ALLHAT Findings Revisited in the Context of Subsequent Analyses, Other Trials, and Meta-analyses

Onuigbo, Macaulay

doi:10.1001/archinternmed.2009.371

Cited by 8 publications

(8 citation statements)

References 39 publications

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“…As well, the CHARM trials revealed a higher rate of doubling of serum creatinine in 82 (6%) candesartan-treated versus 47 (4%) placebo-treated patients (p = 0.002) [99,100]. Additionally, the ALLHAT study demonstrated that among the diabetics studied, more patients in the ACEI lisinopril group progressed to ESRD, when compared to the diuretic chlorthalidone group (25/1,563 vs. 26/2,755, p = 0.05, RR 1.74, 95% CI 1.00–3.01) [101,102]. Furthermore, Jones et al [8] in 2005, after a thorough analysis of the US ESRD population growth, concluded that there was an ESRD epidemic here in the USA, and that the pace of the US ESRD epidemic outpaced the growth of the diabetes mellitus epidemic.…”

Section: The Association Of Aki With Raas Blockade In Generalmentioning

confidence: 99%

Can ACE Inhibitors and Angiotensin Receptor Blockers Be Detrimental in CKD Patients?

Onuigbo

2011

Nephron Clin Pract

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Current epidemiological data from the USA, Europe, Asia and the Indian subcontinent, Africa, the Far East, South America, the Middle East and Eastern Europe all point to the increasing incidence of renal failure encompassing acute kidney injury (AKI), chronic kidney disease (CKD) and end-stage renal disease (ESRD). While the explanations for these worldwide epidemics remain speculative, it must be acknowledged that these increases in AKI, CKD and ESRD, happening worldwide, have occurred despite the universal application of strategies of renoprotection over the last 2 decades, more especially the widespread use of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs). We note that many of the published large renin-angiotensin-aldosterone system (RAAS) blockade randomized controlled trials, upon which current evidence-based practice for the increasing use of ACEIs and ARBs for renoprotection derived from, have strong deficiencies that have been highlighted over the years. From reports in the literature, there is an increasing association of exacerbations of renal failure with ACEIs and ARBs, more so in the older hypertensive patient, >65 years old. The biological plausibility for ACEI and ARB to protect the kidneys against a background of potential multiple pathogenetic pathways to account for CKD progression appears to be not very defensible. We reviewed the literature along these lines and submit that ACEIs and ARBs often cause unrecognized significant worsening renal failure in CKD patients, sometimes irreversible, and that more caution is required regarding their use, especially in the older hypertensive patients, with likely ischemic hypertensive nephropathy. Given the increasing association of concomitant RAAS blockade with worsening renal failure following exposure to iodinated contrast, during acute illness, in the perioperative period and following lower bowel preparations prior to colonoscopy, we submit that, preferably, ACEIs and ARBs be withheld for 2–4 days prior to or during these clinical scenarios. This represents the concept of renoprevention.

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Section: The Association Of Aki With Raas Blockade In Generalmentioning

confidence: 99%

Can ACE Inhibitors and Angiotensin Receptor Blockers Be Detrimental in CKD Patients?

Onuigbo

2011

Nephron Clin Pract

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“…Very interestingly, the worse renal outcomes in the ALLHAT and CHARM‐overall trials with lisinopril and candesartan, respectively, barely received but glancing mention in the various publications (5,30). Even post hoc analyses of these RCTs have consistently and continually failed to address these concerns of potential drug treatment‐related nephrotoxicity (31). For example, the CHARM trials demonstrated a higher rate of doubling of serum creatinine in 82 (6%) candesartan‐treated vs. 47 (4%) placebo‐treated patients (p = 0.002) (5).…”

mentioning

confidence: 99%

“…Correspondingly, the ALLHAT data demonstrated that among diabetics, more patients in the lisinopril group, progressed to ESRD, when compared with the chlorthalidone group – 25/1563 vs. 26/2755, p = 0.05, RR 1.74, 95% CI (1.00–3.01) (30). Recently, we had called the ALLHAT authors to task in a recent editorial comment published in the Archives of Internal Medicine as to why this very important aspect of their findings barely received any mention in the original ALLHAT publication and in subsequent post hoc reports (31).…”

mentioning

confidence: 99%

Is renoprotection with RAAS blockade a failed paradigm? Have we learnt any lessons so far?

Onuigbo

2010

International Journal of Clinical Practice

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“…Surprisingly, all the major studies were performed using higher hydrochlorothiazide doses or hydrochlorothiazide in combination with other antihypertensive agents, so little or no evidence exists for the efficacy of low-dose hydrochlorothiazide in hypertension and cardiovascular disease. The Anti-hypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT), one of the major studies showing equivalent efficacy of diuretics and other antihypertensives, was performed with chlorthalidone, which seems to be more effective than hydrochlorothiazide 41,42. Furthermore, hydrochlorothiazide at higher doses whereby its efficacy might be comparable with that of other antihypertensives, shows many adverse effects, including electrolyte imbalance (hypokalemia, hyponatremia), insulin resistance, and hyperuricemia, making it inappropriate as monotherapy 43.…”

Section: Use Of Aliskiren-hydrochlorothiazide In Hypertensionmentioning

confidence: 99%

First-line treatment of hypertension: critical appraisal of potential role of aliskiren and hydrochlorothiazide in a fixed combination

Savvatis¹,

Westermann²,

Schultheiss³

et al. 2010

IBPC

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Arterial hypertension is one of the major diseases in the Western world. It is an independent cardiovascular risk factor and is associated with increased morbidity and mortality. Several drug classes have been shown to be effective in the treatment of hypertension. Aliskiren is a direct renin inhibitor and belongs to the class of renin-angiotensin-aldosterone system inhibitors. Several large studies have shown that aliskiren is effective in lowering blood pressure, and equivalent in this respect to the angiotensin-converting enzyme (ACE) inhibitors and the angiotensin receptor-1 blockers (ARBs). Furthermore, aliskiren has a safety and tolerability profile comparable with that of the ARBs and slightly better than that of the ACE inhibitors. From a pathophysiologic perspective, it can be combined with hydrochlorothiazide successfully, because it can block the diuretic-induced increase in plasma renin activity. Its combination with hydrochlorothiazide in a single pill has been investigated and shown to be superior to monotherapy with respect to blood pressure control and improvement in patient compliance with therapy. Further studies are needed to show whether aliskiren and its combination with hydrochlorothiazide is effective in preventing cardiovascular events and mortality when end organ damage is present.

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ALLHAT Findings Revisited in the Context of Subsequent Analyses, Other Trials, and Meta-analyses

Cited by 8 publications

References 39 publications

Can ACE Inhibitors and Angiotensin Receptor Blockers Be Detrimental in CKD Patients?

Can ACE Inhibitors and Angiotensin Receptor Blockers Be Detrimental in CKD Patients?

Is renoprotection with RAAS blockade a failed paradigm? Have we learnt any lessons so far?

First-line treatment of hypertension: critical appraisal of potential role of aliskiren and hydrochlorothiazide in a fixed combination

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