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Incremental effects of antihypertensive drugs: instrumental variable analysis.

ABSTRACT: OBJECTIVES:To assess the incremental effects of adding extra antihypertensive drugs from a new class to a patient's regimen. DESIGN:Instrumental variable analysis of data from SPRINT (Systolic Blood Pressure Intervention Trial). To account for confounding by indication-when treatments seem less effective if they are administered to sicker patients-randomization status was used as the instrumental variable. Patients' randomization status was either intensive (systolic blood pressure target <120 mm Hg) or standard (systolic blood pressure target <140 mm Hg) treatment. Results from instrumental variable models were compared with those from standard multivariable models. SETTING:Secondary data analysis of a randomized clinical trial conducted at 102 sites in 2010-15. PARTICIPANTS:9092 SPRINT participants with hypertension and increased cardiovascular risk but no history of diabetes or stroke. MAIN OUTCOMES MEASURES:Systolic blood pressure, major cardiovascular events, and serious adverse events. RESULTS:In standard multivariable models not adjusted for confounding by indication, addition of an antihypertensive drug from a new class was associated with modestly lower systolic blood pressure (-1.3 mm Hg, 95% confidence interval -1.6 to -1.0) and no change in major cardiovascular events (absolute risk of events per 1000 patient years, 0.5, 95% confidence interval -1.5 to 2.3). In instrumental variable models, the addition of an antihypertensive drug from a new class led to clinically important reductions in systolic blood pressure (-14.4 mm Hg, -15.6 to -13.3) and fewer major cardiovascular events (absolute risk -6.2, -10.9 to -1.3). Incremental reductions in systolic blood pressure remained large and similar in magnitude for patients already taking drugs from zero, one, two, or three or more drug classes. This finding was consistent across all subgroups of patients. The addition of another antihypertensive drug class was not associated with adverse events in either standard or instrumental variable models. CONCLUSIONS:After adjustment for confounding by indication, the addition of a new antihypertensive drug class led to large reductions in systolic blood pressure and major cardiovascular events among patients at high risk for cardiovascular events but without diabetes. Effects on systolic blood pressure persisted across all levels of baseline drug use and all subgroups of patients.

SUBMITTER: Markovitz AA

PROVIDER: S-EPMC5736968 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature

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Incremental effects of antihypertensive drugs: instrumental variable analysis.

Markovitz Adam A AA Mack Jacob A JA Nallamothu Brahmajee K BK Ayanian John Z JZ Ryan Andrew M AM

BMJ (Clinical research ed.) 20171222

<h4>Objectives</h4>To assess the incremental effects of adding extra antihypertensive drugs from a new class to a patient's regimen.<h4>Design</h4>Instrumental variable analysis of data from SPRINT (Systolic Blood Pressure Intervention Trial). To account for confounding by indication-when treatments seem less effective if they are administered to sicker patients-randomization status was used as the instrumental variable. Patients' randomization status was either intensive (systolic blood pressur ...[more]

PMID: 29273586

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Project description:Past research on the associations between area-level/contextual social capital and health has produced conflicting evidence. However, interpreting this rapidly growing literature is difficult because estimates using conventional regression are prone to major sources of bias including residual confounding and reverse causation. Instrumental variable (IV) analysis can reduce such bias. Using data on up to 167,344 adults in 64 nations in the European and World Values Surveys and applying IV and ordinary least squares (OLS) regression, we estimated the contextual effects of country-level social trust on individual self-rated health. We further explored whether these associations varied by gender and individual levels of trust. Using OLS regression, we found higher average country-level trust to be associated with better self-rated health in both women and men. Instrumental variable analysis yielded qualitatively similar results, although the estimates were more than double in size in both sexes when country population density and corruption were used as instruments. The estimated health effects of raising the percentage of a country's population that trusts others by 10 percentage points were at least as large as the estimated health effects of an individual developing trust in others. These findings were robust to alternative model specifications and instruments. Conventional regression and to a lesser extent IV analysis suggested that these associations are more salient in women and in women reporting social trust. In a large cross-national study, our findings, including those using instrumental variables, support the presence of beneficial effects of higher country-level trust on self-rated health. Previous findings for contextual social capital using traditional regression may have underestimated the true associations. Given the close linkages between self-rated health and all-cause mortality, the public health gains from raising social capital within and across countries may be large.

Dataset Information

Incremental effects of antihypertensive drugs: instrumental variable analysis.

Publications

Incremental effects of antihypertensive drugs: instrumental variable analysis.

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