Efficacy and Tolerability of Fixed-Dose Combination of Perindopril/Indapamide in Type 2 Diabetes Mellitus: PICASSO Trial

Abstract

BackgroundHypertension and type 2 diabetes mellitus (T2DM) synergistically deteriorate the vascular environment, making blood pressure reduction challenging, and substantially increasing cardiovascular risk.MethodsIn the real-life, open-label, observational, PICASSO study, 9,257 hypertensive patients unsuccessfully treated with antihypertensives were switched to fixed-dose combination of perindopril 10 mg/indapamide 2.5 mg. In this subgroup analysis, we analyzed changes in blood pressure and laboratory parameters of 2,762 hypertensive patients with T2DM or pre-diabetes.ResultsAfter 3 months of treatment, significant decreases in office blood pressure were noted in the whole cohort (−27.0 ± 14.8/−12.7 ± 9.8 mmHg; p < 0.001). Significant decreases were also recorded in patients with grade 1 hypertension (19.2 ± 10.0/−9.4 ± 7.9 mmHg), grade 2 (29.2 ± 10.9/−13.3 ± 8.7 mmHg) and grade 3 (−45.1 ± 15.4/−21.5 ± 11.2 mmHg). Significant decreases in ambulatory blood pressure were also noted (n = 93). In patients previously treated with angiotensin-converting enzyme inhibitor ± hydrochlorothiazide or angiotensin receptor blocker ± hydrochlorothiazide, mean 24-h blood pressure decreased by 23.4 ± 13.9/11.5 ± 9.7 and 22.3 ± 8.7/10.4 ± 13.2 mmHg, respectively (p < 0.001). Treatment was well tolerated and the switch to treatment with perindopril/indapamide was associated with improvements in laboratory parameters.ConclusionsData from this diabetes subgroup analysis suggest that fixed combination of perindopril 10 mg/indapamide 2.5 mg should be routinely considered for the treatment of hypertension in diabetic patients who are unsuccessfully managed with other antihypertensive medications.Electronic supplementary materialThe online version of this article (doi:10.1007/s12325-014-0107-y) contains supplementary material, which is available to authorized users.

Two‐drug fixed‐dose combinations of blood pressure‐lowering drugs as WHO essential medicines: An overview of efficacy, safety, and cost

“…It is possible that the efficacy and safety of the proposed BP‐lowering FDCs were demonstrated in trials of short duration that largely excluded patients with comorbidities. However, we propose the following assures the safety of the proposed FDCs: (a) the individual constituent drugs of the proposed FDCs have been in use for several years and have established efficacy, effectiveness, and safety profiles; (b) drug classes to which the constituent drugs of the proposed FDCs belong are recommended by hypertension guidelines for concomitant use; (c) the individual constituent drugs of the proposed FDCs are widely co‐prescribed for concomitant use; (d) the four FDCs proposed were approved greater than 10 years ago and have accumulated significant safety data including among the real‐world patients through post‐marketing surveillance; (e) drugs within the class have been shown to have similar efficacy and safety profiles 40 ; and (f) studies of real‐world data suggest FDCs provide better BP control, 41–44 do not lead to excess adverse effects, 41–44 and reduce cardiovascular events 45,46 …”

Tolerability of Antihypertensive Medications in Older Adults

“…A comparison of low-dose versus full-dose polypills (consisting of atenolol, ramipril, and hydrochlorothiazide) demonstrated greater BP reduction with the full-dose pill (which also included potassium supplement), with similar tolerability [175]. Several combination therapies have been found effective in BP control [176][177][178], including in diabetic hypertensive patients [179], although tolerability was lower than placebo for some combinations. Thus, use of combination pills for hypertension may be one way to enhance control and tolerability (with fewer adverse effects) and perhaps reduce healthcare costs [180].…”

Ultra-low-dose quadruple combination blood pressure–lowering therapy in patients with hypertension: The QUARTET randomized controlled trial protocol

“…A sample size of 650 patients provides 90% power at P = .05 to detect a difference between randomized groups of 4 mmHg in the primary outcome, assuming a standard deviation (SD) of 15 mmHg. 34 A sample of 650 also has 85% power to detect a 3 mmHg difference in average 24 hr. SBP (SD 12 mmHg) 34 and 85% power to detect a 25% increase in the proportion with controlled blood pressure assuming 50% are controlled in the comparator group.…”

“… 34 A sample of 650 also has 85% power to detect a 3 mmHg difference in average 24 hr. SBP (SD 12 mmHg) 34 and 85% power to detect a 25% increase in the proportion with controlled blood pressure assuming 50% are controlled in the comparator group. All calculations allow for a 10% dropout or data loss rate.…”