Clinical question What is the relationship between antihypertensive choice, BP lowering, and outcomes in patients with normal and elevated BP, and those with and without coronary heart disease?
Bottom line In a very sophisticated and complex meta-meta-analysis, we can put together the following picture of pharmacologic treatment of BP: (1) It's the degree of BP that matters; all drugs are equivalent in decreasing coronary heart disease (CHD) and stroke at a given reduction in BP; (2) betablockers are better, at least in the first few years, than other medicines in patients who have had a coronary event; (3) lowering BP 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 BP is effective even in patients without hypertension; (5) in older patients, three drugs used at half their normal doses prevent outcomes to a greater extent than a single drug at its full dose. (Level of evidence = 1a)
Synopsis The authors assembled data from 147 studies evaluating the outcomes of BP lowering by drug therapy in a total of 464,000 patients. The studies were found by searching three 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 BP 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 BP response to extrapolate a dose-response between the drugs and BP and to determine the relationship between cardiovascular mortality and BP lowering. Their goal? To extrapolate from existing data the relationship between lower doses of medication (and the resulting lesser effect on BP lowering) and patient-oriented outcomes. They had five outcomes from this analysis: (1) As long as BP is lowered, it doesn't matter how. All medications are equivalent in decreasing CHD events and stroke at a given reduction in BP. (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 BP lowering with other medicines. (3) BP 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 because the absolute risk is higher in these patients. (4) The effect on event reduction is due to the relative BP lowering and not due to some other, non-BP effect of drug therapy. (5) BP lowering is helpful for anyone at high risk of CHD or stroke; reducing BP is effective from any initial level (even “normal”), down to 110 mm Hg systolic and 70 mm Hg diastolic. (6) In patients aged 60 to 69 years with hypertension, using three drugs at half their standard doses produces a greater reduction in outcomes than using one drug at its usual dose.
Law MR, Morris JK, Wald NJ. Use of blood pressure lowering drugs in the prevention of cardiovascular disease: metaanalysis of 147 randomised trials in the context of expectations from prospective epidemiologic studies.
BMJ. 2009;338:b1665.