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 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
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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
Treatment
and
follow-up
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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
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, HDLC, 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
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Results for office blood pressure
Mean office SBP/DBP change over three months
 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 change
according to previous other treatments
 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)
Farsang C, on behalf of the PICASSO investigators. Blood Press. 2013;22 Suppl 1:3-10
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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
 In patients previously treated with ACE inhibitor±HCTZ
mean 24-hour pulse pressure, mean arterial pressure,
and mean 24-hour heart rate decreased significantly
over 3 months of treatment (p <0.001)
(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
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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
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Conclusion
Key elements
Significant results relevant
to real life practice
Significant results with
long-term impact to be
further assessed
Results in line with
guidelines
 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
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.
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