What is the relationship between antihypertensive choice, blood pressure lowering, and outcomes in patients with normal and elevated blood pressure, and those with and without coronary heart disease?
In a very sophisticated and complex meta-meta-analysis, we can put together the following picture of pharmacologic treatment of blood pressure: (1) It's the degree of blood pressure that matters; all drugs are equivalent in decreasing coronary heart disease (CHD) and stroke at a given reduction in blood pressure; (2) Beta-blockers are better, at least in the first few years, than other medicines in patients who have had a coronary event; (3) lowering blood pressure is beneficial in patients with and without CHD, though the effect will be greater in the latter group; (4) in patients at high risk, lowering blood pressure is effective even in patients without hypertension; (5) in older patients, 3 drugs used at half their normal doses prevents outcomes to a greater extent than a single drug at its full dose. (LOE = 1a)
Law MR, Morris JK, Wald NJ. Use of blood pressure lowering drugs in the prevention of cardiovascular disease: meta-analysis of 147 randomised trials in the context of expectations from prospective epidemiologic studies. BMJ 2009;338:b1665. [PMID:19454737]
Meta-analysis (randomized controlled trials)
This is one of the most complicated meta-analyses I've read in a long time, running 21 pages long. The authors assembled data from 147 studies evaluating the outcomes of blood pressure lowering by drug therapy in a total of 464,000 patients. The studies were found by searching 3 databases, previous review articles, and citation lists of retrieved articles. Two authors independently extracted the data, using only data from randomized, controlled trials evaluating the effect of blood pressure treatment on CHD events and stroke. Here's where the authors were very creative: They compared the results in the studies with results obtained from epidemiologic studies and trials of drug doses and blood pressure response to extrapolate a dose-response between the drugs and blood pressure and to determine the relationship between cardiovascular mortality and blood pressure lowering. Their goal? To extrapolate from existing data the relationship between lower doses of medication (and the resulting lesser effect on blood pressure lowering) and patient-oriented outcomes. They had 5 outcomes from this analysis: (1) As long as blood pressure is lowered, it doesn't matter how. All medications are equivalent in decreasing CHD events and stroke at a given reduction in blood pressure. (2) Beta-blockers work better than other medications in preventing CHD events in patients with a history of CHD for the first few years after an infarction, reducing subsequent events by 29%, as compared with a 15% decrease with blood pressure lowering with other medicines. (3) Blood pressure lowering is equally effective in preventing CHD and stroke in patients with and without a history of cardiovascular disease, though the absolute risk reduction is greater with secondary prevention since the absolute risk is higher in these patients. (4) The effect on event reduction is due to the relative blood pressure lowering and not due to some other, non-blood pressure effect of drug therapy. (5) Blood pressure lowering is helpful for anyone at high risk of CHD or stroke; reducing blood pressure is effective from any initial level (even "normal"), down to 110 mmHG systolic and 70 mmHg diastolic . (6) In patients aged 60 to 69 years with hypertension, using 3 drugs at half their standard doses produces a greater reduction in outcomes than using 1 drug at its usual dose.
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