This trial was design to address the uncertainty around the cardiovascular benefits of newer antihypertensive medications (ACE inhibitors and CCBs) with older medications (diuretics and beta blockers). This trial enrolled 6614 patients 70-84 years old with BP at least 180/105mmHg. Patients were randomly assigned to conventional drugs (atenolol, metoprolol, pindolol, or HCTZ plus amiloride) or to newer drugs (enalapril, lisinopril, felodipine, or isradipine). The primary endpoint was a combined endpoint of fatal stroke fatal MI, and other fatal CV disease. There was no difference in the primary outcome of the new drugs and older drugs. Limitations to this trial include the fact that it was open-label. This could have influenced the assessment of some cardiovascular events which rely on the presence of signs and symptoms. In addition, there was considerable cross-over in the trial -- only 61-66% of patients were still on their originally-intended randomized medications at the end of the trial.
Counter-Current Multiplication in the Loop of Henle
The descending limb (blue) equilibrates with the increasingly concentrated medullary interstitium, while the thick ascending limb (green) actively pumps out salt, lowering tubular osmolality and raising interstitial osmolality in a stepwise gradient.
Counter-Current Multiplication in the Loop of Henle
Tubular fluid enters the descending limb (left) at 300 mOsm and equilibrates with the increasingly concentrated medullary interstitium by losing water (blue arrows). In the thick ascending limb (right), salt is actively reabsorbed (green arrows), reducing luminal osmolality. The single effect of ~200 mOsm at each level creates a gradient that is amplified by continuous flow.
The STOP-2 Trial: Lindholm, L. H., Hansson, L., Dahlouf, B., Ekbom, T., Hedner, T., De Faire, U., ... & Wester, P. O. (1996). The Swedish Trial in old patients with hypertension-2 (STOP-hypertension-2): a progress report. Blood pressure, 5(5), 300-304.
The STOP-2 Trial PMID: 8879603
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