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Quality-adjusted meta-analysis of the hypertension/coronary dilemma
I Holme1, L G Ekelund, I Hjermann
1Life Insurance Companies' Institute for Medical Statistics, Oslo, Norway.
Insights
High-quality hypertension drug trials show significant coronary heart disease (CHD) prevention. Meta-analysis confirms antihypertensive therapy reduces CHD incidence, with efficacy varying by study quality and patient risk.
Area of Science:
- Cardiovascular Medicine
- Clinical Trials Methodology
- Public Health
Background:
- Antihypertensive drug therapy is a cornerstone in managing hypertension.
- The impact of antihypertensive drug therapy on coronary heart disease (CHD) incidence requires rigorous evaluation.
- Assessing the quality of randomized drug trials is crucial for reliable meta-analyses.
Purpose of the Study:
- To evaluate the quality of randomized drug trials investigating antihypertensive therapy's effect on CHD incidence.
- To determine if antihypertensive drug therapy reduces CHD in hypertensive patients based on trial quality.
Main Methods:
- Primary investigators of 11 randomized drug trials in hypertension were surveyed.
- A quality score was developed using principal component analysis of 12 questions.
- Meta-analysis was performed incorporating the quality score to assess CHD outcome.
Main Results:
- High-quality trials, such as SHEP, demonstrated significant CHD prevention.
- Inclusion of lower-quality trials (e.g., HDFP) altered the estimated treatment effect.
- Meta-analysis of top-quality studies indicated a 14% CHD preventive efficacy, rising to 16% with lower-quality trials included.
- Efficacy varied by trial location (US vs. elsewhere) and patient risk level.
Conclusions:
- Antihypertensive drug therapy effectively reduces CHD incidence.
- Study quality significantly influences the estimated efficacy of antihypertensive therapy.
- Higher-risk patients appear to benefit more from antihypertensive interventions.
Abstract:
Primary investigators of randomized drug trials in hypertension were invited to rate quality of such trials. The intention of the survey was to ask if antihypertensive drug therapy reduces incidence of coronary heart disease (CHD) in hypertensive patients. Response was obtained for 7 of the 11 invited investigators, covering 69% of patients and 75% of CHD cases. Principal component analysis was used to construct a quality score based on answers to 12 questions along visual analog scales. The score correlated well with the answer to a global question of overall quality given by the raters. No systematic tendency toward favoring one's own trial could be demonstrated, therefore, all raters have contributed to the rating. The trials with the highest rated quality to answer the research question were Systolic Hypertension in the Elderly Program (SHEP), Australian National Blood Pressure Study, Medical Research Council, Veterans Administration, and European Working Party of Hypertension in the Elderly. The large Heart Detection and Follow-up Program (HDFP) trial was rated at 11th place among the trials with a score of < 40% of the SHEP. The small trials performed in the 1960s were placed at the bottom of the ranking list. Because SHEP is the only trial without diastolic hypertension, results were given with and without SHEP results. When incorporating the quality score into a meta-analysis of CHD outcome, results were dependent on whether SHEP was included or not. For diastolic hypertension only, the effect of therapy was estimated to be about 8% for all higher quality studies, whereas inclusion of the lower quality HDFP changed it to 14%. When isolated systolic hypertension trial was pooled with the others, no major relation to quality rating was observed. A 14% CHD preventive efficacy was established when pooling the three top quality studies. This stayed unchanged until HDFP at rank 11 was included raising this estimate to 16%. Inclusion of the two latest published trials in the elderly, the Medical Research Council trial of treatment of hypertension in older adults and the Swedish Trial in Old Patients with hypertension, did not change this overall estimate of 16% (standard error = 3.8%). It is concluded that if all randomized drug trials in hypertension had the same treatment efficacy, the estimated CHD prevention would be in the range of 15%. Subgroup analyses revealed no relationship to age, but a difference in efficacy was shown depending on whether the trials were performed in the United States or elsewhere. Also, patients at higher risk levels showed better benefit than lower risk patients.