William C. Cushman

Visit-to-Visit Office Blood Pressure Variability and Cardiovascular Outcomes in SPRINT (Systolic Blood Pressure Intervention Trial).

Studies of visit-to-visit office blood pressure (BP) variability (OBPV) as a predictor of cardiovascular events and death in high-risk patients treated to lower BP targets are lacking. We conducted a post hoc analysis of SPRINT (Systolic Blood Pressure Intervention Trial), a well-characterized cohort of participants randomized to intensive (<120 mm Hg) or standard (<140 mm Hg) systolic BP targets. We defined OBPV as the coefficient of variation of the systolic BP using measurements taken during the 3-,6-, 9-, and 12-month study visits. In our cohort of 7879 participants, older age, female sex, black race, current smoking, chronic kidney disease, and coronary disease were independent determinants of higher OBPV. Use of thiazide-type diuretics or dihydropyridine calcium channel blockers was associated with lower OBPV whereas angiotensin-converting enzyme inhibitors or angiotensin receptor blocker use was associated with higher OBPV. There was no difference in OBPV in participants randomized to standard or intensive treatment groups. We found that OBPV had no significant associations with the composite end point of fatal and nonfatal cardiovascular events (n=324 primary end points; adjusted hazard ratio, 1.20; 95% confidence interval, 0.85–1.69, highest versus lowest quintile) nor with heart failure or stroke. The highest quintile of OBPV (versus lowest) was associated with all-cause mortality (adjusted hazard ratio, 1.92; confidence interval, 1.22–3.03) although the association of OBPV overall with all-cause mortality was marginal (P=0.07). Our results suggest that clinicians should continue to focus on office BP control rather than on OBPV unless definitive benefits of reducing OBPV are shown in prospective trials. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT01206062

20. Major Cardiovascular Outcomes in the EXAMINE Trial According to ACE Inhibitor Use (12-OR)

SamenvattingActivation of the sympathetic nervous system through substance P via DPP-4 inhibition (DPP-4i) in the presence of higher dose ACE inhibition (ACEi) has led to hypothetical concerns of the cardiovascular (CV) safety of these 2 classes of drugs used together. We evaluated adjudicated CV events in EXAMINE, a trial of patients with type 2 diabetes (T2DM) and recent acute coronary syndrome (ACS) according to ACEi use. Patients were randomly assigned to receive alogliptin or placebo added to existing anti-hyperglycemic and CV therapies. Risks of CV death, nonfatal MI and stroke (MACE), and CV death or hospitalized HF (HHF) were analyzed using a Cox proportional hazards model in patients by baseline ACEi use. EXAMINE random ized 5380 patients, 3323 (62%) of whom were using an ACE inhibitor (1681 on alogliptin; 1642 on placebo). Composite rates of MACE were similar for alogliptin vs. placebo with ACEi [11.4% vs. 11.8%, HR = 0.97, 95% CI, 0.79-1.19, p = 0.76] and without ACEi use at baseline [11.2% vs. 11.9%, HR = 0.94, 95% CI, 0.73-1.21, p = 0.62]. The composite of CV death or HHF in patients on ACEi at baseline occurred in 6.8% of patients on alogliptin vs. 7.2% on placebo [HR = 0.93, 95% CI, 0.72-1.2, p = 0.57]. Alogliptin showed no effect on HHF alone in ACEi treated patients, 3.3% vs. 3.1%, (HR = 1.07, 95% CI, 0.73-1.56, p = 0.75) for alogliptin vs. placebo, respectively. Additionally, there was no impact of higher vs. lower doses of ACEi on CV event rates. There were also no differences for these endpoints in patients without ACEi use at baseline. Analyses according to pre-randomization history of HF and ACEi use at baseline showed MACE occurring in 13.9% and 16.5% of patients on alogliptin vs. placebo, respectively [HR = 0.87, 95% CI, 0.63-1.19, p = 0.38] and CV death or HHF in 12.0% and 13.2% of patients on alogliptin vs. placebo, respectively [HR = 1.02, 95% CI, 0.72-1.44, p = 0.92]. In conclusion, CV outcomes were not different for alogliptin compared with placebo in high CV risk patients with T2DM treated with ACE inhibitors in the EXAMINE Trial.