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

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The “bad companions” make blood pressure control challenging

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

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

Ferrannini E, Cushman WC. Diabetes and hypertension: the bad companions. Lancet. 2012;380:601-10 / United States 2010 National Health and Nutrition Examination Survey / International Survey Evaluating Microalbuminuria Routinely by Cardiologists in Patients with Hypertension / ESH-ESC 2013 Guidelines

Methodology involved a retrospective analysis of a subgroup of patients of PICASSO study

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Patient profile

Treatment and

follow-up

Endpoints

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 prediabetes are 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

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

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

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 Suppl 1:3-10 / ESH-ESC 2007 guidelines

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

Results for office blood pressure

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Mean office SBP/DBP change over three months

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±HCTZ or on ARB±HCTZ (both p <0.001)

Mean office SBP/DBP change according to previous other treatments

Farsang C, on behalf of the PICASSO investigators. Blood Press. 2013;22 Suppl 1:3-10

Results for ambulatory blood pressure

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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)

Ambulatory SBP/DBP change after three months

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)

Ambulatory SBP/DBP change after three months and compared with other previous treatments

93 patients were followed up through ambulatory blood pressure monitoring system

Farsang C, on behalf of the PICASSO investigators. Blood Press. 2013;22 Suppl 1:3-10

Results for tolerability

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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

Metabolic parameters change after three months of treatment with fixed dose combination of Perindopril/Indapamide

Farsang C, on behalf of the PICASSO investigators. Blood Press. 2013;22 Suppl 1:3-10

Conclusion

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PICASSO T2D study sticks to the challenges of daily medical practice (uncontrolled hypertension in diabetic or prediabetic patients, despite treatment)

BP was significantly reduced after three months of treatment The treatment was well tolerated and improved laboratory parameters

Ambulatory SBP, BP variability and pulse pressure are predictors of cardiovascular risk

In addition, BP variability through the day is impacting organ damage Thus, a long-term study would be interesting to assess the impact of

perindopril/indapamide on organ damage and cardiovascular risk

For diabetic patients, treatment with ACE inhibitors is recommended for their cardioprotective and nephroprotective effects

This recommendation has been confirmed in a recent analysis (CMAJ 2013) In addition, the British Society of Hypertension has recently recommended

the use of indapamide or chlortalidone rather than HCTZ

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 Suppl 1:3-10 / Lv J, Ehteshami P, Sarnak MJ, et al. CMAJ 2013.