Management of hypertension with fixed dose combinations of candesartan cilexetil and hydrochlorothiazide: patient perspectives and clinical utility

Figures & data

Figure 1 Terms used to describe adherence.

Table 1 Compelling indications and contraindications in the use of antihypertensive drug classes¹⁷

	Conditions favoring use	Compelling or possible contraindications
Thiazide diuretics	Isolated systolic hypertension (elderly) Heart failure Hypertension in blacks	Gout Metabolic syndrome Glucose intolerance Pregnancy
Beta blockers	Angina pectoris Post-myocardial infarction Heart failure Tachyarrhythmias Glaucoma Pregnancy	Asthma A-V block (grade 2 or 3) Peripheral artery disease Metabolic syndrome Glucose intolerance Athletes and physically active patients Chronic obstructive pulmonary disease
Calcium antagonists (dihydropyridines)	Isolated systolic hypertension (elderly) Angina pectoris LV hypertrophy Carotid/coronary atherosclerosis Pregnancy Hypertension in blacks	Tachyarrhythmias Heart failure
Calcium antagonists (verapamil/diltiazem)	Angina pectoris Carotid atherosclerosis Supraventricular tachycardia	A-V block (grade 2 or 3) Heart failure
ACE inhibitors	Heart failure LV dysfunction Post-myocardial infarction Diabetic nephropathy Non-diabetic nephropathy LV hypertrophy Carotid atherosclerosis Proteinuria/microalbuminuria Atrial fibrillation Metabolic syndrome	Pregnancy Angioneurotic edema Hyperkalemia Bilateral renal artery stenosis
Angiotensin receptor antagonists	Heart failure Post-myocardial infarction Diabetic nephropathy Proteinuria/microalbuminuria LV hypertrophy Atrial fibrillation Metabolic syndrome ACEi-induced cough	Pregnancy Hyperkalemia Bilateral renal artery stenosis
Diuretics (antialdosterone)	Heart failure Post-myocardial infarction	Renal failure Hyperkalemia
Loop diuretics	End stage renal disease Heart failure

Figure 2 Four out of 6 recommended dual antihypertensive combination therapies include blockers of the renin–angiotensin system.

Reproduced with permission from Mancia G, De Backer G, Dominiczak A, et al. Guidelines for the Management of Arterial Hypertension: The Task Force for the Management of Arterial Hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). J Hypertens. 2007; 25(6):1105–1187.¹⁷ Copyright © Lippincott Williams & Wilkins.

Notes: Red, recommendation including an angiotensin receptor blocker; green, recommendations including an ACE inhibitor.

Figure 3 Combination therapy as an escalation option and as first-line therapy.

Reproduced with permission from Mancia G, De Backer G, Dominiczak A, et al. Guidelines for the Management of Arterial Hypertension: The Task Force for the Management of Arterial Hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). J Hypertens. 2007; 25(6):1105–1187.¹⁷ Copyright © Lippincott Williams & Wilkins.

Notes: Green, 2-drug combination therapy as an option for treatment escalation; red, 2-drug combination as a first line option in patients with marked elevation of blood pressure and high cardiovascular risk.

Figure 4 Cost savings in the UK by intensifying antihypertensive drug treatment.¹⁵

Notes: Optimizing antihypertensive therapy in the UK will cost £58.4 million and will prevent costs due to prevented stroke/ischemic heart disease (IHD) of £280.4 million resulting in a net benefit of £221.9 million.

Figure 5 Blood pressure reduction with 32 mg candesartan alone or in combination with 12.5 or 25 mg HCTZ in patients not sufficiently controlled on monotherapy.⁴²

Table 2 Laboratory values at baseline, and mean change (±SD) from baseline^a after 8 weeks of treatment⁴²

	Candesartan 32 mg n = 653	Candesartan 32 mg 12.5 mg HCTZ n = 654	Candesartan 32 mg 25 mg HCTZ n = 664
S-urate (μmol/L)
Baseline	334.5 (84.6)	335.2 (82.6)	339.1 (80.6)
Change	5.1 (52.0)	27.4 (52.3)	43.9 (57.8)
S-potassium (mmol/L)
Baseline	4.5 (0.4)	4.5 (0.4)	4.5 (0.4)
Change	0.0 (0.4)	0.1 (0.4)	−0.1 (0.4)
S-glucose (mmol/L)
Baseline	6.0 (1.4)	6.2 (1.9)	5.9 (1.5)
Change	0.0 (1.0)	0.4 (1.0)	0.0 (0.9)
S-triglycerides (mmol/l)
Baseline	2.0 (1.4)	1.9 (1.8)	2.0 (1.5)
Change	0.0 (1.2)	0.0 (1.6)	0.2 (2.2)
S-cholesterol (mmol/L)
Baseline	5.8 (1.1)	5.8 (1.1)	5.9 (1.0)
Change	0.1 (0.7)	0.0 (0.8)	0.1 (0.8)
S-creatinine (μmol/L)
Baseline	79.8 (15.8)	79.9 (14.8)	80.3 (15.4)
Change	0.0 (10.5)	1.8 (9.8)	4.5 (13.1)

a Baseline: after a run-in phase with 16 mg candesartan for 2 weeks and 32 mg candesartan for 6 weeks.

Figure 6 Results of the CHARM trial program.^52–55

Reprinted from Pfeffer MA, Swedberg K, Granger CB, et al. Effects of candesartan on mortality and morbidity in patients with chronic heart failure: the CHARM-Overall programme. The Lancet. 362:759–766.⁵² Copyright © 2003, with permission from Elsevier.

Notes: *p for heterogeneity 0.37; ^†p for heterogeneity 0.33.

Figure 7 Development of diabetes – results of a meta-analysis.

Reprinted from Lam SK, Owen A. Incident diabetes in clinical trials of antihypertensive drugs. The Lancet. 369:1513–1514.⁵⁹ Copyright © 2007, with permission from Elsevier.

Figure 8 Results of the DIRECT trial program.^47,73

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