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Highlights from

European Society of Cardiology

Congress 2018

Munich 25-29 August 2018

CAMELLIA-TIMI 61: Lorcaserin helps weight loss without CV adversity in overweight patients at high CV risk

Take-home messages

Lorcaserin in overweight/ obese patients at high CV risk:

  • resulted in sustained weight loss
  • provided modest improvements in CV risk factors
  • did not increase the risk of major adverse CV events (MACE)
“…lorcaserin resulted in sustained weight loss with modest improvements in CV risk factors, and did not increase the risk of MACE (cardiovascular death, myocardial infarction, or stroke).”

Erin Bohula
Brigham and Women's Hospital, Boston, US

Lorcaserin, an appetite suppressant and weight loss drug, does not increase cardiovascular (CV) events in a high CV risk population, according to late-breaking results from the CAMELLIA-TIMI 61 (NCT02019264) presented at this year’s ESC Congress.

“On a background of lifestyle interventions in overweight and obese patients at high CV risk, lorcaserin resulted in sustained weight loss with modest improvements in CV risk factors, and did not increase the risk of MACE (CV death, myocardial infarction or stroke). There were favourable effects on glycaemic control as well,” reported Dr Erin Bohula, co-investigator and CV medicine and critical care specialist from Brigham and Women's Hospital, Boston, US. “We have been able to show, for the first time, that this weight loss drug does what it is intended to do.”

The European Medicines Agency (EMA) has raised concerns about adverse outcomes with lorcaserin and, as such, has not provided approval for its use in Europe. Meanwhile the US Food and Drug Administration (FDA) has approved use of lorcaserin for weight loss in obese individuals (BMI >30 kg/m2) or in overweight adults (BMI >27 kg/m2) if they have at least one weight-related health condition, but they have requested more data to align with data required for all weight loss agents marketed in the US; the CAMELLIA-TIMI 61 trial was designed to provide these data.

“Weight loss can improve CV risk factors, but is difficult to achieve and maintain,” said Dr Bohula, explaining the unmet need. “Weight loss agents are guideline-recommended adjuncts to lifestyle modification; however, no agent has convincingly demonstrated CV safety in a rigorous clinical outcomes study. In fact, several agents have been shown to precipitate CV or psychiatric side effects.” Adverse findings also include tumours from animal studies and problems with heart valves.

The 12,000 participants in the CAMELLIA-TIMI 61 study were obese or overweight (BMI≥ 27 kg/m2) and had either established cardiovascular disease (CVD) (with or without diabetes), or diabetes and at least one other CV risk factor. In fact, 57% of participants had diabetes, 90% hypertension, 94% hyperlipidaemia, and 19% chronic kidney disease. In addition to being advised about exercise and following a healthy diet, participants were randomised 1:1 to lorcaserin (10 mg twice a day) or placebo and were followed up for a median of 3.3 years.

An interim primary safety analysis (after 460 events) for a FDA-specified non-inferiority endpoint versus placebo assessed CV death, myocardial infarction or stroke; after reaching this safety endpoint, a superiority analysis, comprising the primary CV efficacy endpoint of MACE plus hospitalisation for heart failure, unstable angina or coronary revascularisation, was performed at study completion. Secondary endpoints were delay or prevention of conversion from pre-diabetes to type 2 diabetes, as well as effect on weight, heart rate, blood pressure, lipids and blood sugar.

At 1 year, lifestyle interventions with lorcaserin plus lifestyle interventions lead to a 4.2 kg weight loss versus 1.4 kg in patients on placebo (p<0.001). Also at 1 year, 39% of participants on lorcaserin had lost at least 5% body weight versus 17% of participants on placebo (p<0.001), while there was a 10% body weight reduction in 15% on lorcaserin versus 5% on placebo (p<0.001).

Regarding safety, “Lorecaserin did not increase the risk of MACE and is deemed safe from the CV perspective,” reported Dr Bohula. The annualised rate of the primary safety endpoint was 2.0% and 2.1% with drug versus placebo (hazard ratio: 0.99) and a highly significant p-value for non-inferiority (p<0.001).

No difference was seen in efficacy at study completion, with the hazard ratio for extended CV endpoint of MACE-plus of 0.97.

Serious adverse events showed no difference between groups with a 3% increase in drug-related adverse events that lead to discontinuation and included fatigue, nausea, dizziness and headache. No difference in malignancy was seen between the two groups and in a dedicated echocardiographic sub-study, there was a non-significant difference in the incidence of valvulopathy at 1 year between the lorcaserin and placebo groups (1.8% versus 1.3%, respectively; p=0.24). Severe hypoglycaemia was greater with lorcaserin than with placebo (0.2% versus 0.1%, respectively).

Based on Bohula E, et al. CAMELLIA-TIMI 61 - cardiovascular and metabolic effects of lorcaserin in overweight and obese patients-thrombolysis in myocardial infarction 61 trial (2069). Presented Sunday, 26 August 2018.

These results from the CAMELLIA-TIMI 61 trial were published online in New England Journal of Medicine August 26, 2018. View the paper >

Top image: © Mutlu Kurtbas

Article image: © Ahmet Yarali

The content and interpretation of these conference highlights are the views and comments of the speakers/authors.

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