Diuretic or Calcium Channel Blocker for CKD

It has been suggested by researchers that the diuretic clorthalidone should be the first line of antihypertensive therapy with a few caveats. Firstly in the presence of certain co-morbidities other drugs with a proven track record of reducing end organ damage should be instituted as first line instead. Thus it has been suggested that in patients with diabetic kidney disease and angiotensin receptor blocker (ARB) be commenced early due to its proven reno-protective effects in type 2 diabetics with kidney disease.
The results of the ACCOMPLISH trial as reported in the LANCET may change the above approach.
From the available abstract of the trial;
“ACCOMPLISH was a double-blind, randomised trial undertaken in five countries (USA, Sweden, Norway, Denmark, and Finland). 11 506 patients with hypertension who were at high risk for cardiovascular events were randomly assigned via a central, telephone-based interactive voice response system in a 1:1 ratio to receive benazepril (20 mg) plus amlodipine (5 mg; n=5744) or benazepril (20 mg) plus hydrochlorothiazide (12·5 mg; n=5762), orally once daily. Drug doses were force-titrated for patients to attain recommended blood pressure goals. Progression of chronic kidney disease, a prespecified endpoint, was defined as doubling of serum creatinine concentration or end-stage renal disease (estimated glomerular filtration rate <15 mL/min/1·73 m2or need for dialysis). Analysis was by intention to treat (ITT).”
Of note this is a relatively large trial with a mean follow up of 2.9 years which is adequate. The trial was sponsored by Novartis a large company that manufactures Lotrel a brand of amlodipine. Novartis is one of the largest pharmaceutical companies in the world with annual sales of 42.6 billion USD. The three biggest selling drugs from its pharmaceutical division are DIOVAN, LOTREL and GLEEVEC.
Although a certain degree of bias is suggested by this I would also like to point out that the drug DIOVAN which is one of the major products of the company would also be negatively impacted by the results of this trial. The findings of the study will have to be debated in the scientific literature, however as it stands this interesting finding should give many food for thought when contemplating first line therapy for hypertension.
In my personal experience amlodipine has been a very effective drug at lowering blood pressure however in the past I have tried to avoid using it as first line in those with kidney disease due a theoretical possibility of reducing renal survival and the recommendations of the JNC.
However this study has gone a long way in putting any fears I may have had at rest because at the very least it is not inferior to the diuretic used.
The question does remain though is HCTZ as good an antihypertensive as chlorthalidone and why wasn’t chlorthalidone used in this study. This would have allowed the results to be more directly compared with the ALLHAT study one of the most significant studies in hypertension.