Triple antihypertensive therapy with amlodipine, valsartan, and hydrochlorothiazide: a randomized clinical trial.

Sleep/Wake Disorders Center, University of Alabama at Birmingham, 35294, USA.
Hypertension (Impact Factor: 7.63). 08/2009; 54(1):32-9. DOI: 10.1161/HYPERTENSIONAHA.109.131300
Source: PubMed

ABSTRACT Many patients with hypertension require > or =3 agents to achieve target blood pressure (BP). The efficacy/safety of the dual combinations of valsartan (Val)/hydrochlorothiazide (HCTZ) and amlodipine (Aml)/Val in hypertension are well established. This randomized, double-blind study evaluated the efficacy/safety of triple therapy with Aml/Val/HCTZ for moderate or severe hypertension (mean sitting systolic BP: > or =145 mm Hg; mean sitting diastolic BP: > or =100 mm Hg). The study included a single-blind, placebo run-in period, followed by double-blind treatment for 8 weeks; patients were randomly assigned to 1 of 4 groups titrated to Aml/Val/HCTZ 10/320/25 mg, Val/HCTZ 320/25 mg, Aml/Val 10/320 mg, or Aml/HCTZ 10/25 mg once daily. Dual-therapy recipients received half of the target doses of both agents for the first 2 weeks, titrating to target doses during week 3. Those on triple therapy received Val/HCTZ 160.0/12.5 mg during week 1, Aml/Val/HCTZ 5.0/160.0/12.5 mg during week 2, and target doses of all 3 of the agents during week 3. Of the 4285 patients enrolled, 2271 were randomly assigned to treatment, and 2060 completed the study. Triple therapy was significantly superior to all of the dual therapies in reducing mean sitting systolic BP and mean sitting diastolic BP from baseline to end point (all P<0.0001). Significantly more patients on triple therapy achieved overall BP control (<140/90 mm Hg; P<0.0001) and systolic and diastolic control (P< or =0.0002) compared with each dual therapy. Aml/Val/HCTZ was well tolerated. The benefits of triple therapy over dual therapy were observed regardless of age, sex, race, ethnicity, or baseline mean sitting systolic BP. In conclusion, this study demonstrates the efficacy/safety of treating moderate and severe hypertension with Aml/Val/HCTZ 10/320/25 mg.

  • [Show abstract] [Hide abstract]
    ABSTRACT: Hypertension is one of the most popular fields of research in modern medicine due to its high prevalence and its major impact on cardiovascular risk and consequently on global health. Indeed, about one third of individuals worldwide has hypertension and is under increased long-term risk of myocardial infarction, stroke or cardiovascular death. On the other hand, resistant hypertension, the "uncontrollable" part of arterial hypertension despite appropriate therapy, comprises a much greater menace since long-standing, high levels of blood pressure along with concomitant debilitating entities such as chronic kidney disease and diabetes mellitus create a prominent high cardiovascular risk milieu. However, despite the alarming consequences, resistant hypertension and its effective management still have not received proper scientific attention. Aspects like the exact prevalence and prognosis are yet to be clarified. In an effort to manage patients with resistant hypertension appropriately, clinical doctors are still racking their brains in order to find the best therapeutic algorithm and surmount the substantial difficulties in controlling this clinical entity. This review aims to shed light on the effective management of resistant hypertension and provide practical recommendations for clinicians dealing with such patients.
    World Journal of Cardiology (WJC) 10/2014; 6(10):1080-90. · 2.06 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: To improve the management of resistant hypertension, the French Society of Hypertension, an affiliate of the French Society of Cardiology, has published a set of eleven recommendations. The primary objective is to provide the most up-to-date information, based on the strongest scientific rationale and which is easily applicable to daily clinical practice for health professionals working within the French health system. Resistant hypertension is defined as uncontrolled blood pressure (BP) both on office measurements and confirmed by out-of-office measurements despite a therapeutic strategy comprising appropriate lifestyle and dietary measures and the concurrent use of three antihypertensive agents including a thiazide diuretic, a renin-angiotensin system blocker (ARB or ACEI) and a calcium channel blocker, for at least four weeks, at optimal doses. Treatment compliance must be closely monitored, as most factors that are likely to affect treatment resistance (excessive dietary salt intake, alcohol, depression and drug interactions, or vasopressors). If the diagnosis of resistant hypertension is confirmed, the patient should be referred to a hypertension specialist to screen for potential target organ damage and secondary causes of hypertension. The recommended treatment regimen is a combination therapy comprising four treatment classes, including spironolactone (12.5 to 25mg/day). In the event of a contraindication or a non-response to spironolactone, or if adverse effects occur, a β-blocker, an α-blocker, or a centrally acting antihypertensive drug should be prescribed. Because renal denervation is still undergoing assessment for the treatment of hypertension, this technique should only be prescribed by a specialist hypertension clinic. Copyright © 2014 Elsevier Masson SAS. All rights reserved.
    Presse medicale (Paris, France : 1983). 11/2014; 43(12P1):1325-1331.
  • [Show abstract] [Hide abstract]
    ABSTRACT: All national guidelines for the management of hypertension recommend angiotensin receptor blockers (ARBs) as an initial or add-on antihypertensive therapy. The eight available ARBs have variable clinical efficacy when used for control of hypertension. Additive blood pressure-lowering effects have been demonstrated when ARBs are combined with thiazide diuretics or dihydropyridine calcium channel blockers, augmenting hypertension control. Furthermore, therapeutic use of ARBs goes beyond their antihypertensive effects, with evidence-based benefits in heart failure and diabetic renal disease particularly among angiotensin-converting enzyme inhibitor-intolerant patients. On the other hand, combining renin-angiotensin system blocking agents, a formerly common practice among medical subspecialists focusing on the management of hypertension, has ceased, as there is not only no evidence of cardiovascular benefit but also modest evidence of harm, particularly with regard to renal dysfunction. ARBs are very well tolerated as monotherapy, as well as in combination with other antihypertensive medications, which improve adherence to therapy and have become a mainstay in the treatment of stage 1 and stage 2 hypertension.
    Drug Safety 11/2014; · 2.62 Impact Factor