increase in HDL-cholesterol. The evidence for clinical benefit of fibrates is limited.

Front 13

HPS-2 THRIVE

Back 13

Atherosclerosis trial that looked at niacin/laropiprant, and found there was no significant benefit on the primary outcome of major vascular events when added to effective statin based LDL lowering therapy. There were significant side effects due to known/unknown effects, and no clear evidence of differences in efficacy or safety of different types of patients.

Front 14

IMPROVE-IT

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Atherosclerosis trial that looked at the effect of ezetimibe in post ACS patients. When added to statins, it showed a slight but significant benefit.

Front 15

CUTLASS

Back 15

2006 multicentre RCT for schizophrenia that compared first generation antipsychotics vs second generation antipsychotics (18 different drugs). They found that they were both as effective as each other, and symptoms were assessed using quality of life scales. However, quality of life scales are very subjective, there was limited statistical power and sample size, large heterogeneity within drug classes (not all drugs in the class have the same mechanism of action) and depot preparations were only in the first generation antipsychotics.

Front 16

CATIE

Back 16

2005 multicentre RCT that compared perphenazine (first generation antipsychotic) vs 4 second generation antipsychotics, then looked at how long people continued using the drugs as a measure of how good they are. They found 70% patients stopped using drugs and there was no difference in treatment scores. In secondary analysis, they saw that time to discontinuation was longer in olanzapine and perphenazine, but olanzapine caused large weight gain. However, not sure why they looked at perphenazine - it isn't really used, is less effective and has a better side effect profile so the study would be biased. Also there was a broad inclusion criteria, including people with coexisting conditions.

Front 17

FINGER

Back 17

Alzheimer's trial that looked at lifestyle intervention including dietary supplements and exercise on cognitive impairment. They found that these were as effective as other drugs.