The efficacy and safety of dapagliflozin in women and men with type 2 diabetes mellitus.

AIMS/HYPOTHESIS: Women remain underrepresented in clinical trials and those with type 2 diabetes mellitus are at high risk for cardiovascular (CV) events. The sodium-glucose cotransporter 2 (SGLT2) inhibitor dapagliflozin reduces the risk of CV death or heart failure hospitalisations in individuals with type 2 diabetes. Here, we performed a pre-specified analysis to examine whether sex modifies these effects. METHODS: The DECLARE-TIMI 58 trial randomised 17,160 patients with type 2 diabetes with or at risk for atherosclerotic disease to dapagliflozin or placebo (median follow-up 4.2 years). The dual efficacy outcomes were CV death or heart failure hospitalisations, and major adverse cardiovascular events (MACE; CV death, myocardial infarction or ischaemic stroke). The renal-specific composite outcome was a sustained ≥40% drop in eGFR to <60 ml min-1 [1.73 m]-2, new end-stage renal disease or renal death. Cox models were run separately by sex with treatment-by-sex interaction testing for each outcome. RESULTS: At baseline, women (n = 6422, 37.4%) had higher HbA1c, longer type 2 diabetes duration, and were on fewer glucose-lowering medications. There was no evidence of modification of the effect of dapagliflozin by sex for (1) CV death or heart failure hospitalisations: women (3.8% vs 4.5%; HR 0.84, 95% CI 0.66, 1.07) and men (5.3% vs 6.4%; HR 0.83, 95% CI 0.71, 0.96; pinteraction = 0.90); (2) MACE: women (6.3% vs 6.8%; HR 0.93, 95% CI 0.77, 1.12) and men (10.0% vs 10.7%; HR 0.93, 95% CI 0.83, 1.05; pinteraction = 0.99); or (3) renal-specific composite: women (1.4% vs 2.8%; HR 0.50, 95% CI 0.35, 0.70) and men (1.5% vs 2.5%; HR 0.55, 95% CI 0.42, 0.73; pinteraction = 0.64). The overall safety profile of dapagliflozin was similar for women and men. CONCLUSIONS/INTERPRETATION: Dapagliflozin offers comparable CV and renal benefits and a comparable safety profile in women and men. FUNDING: AstraZeneca. TRIAL REGISTRATION: clinicaltrials.gov NCT01730534.

Perceptions of Canadian vascular surgeons toward pharmacological risk reduction in patients with peripheral arterial disease.

Patients with peripheral arterial disease (PAD) are at a markedly higher risk of cardiovascular morbidity and mortality, with evidence indicating that risk-reduction pharmacotherapy can serve to attenuate cardiovascular events in these patients. Given the central role of vascular surgeons in the treatment of patients with PAD, we sought to determine their perceptions and knowledge of risk-reduction pharmacotherapy in patients with PAD. We conducted a cross-sectional survey of 79 Canadian vascular surgeons who attended the 2004 annual meeting of the Canadian Society for Vascular Surgery, the largest and most representative meeting of its kind in Canada. The recommended targets of low-density lipoprotein cholesterol, blood glucose, and blood pressure were known to 53.8%, 40.4%, and 57.7% of vascular surgeons, respectively. The majority of vascular surgeons (65.4%) reported screening for risk factors in <50% of cases. Although 90.4% of vascular surgeons would recommend antiplatelet therapy for PAD, only 5.8% would recommend angiotensin converting enzyme (ACE) inhibitors and 19.2% would recommend lipid-lowering therapy with statins. Eighty-four percent of Canadian vascular surgeons indicated that their self-assessment of risk reduction in PAD was average to below average, yet 90.4% of them believed that risk-reduction therapy should be recommended or initiated by vascular surgeons. Canadian vascular surgeons' perceptions toward risk reduction in PAD identify knowledge and action gaps, despite the recognition that recommending and instituting therapy is important to patient care. Given the heightened risk of cardiovascular disease in patients with PAD, these data have important implications.