Trandolapril/Verapamil Hydrochloride

Recently, the Action to Control Cardiovascular Risk in Diabetes (ACCORD) blood pressure (BP) trial enrolled 4733 participants with type 2 diabetes and randomized them to a target systolic blood pressure (SBP) of less than 120 mm Hg or 140 mm Hg. Despite the significant difference in the achieved SBP, there was no significant difference in the incidence of primary outcomes. Based on this evidence, the target SBP for diabetics has been revised in the majority of major guidelines. However, there is a steeper association between SBP and stroke in Asians than other ethnicities, with stroke being the leading cause of cardiovascular mortality. This suggests that target BP in the Asian region should be tailored towards prevention of stroke. In the ACCORD study, the intensive BP treatment was associated with significant reductions in both total stroke and non-fatal stroke. The results from the ACCORD study are supported by a subgroup analysis from the ONgoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial (ONTARGET) study, which showed that, in diabetic patients, the risk of stroke continues to decrease to a SBP value of 115 mm Hg with no evidence of J curve. As diabetes is highly associated with underlying coronary artery disease, there is a justified concern for adverse effects resulting from too much lowering of BP. In a post hoc analysis of 6400 diabetic subjects enrolled in the International Verapamil SR-Trandolapril (INVEST) study, subjects with SBP of less than 110 mm Hg were associated with a significant increase in all-cause mortality. In the ONTARGET study, at any levels of achieved SBP, diastolic blood pressure (DBP) below 67 mm Hg was associated with increased risk for cardiovascular outcomes. As such, a prudent approach would be to target a SBP of 130-140 mm Hg and DBP of above 60 mm Hg in diabetics with coronary artery disease. In conclusion, hypertension, in association with diabetes, has been found to be significantly correlated with an elevated risk for cardiovascular events. As the association between stroke and BP is stronger in Asians, compared to other ethnicities, consideration should be given for a target BP of 130/80 mm Hg in Asians.

Resistant hypertension (res-HTN) is a challenging problem, but little is known of res-HTN in patients with coronary artery disease (CAD). In this post-hoc INternational VErapamil SR-Trandolapril STudy (INVEST) analysis, we assessed prevalence, predictors, and impact on outcomes of res-HTN in CAD patients with hypertension.

Participants (n=17190) were divided into three groups according to achieved blood pressure (BP): controlled (BP <140/90 mmHg on three or fewer drugs); uncontrolled (BP ≥ 40/90 mmHg on two or fewer drugs); or resistant (BP ≥ 40/90 mmHg on three drugs or any patient on at least four drugs).

The prevalence of res-HTN was 38%: significant predictors of res-HTN included heart failure [odds ratio (OR) 1.73], diabetes (OR 1.63), Black race (OR 1.50), and US residence (OR 1.50). Compared with controlled HTN, res-HTN had multivariate-adjusted association with higher risk of adverse outcomes {first occurrence of all-cause death, nonfatal myocardial infarction, or nonfatal stroke [hazard ratio 1.27, 95% confidence interval (CI) 1.13-1.43], and individual outcomes of all-cause death (hazard ratio 1.29, 95% CI 1.13-1.48), cardiovascular mortality (hazard ratio 1.47, 95% CI 1.21-1.78), and nonfatal stroke (hazard ratio 1.61, 95% CI 1.17-2.22), but not nonfatal myocardial infarction (hazard ratio 0.98, 95% CI 0.72-1.34)}. Adverse outcomes, except nonfatal stroke, did not differ in patients with res-HTN compared to uncontrolled HTN.

Res-HTN is common in patients with CAD and hypertension, associated with poor prognosis, and linked with a number of conditions. Emphasis should be placed on recognizing those at risk for res-HTN and future studies should examine whether more aggressive treatment of res-HTN improves outcomes.