I want to talk today about combination therapy.

When the VALUE study was reanalyzed, they found that people whose blood pressure was controlled quickly in that study seemed to do better. By "quickly" I mean within a month and certainly within the first year. Two-drug therapy has been recommended by Joint National Committee 7 and to some degree by the Europeans and also by the recent National Institute for Health and Clinical Excellence guidelines from the United Kingdom, but it seems that very few clinicians actually start patients with 2 drugs. One of the ideas was to see how patients who were started on 2 drugs did relative to people who were started on 1 drug. This is a very important question and one that would be very difficult to solve with the usual clinical trial, so in Lombardi, Italy,[1] where close to 9 million people receive care and prescriptions through their national health service, investigators looked at what happened over a 5-year period (on average) in people who began antihypertensive therapy with 2 drugs compared with those who received 1 drug. These investigators did a very interesting analysis in which the 9 million people were reduced down to about 209,000 by excluding patients who didn't have 1 year of follow-up, patients who already had cardiovascular disease, and those who had been receiving treatment in the previous 3 years. These investigators conducted a nested case-control study. They looked at the patients who had cardiovascular disease (both cerebrovascular and coronary disease) and the patients who didn't, and matched them as well as possible. There were more than 10,000 cases of cardiovascular disease in that time period, and these were compared with 32,000 individuals who didn't have cardiovascular disease but were also in the database. Of interest, relatively few individuals began with 2 drugs. Many were switched from 1 drug to 2 drugs during the observational period. Some stayed on only 1 drug for the entire time. Relatively few individuals who started with 2 drugs did significantly better with respect to number of events than people who started with 1 drug. The people who started with 1 drug and had a second drug added did exactly the same with respect to outcomes as people who started with and stayed on only 1 drug. In a somewhat different way, this supports the idea that we should be starting with 2 drugs, certainly in high-risk individuals. There was an 11% reduction in overall cardiovascular mortality -- 8% for coronary disease and 12% for cerebrovascular disease. Of interest, even in this Italian population, the number of individuals with cerebrovascular disease was almost as high as the number who had coronary disease. This supports the idea that we should be aggressive with therapy. These investigators looked at various adjustments of therapy and whether the patients had other cardiovascular risk factors. It wasn't clear what drugs were being used to treat these patients. We can glean important information from studies other than clinical trials. Clinical trials suffer from not necessarily resembling real life. This Lombardi study resembled real life: This is what people did; these are the drugs people took; this is where they went to get their medicine, and it was possible to tell whether prescriptions were refilled. It is very important for us to bear in mind that we might need to start most patients with hypertension on more than 1 drug. Thank you very much