Cardiovascular safety of gabapentinoids gabapentin & pregabalin: A systematic review

Background & objectives A few propensity-score-matched cohort studies have suggested increased cardiovascular events with gabapentinoids (gabapentin/pregabalin). This systematic review analysed the cardiovascular safety of gabapentin and pregabalin in clinical practice. Methods Databases were searched for articles examining the occurrence of cardiovascular events with gabapentin and pregabalin in different clinical conditions. The primary outcome was to look at the occurrence of myocardial infarction (MI) and stroke. Secondary outcomes were to look at the occurrence of deep venous thrombosis (DVT), peripheral artery disease (PAD), pulmonary thrombo-embolism (PTE), heart failure (HF) and atrial fibrillation (AF). Results Data from five cohort studies (10,85,488 patients) were analysed. Gabapentin use was associated with increased risk of MI after one year of [Hazard ratio (HR) 1.31(1.14,1.52); I2=0%; P=0.0002] use. Gabapentinoids were associated with increased risk of stroke after five years of use [HR 1.44 (1.04, 2.01); I2=86%; P=0.03]. Heart failure was not increased with the use of gabapentinoids. Their chronic use was associated with increased risk of PVD after one year [HR 1.41(1.18, 1.67); P=0.0001] and five years [HR 1.58 (1.16, 2.15); I2=83%; P=0.003] use. Gabapentinoid use was associated with increased risk of DVT after three months [HR 1.37(1.21, 1.55); P<0.00001], one-year [HR 1.42 (1.15, 1.74); P=0.0009], and five years [HR 1.78 (1.31,2.40); I2=71%; P=0.0002] use. Their use was associated with increased risk of pulmonary embolism after three months [HR 1.27 (1.09, 1.46); P=0.002], one-year [HR 1.23 (1.01, 1.40); P=0.04], and five years of [HR 1.86 (1.64, 2.09); I2=0%; P<0.0001] use. Interpretation & conclusions The use of gabapentinoids was associated with increased risks of thrombotic events as early as three months of use, and with increased risk of cardiovascular events on prolonged use of more than a year duration.