Long-term cardiovascular outcomes after orlistat therapy in patients with obesity: a nationwide, propensity-score matched cohort study

• Published in: European heart journal. Cardiovascular pharmacotherapy Vol. 8; no. 2; pp. 179 - 186
• Main Authors: Ardissino, Maddalena, Vincent, Matthew, Hines, Oliver, Amin, Ravi, Eichhorn, Christian, Tang, Alice R, Collins, Peter, Moussa, Osama, Purkayastha, Sanjay
• Format: Journal Article
• Language: English
• Published: England Oxford University Press 01.03.2022
• Subjects: Analysis; Brain Ischemia - chemically induced; Brain Ischemia - epidemiology; Brain Ischemia - etiology; Cardiovascular Diseases - chemically induced; Cardiovascular Diseases - epidemiology; Cardiovascular Diseases - etiology; Care and treatment; Chronic kidney failure; Cohort analysis; Cohort Studies; Comorbidity; Coronary artery bypass; Heart attack; Heart attacks; Heart failure; Humans; Hypoglycemic agents; Ischemia; Medical research; Medicine, Experimental; Mortality; Obesity; Obesity - complications; Obesity - diagnosis; Obesity - drug therapy; Obesity - epidemiology; Orlistat; Orlistat - adverse effects; Patient outcomes; Risk factors; Stroke - chemically induced; Stroke - epidemiology; Stroke - etiology; United Kingdom; Weight control; Weight loss; United Kingdom; Orlistat; Obesity; Cardiovascular; outcomes; Weight loss
• ISSN: 2055-6837; 2055-6845
• DOI: 10.1093/ehjcvp/pvaa133

Abstract Aims The rising prevalence of obesity and its associated comorbidities represent a growing public health issue; in particular, obesity is known to be a major risk factor for cardiovascular disease. Despite the evidence behind the efficacy of orlistat in achieving weight loss in patients with obesity, no study thus far has quantified its long-term effect on cardiovascular outcomes. The purpose of this study is to explore long-term cardiovascular outcomes after orlistat therapy. Methods and results A propensity-score matched cohort study was conducted on the nation-wide electronic primary and integrated secondary healthcare records of the Clinical Practice Research Datalink (CPRD). The 36 876 patients with obesity in the CPRD database who had completed a course of orlistat during follow-up were matched on a 1:1 basis with equal numbers of controls who had not taken orlistat. Patients were followed up for a median of 6 years for the occurrence of the primary composite endpoint of major adverse cardiovascular events (fatal or non-fatal myocardial infarction or ischaemic stroke), and a number of secondary endpoints including primary endpoint components individually, the occurrence of new-onset heart failure, coronary revascularization, new chronic kidney disease stage III+ (CKD3+), and all-cause mortality. During the median study follow-up of 6 years, the occurrence of major adverse cardiovascular events was lower in the orlistat cohort [hazard ratio (HR) 0.74; 95% confidence interval (CI) 0.66–0.83, P < 0.001]. Patients who took orlistat experienced lower rates of myocardial infarction (HR 0.77; 95% CI 0.66–0.88, P < 0.001) and ischaemic stroke (HR 0.68; 95% CI 0.56 to −0.84, P < 0.001) as well as new-onset heart failure (HR 0.79; 95% CI 0.67–0.94, P = 0.007). There was no differences in revascularization rates (HR 1.12; 95% CI 0.91–1.38, P = 0.27), but a lower rate of both CKD3+ development (HR 0.78; 95% CI 0.73–0.83, P < 0.001) and mortality (HR 0.39, 95% CI 0.36 to −0.41, P < 0.001) was observed. Conclusion In this nation-wide, propensity-score matched study, orlistat was associated with lower rates of overall major adverse cardiovascular events, new-onset heart failure, renal failure, and mortality. This study adds to current evidence on the known improvements in cardiovascular risk factor profiles of orlistat treatment by suggesting a potential role in primary prevention.