Cardiovascular Outcomes Trial (CVOT) and MACE Explained
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Cardiovascular outcomes trial

Also called CVOT, heart outcomes trial, MACE, major adverse cardiovascular events · Reviewed

Definition: A cardiovascular outcomes trial (CVOT) is a large, long randomized trial that counts real heart events instead of lab numbers. The usual main result is MACE (major adverse cardiovascular events): the first of heart death, nonfatal heart attack or nonfatal stroke. Label lines such as "lower the risk of major heart events" come from these trials.

Three trials behind label claims

Main result of each trial, from its PubMed abstract
TrialPeopleMain result vs placebo
LEADER (liraglutide, Victoza)9,340 with type 2 diabetes; median 3.8 years13.0% vs 14.9%; hazard ratio 0.87
SELECT (semaglutide 2.4 mg, Wegovy)17,604 with heart disease and BMI 27 or more, no diabetes6.5% vs 8.0%; hazard ratio 0.80
FOURIER (evolocumab, Repatha)27,564 with heart disease on a statin; median 2.2 years9.8% vs 11.3%; hazard ratio 0.85 (a 5-part outcome)

How to read one

Worked example: SELECT

  1. Events: 6.5% on semaglutide vs 8.0% on placebo over about 40 months.
  2. Absolute difference: 8.0 - 6.5 = 1.5 percentage points.
  3. The hazard ratio of 0.80 is the relative figure, about a 20% lower rate.

Some trials first set out to show a medicine is not worse. LEADER was designed as a noninferiority trial with a margin of 1.30, and then also showed fewer events.

Why it matters for your log

Trial benefits come from people taking the medicine for years. A dose log shows how steady your own use has been, which helps when talking with a prescriber about results like these.

Read more on Dose Track: Do GLP-1 medicines lower heart attack risk? · Wegovy side effects · Victoza side effects · Praluent vs Repatha

General education drawn from labels and published studies, not personal medical advice. Your prescriber, pharmacist and the label that came with your product are the final word.
Hazard ratioA hazard ratio (HR) compares how often an event happens over time in one group with how often it happens… Relative vs absolute riskRelative risk compares the risk of an event in one group with the risk in another; the NCI says a relative… Noninferiority trialA noninferiority trial tests whether a new treatment is not worse than an active treatment it is compared… Randomized controlled trialA randomized controlled trial (RCT) is a study that splits people into groups by chance and gives each… Heart attackA heart attack , also called a myocardial infarction (MI), happens when blood flow to part of the heart… PlaceboA placebo is an inactive substance or other treatment that looks the same as, and is given the same way…

Frequently asked questions

What does MACE mean?+
Major adverse cardiovascular events. In most trials it means the first of heart death, nonfatal heart attack or nonfatal stroke. Some trials add more events, as FOURIER did.
What did the SELECT trial find?+
Its abstract reports major heart events in 6.5% on semaglutide 2.4 mg vs 8.0% on placebo, a hazard ratio of 0.80, in people with heart disease and overweight or obesity but no diabetes.

Sources

  1. Marso et al. Liraglutide and cardiovascular outcomes in type 2 diabetes (LEADER). N Engl J Med 2016
  2. Lincoff et al. Semaglutide and cardiovascular outcomes in obesity without diabetes (SELECT). N Engl J Med 2023
  3. Sabatine et al. Evolocumab and clinical outcomes in patients with cardiovascular disease (FOURIER). N Engl J Med 2017
  4. Victoza (liraglutide) US prescribing information, DailyMed
  5. Wegovy (semaglutide) US prescribing information, DailyMed
  6. Repatha (evolocumab) US prescribing information, DailyMed

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