The missing link ACCOMPLISH

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The missing link is not ACCOMPLISHED yet (I) : 

The missing link is not ACCOMPLISHED yet (I) An analysis that is based on potassium levels or the presence of hypokaliemia is lacking from the study may explain the differences SHEP: those receiving clorthalidone who presented hypokaliemia had a risk fro events similar to the risk among those receiving placebo The use of HCTZ may have had an effect on the results\ MRFIT: amended to recommend the use of chlorthalidone rather than HCTZ at the initial diuretic for the intervention group (increased mortality in clinics using predominantly HCTZ, while shifting in chrorthalidone at these clinics was associated with improved outcomes) Renin levels??????? Maybe it is time to better define the population that was tested in studies such as ACCOMPLISH trial Parra D, Rosenstein R, NEJM 2009;360: 1147-1148

The missing link is not ACCOMPLISHED yet (II) : 

The missing link is not ACCOMPLISHED yet (II) At baseline >50% had a previous CAD event Withdrawal of CCBs in 36% of patients who were receiving CCBs at baseline, lack of washout phase, exclusion of CCBs fro symptomatic angina Concomitant drug therapy (??) 47% of patients at baseline were taking b-blocker. Did they continue receiving such drugs (it is not recommended in high risk patients)? Use of loop diuretics was permitted but not reported. ABPM not yet available

Slide 3: 

Jamerson K et al, NEJM 2008;359:2417-28

ALLHAT vs. ACCOMPLISHa full spectrum outcome difference : 

ALLHAT vs. ACCOMPLISHa full spectrum outcome difference HCTZ 25mg or less/day are less protective than full doses of amlodipine or doses of diurerics used in previous trials

Authors reply : 

Authors reply Hypokaliemia had no significant interaction with CV events MRFIT data are not definitive (experts opinion to recommend thiazide-like diuretics) Renin assays would be reasonable in clinical studies without combination regimens (like ACCOMPLISH) targeting both the renin and volume components of hypertension. B-blockers were continued in all patients for whom these drugs were indicated Furosemide 5% (HCTZ group) vs. 8% (amlodipine group) ALLHAT vs. ACCOMPLISH had different designs (monotherapies vs. combinations) The difference on outcomes might reflect the overall lower BP achieved in ACCOMPLISH

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