Overcoming the challenge of blood pressure control in prediabetic and diabetic patients: PICASSO T2D Study Efficacy and tolerability of fixed dose combination perindopril/indapamide in type 2 diabetes
Background and objective of the study The “bad companions” make blood pressure control challenging • Hypertension and type 2 diabetes deteriorate the vascular environment and lead to micro- and macrovascular disease • Epidemiologic data from key studies (NHANES and I-SEARCH) highlight the need for improving treatment strategies • Diabetic patients are more likely to be treated with antihypertensive drugs • However, they were 53% less likely to reach control than non diabetic patients Recent guidelines recommend to use combinations • For diabetic hypertensive patients, European guidelines (ESH/ESC 2013) recommend the use of combination therapy, especially including RAAS inhibitors • Perindopril/indapamide is thus well suited for the treatment of diabetic patients Objective of the study • The objective of PICASSO T2D study is to assess the efficacy and the tolerability of a fixed-dose combination of perindopril and indapamide in lowering blood pressure Ferrannini E, Cushman WC. Diabetes and hypertension: the badcompanions. Lancet. 2012;380:601-10 / United States 2010 National Health and Nutrition ExaminationSurvey / International Survey EvaluatingMicroalbuminuriaRoutinely by Cardiologists in Patients withHypertension / ESH-ESC 2013 Guidelines
Methodology involved a retrospective analysis of a subgroup of patients of PICASSO study • PICASSO study was a 3-month observational study conducted on 9 257 uncontrolled hypertensive patients • Data of a subgroup of 2 762 patients with type 2 diabetes (T2D, N=1 887) or prediabetes(N=875) were retrospectively analyzed Patient profile • Patients with hypertension as defined by 2007 ESC/ESH guidelines, with systolic blood pressure (SBP)/diastolic blood pressure (DBP) <130/80 mm Hg • Blood pressure targets for patients with prediabetesare defined as <140/90 mm Hg • Patients with T2D were reported on case files, prediabetic patients were defined as patients with a fasting blood glucose 5.6-6.9 mmol/L or with a positive oral glucose tolerance test Treatment and follow-up • Patients received a fixed-dose combination of perindopril/indapamide 10mg/2.5mg for 3 months • Additional antihypertensive agents were allowed to be maintained or added according to the doctor’s appreciation • Patients were measured at baseline, after one month and after 3 months of treatment Endpoints • Office and ambulatory blood pressure (SBP/DBP) • Laboratory parameters to assess tolerance (fasting plasma glucose, serum total cholesterol, HDL-C, LDL-C, triglycerides, potassium, creatinine and uric acid), at baseline and at 3 months Farsang C, on behalf of the PICASSO investigators. Blood Press. 2013;22 Suppl1:3-10 / ESH-ESC 2007 guidelines
Results for office blood pressure Mean office SBP/DBP change over three months Mean office SBP/DBP change according to previous other treatments • Changes from baseline to 3 months were statistically significant (-26.9±14.8/-12.7±9.8 mm Hg; p <0.001) • After 3 months of treatment, blood pressure control was reached in 69% of patients • Significant reductions were achieved regardless of the severity of hypertension at inclusion • Mean office SBP/DBP decreased significantly regardless of previous other treatments • In particular, office blood pressure decreased significantly in patients previously treated by a RAAS inhibitor±HCTZ(n = 1991), from 159.5±14.7/92.5±9.7 to 132.3±9.8/80.0±6.3 mm Hg (p <0.001) • The decrease in office blood pressure was similar for patients previously on ACE inhibitors±HCTZor on ARB±HCTZ(both p <0.001) Farsang C, on behalf of the PICASSO investigators. Blood Press. 2013;22 Suppl 1:3-10
Results for ambulatory blood pressure • 93 patients were followed up through ambulatory blood pressure monitoring system Ambulatory SBP/DBP change after three months Ambulatory SBP/DBP change after three months and compared with other previous treatments • Mean day-time, night-time, and 24-hour BP as well as mean 24-hour pulse pressure, mean arterial pressure, and mean 24-hour heart rate decreased significantly over 3 months of treatment (p <0.001) • In patients previously treated with ACE inhibitor±HCTZ(n = 67) or ARB±HCTZ (n = 10), mean 24-hour blood pressure decreased by 23.4±13.9/11.5±9.7 mm Hg and 22.3±8.7/10.4±13.2 mm Hg, respectively (p <0.001) Farsang C, on behalf of the PICASSO investigators. Blood Press. 2013;22 Suppl 1:3-10
Results for tolerability Metabolic parameters change after three months of treatment with fixed dose combination of Perindopril/Indapamide • Metabolic markers were measured according to doctors’ willingness • Significant reductions of total cholesterol, LDL-C, glucose and triglycerides were measured after three months • Treatment was overall well tolerated, with 36 cases of drug-related adverse events reported, including • Ankle edema (N=11 patients, 0.4% of patients) • Dizziness (N=7 patients, 0.3% of patients) • Cough (N=6 patients, 0.2% of patients) • Seven serious adverse events were reported, none of which related to the study Farsang C, on behalf of the PICASSO investigators. Blood Press. 2013;22 Suppl 1:3-10
Conclusion Key elements Significant results relevant to real life practice Significant results withlong-term impact to be further assessed Results in line with guidelines Farsang C, on behalf of the PICASSO investigators. Blood Press. 2013;22 Suppl1:3-10 / LvJ, Ehteshami P, Sarnak MJ, et al. CMAJ 2013.