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The effects of antihypertensive drugs in different clinical settings : lessons learned from two systematic reviews and a clinical trial Perez Garcia, Marco Antonio I.


Context: The ultimate goal when using anti-hypertensive drugs is to reduce adverse health outcomes. In acute clinical settings, total all-cause mortality is the best measure of net health effect (benefit minus harm). Objectives: a) To determine the effects of anti-hypertensive drugs on all-cause mortality compared to a control in hypertensive emergencies and acute cardiovascular events b) To learn randomized controlled trial (RCT) methodology. Methods: Two systematic reviews were conducted of published RCTs evaluating blood pressure (BP) lowering drugs. The first review was limited to patients with a hypertensive emergency. The second was limited to patients treated within 24 hours of an acute cardiovascular event. A parallel RCT was conducted in hypertensive outpatients comparing the blood pressure lowering effect of hydrochlorothiazide with two psychological interventions. Results: In hypertensive emergency patients, 15 RCTs (N=869) studying nitrates, ACE inhibitors, calcium channel blockers (CCBs), alpha-1 adrenergic antagonists, diuretics, and direct vasodilators were analyzed. There was no evidence for an effect on mortality with any of these drug classes. In the acute cardiovascular event review, sixty-five RCTs (N=166,206) were analyzed, involving four classes of anti-hypertensive drugs. Acute stroke was studied in 6 RCTs and acute myocardial infarction (AMI) in 59 RCTs. Immediate treatment with nitrates in patients with AMI significantly reduced all-cause mortality at 2 days (RR 0.81, 95%CI [0.74, 0.89], p<0.0001, ARR 0.4 %). Immediate treatment with ACE-inhibitors significantly reduced mortality only when continued for 10 days (RR 0.93, 95%CI [0.87, 0.98] p=0.01, ARR 0.4%). The other classes did not reduce all-cause mortality. Conducting the RCT assisted with and improved the critical appraisal of RCTs analyzed in the systematic reviews and prepared me to design and conduct a large high-quality RCT. Conclusion: In patients with suspected or definite acute myocardial infarction nitrates administered immediately and continued for 2 days reduce all-cause mortality at 2 days. In the same clinical setting ACE inhibitors started within 24 hours and continued for 10 days reduce mortality at 10 days. There is no RCT evidence that anti-hypertensive drugs reduce mortality in hypertensive emergencies.

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