Smoking, Antihypertensive Treatment Benefit, and Comprehensive Antihypertensive Treatment Approach: Some Thoughts on the Results of the International Prospective Primary Prevention Study in Hypertension

Several major studies investigated the possibility of a primary preventive effect of β-blockers. The International Prospective Primary Prevention Study in Hypertension (IPPPSH) compared a β-blocker-containing vs. a non-β-blocker-containing antihypertensive regimen in 6,357 moderate-severe hypertensive men and women treated over 3–5 years. Blood pressure (BP) control was comparable with either regimen. β-Blocker treatment was associated with less hypokalemia, earlier electrocardiogram normalization, and fewer withdrawals for uncontrolled hypertension. In agreement with the Medical Research Council (MRC) trial on mild hypertension and the Heart Attack Primary Prevention in Hypertension (HAPPHY) trial, but at variance with the Primary Prevention Metoprolol in Patients with Hypertension (MAPHY) study, cardiac event rates were similar in β-blocker- and non-β-blocker-treated patients. With either regimen, in-study BP reduction was associated with a lower rate of stroke as well as of cardiac events. In a subgroup analysis, nonsmokers appeared to derive β-blocker benefit, the results being similar to those of the MRC. Smokers required higher doses of drugs to achieve diastolic target pressure, had a higher heart rate and hematocrit, and a higher cardiac event rate than nonsmokers at any given level of diastolic pressure. Except for the MAPHY trial, these primary prevention studies do not support the concept of a cardiac primary preventive effect of antihypertensive β-blockade but stress the importance of good BP control and a comprehensive risk factor prevention approach in the management of hypertensive patients.