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Abstract

People with no previous cardiovascular events or cardiovascular disease represent a primary prevention population. The benefits and harms of treating mild hypertension in primary prevention patients are not known at present. This review examines the existing randomised controlled trial (RCT) evidence. To quantify the effects of antihypertensive drug therapy on mortality and morbidity in adults with mild hypertension (systolic blood pressure (BP) 140-159 mmHg and/or diastolic BP 90-99 mmHg) and without cardiovascular disease. We searched CENTRAL (2011, Issue 1), MEDLINE (1948 to May 2011), EMBASE (1980 to May 2011) and reference lists of articles. The Cochrane Database of Systematic Reviews and the Database of Abstracts of Reviews of Effectiveness (DARE) were searched for previous reviews and meta-analyses of anti-hypertensive drug treatment compared to placebo or no treatment trials up until the end of 2011. RCTs of at least 1 year duration. The outcomes assessed were mortality, stroke, coronary heart disease (CHD), total cardiovascular events (CVS), and withdrawals due to adverse effects. Of 11 RCTs identified 4 were included in this review, with 8,912 participants. Treatment for 4 to 5 years with antihypertensive drugs as compared to placebo did not reduce total mortality (RR 0.85, 95% CI 0.63, 1.15). In 7,080 participants treatment with antihypertensive drugs as compared to placebo did not reduce coronary heart disease (RR 1.12, 95% CI 0.80, 1.57), stroke (RR 0.51, 95% CI 0.24, 1.08), or total cardiovascular events (RR 0.97, 95% CI 0.72, 1.32). Withdrawals due to adverse effects were increased by drug therapy (RR 4.80, 95%CI 4.14, 5.57), ARR 9%. Antihypertensive drugs used in the treatment of adults (primary prevention) with mild hypertension (systolic BP 140-159 mmHg and/or diastolic BP 90-99 mmHg) have not been shown to reduce mortality or morbidity in RCTs. Treatment caused 9% of patients to discontinue treatment due to adverse effects. More RCTs are needed in this prevalent population to know whether the benefits of treatment exceed the harms.

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Health outcomes associated with various antihypertensive therapies used as first-line agents: a network meta-analysis.

Bruce M. Psaty, Thomas Lumley, Curt Furberg … (2003)

Establishing relative benefit or harm from specific antihypertensive agents is limited by the complex array of studies that compare treatments. Network meta-analysis combines direct and indirect evidence to better define risk or benefit. To summarize the available clinical trial evidence concerning the safety and efficacy of various antihypertensive therapies used as first-line agents and evaluated in terms of major cardiovascular disease end points and all-cause mortality. We used previous meta-analyses, MEDLINE searches, and journal reviews from January 1995 through December 2002. We identified long-term randomized controlled trials that assessed major cardiovascular disease end points as an outcome. Eligible studies included both those with placebo-treated or untreated controls and those with actively treated controls. Network meta-analysis was used to combine direct within-trial between-drug comparisons with indirect evidence from the other trials. The indirect comparisons, which preserve the within-trial randomized findings, were constructed from trials that had one treatment in common. Data were combined from 42 clinical trials that included 192 478 patients randomized to 7 major treatment strategies, including placebo. For all outcomes, low-dose diuretics were superior to placebo: coronary heart disease (CHD; RR, 0.79; 95% confidence interval [CI], 0.69-0.92); congestive heart failure (CHF; RR, 0.51; 95% CI, 0.42-0.62); stroke (RR, 0.71; 0.63-0.81); cardiovascular disease events (RR, 0.76; 95% CI, 0.69-0.83); cardiovascular disease mortality (RR, 0.81; 95% CI, 0.73-0.92); and total mortality (RR, 0.90; 95% CI, 0.84-0.96). None of the first-line treatment strategies-beta-blockers, angiotensin-converting enzyme (ACE) inhibitors, calcium channel blockers (CCBs), alpha-blockers, and angiotensin receptor blockers-was significantly better than low-dose diuretics for any outcome. Compared with CCBs, low-dose diuretics were associated with reduced risks of cardiovascular disease events (RR, 0.94; 95% CI, 0.89-1.00) and CHF (RR, 0.74; 95% CI, 0.67-0.81). Compared with ACE inhibitors, low-dose diuretics were associated with reduced risks of CHF (RR, 0.88; 95% CI, 0.80-0.96), cardiovascular disease events (RR, 0.94; 95% CI, 0.89-1.00), and stroke (RR, 0.86; 0.77-0.97). Compared with beta-blockers, low-dose diuretics were associated with a reduced risk of cardiovascular disease events (RR, 0.89; 95% CI, 0.80-0.98). Compared with alpha-blockers, low-dose diuretics were associated with reduced risks of CHF (RR, 0.51; 95% CI, 0.43-0.60) and cardiovascular disease events (RR, 0.84; 95% CI, 0.75-0.93). Blood pressure changes were similar between comparison treatments. Low-dose diuretics are the most effective first-line treatment for preventing the occurrence of cardiovascular disease morbidity and mortality. Clinical practice and treatment guidelines should reflect this evidence, and future trials should use low-dose diuretics as the standard for clinically useful comparisons.