Clinical trial NCT06583161: Emulation of the Moderate Alcohol and Cardiovascular Health Trial (MACH15)
Official title: Emulation of the Moderate Alcohol and Cardiovascular Health Trial (MACH15)
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Myocardial Infarction
Ischemic Stroke
Angina Pectoris
Coronary Revascularization
All-cause Mortality
Cardiovascular Death
Type 2 Diabetes
Heart Failure
Atrial Fibrillation
Cancer
Dementia
Depression
Infections
Injuries
Liver Cirrhosis
Lead sponsor: Harvard School of Public Health (HSPH)
Sponsor class: OTHER
First posted: 2024-09-03
Enrollment: 503325
Sex: ALL
Minimum age (years): 40
Maximum age (years): 69
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: All people aged 40-69 years who were registered with the National Health Service and lived within 25 miles of one of the 22 study assessment centers in England, Wales, and Scotland were invited to participate. Overall, about 9.2 million invitations were mailed in order to recruit 503,325 participants (i.e. a response rate of 5.47%)

Brief summary: The aim of this study is to assess how long-term alcohol consumption influences health risks by emulating the Moderate Alcohol and Cardiovascular Health Trial (MACH15). In the first step, the protocol of the emulation of MACH15, including eligibility criteria, alcohol regimens and assignment, follow-up, endpoints, causal contrasts of interest, and statistical analysis was specified. In the second step, the investigators will emulate an adapted version of MACH15 following the specified protocol using data from the UK Biobank.

Detailed description: Observational data suggests that alcohol consumption lowers the risk of cardiovascular disease (CVD) compared to no consumption. Whether this relationship is truly causal remains uncertain because of the inherent limitations of observational studies, including unmeasured confounding and reverse causation. Mendelian randomization studies using genes as instrumental variables for alcohol are partially protected from these biases and have found no or harmful associations between alcohol consumption and CVD.

To date, there has only been one long-term randomized controlled trial to investigate the cardiovascular effects of alcohol consumption: the Moderate Alcohol and Cardiovascular Health Trial (MACH15; NCT Number: NCT03169530). It was, however, terminated shortly after initiation. An alternative to a real randomized trial like MACH15, which must first be completed and is subject to strict eligibility criteria to ensure safety, is to use observational data to emulate a (hypothetical) pragmatic randomized trial.

In this study, the investigators will emulate an adapted version of MACH15 using observational data from the UK Biobank, a large prospective cohort study of over 500,000 participants. The cardiometabolic effects of moderate drinking vs quitting, as originally planned in MACH15, as well as the effects of social and heavy/binge drinking on CVD, type 2 diabetes, other alcohol-related health outcomes, and death will be quantified.

Eligibility criteria: Inclusion criteria:

* 40-69 years old at enrollment
* Currently drinking

Exclusion criteria:

* Within the six months prior to baseline, cardiovascular disease event (myocardial infarction, revascularization procedure, or stroke)
* Hospitalization due to heart failure
* History of any of the following alcohol-related conditions, confirmed by a hospital record: alcoholic cardiomyopathy, alcoholic gastritis, alcoholic liver disease, degeneration of the nervous system due to alcohol, alcoholic myopathy, alcoholic polyneuropathy, alcohol-induced acute or chronic pancreatitis, alcohol use disorder; or self-reported history of alcoholic liver disease or alcohol use disorder
* Dual antiplatelet therapy or coumarin anticoagulants
* Serious chronic liver disease (active hepatitis B or C infection) in the past 6 months before baseline
* Personal history of any colon or liver cancer
* Personal history of breast cancer
* Diagnosis of dementia
* Not willing or able to provide a signed and dated informed consent form
* Reduced alcohol compared to 10 years ago due to illness, ill health, or doctor's advice
* Self-reported poor health

Primary outcomes:
measure: Cardiovascular disease or death
timeFrame: From date of baseline measurement until the date of first cardiovascular disease or death documented in hospital or death registry data, administrative censoring, or loss to follow-up, whichever came first, assessed up to 200 months
Secondary outcomes:
measure: Cardiovascular disease
timeFrame: From date of baseline measurement until the date of first cardiovascular disease documented in hospital or death registry data, administrative censoring, loss to follow-up, or death from other causes, whichever came first, assessed up to 200 months
measure: Type 2 diabetes
timeFrame: From date of baseline measurement until the date of first type 2 diabetes documented in hospital or death registry data, administrative censoring, loss to follow-up, or death from other causes, whichever came first, assessed up to 200 months
measure: Alcohol-related disease or death
timeFrame: From date of baseline measurement until the date of first alcohol-related disease or death documented in hospital, cancer, or death registry data, administrative censoring, or loss to follow-up, whichever came first, assessed up to 200 months
Other outcomes:
measure: Hard cardiovascular disease or death
timeFrame: From date of baseline measurement until the date of first hard cardiovascular disease or death documented in hospital or death registry data, admin. censoring, loss to follow-up, or death from other causes, whichever came first, assessed up to 200 months
measure: Cardiovascular death
timeFrame: From date of baseline measurement until the date of cardiovascular death documented in death registry data, administrative censoring, loss to follow-up, or death from other causes, whichever came first, assessed up to 200 months
measure: Non-fatal myocardial infarction
timeFrame: From date of baseline measurement until the date of first non-fatal myocardial infarction documented in hospital data, administrative censoring, loss to follow-up, or death, whichever came first, assessed up to 200 months
measure: Non-fatal ischemic stroke
timeFrame: From date of baseline measurement until the date of first non-fatal ischemic stroke documented in hospital data, administrative censoring, loss to follow-up, or death, whichever came first, assessed up to 200 months
measure: Hospitalization for angina
timeFrame: From date of baseline measurement until the date of first hospitalization for angina documented in hospital data, administrative censoring, loss to follow-up, or death, whichever came first, assessed up to 200 months
measure: Coronary/carotid revascularization
timeFrame: From date of baseline measurement until the date of first coronary/carotid revascularization documented in hospital data, administrative censoring, loss to follow-up, or death, whichever came first, assessed up to 200 months
measure: All-cause mortality
timeFrame: From date of baseline measurement until the date of death documented in death registry data, administrative censoring, or loss to follow-up, whichever came first, assessed up to 200 months
Locations:
Study officials:
References:
citation: Spiegelman D, Lovato LC, Khudyakov P, Wilkens TL, Adebamowo CA, Adebamowo SN, Appel LJ, Beulens JW, Coughlin JW, Dragsted LO, Edenberg HJ, Eriksen JN, Estruch R, Grobbee DE, Gulayin PE, Irazola V, Krystal JH, Lazo M, Murray MM, Rimm EB, Schrieks IC, Williamson JD, Mukamal KJ. The Moderate Alcohol and Cardiovascular Health Trial (MACH15): Design and methods for a randomized trial of moderate alcohol consumption and cardiometabolic risk. Eur J Prev Cardiol. 2020 Dec;27(18):1967-1982. doi: 10.1177/2047487320912376. Epub 2020 Apr 6.